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If you stepped outside and were immediately met with a disgusting amount of smoke, then you came to the right place. Originally gaining traction for their ability to protect against Covid-19, N95 face masks are resurfacing due to the ongoing Canadian wildfires. If you, like me, reside in hazy New York City (the place with the worst air quality in the world, according to IQAir), then you should really listen up.

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Per the Centers for Disease Control and Prevention (CDC), “An ‘N95’ mask, properly worn, will offer some protection. If you decide to keep a mask on hand, see the Respirator Fact Sheet provided by CDC’s National Institute for Occupational Safety and Health.”

The CDC’s endorsement is all you need to know that it’s time to stock up on N95 masks again. Keep reading for must-know information regarding the wildfire smoke and which N95 masks have been approved by the National Institute for Occupational Safety and Health (NIOSH). Many of them are available on Amazon, and if you have a Prime membership, you can get them shipped to you even faster.

What is wildfire smoke?

The CDC explains, “Wildfire smoke is a mix of gases and fine particles from burning vegetation, building materials, and other materials. Wildfire smoke can make anyone sick. Even someone who is healthy can get sick if there is enough smoke in the air. Breathing in smoke can have immediate health effects.”

What are the health effects of wildfire smoke?

According to the CDC:

You should note that older adults, pregnant women, children and people with pre-existing respiratory and heart conditions are especially prone to these health effects after breathing in wildfire smoke.

How to protect yourself against wildfire smoke

According to the CDC:

  • Look at local air quality reports and the US Air Quality Index

  • Check out visibility guidelines if available

  • If told to do so, stay indoors and keep your indoor air as clean as possible

  • Use an air filter

  • Do not add to indoor pollution

  • Follow your doctor’s instructions if you have a respiratory or heart condition

  • Do not solely rely on dust masks for protection

  • Avoid smoke exposure when outdoors

We’ve also found it helpful to follow Dr. Lucky Tran, the Director of Science Communication and Media Relations and Columbia University Irving Medical Center, on Twitter for insights as to what the heck is going on with the wildfire smoke.

Don’t forget, N95 respirator masks also protect against Covid-19, which is not as rampant as before, but is still present. Keep reading for more information on the coronavirus and how N95 masks can help keep you safe.

Covid-19 is still affecting people, despite its spread slowing down recently. The best precaution you can take is to wear a face mask. To help combat the spread of this particularly contagious variant, the CDC recommends that we all opt for N95 and KN95 masks.

While any mask is better than no mask, it’s a well known fact that N95 options are more ideal to protect yourself and others against Covid-19. It might be time to ditch your cloth face masks, since they don’t provide the best defense against the virus.

You might be wondering about the difference between masks (i.e. cloth) and respirators (i.e. N95). “Masks are designed to contain your respiratory droplets and particles. They also provide you some protection from particles expelled by others,” according to the CDC’s website. Meanwhile, “Respirators are designed to protect you from particles, including the virus that causes COVID-19, and in doing so they also contain your respiratory droplets and particles so you do not expose others.”

Getting the correct type of respirator mask is super important. “The N95 respirator is the most common of the seven types of particulate filtering facepiece respirators,” wrote the CDC. “This product filters at least 95 percent of airborne particles but is not resistant to oil-based particles.”

When worn, an N95 mask should form a tight seal on your face. Make sure you don’t try to wash your N95 respirators, since they’re disposable (a.k.a intended for single-use). Definitely throw yours away when it has become dirty, broken or difficult to breathe through.

You’ll know you have an N95 mask when it has a cup, flat fold or duck bill shape, two straps that wrap around your head and a bendable wire nose bridge. You should not wear an N95 mask if you have certain types of facial hair, mistakenly purchased a counterfeit mask or if you’re already wearing a mask or second respirator.

Additionally, the CDC advises against using N95 respirators with “surgical” in the name, as healthcare personnel should get those masks first. 

The next question is what the heck are KN95 masks and how do they vary from N95 ones? KN95 face masks are manufactured in China and therefore must fulfill different certification requirements than ones made in the United States. They also fasten around your ears. On the other hand, N95 masks must satisfy guidelines established by the National Institute for Occupational Safety and Health (NIOSH), and they wrap around your head for a closer fit. The CDC has a list of NIOSH-approved N95 respirator masks posted on its website, as well as a list of counterfeit respirators and how to spot fakes

A quick note on KN95 face masks: “About 60 percent KN95 respirators in the United States are counterfeit (fake) and DO NOT meet NIOSH requirements,” wrote the CDC. So, before you check out, be sure you know for certain that the one you’re buying is real. 

Either way, N95 and KN95 options are far more effective than cloth and surgical ones, and certainly better than not wearing a face mask at all. But to make things easier on you, we’ve rounded up nine NIOSH-approved N95 respirator masks that you can shop right now. (For the sake of being able to cross check with the CDC’s list of NIOSH-approved N95 respirators, we’ve only included N95 options, below.)

Shop the following eight NIOSH-approved N95 masks to stay safe out there.

Kimberly-Clark Professional N95 Pouch Respirator Amazon

Photo: Kimberly-Clark.

Kimberly-Clark Professional N95 Pouch Respirators

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This mask’s pouch design gives you tons of breathing space and added comfort. The box of 50 masks is great for the long haul and also happens to be a whopping 55 percent off right now.

Fangtian N95 Masks Amazon

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Fangtian N95 Masks

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$18.88


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This 10-pack of masks has all the makings of a quality N95 respirator. Plus, it’s marked down by an impressive 42 percent.

Xiantao Zhong Yi N95 Face Masks

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Xiantao Zhong Yi NIOSH N95 Foldable Masks

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This cup style N95 respirator mask has a foldable design that makes it easy to store. Stock up on this on-sale pack of 20.

3M Aura Particulate Respirator N95 Foldable Masks The Home Depot

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3M Aura Particulate Respirator N95 Foldable Masks

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These masks sport a three-panel design that allows for comfortable movement. The box includes 10 foldable masks.

Honeywell N95 Particulate Disposable Respirators

Photo: Honeywell.

Honeywell N95 Particulate Disposable Respirators

$29.50


$51.25


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These N95 masks are suited with a multilayered absorption media that’s humidity- and moisture-resistant. Grab your box of 50 on major discount.

Harley N95 Respirator Face Masks Bone Fide Masks

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Harley N95 Respirator Face Masks

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These respirator masks are foldable, making them easy to tuck into a bag or drawer. The adjustable nose piece has padded foam to make the masks more comfortable and secure. Get as few as 20 masks in a box or as many as 10,000 (and at a discount, too).

DemeTECH NIOSH N95 Respirator Face Masks Amazon

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DemeTECH NIOSH N95 Respirator Face Masks

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Each of the 20 masks in this pack has six layers of filtration. 

Makrite 9500-N95 Masks

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Makrite 9500-N95 Masks

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This mask’s premium filter material provides low breathing resistance and full protection for at least eight hours.

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In a recent article published in the Lancet Rheumatology, researchers used data from a long-term ongoing prospective cohort study in the Netherlands to compare the characteristics of long-COVID in inflammatory rheumatic diseases patients and healthy controls during the period when the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants, BA.1/BA.2 were dominant.

Study: Post-COVID condition in patients with inflammatory rheumatic diseases: a prospective cohort study in the Netherlands. Image Credit: peterschreiber.media/Shutterstock.com
Study: Post-COVID condition in patients with inflammatory rheumatic diseases: a prospective cohort study in the Netherlands. Image Credit: peterschreiber.media/Shutterstock.com

Background

The symptoms of inflammatory rheumatic diseases and long COVID are overlapping. Hence, it is tedious to classify patients of long COVID among patients of inflammatory rheumatic diseases.

Post-COVID condition is inherently heterogenous and poorly defined; however, it might include many persistent symptoms, such as fatigue, beyond the acute SARS-CoV-2 infection phase. Also, findings of epidemiological studies investigating long COVID have fetched immensely heterogeneous results and remained largely inconclusive.

Per recent studies, persistent inflammation and auto-immune reactions after the acute infection phase play a crucial role in the progression of post-COVID. However, all pathophysiological mechanisms underlying this condition also remain unclear. Thus, it is still unknown whether rheumatic disease patients are more susceptible to long-COVID and their clinical phenotype varies from other people.

About the study

Researchers invited patients aged ≥18 with inflammatory rheumatic diseases from the Rheumatology and Immunology Center in Amsterdam to participate in this retrospective cohort study between April 26, 2020, and March 1, 2021.

The study participants self-recruited their healthy controls with and without a history of coronavirus disease 2019 (COVID-19). Also, they were of comparable age (±5 years) and same gender and had no inflammatory rheumatic disease. It helped the researchers investigate the risk of the post-COVID condition, its symptoms, and the time taken to recover across the two cohorts while accounting for the shared symptoms of both diseases.

They used Kaplan-Meier survival analyses to compare the time taken to recover from long-COVID following Omicron infection between patients of two study cohorts during the first 26 weeks after disease onset. Likewise, they presented the variations in the symptomology of post-COVID condition across both cohorts as bar charts.

The researchers used a regression-based approach for causal mediation analyses to test the hypothesis that the severity of the acute phase of SARS-CoV-2 infection could be a mediator in the association between participant status and long-COVID, as studies have demonstrated that disease severity is a risk factor for the long-COVID in patients with mild COVID-19.

To this end, they collected demographic data of all the study participants using a baseline questionnaire sent on June 25, 2022. The study analyses on long-COVID condition post-Omicron infections covered only those participants who completed this first questionnaire.

 

Further, they calculated E-values for the association between participant status and post-COVID condition, an approach that establishes the robustness of the main study results. In the follow-up questionnaires, they reported their pre-existing diseases, medications, and COVID-19 clinical characteristics. They also collected serum samples during follow-up for analyses of SARS-CoV-2 antibodies testing.

Results

The final analysis set of the study comprised 1974 inflammatory rheumatic disease patients and 733 controls, whose mean age was 59 years. Patients with inflammatory rheumatic disease more frequently suffer from cardiovascular and pulmonary diseases and other health issues like diabetes and obesity.

The World Health Organization (WHO) defines participants with post-COVID as people with symptoms lasting at least eight weeks post-onset or three months of a diagnostic test, like reverse transcription-polymerase chain reaction (RT-PCR) that an alternative diagnosis cannot explain.

After applying the WHO criteria, the authors observed that more inflammatory rheumatic disease patients vs. healthy controls developed long-COVID; however, their symptomology and time to recovery were similar. Though the distribution of symptom types was comparable across groups, insomnia was more common in participants without a COVID-19 history.

Furthermore, they observed that inflammatory rheumatic disease patients with no COVID-19 history were more likely to complain of persistent symptoms characterizing long-COVID than healthy controls with an odds ratio (OR) of 2·52, which exceeded the computed E-values of 1·74 and 1·96.

Conclusions

The study data highlighted that the current WHO criteria for defining long-COVID in inflammatory rheumatic disease patients are inadequate. Thus, rheumatologists should carefully interpret all studies investigating long-COVID based on the WHO criteria. In addition, the authors advocated that rheumatologists adopt a nuanced attitude when informing their patients about the long-term repercussions of COVID-19.

Journal reference:

  • Post-COVID condition in patients with inflammatory rheumatic diseases: a prospective cohort study in the Netherlands, Laura Boekel, Sadaf Atiqi, Maureen Leeuw, Femke Hooijberg, Yaëlle R. Besten, Rosa Wartena, Maurice Steenhuis, Erik Vogelzang, Casper Webers, Annelies Boonen, Martijn Gerritsen, Willem F Lems, Sander W Tas, Ronald F van Vollenhoven, Alexandre E Voskuyl, Irene van der Horst-Bruinsma, Mike Nurmohamed, Theo Rispens, Gertjan Wolbink, Lancet Rheumatol 2023 Published Online May 31, 2022, doi: doi.org/10.1016/ S2665-9913(23)00127-3
    www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(23)00127-3/fulltext
     

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Introduction

Chronic obstructive pulmonary disease (COPD) is a common, preventable, and treatable global health problem characterized by persistent airflow limitation and respiratory symptoms, the most common of which include dyspnea, cough, or sputum. According to the World Health Organization (WHO), COPD is the third leading cause of death worldwide,1 with more than 80% of deaths occurring in low- and middle-income countries.2,3 According to the Burden of Obstructive Lung Disease (BOLD) program and other large-scale epidemiological studies, the prevalence of COPD is expected to increase over the next 40 years as smoking rates increase in developing countries and populations in high-income countries age. As a result, more than 5.4 million people may die annually from COPD and related diseases by 2060.4,5 COPD poses a significant economic and social burden to the public health sector, and therefore effective therapeutic interventions for COPD are currently a research hotspot in the medical field.

It has been found that COPD patients have significantly lower than normal exercise levels in daily life for long periods of time, with a corresponding decrease in muscle mass and strength and associated disuse atrophy,6 leading to a decrease in exercise capacity and quality of life. On March 12, 2020, the World Health Organization (WHO) declared the COVID-19 outbreak a global pandemic.7 The coronavirus attacks the human respiratory system and causes severe respiratory syndrome.8 The pandemic raises questions about the management and treatment of patients with COPD. There is no clear evidence of an increased risk of novel coronavirus infection in COPD patients, and more clinical trials are needed.9 To reduce the virus’s transmission risks, hospital visits for pulmonary rehabilitation for COPD patients are suspended, and COPD patients should be encouraged to stay at home and engage in moderate exercise under professional guidance. Therefore, we believe that in the context of the COVID-19 pandemic, more resources will be devoted to exercise and COPD in the future.

In addition to pharmacological treatments, non-pharmacological treatments can be used as a complement to manage the health of COPD patients. Globally, it is estimated that one in three people currently have a health condition that could benefit from rehabilitation,10 and pulmonary rehabilitation is an important component of non-pharmacological treatment, and pulmonary rehabilitation has been shown to be the most effective treatment strategy for improving shortness of breath, health, and exercise tolerance.11 Exercise is a core component of pulmonary rehabilitation and the most appropriate option for patients in their home conditions. Exercises include endurance training, resistance training, interval training, and flexibility training.12 Multiple lines of evidence suggest that long-term exercise-based pulmonary rehabilitation is better at improving dyspnea, muscle strength, exercise capacity, and quality of life in COPD patients compared to non-exercise programs,13 while reducing the psychological impact of COPD. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends that people with COPD participate in supervised exercise training at least three times a week for 20–30 minutes per exercise session, with a combination of moderate-intensity constant-load or interval training and strength training.14 Moderate-intensity exercise can produce a wide range of health benefits, including reduced inflammation, improved immunity, and reduced respiratory viral infections.15 Therefore, active exercise interventions should be considered a treatment priority for this population.

Bibliometric analysis is a method of statistical analysis of research results from the perspectives of authors, institutions, keywords, countries, cited authors, journals, and references using analysis software, which helps researchers have a clear understanding of the research field and grasp the research basis, hot issues, and frontier trends in the field.16 In recent years, bibliometrics has been widely used in medical fields such as acupuncture, pain, and regenerative medicine.17–19 Although there have been many publications on exercise interventions and COPD, to the best of our knowledge, these publications have not been analyzed bibliometrically with a visual approach to exercise interventions in COPD. Therefore, this study aims to help researchers understand the research progress and emerging research hotspots in this field by surveying the important collaborative forces, classic conferences, key conferences, and research hotspots in the field of exercise interventions for COPD in the past 22 years, in order to provide better exercise guidance and recommendations for COPD patients.

Materials and Methods

Search Strategy

All publication papers were searched from the Web of Science core collection database. We also used the Science Citation Index Expanded (SCI-Expanded) database of Web of Science (WOS) as the source of available databases. We set the period of publication paper retrieval from January 1, 2000, to December 31, 2021. The data search strategy was “TI = (exercise* OR kinesitherapy OR training OR “physical activity*” OR sport* OR fitness OR walk* OR run* OR swim* OR jog* OR cycling OR pilates* OR yoga OR qigong OR “tai chi”)20 AND TI = (“Pulmonary Disease, Chronic Obstructive” OR “Chronic Obstructive Lung Disease” OR “Chronic Obstructive Pulmonary Diseases” OR “COAD” OR “COPD” OR “Chronic Obstructive Airway Disease” OR “Chronic Obstructive Pulmonary Disease” OR “Airflow Obstruction*Chronic” OR “Chronic Airflow Obstruction*”) AND Language = English”. The publication types were restricted to “article” or “review”, letters, meeting abstracts, published editorials, materials, book reviews, conference presentations, news items, and corrections were excluded.

Analytical Tools

The data was cleaned up before the analysis, including removing duplicate documents and merging similar words. Graphs of the annual number of publications, the annual cumulative number of publications, and the annual total number of citations were produced by Microsoft Excel 2019 to analyze the global outputs and trend of articles related to COPD and exercise. VOSviewer (1.6.17) (Leiden University, Leiden, Netherlands)21 was used to identify productive countries or regions, institutions, the main co-cited journals, co-occurring keywords, and related visual networks. The network map was produced by VOSviewer; the size of nodes reflected the number of articles or the frequency of co-occurrence; the different colors of nodes represented different categories of research topics; the link between nodes represented the co-occurrence relationship, and the size of the link represented the co-occurrence frequency of two nodes. CiteSpace (5.8.R3) (Drexel University, Philadelphia, PA, USA)22 was used to analyze authors and co-cited authors, journals, the strongest citation bursts of references, and keywords. The strongest citation bursts show the growing interest of researchers in potential research at a given time and are a key indicator for identifying emerging hot trends.23 To obtain key clusters, three specialized measures were used: latent semantic indexing (LSI), logarithmic likelihood test (LLR), and the mutual information test (MI). Modular Q values > 0.3 mean that the delineated clustering structure is significant, average silhouettes > 0.5 are considered reasonable for clustering, and average silhouettes > 0.7 indicate that the clustering results are convincing. CiteSpace can help researchers understand the development trend of a field and find research hotspots. CiteSpace was also used to identify centrality, high centrality is often considered a pivotal point in a field.

Results

Annual Publication Outputs and Growth Trend

From 2000 to 2021, a total of 1889 publications met the inclusion criteria, including 1714 articles and 175 reviews (Figure 1), with an average annual production of 85. Graphs of the number of articles and frequency of citations were obtained using Microsoft Excel (Figure 2). Although there were fluctuations during the period, there was an overall upward trend in the annual volume of publications on exercise and COPD. We fitted a polynomial to the annual cumulative volume of publications in Figure 2A, with a growth trend model R² = 0.9991, predicting that more articles on COPD and exercise will be published in the future. Figure 2B shows that 1889 articles were cited 57,747 times (H-index 106), with an average annual citation frequency of 2624 and an all-time high of 5906 citations in 2021. These results suggest that interest in exercise and COPD continues to grow, and the intensity of research will continue to increase.

Figure 1 The flow chart of study screening process.

Figure 2 Number of publications and citations.

Notes: (A) The number of publication outputs and growth trend from 2000 to 2021. (B) The number of annual citations from 2000 to 2021.

Analysis of Country

The 1889 articles were published in 69 countries. For better visualization, we only selected 38 countries with more than 5 articles via VOSviewer (Figure 3). Each node represents a country, and the size of the node represents the number of posts in that country. The larger the node, the greater the number of articles published in this field in that country. In addition, the lines between the nodes represent the connections between countries, and the closer the connections, the thicker the lines. The countries or regions are presented on the world map in Figure 4.

Figure 3 The item density visualization of active countries.

Notes: The higher the density, the closer it is to red. Conversely, the lower the density, the closer it is to blue.

Figure 4 World Map of active countries.

The list of the top 5 countries is presented in Table 1. The USA ranked first with 333 publications, followed by Canada and the United Kingdom, followed by Brazil, and finally Australia. The top five countries in terms of centrality were the USA, followed by the United Kingdom, Canada, Brazil, and Australia.

Table 1 Top 5 Active Countries with Count and Centrality

Analysis of Institution

Overall, 1889 publications on exercise and COPD were coauthored by 2289 institutions. To obtain a better visualization, we only included institutions with at least 20 publications (Figure 5).

Figure 5 Map of active institutions.

The list of the top 5 institutions was presented in Table 2. Queens University has published the largest number of publications (80), followed by the University of Laval (63), the Katholieke University Leuven (54), the University of Sydney (53), and the Maastricht University (46). The University of Laval showed the highest centrality (0.18). From the timeline of articles published by the institution using VOSviewer, the Hasselt University and the Harvard medical school pay more attention to exercise and COPD around 2016.

Table 2 Top 5 Active Institutions with Count and Centrality

Distribution of Journals and Co-Cited Journals

A total of 310 journals published papers on exercise and COPD. Figure 6 shows a dual-map of journals. Citing journals were represented on the left, and cited journals were represented on the right. A line connects the reference logs on the left and the right. In a double-map overlay, the labels are labeled according to the subject discipline. The dual map shows that most journals are from the fields of medicine, medical and clinical. At the same time, most of the journals are cited in the fields of health, nursing, and medicine. Table 3 shows the top 10 academic journals publishing articles related to exercise and COPD research. Respiratory Medicine led the way with 149, followed by the International Journal of Chronic Obstructive Pulmonary Disease with 137, followed by CHEST with 105, European Respiratory Journal with 95, and finally the Journal of Chronic Obstructive Pulmonary Disease with 80. The average impact factor of the top 10 journals by the number of publications was 7.67, with the highest impact factor being the Sixth Ranked American Journal of Respiratory and Critical Care Medicine (IF=21.405). We only included 50 co-cited journals with at least 150 times via using VOSviewer (Figure 7). Ranked by co-citations, the American Journal of Respiratory and Critical Care Medicine ranked first with 1722, followed by the European Respiratory Journal with 1693, CHEST with 1622, THORAX with 1345, and Respiratory Medicine with 1157 (Table 4). The centrality was calculated by CiteSpace, and the journal with the highest centrality was JAMA-Journal of the American Medical Association (0.06).

Table 3 Top 10 Academic Journals

Table 4 Top 5 Co-Cited Journals and Centrality

Figure 6 The dual-map overlay of journals with publications.

Figure 7 Map of co-cited journals with publications.

Analysis of Authors and Co-Cited Authors

The authors’ map was generated using CiteSpace, and 1889 papers were published by 6805 study authors (Figure 8). Each node represents an author, and the larger the node, the more papers were published. The connections between nodes represent cooperation, and the more extensive the connections, the closer the cooperation. The authors’ cooperation map was generated by Cite Space with 770 nodes and 1212 links (Figure 8). The network density was 0.0041. Table 5 lists the top 10 authors who have published papers related to exercise and COPD. They are active professional writers from Canada, the Netherlands, the United Kingdom, Australia, and Spain. The collaboration between authors can be seen in Figure 8. Among the authors, O’Donnell DE, Maltais F, and Neder JA from Canada are closely related, as are Spruit MA and Wouters EFM from the Netherlands, which are mainly related to the region, but there is little connection between the authors from different countries. It indicates that scientific research exchanges and cooperation among countries should be strengthened.

Table 5 Top 5 Active Authors and Co-Cited Authors

Figure 8 Map of authors with publications.

A total of 852 authors had been cited. To get better visualization, we obtained a simplified network structure diagram (Figure 9, N = 852, E = 1246) by pruning the map through Pathfinder. Among all co-cited authors, anonymous authors had been cited 437 times. We would not discuss anonymously cited authors in this part. In addition, Denis E. O’Donnell ranked first, followed by Robert O. Crapo, Spruit Martijn A, Thierry Troosters, and Francois Maltais (Table 5).

Figure 9 Map of co-cited authors with publications.

In CiteSpace, the importance of nodes is highlighted through centrality. In other words, nodes with higher centrality play a greater role in the network. Griffiths, Timothy L, ranked first with the highest centrality (0.26), and he came from the University Hospitals of North Midlands.

Analysis of Co-Cited References

A total of 28,049 references were generated from 1889 records for the analysis of co-cited references. According to the period from 2000 to 2021, the time slice is 1, and the top 5 items with the most citations and the highest centrality during 2000–2021 are selected by CiteSpace.

As shown in Table 6, a key literature review jointly published by author Martijn A. Spruit and other experts in 2013 ranked first with 154 co-citations. This article presented a new definition of pulmonary rehabilitation and described the science and application of pulmonary rehabilitation, including its effectiveness in acutely ill individuals with chronic obstructive pulmonary disease.12 In the co-cited literature, the article with the highest centrality (0.16) was published by Henrik Watz et al in 2008 (Table 6). In a cross-sectional study, high values of systemic inflammation and left heart insufficiency in COPD patients were associated with reduced exercise.24 These cited studies are landmark publications in this field, laying the foundation for future research.

Table 6 Top 5 Co-Cited References in Terms of Counts and Centrality

Analysis of Co-Occurring Keywords

From 2000 to 2021, a total of 4154 keywords appeared in the fields of exercise and COPD. In the VOSview software, we set the display co-occurrence frequency to at least 100 times (Figure 10). Therefore, a total of 23 keywords were frequently cited and grouped into three clusters. The green cluster represents the study of COPD disease manifestations and diagnostic evaluation measures; the blue cluster represents the study of exercise intensity, exercise type, and action site in COPD patients; and the red cluster represents the study of exercise ability, functional status, quality of life and disease prognosis in the process of COPD rehabilitation.

Figure 10 Map of co-occurring keywords with publications.

The centrality of each keyword was calculated using the CiteSpace software. Based on the analysis of co-occurrence frequency and centrality (Figure 10, Table 7), it was found that the maximum co-occurrence frequency was 901 times for “COPD”, followed by “obstructive pulmonary- disease” (673 times), “chronic obstructive pulmonary disease” (556 times), “exercise” (549 times), and “rehabilitation” (501 times). The highest centrality was for “lung disease” (0.07).

Table 7 Top 10 Keywords

Discussion

Research Trends for Exercise and COPD

Based on data collected from the Web of Science core collection database from 2000 to 2021, a total of 1889 articles on exercise and COPD were published in 310 journals. A total of 2289 institutions participated in the research and published papers, which were distributed in 69 countries around the world. From 2000 to 2021, the 1889 papers were cited 57,747 times. To the best of our knowledge, this is the first study using bibliometrics and visual analysis to evaluate trends in exercise and COPD, prospective outcomes, and research hotspots, which may provide directions for future research.

As shown in Figure 2, although the number of publications decreased in 2005, 2013, 2017, and 2019, the number of publications per year increased dramatically from 2019 to 2021, reaching 168 papers and 5906 citations in 2021. With the spread of the idea of “exercise as medicine”,31 appropriate exercise is essential to improving the daily living abilities of COPD patients. In addition, most COPD patients are elderly and have multiple comorbidities such as cardiovascular disease and diabetes, making them more vulnerable to serious complications of COVID-19.32 However, home isolation can delay COPD patients’ recovery. For COPD patients, in addition to regular medication, increased exercise at home for cardiopulmonary rehabilitation is necessary. For example, tai chi increases lung capacity by counteracting the formation of fibrotic scars, thus improving the quality of life and mental status of COPD patients,33 and it is also considered an effective rehabilitation tool for people affected by post-COVID-19. Many countries are gradually starting to focus on the field of exercise interventions for COPD research. The growing trend in the number of papers indicates that this research area has received increasing attention in recent years, and we predict great potential for growth in this research area.

Quality of Global Publications on Exercise and COPD

Countries

As shown in Table 2, the United States ranked first in the exercise and COPD topic studies with the highest number of publications (333) and the highest centrality (0.6). COPD poses a significant economic threat to the United States, and it is the second leading cause of disemployment-adjusted life years (DALY) loss in the United States34, after ischemic heart disease.

In item density visualization (Figure 3), each node on the graph fills in with the color based on the density of the elements surrounding that node. The higher the density, the closer it is to red. Conversely, the lower the density, the closer it is to blue. The density depends on the number of elements in the surrounding area and the importance of those elements. As can be seen from Figure 3, the countries with the most frequent cooperation with the United States include the United Kingdom, Brazil, Canada, Australia, Italy, and Japan, and the countries with the most close cooperation are all developed countries. A strong research culture underpinned by significant public and private funding no doubt supports this. In addition, the top five countries in terms of the number of publications also have high centrality, which indicates that these countries are more active in the international community and have closer cooperation with other countries. It can also be seen from Table 1 that, among the top five countries, only Brazil is a developing country, indicating that developed countries have invested a lot in this aspect.

Institutions

In Table 2, Queens University and Laval University, both from Canada, are ranked first in several publications and centrality respectively. As can be seen from Figure 5, Queens University has the closest connection with Kingston General Hospital, but it still needs to strengthen cooperation with other institutions. The University of Laval has the highest centrality, this shows that the University of Laval is active in this field and works closely with other institutions. Collaboration helps researchers who investigated exercise and COPD share resources and exchange knowledge and ideas, which is crucial for further development. Thus, stronger collaboration networks should be established among more institutions.

Journals and Co-Cited Journals

A total of 310 journals have published papers on exercise and COPD. From the dual map of the journals (Figure 6), most journals focus on the fields of medicine, medical, and clinical, while most of the co-cited journals focus on the fields of health, nursing, and medicine. Table 3 showed that Respiratory Medicine has published more exercise and COPD papers over the past 22 years, with 149 papers, and is the favorite journal of exercise and COPD researchers (IF = 3.415). However, from the perspective of publications, it is not enough to consider only the most influential journal on exercise and COPD. As shown in Figure 7 and Table 4, the most frequently cited journal is the American Journal of Respiratory and Critical Care Medicine, with 1722 co-citation counts and three of the top five citations. We found that the first paper cited in terms of counts was also from the American Journal of Respiratory and Critical Care Medicine. Therefore, we can say that the American Journal of Respiratory and Critical Care Medicine has the greatest influence in this field (IF = 21.405). In terms of centrality, the journal active in exercise and COPD is JAMA-Journal of the American Medical (Table 4), which works closely with other journals. Future scholars should pay more attention to these journals to obtain international information and the latest advances in exercise and COPD.

Authors and Co-Cited Authors

In this study, CiteSpace helped to identify the top authors in terms of numbers of publications and the number of citations (Figures 8 and 9), and the information about author citations in the field contributed to establishing potential co-authorships. As shown in Table 5, Denis E. O’Donnell has the highest number of publications (54) and co-citation counts (563). Griffiths Timothy L. is ranked as the first co-cited author in terms of centrality (0.26). Two authors have made outstanding contributions to this field. Denis E. O’Donnell comes from the department of Respiratory and Critical Care Medicine at Queen’s University and Kingston General Hospital. Robert O. Crapo is from the Division of Pulmonary and Critical Care Medicine at the University of Utah and LDS Hospital. Spruit Martijn A and Thierry Troosters are from the Katholieke Universiteit Leuven, specializing in respiratory rehabilitation and rehabilitation science. Francois Maltais is from the University of Laval.

Denis E. O’Donnell, was the most productive author, with 54 publications. Denis E. O’Donnell mainly studied the respiratory system, general internal medicine, and physiology, including exercise measurement, medical intervention, and improvement of exercise capacity (lung capacity, lung ventilation, etc.) in COPD patients with exercise intolerance.35–39 More attention to his research direction and results will help broaden our thinking and promote innovation. Griffiths Timothy L. is the co-cited author from University Hospitals of the North Midlands, ranking first in terms of centrality. His research direction is the respiratory system, focusing on effective measures to promote lung rehabilitation, such as encouraging outpatient rehabilitation programs for COPD patients, encouraging COPD patients to gradually carry out aerobic physical exercise and lung rehabilitation education to improve the respiratory and skeletal muscle function of COPD patients, and promoting the rehabilitation of lung function.40–42

Greater attention to the research findings of key authors in the field will help open up our thinking and encourage innovation in research.

Research Hotpot for Exercise and COPD

Co-Cited Reference and Reference with the Strongest Citation Bursts

In bibliometric studies, CiteSpace was used to identify landmark publications that are highly cited by scientists and that reflect active frontiers and developments in research.

The article with the highest co-citation counts (Table 6), published in 2013, was found by Spruit et al (154). The author introduced the pulmonary rehabilitation science to the latest data and applications, including various forms of exercise training for patients with chronic obstructive pulmonary disease (COPD), whose condition improved, was clinically safe and effective, and had a curative effect on individual random respiratory diseases, and stressed the importance of pulmonary rehabilitation in chronic disease management.12 The article with the highest centrality (Table 6) was published by Watz et al in 2008 (0.16). In this paper, a cross-sectional study has found that reduced exercise in patients with COPD is associated not only with clinical stages of COPD severity but also with left heart dysfunction and systemic inflammation. The authors advocate that COPD patients should increase exercise. Regular exercise can improve the decline of lung function and reduce mortality.24

The co-cited references in Table 6 showed that the daily exercise level of COPD patients will decrease due to pulmonary dysfunction. However, reduced exercise hurts lung function. Therefore, we should pay attention to the physical management of COPD patients and emphasize the important role of exercise training in pulmonary rehabilitation therapy in COPD management. Strengthening exercise rehabilitation to reduce the degree of lung function decline and speed up the recovery of physical function, the application of home lung rehabilitation training is also increasingly supported.

The significant increase in interest in exercise and COPD is highlighted in the literature with citation bursts. Figure 11 shows the top 20 references co-citations with the strongest citation bursts from 2000 to 2021. From the bursts of cited references, literature from 2001 to 2017 has opened up a hot spot in the study of exercise in COPD.

Figure 11 Top 20 references co-citation with the strongest citation bursts.

Notes: Bold: citation burst strength >30. The light blue bar indicates that the reference has not yet appeared, the dark blue bar indicates that the reference has started to appear, and the red line represents the burst time.

The co-cited references with bursts first occurred in 2003. Between 2003 and 2018, most references had citation bursts. The authors of the top four strongest burst references are Spruit MA, Rabe KF, McCarthy B, and Holland AE. Starting in 2013, the strongest burst came from Spruit MA and her team,12 who updated data on the scientific and applied aspects of pulmonary rehabilitation therapy and highlighted the important role of pulmonary rehabilitation therapy in the management of the chronic disease.

Labels chosen by the log-likelihood ratio test method (LLR) are used in the subsequent discussions.43 The modular Q is 0.6982, the average silhouette is 0.8839, and the map consists of 1196 nodes and 5932 links. The Modular Q values and average silhouettes obtained in the map suggest that the clusters are reasonable. I have compiled six clusters related to the theme (Table 8).

Table 8 Top-Ranked Clusters

“Cycle exercise” is the largest cluster, with 157 references. The cluster has a silhouette of 0.919, indicating that the results make sense. The most active participant in this group is described in a paper published by Bernard et al. This study demonstrated that weakness in COPD was due to muscle atrophy. Periods of prolonged inactivity or lower than normal activity levels in COPD patients lead to a decrease in muscle mass and strength, resulting in peripheral skeletal muscle dysfunction.5

The second cluster is “regular physical activity”, with a silhouette of 0.867, which is one of 134 references. The most actively cited reference in the cluster is a paper published by Rabe et al. This study updated the definition of COPD, spirometry classification, and treatment, and provided new data on COPD morbidity and mortality based on the 2001 report. In addition to smoking as a risk factor, indoor air pollution from other risk factors such as biomass cooking and heating in poorly ventilated dwellings should be considered whenever possible. The study also suggested that emphasis should be placed on establishing good health care teams to ensure that COPD patients are diagnosed and receive timely and effective treatment.27

The third cluster was “physical activity”, with a silhouette of 0.879 and 125 references. The most active reference in this group is a paper published by Vestbo et al. The study revised the original recommendations and proposed three new recommendations: a change in treatment goals, a change in the COPD severity classification system, advocating for a new clinical management approach, and a new assessment system.25

Keywords with the Strongest Citation Bursts

Burst keywords are considered to be indicators of frontier topics or emerging trends. Keywords with citation bursts can reflect the development of a knowledge field. By using CiteSpace, we obtained the top 20 keywords with the strongest citation bursts (Figure 12). The keywords with earlier citation bursts could reflect the subjects that were of concern in the early stages. As can be seen from Figure 12, the words that were concerned in the early stage were lung disease (2000–2004), breathlessness (2000–2005), and randomized controlled trial (2000–2004). The emerging research keywords in recent years are association (2019–2021), impact (2017–2021), and statement (2018–2021). Figure 12 shows us that the early keywords with the strongest citation bursts included lung disease, breathlessness, and randomized controlled trial. We grouped this into three areas:

Figure 12 Top 20 Keywords with the Strongest Citation Bursts.

Notes: The blue bars mean the reference was published; the red bars mean citation burstness.

Disease

According to the statistics of the World Health Organization, respiratory disease is one of the three leading causes of death in the world. Chronic obstructive pulmonary diseases, as common and frequently-occurring diseases of the respiratory system, are common diseases characterized by continuous airflow restriction, with high disability and mortality rates worldwide.44

Clinical Symptoms

Common symptoms of COPD develop from mid-life on, including breathlessness or difficulty breathing, a chronic cough, often with phlegm, and tiredness.44

Intervention

To compare the effects of different interventions on lung function in COPD patients in randomized controlled trials.

The emerging research keywords are “association”, “impact”, and “statement”. Association is defined as the connection between objects. It enables one object to know the properties and methods of another object. Scholars continue to pay attention to the relationship between changes in exercise levels and COPD. According to a study in patients with and without COPD, a decline to a low exercise level was associated with the highest all-cause mortality risk in subjects with and without COPD. Moreover, it seems that being moderately physically active may already have important beneficial consequences in subjects with and without COPD.45 The Respiratory Society addressed various aspects of lung rehabilitation in its 2006, 2013, 2015, and 2018 statements.29 From emphasizing the importance of pulmonary rehabilitation to strengthening pulmonary rehabilitation education for COPD patients. Pulmonary rehabilitation should be included as a primary treatment for patients with COPD.46 An American Thoracic Society/European Respiratory Society statement on pulmonary rehabilitation noted that COPD patients accounted for the majority of the pulmonary rehabilitation treatment population.12 Pulmonary rehabilitation is clinically proven to be effective in improving the clinical outcomes of patients with COPD, such as increased exercise endurance, improved dyspnea, and ultimately improved overall quality of life for patients with COPD. Health care systems are encouraged to provide affordable rehabilitation for COPD patients, which can reduce health care resources and ultimately achieve long-term benefits.47–49 In addition, individualized treatment options, such as optimal exercise intensity and duration, should be provided for patients with COPD. Finally, patients with COPD should improve their compliance and actively participate in pulmonary rehabilitation.29 While there is a lack of evidence that education has a significant effect on the treatment of patients with COPD, self-managed educational activities have a positive impact on improving patients’ quality of life compared to routine care alone, according to the 2018 Respiratory Society statement.49,52 To improve the compliance of pulmonary rehabilitation in COPD patients, it is necessary to change the concept of patients’ education, so that they can actively participate in pulmonary rehabilitation treatment. We believed that a combination of strength and endurance training may be the best strategy for treating chronic respiratory diseases.

The change in focus reflects a trend in the field, with researchers now focusing more on the effects of the disease and providing better advice to patients with COPD.

Strengths and Limitations

This study describes the research status of exercise and COPD through countries, institutions, journals, authors and co-cited authors, keywords, co-occurrence, etc. This provides a great deal of information from different perspectives, showing current and future research trends in this field. As far as we know, this is the first time that VOSviewer and CiteSpace are used for literature analysis in this field. However, there are some limitations in the accuracy of our analysis. First, this study only included literature from the WOS core collection database, which may lead to insufficient data collection and have a certain impact on the outcome. Second, we limited the language to English and omitted non-English literature, which may lead to bias in the study of language-published literature. Furthermore, recently published research is likely to be underestimated, while existing publications with real impact will largely influence the citation indicators of journals, authors, institutions, and countries in the field more significantly over time.

Conclusion

This study analyzed trends and hot spots in exercise and COPD research from 2000 to 2021 using VOSviewer and CiteSpace. The study suggests that the number of papers published in this field will continue to increase in the future. The United States has made the largest contribution to exercise and COPD research, with Queens University and Laval University in Canada as the core institutions. Denis E. O’Donnell is an academic authority on the subject, both in terms of the number of publications and the most cited publications. The American Journal of Respiratory and Critical Care Medicine is the most frequently cited journal (IF = 21.405) and the most influential in the field. The main research interests include COPD manifestations and diagnostic evaluation methods, exercise prescription setting for COPD patients, and changes in exercise ability, functional status, quality of life, and disease prognosis after rehabilitation intervention in COPD. Emerging research focuses on the association between exercise level and COPD and the impact of pulmonary rehabilitation on clinical outcomes and quality of life in patients with COPD, according to COPD-related statements released by the Respiratory Society. Countries, institutions, and scholars should start with exercise and COPD research hotspots, strengthen academic cooperation, and improve the quality of research. The findings of this paper lay the framework for future development of research on exercise and COPD.

Research Ethics

All data used in this study were obtained from the Internet and no animal or human subjects were involved. Therefore, ethics committee approval is not required.

Acknowledgments

The authors show gratitude for Van Eck and Waltman, the inventor of the VOSviewer. The authors also would like to express their appreciation to Professor CM Chen, who invented CiteSpace, which is free to use.

Funding

This study was supported by Grant No.201904010065 from the science and technology program of Guangzhou.

Disclosure

The authors report no conflicts of interest in this work.

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COVID-19 is the disease caused by the coronavirus, SARS-CoV-2.  

COVID-19 variants are continuing to emerge. The World Health Organization (WHO) is responsible for tracking variants of concern and interest

Learn more about variants of concern in Australia.  

Current status

The World Health Organization (WHO) declared the novel coronavirus (COVID-19) a worldwide pandemic on 11 March 2020.

The COVID-19 pandemic declaration is still active.

Learn more about the pandemic and how we are managing it.

Symptoms

COVID-19 is a disease caused by the coronavirus, SARS-CoV-2 virus.

The symptoms of COVID-19 can range from mild to severe.

Some people recover easily while others get very sick. If you test positive for COVID-19 you can experience:

  • fever
  • coughing
  • sore throat
  • shortness of breath.

For more information, see our fact sheet on identifying the symptoms of COVID-19.

Some people do not experience any symptoms (are asymptomatic) but can still pass on the virus.

Long term effects

Most people who test positive for COVID-19 recover completely, but some people may develop Long COVID.

The syptoms of Long COVID differ from that of COVID-19. You can experience:

  • extreme fatigue (tiredness)
  • shortness of breath, heart palpitations, chest pain or tightness
  • problems with memory and concentration
  • changes to taste and smell
  • joint and muscle pain.

Sometimes these symptoms can last weeks or months.

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Early studies of COVID-19 focused on the acute phase of the disease. However, attention has now turned to the long-term consequences of the disease, which are also significant causes of morbidity and mortality. Two studies reported in The American Journal of Pathology, published by Elsevier, seek to understand the drivers of the chronic and sometimes progressive phase of the disease and identify possible pathways for drug treatment.

The COVID-19 pandemic has highlighted the need to better understand both acute and chronic disease triggered by severe respiratory viral infection. The acute phase of disease with severe pneumonia and lung injury dominated early management efforts and research priorities. However, progressive and often long-term disease is also a significant cause of morbidity and mortality. A high percentage of patients with COVID-19 survived the acute infectious illness only to experience a considerable degree of organ dysfunction over a more prolonged period during and after initial hospitalization.

In the first study highlighted here, investigators deliver a roadmap for the pathogenesis of post-viral lung disease and the basis for a drug therapy for long-term COVID-19 and related post-viral conditions. In the second study, investigators used a hamster model of human COVID-19 to study the cause of coagulation abnormalities and microscopic indicators of pulmonary vascular damage associated with severe cases of COVID-19 in humans. Results showed indirect vascular damage, possibly secondary to immune dysfunction, to be a major contributor to vascular damage, suggesting that novel therapeutics targeting the dysregulated immune system may prove effective.

In the study led by Michael J. Holtzman, MD, Pulmonary and Critical Care Medicine, Department of Medicine, and Department of Cell Biology and Physiology, Washington University School of Medicine, Saint Louis, investigators examined a series of autopsies of patients performed long after COVID-19 onset.

Dr. Holtzman explained, "Our research was inspired by the pressing need to understand the COVID-19 crisis, and especially to define the cause of the disease. We examined a series of consecutive fatal cases that came to autopsy between 27 and 51 days after hospital admission. In each patient, we identified a stereotyped bronchiolar-alveolar pattern of lung remodeling with basal epithelial cell hyperplasia, immune activation, and mucinous differentiation. Remodeling regions also featured macrophage infiltration and apoptosis and a marked depletion of alveolar type 1 and 2 epithelial cells. This pattern was very similar to our experimental models of progressive lung disease after respiratory viral infection."

The investigators noted several key scientific impacts based on identifying remodeling regions with basal epithelial cell hyperplasia and metaplasia extending into former alveolar spaces; concomitant dropout of both types of alveolar epithelial cells normally found in these spaces; epithelial stem-progenitor cell differentiation to mucous cells with a mixture of mucosal and submucosal types of mucin production; and macrophage infiltration linked to basal epithelial cell-specific chemokine production.

Dr. Holtzman commented, "Taken together with the results of our previously published animal models of post-viral lung disease, these studies deliver a roadmap for the pathogenesis of post-viral lung disease and the basis for a disease-modifying strategy for long-term COVID-19 and related post-viral conditions. The research defines a pattern of disease that implicates specific cell and molecular targets for therapy. Indeed, we are now developing a drug therapy that aims precisely at fixing those targets."

As the pandemic progressed, physicians frequently reported clinical evidence of coagulation abnormalities and microscopic indicators of pulmonary vascular damage associated with severe human cases of COVID-19, noted Erin E. Ball, DVM, PhD, Department of Pathology, Microbiology, and Immunology, University of California, Davis, and colleagues. A team of investigators led by Dr. Ball injected severe acute respiratory syndrome coronavirus 2 (SARSCoV2) that causes COVID-19 into a Syrian golden hamster model of human COVID-19 to determine the cause of pulmonary vascular damage. At three to seven days post inoculation, they detected SARS-CoV-2 antigen and RNA within airway epithelial cells, pneumocytes, and macrophages, but not associated with blood vessels.

Their results showed that regions of active pulmonary inflammation in SARS-CoV-2 infection were characterized by ultrastructural evidence of endothelial damage with platelet marginalization and perivascular and subendothelial macrophage infiltration. SARS-CoV-2 antigen or RNA was not detectable within affected blood vessels. The investigators had initially assumed the prominent microscopic vascular lesions noted in hamsters between three and seven days post SARS-CoV-2 inoculation would be the result of direct viral infection of cells comprising blood vessels; however, this was not the case.

Dr. Ball added, "These findings suggest that indirect vascular damage, possibly secondary to immune dysfunction, is a major contributor to vascular damage observed in SARS-CoV-2-inoculated hamsters and potentially severe COVID-19 infection in humans. Immune dysregulation resulting in excessive production of pro-inflammatory cytokines, endothelial damage, and platelet hyperactivation is a plausible driving force behind the hypercoagulable state and microthrombosis observed in some COVID-19 patients."

Although this was an observational study, these findings, and particularly the lack of viral association with inflamed vessels together with published data, collectively support a primarily indirect mechanism linking inflammation and hypercoagulability in severe cases of COVID-19. These results suggest that novel therapeutics targeting the dysregulated immune system may prove effective medical countermeasures against COVID-19.

Source:

Journal references:

  • Wu, K., et al. (2023) Lung Remodeling Regions in Long-Term Coronavirus Disease 2019 Feature Basal Epithelial Cell Reprogramming. The American Journal of Pathology. doi.org/10.1016/j.ajpath.2023.02.005.
  • Ball, E. E., et al. (2023) Severe Acute Respiratory Syndrome Coronavirus 2 Vasculopathy in a Syrian Golden Hamster Model. The American Journal of Pathology. doi.org/10.1016/j.ajpath.2023.02.013.

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Guwahati: Covid survivor Nikhilesh Dutta, who fought the virus during the deadly second wave of the pandemic and was hospitalised for nasal bone surgery a few months later in 2021 that compelled him to skip last year’s Class 12 state board exam, pulled off a spectacular success by becoming the state topper in science this year as a private candidate.
Nikhilesh, who hails from Ramdia in Hajo area in lower Assam’s Kamrup district lost his uncle (elder brother of his father), who was a mentor and guide for the joint family, to Covid. Seven members of the family were infected by coronavirus.
In October 2021, just a few months before he was scheduled to appear in Class 12 board examination, he had to undergo the nasal bone surgery in Chennai and it took almost four months for him to recover fully.
By then the exams were just weeks away and the teachers advised him not to appear in the exam due to lack of preparation.
A brilliant student since childhood, Nikhilesh got eighth rank in Class X boards and losing an academic year hurt him. But Nikhilesh had full faith in his capabilities. “Covid almost shattered our dreams. After I recovered from Covid by June, I had breathing problems. I had to undergo surgery in Chennai in October 2021 and could not prepare for board exams. Losing an academic year was painful as I could not appear in the board exam next year,” Nikhilesh told TOI. Nikhilesh’s family took advice from the teachers who suggested skipping the board exam for a year so that below-par performance does not upset him.
Nikhilesh’s father Nagendra Nath Dutta, a retired teacher of Ramdia Girls HS School, was overjoyed at his son’s success. “We had full faith in Nikhilesh’s calibre. Had he not fallen ill, Nikhilesh could have tasted success last year itself,” said Nagendra Nath. He expressed gratitude to Ramanujan Senior Secondary School, where Nikhilesh studied in Class 11 and 12, for giving him the opportunity to do regular classes for an extra year.
Nikhilesh appeared in the all-India medical entrance NEET this year and is eagerly waiting for the results. “There are many entrance tests ahead but I would love to study medical science to serve the society,” he said.



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Human milk-derived extracellular vesicles (HMEVs) are essential components in breast milk that play a significant role in infant health and development. Maternal health could impact the HMEV load; however, the effects of infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remain unclear.

A recent study published on the bioRxiv* preprint server analyzes the impact of SARS-CoV-2 infection during pregnancy on postpartum HMEV molecules.

Study: Prenatal SARS-CoV-2 infection alters postpartum human milk-derived extracellular vesicles. Image Credit: parinoi / Shutterstock.com Study: Prenatal SARS-CoV-2 infection alters postpartum human milk-derived extracellular vesicles. Image Credit: parinoi / Shutterstock.com

*Important notice: bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Background

Human milk provides important nutrients that support infant growth and protect the vulnerable infant against various diseases, including respiratory infections. Bioactive components, including cytokines, adipokines, hormones, lipids, immunoglobulins, growth factors, cells, and extracellular vesicles (EVs) are present in human milk and deliver positive health outcomes to children.

HMEVs are lipid bilayer-enclosed nanoscale vesicles that carry selective molecular cargo from mammary glands. These vesicles can modulate gene expression and cell signaling in infant tissues, with the infant intestinal mucosa appearing to be the primary target of HMEVs.

Previous research has shown that maternal pathological conditions during pregnancy could affect HMEV cargos and lead to potential functional changes in breastfed infants. The exact mechanisms for this have yet to be elucidated.

The coronavirus disease 2019 (COVID-19) pandemic has presented a significant challenge to public health globally. Exposure to SARS-CoV-2 can affect human milk components; however, limited knowledge is available on the impact of maternal SARS-CoV-2 infection during pregnancy on HMEVs.

About the study

Milk samples were retrieved from the IMPRINT birth cohort, with nine prenatal SARS-CoV-2 and nine controls included. After casein micelle disaggregation and defatting, one milliliter (ml) of milk was subjected to a sequential process of centrifugation, ultrafiltration, and qEV-size exclusion chromatography (SC-UF-qEV).

Subsequently, protein and particle characterizations were conducted according to MISEV2018 guidelines. Proteomics and miRNA sequencing were used to analyze EV lysates.

The EVs that were intact were biotinylated for surfaceomic analysis. To predict HMEV functions correlated with prenatal SARS-CoV-2 infection, multi-Omics were employed.

Key findings

Sufficient EVs were isolated from human milk using SC-UF-qEV. Initially, low-speed centrifugation of milk samples enabled the removal of milk fat.

In the early phase of the SC-UF-qEV method, sodium citrate (calcium chelator) was added to disrupt casein micelles. The International Society for Extracellular Vesicles (ISEV) guidelines were followed to validate the presence of HMEVs.

The concentration and size distribution of the isolated HMEV particles were determined through Nanoparticle Tracking Analysis (NTA). The size of the majority of the particles in the HMEV isolate was less than 200 nanometers (nm), which is consistent with the size of a small EV subpopulation. Transmission electron microscopy (TEM) provided information on the cup-shaped nano-scale morphology of the HMEV particles.

Three common EV markers, including CD9, ALIX, and HSP70, were detected using Western immunoblot, which was enriched in the HMEV isolate but not in human milk (HM), microvesicles (MVs), or defatted HM (dHM). CD9 is a surface tetraspanin, ALIX is a membrane protein associated with EV biogenesis, and HSP70 is a cytosolic protein present in EVs.

Principal Component Analysis (PCA), an application of machine learning, was also used to differentiate between HMEVs from HM, dHM, and MVs. Targeted analysis revealed an abundance of CD9, ALIX, and HSP70, along with xanthine dehydrogenase (XDH), lactadherin, and butyrophilin in HMEVs.

Maternal demographic data and HMEV parameters, such as particle number, RNA content, and protein, were not statistically different between the two study groups. The prenatal COVID-19 group tested positive for SARS-CoV-2 about three months before delivery.

Notably, participants from both groups were not vaccinated against COVID-19 before milk collection. HMEV analysis after two weeks of lactation provided insights into how COVID-19 influences the mammary glands and lactation physiology.

The HMEVs isolated from the COVID-19 group were analyzed using surfaceomics, proteomics, and miR-seq. A total of 1,189 proteins and 232 miRs were detected, identified, and quantified in HMEVs. Interestingly, 91 significantly altered proteins upregulated and 35 downregulated were identified.

Based on multi-omics analysis, mothers with prenatal COVID-19 synthesized HMEVs with enhanced functionalities associated with mucosal tissue development and metabolic reprogramming. These also mitigated inflammation and decreased EV transmigration potential.

These findings indicate that breastfed infants appear to be protected against respiratory and intestinal diseases. In vitro, experiments revealed a broad-ranging antiviral activity of HMEVs. 

Conclusions

The authors claim this to be the first study to reveal that prenatal SARS-CoV-2 infection provides protection to infants against viral infections through the enhancement of mucosal site-specific functions of HMEVs.

Nevertheless, these findings require further validation through the use of larger samples. In addition, follow-up across multiple stages of lactation is essential to understand whether changes in HMEV after prenatal COVID-19 are permanent or temporary.

*Important notice: bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:

  • Preliminary scientific report.
    Chutipongtanate, S., Cetinkaya, H., Zhang, X., et al. (2023) Prenatal SARS-CoV-2 infection alters postpartum human milk-derived extracellular vesicles. bioRxivdoi:10.1101/2023.06.01.543234

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The onset of the coronavirus disease 2019 (COVID-19) pandemic led to two years of mounting waves of illness and death, affecting hundreds of millions of people around the world. Even after the outbreak's severity subsided, the potential long-term sequelae of the infection or COVID-19 vaccination continue to be a matter of concern.

A new paper published in the Vaccine Journal reports on the association of COVID-19 vaccination with menstrual cycle abnormalities.

Study: COVID-19 vaccination and menstrual cycle characteristics: A prospective cohort study. Image Credit: GroundPicture/Shutterstock.comStudy: COVID-19 vaccination and menstrual cycle characteristics: A prospective cohort study. Image Credit: GroundPicture/Shutterstock.com

Introduction

Thousands of social media posts and vaccine safety surveillance system reports have described disruption of the menstrual cycle following vaccination with the COVID-19 vaccines. Women have reported longer, heavier, irregular periods and, in some cases, breakthrough bleeding in postmenopausal women.

This has led to many expressing concern about whether these vaccines compromise female reproductive health.

Biologically, a pathway whereby the immune response evoked by a vaccine produces a short-term effect on the endocrine master gland, the hypothalamus, and the linked pituitary-ovarian axis, is quite plausible. This could explain how vaccination could theoretically affect the menstrual cycle.

Acute and temporary effects on menstruation have been reported with typhoid, hepatitis B, and human papillomavirus (HPV) vaccines in prior research.

The current study looks at six major characteristics of the menstrual cycle in association with the menstrual cycle: length, regularity, duration of bleeding, intensity of bleeding, and period pain.

Earlier studies introduced reporting bias, lacked a control group, did not adjust for confounding factors, failed to assess menstrual characteristics other than cycle length, or lacked sufficient follow-up length.

The researchers used data from the Pregnancy Study Online (PRESTO) in the present study. This is a cohort of couples recruited to the survey online.

They were followed up from before conception, none being on fertility treatment. The study period was from January 2021 to August 2022, and the cohort included couples from the USA or Canada.

The study contained approximately 1,100 couples between 21 and 45 years of age. Questionnaires assessed them at baseline, and every eight weeks after that, for up to 12 months. They were asked about COVID-19 vaccination as well as their menstrual cycle characteristics.

What did the study show?

Of the more than one thousand participants, about 14% sent in six follow-up questionnaires, while 65% conceived within the next year. Just over one in ten began fertility treatment, and 2% stopped attempts to conceive. The rest, about 9%, stopped follow-up.

None of the participants were COVID-19 vaccinated at the outset, but almost 40% took one or more doses during the study period. Most of them took the Moderna or Pfizer vaccines, at 32% and 61%, respectively.

Among the vaccinated, seven out of eight were vaccinated from February to May 2021. The majority were better educated, with a higher income, and trying to have their first babies, compared to the unvaccinated group.

After compensating for sociodemographic factors, reproductive and lifestyle factors, and any medical conditions, the researchers estimated any differences in menstrual characteristics in relation to COVID-19 vaccination.

After adjustment, the first dose of the COVID-19 vaccine was associated with a lengthening of the next cycle by a mean of one day. The corresponding increase in the first cycle after the second dose was 1.3 days. Interestingly, the association was stronger from April 2021 to August 2022 than from January to March 2021.

By the second cycle following vaccination, these associations had weakened, indicating the effect to be temporary. Thus, long cycles became more prevalent after the first dose, from ~6% to 11%, but decreased in prevalence for the next cycle, at 7.3%.

There were no strong associations between the vaccination and menstrual cycle regularity, bleed intensity, duration of bleeding, or dysmenorrhea.

Irrespective of the vaccine brand, there was no significant change in the proportion of participants with irregular cycles (15%) after vaccination following the first or second doses. There was no change even after adjusting for a history of COVID-19 or infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

It must be remembered that these were couples trying to conceive, not on contraception, and many were successful. Thus, they could not be followed up for more than a few months after each vaccine dose.

Also, older women were not included in the study by design. Thirdly, most participants were White college graduates.

What are the implications?

The current study shows no significant link between COVID-19 vaccination and menstrual function beyond a short delay of one day in the first cycle following each dose and an equally short-lived increase in the prevalence of long cycles. Both of these changes disappeared by the second cycle post-vaccination.

This temporary effect is probably due to immune system activation, mediated by cytokines that interfere with the hypothalamo-pituitary-ovarian (HPO) axis.

No association with fertility was observed, nor were any other menstrual cycle characteristics shown to undergo alteration in association with COVID-19 vaccination.

Taken together, these results indicate that short-term changes in menstrual cycle characteristics likely do not translate into meaningful differences in fertility."

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In a recent report by the New York Times, it was initially claimed that Meta CEO Mark Zuckerberg was rendered unconscious during a jiu-jitsu match. However, conflicting accounts have emerged since then.

According to Zuckerberg himself and his coach, the incident did not result in him being knocked out but rather involved intense exertion that led to audible grunts. They refute the claim that he was rendered unconscious.

To clarify the situation, Joe Bernstein, the reporter from the New York Times, shared a tweet providing further details on the matter.

The 38-year-old tech billionaire told an interviewer last year that he began studying martial arts during the coronavirus pandemic.

He told podcaster Joe Rogan that the sport’s “primal" nature helped him boost his energy level and tackle challenges at work.

What is Jiu Jitsu and How is it Different from MMA?

Zuckerberg trains with coach Dave Camarillo, who has taught several UFC mixed martial arts (MMA) champions. Unlike MMA, Brazilian-style jiu-jitsu emphasizes fighting opponents through holds and control instead of kicks or striking.

The term “jiu jitsu" originates from the Japanese words “Jū," meaning “gentle," and “Jutsu," meaning “art." It is commonly referred to as the “gentle art."

Also known as yawara, is a form of martial art and combat technique that focuses on unarmed combat using holds, throws, and disabling strikes to subdue an opponent, as per Britannica. It originated among the samurai or warrior class in Japan around the 17th century. Originally developed to complement swordsmanship, jujitsu was a ruthless and pragmatic style aimed at incapacitating or killing adversaries in warfare.

Jujitsu encompassed various fighting systems that involved techniques such as striking, kicking, kneeing, throwing, choking, immobilizing holds, and the use of specific weapons. Central to these systems was the concept of jū, derived from a Chinese character often interpreted as “gentle." However, the term “gentle" in this context refers to the idea of redirecting or yielding to an opponent’s attack while seeking to control it. Additionally, jujitsu practitioners employed the hard or tough parts of their bodies, such as knuckles, fists, elbows, and knees, to target vulnerable points on their opponents.

The popularity of jujitsu declined following the Satsuma Rebellion in 1877 but experienced a resurgence since the 1990s, gaining renewed interest and recognition.

Jijitsu differs from MMA. MMA, short for mixed martial arts, is a comprehensive term that highlights the diverse nature of the sport. Accomplished MMA fighters receive training in a range of disciplines, including karate, muay thai, kickboxing, boxing, taekwondo, sambo, and judo, as per a report by Elite MMA.

The sport gained significant media attention and widespread popularity in the early 1990s, primarily due to the emergence of the successful TV show, UFC (Ultimate Fighting Championship).

The main distinction lies in the focus and techniques employed in each discipline. Brazilian Jiu Jitsu (BJJ) primarily centers around ground grappling, emphasizing takedowns and submissions. It involves techniques to control and submit opponents through joint locks and chokes while on the ground.

On the other hand, MMA (Mixed Martial Arts) combines a variety of striking and grappling techniques. It incorporates strikes, kicks, throws, and ground wrestling styles, along with other martial arts disciplines. MMA fighters need to be proficient in both stand-up striking and ground-based grappling, including takedowns and submissions.

While BJJ is commonly practiced as a component of MMA training, MMA itself encompasses a broader range of techniques and skills. In other words, BJJ techniques can be found in MMA, but MMA practices are not typically incorporated into Brazilian Jiu Jitsu training.

What is the Controversy?

As per MMA News, Mark Zuckerberg encountered a match where things didn’t go in his favor. During this particular bout, it appeared as though he was rendered unconscious by his opponent, as per the referee’s assessment.

However, after the New York Times published an article on Zuckerberg’s Jiu-Jitsu endeavors, both Zuckerberg and his coach, Dave Camarillo, promptly disputed the account. They clarified that the match was halted by the referee upon hearing what was mistaken for snoring, indicating unconsciousness. Zuckerberg and Camarillo assert that the referee misunderstood the situation, as the sounds heard were actually due to heavy breathing, not unconsciousness.

The question of whether Zuckerberg was truly rendered unconscious remains unanswered. Instances have arisen in which referees mistakenly believed a competitor was choked out, only to discover they were not. Conversely, there have also been cases where a competitor was briefly unaware of their unconsciousness, later realizing they had lost consciousness. As a result, the true nature of this particular incident could fall into either category.

When Did Zuckerberg Get Into Training?

Cultural critic Casey Johnston told the New York Times that sports like Brazilian Jiu-Jitsu hold appeal for Silicon Valley individuals as they provide an opportunity to reconnect with a primal fighting spirit, but within a highly structured and formalized context.

“It’s like being on a playground with a bully, but in this new framework," Johnston explained. “It’s not quite choreographed, but the stakes and rules are clear."

For Mark Zuckerberg, who has faced numerous challenges in recent years, including election interference controversies, struggles with his metaverse project, and significant layoffs, this seems to be an opportune time for him to fight back and assert himself, the report says.

It further explains how Zuckerberg is not the only tech mogul to prioritize physical fitness. Amazon’s Jeff Bezos, in his 50s, has notably developed muscular arms, strong shoulders, and impressive vascularity. However, friends of Zuckerberg claim that his newfound fitness routine does not come as a surprise.

Although Zuckerberg initially gained attention as an “indoor cat," a millennial nerd who outsmarted the athletic elites at Harvard, the 39-year-old has been dedicated to physical activities throughout his life. He captained his prep school’s fencing team and became an avid runner in the 2010s.



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An archive photo from the 1950s of medical staff caring for patients in iron lungs in the United States.

‘Iron lungs’ were used to ventilate patients in polio epidemics in the 1950s.Credit: Science History Images/Alamy

The Autumn Ghost: How the Battle Against a Polio Epidemic Revolutionized Modern Medical Care Hannah Wunsch Greystone Books (2023)

The COVID-19 pandemic has brought home the central role of intensive care units (ICUs) in saving the lives of those in critical condition in hospitals today. Yet if you asked most people where the ICU concept came from, few would know that it was an outgrowth of a polio epidemic in Denmark. In her brilliant new book, Hannah Wunsch, an anaesthesiologist and critical-care-medicine specialist at the University of Toronto, Canada, traces the origins of the modern ICU to 1952 and the Blegdam hospital in Copenhagen — something she has written about before in Nature (go.nature.com/45B6snd). There, a series of innovations arose out of dire need, including positive-pressure ventilation (the precursor to mechanical ventilators), blood-gas measurements for pH and carbon-dioxide levels and close monitoring by an interdisciplinary team of nurses, doctors (notably anaesthesiologists), pharmacists and others.

The treatment of one patient, a 12-year-old girl named Vivi Ebert who presented with bulbar paralytic poliomyelitis — in which poliovirus infects the brainstem — forms the centrepiece of Wunsch’s book. Of the first 31 people to be admitted to the Blegdam in the summer of 1952 with paralytic or respiratory polio symptoms, 87% died, 70% within three days. Thanks to interventions including manual ventilation, supervised by anaesthesiologist Bjørn Ibsen, Ebert survived another twenty years, eventually succumbing to pneumonia at the age of 32.

In those early days it took 50 people to provide the muscle power required for round-the-clock ventilation for 6–8 people with paralytic polio. The hospital’s initial success led to more than 1,500 medical and dental students being employed as manual ventilators for patients admitted in the summer and autumn of 1952. Eventually, ‘iron lungs’ — mechanical ventilator machines — took the place of humans, and the ICU concept was built, focusing on the sickest patients, who required a breathing machine and constant monitoring. Over the next few years, the use of ICUs expanded to the treatment of people with major trauma, shock, tetanus and a variety of other acute, life-threatening conditions.

The treatment of polio, the main story of The Autumn Ghost, has rich parallels to the COVID-19 pandemic. In the 1950s, the prevailing hypothesis about the spread of polio was that the virus was inhaled into the body’s upper airways. It took decades for the gastrointestinal transmission route — oral contact with the faeces of an infected person — to become accepted. Similarly, for COVID-19, there was an initial fixation on liquid droplets on surfaces and in the air as the main means of transmission, whereas it was determined later that it was spread predominantly within tiny droplets or aerosols in the air.

Furthermore, a substantial proportion of both poliovirus and SARS-CoV-2 infections were asymptomatic. And both viruses have long-term consequences: for polio, not only potential paralysis, but also the debilitating neuromuscular syndrome that can occur decades later. Long COVID affects 10–12% of infected individuals, with a variety of enduring symptoms that can be incapacitating with potentially more longer-term effects that are yet unknown.

A medical worker takes care of a Covid-19 coronavirus patient on a mechanical ventilator in Japan.

Mechanical ventilators have been at the fore in the COVID-19 pandemiic.Credit: Yasuyoshi Chiba/AFP via Getty

Polio taught us about the efficacy of positive-pressure ventilation for those having difficulty with breathing. With COVID-19, we learnt that ventilating patients while they were lying face down was crucial to good outcomes. For poliovirus, large, randomized trials of γ-globulin — a substance derived from bone marrow and lymph gland cells containing antibodies thought to help fight the virus — had some success in the years before a vaccine became available. For COVID-19, large observational studies were undertaken of treatment with blood plasma from those who had recovered, although a lack of randomized studies makes it hard to assess the treatment’s effectiveness.

Perhaps the most striking difference between the two viruses is how long it was before a vaccine was developed. For SARS-CoV-2, it was 10 months from sequencing the virus to producing results from large, randomized trials demonstrating high levels of vaccine efficacy. Large-scale distribution quickly followed. Poliovirus was identified as the pathogen for polio in 1908, but it wasn’t until 1955 that US virologist Jonas Salk developed the first effective vaccine to be delivered by means of an injection, followed quickly by an oral vaccine developed by US physician and microbiologist Albert Sabin in 1961.

Wunsch provides a detailed history of polio, the iron lung, the rise of the field of anaesthesiology, the development of the Salk and Sabin vaccines and the work at Denmark’s Statens Serum Institute, a medical laboratory in Copenhagen, in manufacturing and rolling out the Salk vaccine ten days after it was announced. But she really hits her stride when she describes those whose lives were saved. Another early patient treated by tracheostomy and hand ventilation at the Blegdam hospital was 26-year-old Rosa Abrahamsen. She was a poet, and her beautiful poems, translated into English for the book, begin several chapters.

The Autumn Ghost might have been improved with a timeline, given that it bounces back and forth at many points. Although the extraordinary progress and innovations made in Denmark were central to the development of ICUs, the contribution of parallel efforts from around the world might not have been adequately highlighted.

When I was at the University of Virginia in Charlottesville in the 1970s, I worked as a respiratory technician on the night shift, maintaining Engström ventilators (alluded to in the book as the “Rolls Royce of artificial respiration”) for patients in the ICU. I had no idea how those ventilators, or indeed ICUs, came to be. But seeing many patients ‘come back to life’ inspired me to go to medical school. Only five decades later, thanks to reading this book, have I learned the remarkable background to these profound innovations — and how the poliovirus radically transformed the future of medicine.

Competing Interests

The author declares no competing interests.

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In a recent article published in JAMA Network Open, researchers performed a cohort study on a voluntary cohort in the United States (US) who opted to share data of surveillance collected using smartphone applications attached to commercially available thermometers. 

This data encompassed body temperature measurements of multiple household members of participating households for October 2019 to October 2022. It helped researchers estimate within-household viral transmission during multiple periods spanning the coronavirus disease 2019 (COVID-19) pandemic.

Study: Smart Thermometer–Based Participatory Surveillance to Discern the Role of Children in Household Viral Transmission During the COVID-19 Pandemic. Image Credit: DarrenBaker/Shutterstock.comStudy: Smart Thermometer–Based Participatory Surveillance to Discern the Role of Children in Household Viral Transmission During the COVID-19 Pandemic. Image Credit: DarrenBaker/Shutterstock.com

Background

The traditional method of discerning within-household viral transmission at a national scale was contact tracing, which is time-consuming and labor-intensive. On the contrary, smart thermometer–based participatory surveillance enables quicker collection of public health-related data using new-age devices, e.g., smartphones. 

More importantly, this syndromic surveillance detects clinical case features early on to complement traditional methodologies.

Notably, during the COVID-19 pandemic, transmission rates of enveloped viruses, such as respiratory syncytial (RSV) and influenza), were low relative to respiratory infections due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

About the study

In the present retrospective study, researchers divided the COVID-19 pre- and pandemic time into multiple periods, as follows:

  1. pre-COVID-19 pandemic period in the US spanned between October 1, 2019, and February 29, 2020; 
  2. between the first COVID-19 outbreak, i.e., from March 1-May 15, 2020, and the fourth ending July 2021, there was a second transmission outbreak that began in May 2020 and ended in September 2020, and a winter wave that ended by March 6, 2021; 
  3. fourth transmission period spanned March 7 and July 14, 2021; 
  4. Delta wave began on July 15 and December 18, 2021; 
  5. Two Omicron waves by sub-variants BA.1/BA.2 and BA.4/BA.5 occurred between December 19, 2021, June 19, 2022, June 20, 2022, and October 29, 2022, respectively.

They considered participants aged 18 years or older as adults and volunteers aged zero to eight as younger, and nine to 17 as older children, respectively. They self-reported their age and gender.

All participating households comprised one or more individuals who used the same thermometer. Thermometer data encompassed body temperature, a timestamp, and the location of the person whose temperature the smartphone-connected thermometer app recorded.

The researchers analyzed inferred household transmission patterns for participating households and compared those across pandemic periods, considering whether schools were open (or not) during that time.

For this, the researchers categorized these patterns, beginning with the index case, as child to child, adult to adult, child to adult, and vice versa. They also analyzed variations based on whether the index case occurred in younger or older children.

Results

The study analysis covered 320,073 households with multiple participants, where 53.6% and 53.7% were female and male adults, respectively. The participants in total, including adults and children, were 862,577. 

Overall, based on participatory surveillance data of >1.4 million individuals in over 800,000 households who all used a smartphone app-connected thermometer, children played an essential role in within-household viral transmissions. 

Based on periods evaluated in this study, household transmissions increased from the fourth pandemic period to the Omicron BA.1/BA.2 wave. 

The number of febrile episodes is a tool for indicating new COVID-19 cases, and the index case is the first fever onset in an inferred household transmission sequence.

There were 354,602 febrile episodes in households with multiple participants, of which 54,506, i.e., 15.4% of cases were inferred household transmissions, which increased from 10.1% between the fourth pandemic period to 17.5% in the Omicron BA.1/BA.2 wave.

During a febrile episode, fever onset is the first body temperature at or exceeding 38°C for rectal and aural readings, 37.8 °C for oral readings, and 37.2 °C for axillary readings.

Over 70% of participating households had a pediatric index case, but this percentage fluctuated weekly between 36.9% and 84.6%. Pediatric-driven viral transmission was higher when schools were open during 2020-2021 and 2021-2022, i.e., two consecutive academic sessions. Children contributed less to inferred within-household transmission during summer and winter school breaks, a consistent pattern for these two US school years.

On average, 70.4% of 38,787 transmissions in 166,170 households with adults and children had a pediatric origin. However, intriguingly, a pediatric index case was up to 0.8 times less frequent during school breaks in the US.

By the end of 2020, viral transmission dropped from 68.4% to 41.7% and from 80.3 to 54.5% at the beginning of 2022. Likewise, viral transmission rates dropped from 81.4% to 62.5% during summer breaks by 2021 and from 83.8% to 62.8% by 2022. The patterns of inferred household transmission persisted over two academic sessions, 2020-2021 and 2021-2022.

Conclusions

Prior studies have also shown that school opening increased respiratory viral transmission, and school holidays decreased the same. Accordingly, in this study, US children represented the majority of index cases after schools reopened in both school years, though these transmissions decreased during summer and winter school breaks.

The study results demonstrated that participatory surveillance using smartphone-connected devices enabled the measurement of infectious disease dynamics at a scale unfeasible with traditional methods.

Also, study personnel or contact tracers did not have to visit households for research investigations. In the future, researchers could collect additional data with onsite visits and validate the inferred respiratory viral transmissions by laboratory testing.

Nonetheless, ensuring equitable access to all systems that leverage digital technologies for data collection is crucial.

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‘36% of people who develop Middle-East Respiratory Syndrome (MERS) have died. While there is no cause for alarm, scientists are stepping up the search for a vaccine.’

A coronavirus, apparently originating in animals before spreading to humans, causing severe respiratory illness. It may sound like a familiar story but it takes a very different turn to the one that led to the global COVID-19 pandemic. 

  • MERS-CoV was first identified in 2012 ‒ it is caused by a coronavirus
  • Large outbreaks have been reported in Saudi Arabia and South Korea
  • Symptoms include fever, cough and shortness of breath, as well as pneumonia and gastrointestinal problems in some patients 
  • MERS is transmitted from camels to humans and from human to human in close contact (such as a healthcare setting)
  • MERS vaccine research helped to catalyse COVID-19 vaccine development ‒ now advances in COVID-19 vaccines may accelerate work on MERS vaccines

 

 

The story begins in Saudi Arabia in 2012 where doctors treating a patient who had presented with a mystery illness identified a new disease. It looked a little like the Severe Acute Respiratory Syndrome (SARS) first seen in 2003, but the fatality rate turned out to be much higher. 

Concern grew as major outbreaks were recorded in Saudi Arabia and South Korea, with cases reported in multiple countries. The disease appears to come from dromedary camels and is most commonly found in regions with relatively high populations of camels. Person-to-person transmission has also been seen in the UK and France. 

As well as posing a public health threat, outbreaks come at an economic cost. South Korea’s 2015 epidemic cost an estimated $8 billion (USD). 

Where are we now?

The good news is that cases appear to have fallen sharply over the past decade. And, where they occur, the size of the epidemics since 2015 have been small ‒ usually less than a dozen cases. 

‘The peaks are getting smaller and smaller,’ Dr Sophie von Dobschuetze,WHO technical lead for MERS-CoV, told a webinar in late May 2023. ‘There has been a real dip since 2020.’ This may be the result of a combination of factors including cases going unreported, the impact of COVID-related social distancing measures, and possible cross-protection from COVID-19 vaccines or infection. 

 

As there are no licensed treatments or vaccines, MERS remains a priority for the WHO, particularly given its potential to spread more widely. ‘The Risk of MERS-CoV emergence and spillover is higher in northern Africa and the Middle East,’ Dr von Dobschuetze said, adding that MERS should be considered in preparing for future pandemics. 

In fact, just as countries that have responded to MERS outbreaks were well prepared for the COVID-19 pandemic, the COVID-19 response will inform preparations for outbreaks of MERS or other respiratory infections. 

 

Dr Emad Almohammadi, Chief Officer for Communicable Diseases in Saudi Arabia, said his country’s One Health Approach ‒ which aims to address human, animal and environmental health in a holistic way, helped it to prepare. 

‘We are using this experience and COVID-19 to prepare for the next pandemic,’ he said. ‘We have put in place stronger surveillance and data sharing, standards and audit of hospitals, training for community engagement, and improved lab capacity.’

The global lab network developed to manage MERS was used to rapidly sequence the SARS-CoV-2 virus ‒ a key step in developing vaccines and COVID-19 tests. 

‘Years of vaccine development for MERS were quickly used for COVID-19,’ said Dr Maria Van Kerkhove, WHO lead on Emerging Diseases & Zoonoses, as well as being the COVID-19 Technical lead. ‘The work we’ve done for MERS, SARS-CoV-2, influenza and arboviruses will help us to prepare for the next pandemic ‒ whatever it may be.’

Preparation, not panic

Experts say there is no need to worry unduly about the threat of MERS. Instead, the goal of highlighting the risk of outbreaks, and experiences of Saudi Arabia and South Korea, is to boost overall pandemic preparedness. 

Dr Sylvie Briand, Director of the Pandemic and Epidemic Diseases Department at the WHO, referred to some of the commentary on social media suggesting that the focus on MERS was a deliberate attempt to replace COVID-related anxiety. ‘That’s not the purpose at all,’ Dr Briand said. ‘MERS has been with us since 2012. If we know the risk well, we can manage it well. Preparedness counts.’

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In a recent study published in the Scientific Reports Journal, researchers compared the expected and actual changes in life expectancy from 2019 to 2020 to assess the coronavirus disease 2019 (COVID-19)-related loss of life expectancy in 27 countries.

Study: The effect of the COVID-19 pandemic on life expectancy in 27 countries. Image Credit: ANDREI_SITURN/Shutterstock.comStudy: The effect of the COVID-19 pandemic on life expectancy in 27 countries. Image Credit: ANDREI_SITURN/Shutterstock.com

Background

The COVID-19 pandemic was one of the most significant public health crises recently, with nearly 600 million cases worldwide and around six million deaths.

However, it is believed that with COVID-19 testing being insufficient and a significant number of mortalities going unreported, the actual mortality rate is higher than what was estimated.

Furthermore, the effect of COVID-19 on various other comorbidities and inconsistencies in classifying COVID-19-related deaths make it challenging to estimate the COVID-19 mortality rates accurately.

Since life expectancy is not affected by age structure or population size and is age-standardized, many studies have used comparisons between life expectancies in 2019 and 2020 to estimate the impact of COVID-19 on mortality rates.

The results indicate that COVID-19 had a significant impact in lowering life expectancy in 2020, with men and racial minorities being disproportionately affected.

However, this method does not account for the intrinsic variations in life expectancy throughout the year due to mortality variations over time, and the year-on-year variations in mortality have to be accounted for to obtain an accurate estimate of the impact of COVID-19 on life expectancy.

About the study

In the present study, the researchers used an improved method for assessing the loss of life expectancy due to COVID-19 while considering the effects of profound and unexpected events on changes in mortality rates.

They used the Lee-Carter model to project the mortality trajectory for 2020, which was then used as a baseline for measuring the impact of COVID-19 on mortality.

The data from the Eurostat, Human Mortality Database, and the Office of National Statistics of the United Kingdom were used to analyze and estimate the life expectancy changes for 27 chosen countries based on the data availability.

These countries were also the earliest affected after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread outside China. The countries included in the study were Canada and the United States (U.S.) from North America, Australia, Japan, Chile, and 22 European countries.

Life tables were constructed for all 27 countries using the mortality data, and life expectancies were estimated for ages 15 and 65 for both sexes since 15 is a significant age in terms of fertility and participation in the labor force, and 65 years is considered the minimum age to be defined as elderly.

The advantage of the Lee-Carter model in projecting life expectancies lies in its ability to consider variations in mortality data from the past years, the minimum involvement of subjective judgment in the process, and its effective model parameter interpretations.

The Lee-Carter model is believed to estimate the loss of life expectancy better since it not only considers the actual decline in life expectancy in 2020 but can also consider the other possible life expectancy variations in the absence of COVID-19.

The model used mortality data since 1990 (except for Chile, which was since 1992) to project the life expectancy trajectory for 2020.

Results

The results indicated that in the absence of COVID-19, the life expectancies in 21 out of the studied 27 countries would have increased in 2020.

Based on the expected changes in mortality between 2019 and 2020, the loss of life expectancy due to COVID-19 in the 27 countries was estimated to be 1.33 years at 15 years of age and 0.91 years at age 65.

These findings indicated that after considering the intrinsic variations across the years, the impact of COVID-19 on mortality was stronger than previously estimated, especially for those countries that had recently been experiencing an increase in life expectancy.

The loss of life expectancy for the 27 countries estimated in the present study was also higher than those reported by previous studies that did not consider the intrinsic variations across the years.

Previous studies reported the loss of life expectancy in the U.S. to be between 1.18 and 1.87 years, while the present study estimated it to be 2.33 years at age 15. Similar increases in the estimates for loss of life expectancy were observed for England and Wales, Italy, Spain, Poland, Bulgaria, and Slovakia.

Furthermore, while the estimates for Switzerland, Denmark, and Belgium were not more significant than previous estimates, the impact of COVID-19 on mortality was primarily underestimated by previous studies.

Conclusions

Overall, based on comparisons between actual life and expected expectancy changes for 2019 and 2020, the findings from this comprehensive assessment of the impact of COVID-19 on mortality suggested that the loss of life expectancy in 2020 due to COVID-19 was more profound than estimated by previous studies, even in high-income countries.

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The non-structural protein 1 (Nsp1) produced by coronaviruses appears to inhibit host protein synthesis in infected cells. Previous studies have shown that the C-terminal domain (CTD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Nsp1 binds to the small ribosomal subunit and inhibits translation. However, it remains unknown whether this is a mechanism that is broadly used by coronaviruses.

In a recent study published on the bioRxiv* preprint server, researchers investigate Nsp1 from SARS-CoV-2, Middle East respiratory syndrome coronavirus (MERS-CoV), and Bat-Hp-CoV using biophysical, structural, and biochemical assays.

Study: Universal features of Nsp1-mediated translational shutdown by coronaviruses. Image Credit: Jerome-Cronenberger / Shutterstock.com Study: Universal features of Nsp1-mediated translational shutdown by coronaviruses. Image Credit: Jerome-Cronenberger / Shutterstock.com

*Important notice: bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Background

Infection with members of the Betacoronavirus (β-CoV) genus causes serious respiratory diseases in humans. A capped 5' untranslated region (5'UTR) marks the start of the approximately 30 kilobase (kb) β-CoV genome, which contains several protein-encoding open reading frames (ORFs) and ends with a polyadenylated 3'UTR.

Many Nsps collectively aid in viral infection through unclear mechanisms. Thus, understanding these mechanisms better could accelerate the development of new therapeutics.

The SARS-CoV-2 Nsp1 CTD binds to the entry region of the messenger ribonucleic acid (mRNA) channel on the 40S subunit, where it sterically clashes with mRNA and inhibits translation. It remains unclear whether Nsp1 proteins from other β-CoVs share this mechanistic action.

About the study

In the current study, Nsp1 proteins from three representative β-CoVs were selected. These included the SARS-CoV-2 subgenus Sarbecovirus, MERS-CoV subgenus Merbecovirus, and Bat-Hp-CoV. Bat-Hp-CoV, which is the only member of the Hibecovirus subgenus, was selected as it binds the human ribosome.

A key aim of this study is to obtain biochemical and structural evidence demonstrating that Nsp1 from all selected β-CoVs mutes the translation of host mRNAs by binding to the mRNA channel of the 40S ribosomal subunit. To this end, paired structural and single-molecule analyses were used to show that the N-terminal domain (NTD) of Bat-Hp-CoV Nsp1 binds to the decoding center of the 40S subunit.

Key findings

The binding of the Nsp1 CTD to the mRNA channel of the 40S subunit was shown to be the conserved mechanism. Furthermore, the evasion of Nsp1-mediated translation inhibition by mRNAs was also documented. Furthermore, the binding of the elusive NTD of Nsp1 to the decoding center of the 40S subunit was visualized using the Bat-Hp-CoV protein as a model system.

Although only the NTD for Bat-Hp-CoV Nsp1 was visualized, the biochemical data suggest that the Nsps from all selected β-CoVs elicit mechanistic effects on translation and binding mode. In vitro translation experiments showed that both the NTD and CTD significantly contribute to translation inhibition across all tested viral systems. Furthermore, the regions of Nsp1 responsible for ribosome interactions appear to be crucial for the selective translation of viral mRNAs.

The evaluation of the relative occupancies of Nsp1 domains on the 40S subunit revealed that Nsp1 forms a bi-partite interaction with the 40S subunit. The CTD of Nsp1 appears to bind with the 40S mRNA entry channel with high affinity. These findings are consistent with a previous model in which the CTD domain anchors the protein on the 40S subunit, and the Nsp1 NTD quickly samples the 40S decoding center.

The Nsp1 NTDs and viral mRNAs first co-evolved and evaded translation inhibition by matching the Nsp1 proteins from the three viruses to their corresponding viral mRNAs.

The next stage was the loss of the translation evasion function, which was caused by mutation of either the critical nucleotides in stem-loop one of the viral 5'UTR or conserved residues of Nsp1 NTD. Thus, the inhibitory potential of Nsp1 is likely reduced if viral mRNAs compete with the 40S subunit to interact with the Nsp1 NTD and block its accommodation into the decoding center.

Conclusions

A fundamental limitation of this study is that an interaction between the viral mRNA and ribosome-bound Nsp1 NTD has yet to be observed directly. Nevertheless, the framework provided here rationalizes a significant amount of scientific literature on the role of Nsp1.

These findings also provide the foundation for additional investigation into how coronaviruses, using viral protein synthesis, balance suppression of the host immune response. Future research is needed to expand upon these findings to ultimately develop effective anti-viral therapeutics targeting Nsp1 activity across Betacoronaviruses.

*Important notice: bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:

  • Preliminary scientific report.
    Schubert, K., Karousis, E. D., Ban, I., et al. (2023) Universal features of Nsp1-mediated translational shutdown by coronaviruses. bioRxiv. doi:10.1101/2023.05.31.543022

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A recent study published in the British Medical Journal evaluated long-term symptoms and outcomes associated with post-coronavirus disease 2019 (COVID-19) condition.

Around 20% to 30% of non-vaccinated individuals suffer from the post-COVID-19 condition. Multiple studies investigating the long-term outcomes of the post-COVID-19 condition have reported that 22% to 75% of affected individuals experienced symptoms longer than one year after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Many such studies comprised specific populations, focused on certain dimensions of the condition, and did not include a prospective follow-up. Moreover, their generalizability could be limited across the spectrum of COVID-19 severity. As such, limited knowledge and the lack of consensus on the core outcome set of the post-COVID-19 condition have resulted in using different outcome measures in observational studies, impacting their comparability.

Study: Recovery and symptom trajectories up to two years after SARS-CoV-2 infection: population based, longitudinal cohort study. Image Credit: p.ill.i / ShutterstockStudy: Recovery and symptom trajectories up to two years after SARS-CoV-2 infection: population based, longitudinal cohort study. Image Credit: p.ill.i / Shutterstock

About the study

The present study comprehensively characterized the post-COVID-19 condition in the longitudinal population-based Zurich SARS-CoV-2 cohort. Adult residents of the Zurich canton, Switzerland, were eligible if they could follow study protocols. Subjects with a confirmed SARS-CoV-2 infection diagnosis between August 6, 2020, and January 19, 2021, were recruited. The comparator group included participants from another study without SARS-CoV-2 infection.

Data obtained from questionnaires were used for analysis. At baseline, the questionnaire captured data on sociodemographics, comorbidities, pre-infection health status, and acute infection. Follow-up questionnaires were administered at multiple time points after infection, which collected information on symptoms and mental and physical health.

The primary outcome was the relative health status at 6, 12, 18, and 24 months post-infection. The outcome was defined using self-reported recovery status and overall health status. Secondary outcomes were the prevalence and severity of symptoms. Self-perceived severity was evaluated using a five-point Likert scale and stratified into mild, moderate, and severe categories. Further, the team assessed the trajectories of symptoms and relative health status between six and 24 months.

Additional scale-based assessments were used to investigate adverse outcomes, such as fatigue, dyspnea, depression, anxiety, stress, and quality of life. Data after reinfection were not considered for analysis. The point prevalence and severity of symptoms and the relative health status were descriptively evaluated at follow-up. The characteristics of participants with different trajectories were compared. The excess risk of symptoms and adverse outcomes was assessed at six months.

Findings

Overall, 1106 individuals participated in the Zurich SARS-CoV-2 cohort. Of these, 788 completed the assessment at 24 months, and 776 completed all questionnaires between six and 24 months. Most participants were symptomatic (86%) during acute COVID-19 and 4.3% required hospitalization. Around 51.2% of participants were females, and 55.2% returned to normal health status in less than one month post-infection. However, nearly 23% of participants did not recover by six months post-infection.

Mild, moderate, and severe health impairment was observed in 16.2%, 3.6%, and 2.7% of participants, respectively. The proportion of participants reporting non-recovery declined over time and was 18.5% at 12 months and 17.2% at 24 months. More than 68% of participants reported continued recovery over time. By 24 months, 13.5% had improved or recovered, 5.2% had worsened health status, and 4.4% had stable health impairment. 

The prevalence of symptoms was similar at follow-up time points at around 51%. However, the prevalence of COVID-19-related symptoms declined from about 29% at six months to 18.1% at 24 months. Notably, most participants with COVID-19-related symptoms reported non-recovery at 24 months. The common symptoms were fatigue, dyspnea, post-exertional malaise, poor concentration or memory, and altered smell or taste.

The proportion of participants with adverse outcomes on scale-based assessments increased shortly after the infection and decreased from one month onwards. By 24 months, the proportion of participants with fatigue, dyspnea, depression, anxiety, and stress was 36.8%, 23.4%, 12.5%, 11.7%, and 7%, respectively. The prevalence of any symptom was higher in the Zurich SARS-CoV-2 cohort compared to non-infected subjects in the comparator group.

The excess risks among infected subjects relative to non-infected participants were the highest for altered smell or taste, post-exertional malaise, reduced memory or concentration, dyspnea, and fatigue. Further, more infected participants had anxiety symptoms at six months than non-infected subjects. There were no differences in the proportions of subjects with stress, depression, or other adverse outcomes.

Conclusions

In sum, around 18% of subjects infected with SARS-CoV-2 reported post-COVID-19 symptoms, and 17% did not attain their normal health status by 24 months after infection. Although many subjects recovered or improved over time, some had worsened health status or alternating courses. In addition, there was strong evidence that infected individuals had an excess risk of symptoms than non-infected subjects.

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In a recent article published in The Lancet, researchers described the heterogeneous nature of long coronavirus disease (Long-COVID), focusing on its pulmonary and extrapulmonary sequelae. They reviewed pre-existing respiratory issues [e.g., lung fibrosis, asthma, and chronic obstructive pulmonary disease (COPD)] that possibly aggravate pulmonary sequelae of COVID-19 or affect its outcomes. Additionally, the discussed clinical care, rehabilitation, and non-pharmacological strategies for people affected by post-COVID-19 dyspnea, a type of persistent disabling breathlessness.

Study: Respiratory sequelae of COVID-19: pulmonary and extrapulmonary origins, and approaches to clinical care and rehabilitation. Image Credit: Lightspring / ShutterstockStudy: Respiratory sequelae of COVID-19: pulmonary and extrapulmonary origins, and approaches to clinical care and rehabilitation. Image Credit: Lightspring / Shutterstock

Background

The post-acute sequelae of COVID 2019 (COVID-19), or PASC, systematically affects multiple organs, especially people with chronic lung diseases like thromboembolic disease.

Multiple previous studies have described worsening of respiratory systems during PASC due to destabilizing of pre-existing symptoms or COVID-19-related effects, independent of the severity of acute illness; however, the exact mechanisms governing these changes remain unclear. 

Several published studies have also described, using a large dataset, the cluster of respiratory symptoms constituting PASC, for instance, erratic breathing, hyperventilation, and persistent cough. Perhaps, mechanisms like viral persistence, autoimmunity, and systemic inflammation, including activation of interferon (IFN) I and III and interleukin 6, contribute to the worsening of respiratory systems during PASC.

By March 2023, worldwide COVID-19 mortality had reduced from 101,600 deaths to 6,500 deaths per week. Also, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related hospital admissions have reduced drastically. Researchers have attributed these improvements, in part, to the increased availability of vaccines and treatments, such as IL-6 therapies. However, it remains critical to understand the long-term effects of COVID-19 on the respiratory system for studies focused on the post-COVID-19 landscape.

About the study

To this end, in the present study, researchers extensively searched databases, such as PubMed and CINAHL, using keywords like dysfunctional breathing, post-COVID fibrosis, fibrosis, and rehabilitation, to name a few.

Regarding post-COVID-19 conditions, they uncovered that the most prevalent symptoms were independent of the severity of acute illness. For instance, understanding the precise mechanisms that underlie symptoms of acute lung injury, the dominant insult in severe acute COVID-19 patients requiring mechanical ventilation, in contrast to any post-COVID-19 sequelae, requires proper assessments and targeted interventions.

The team identified a meta-analysis that covered 54 studies and two medical records that discussed respiratory symptoms as an important cluster alongside fatigue and cognitive problems post-long COVID. In contrast, another study defined a positive correlation between the burden of symptoms and their severity with all the symptoms combined.

Extrapulmonary and pulmonary sequelae of COVID-19

In this study, researchers discussed the incidence and mechanisms of pulmonary fibrosis, pulmonary emboli, and microvascular thrombi, COPD, reduced exercise tolerance, and frailty after COVID-19. In addition, they highlighted studies discussing all these features of long COVID to bring attention to the fact that these contribute to breathlessness and breathing pattern disorders, hence, need attention when devising therapeutic and rehabilitative strategies.

Here it is noteworthy that conventional measures of lung function cannot consistently predict breathlessness. It is a complex condition, which, if pathologically triggered, does not necessarily improve after treatment with bronchodilators. Thus, treatment approaches for breathlessness should be guided by an extensive assessment that covers routine spirometry.

The largest cohort study conducted among 1,733 people discharged from the hospital after COVID-19 recovery performed lung function tests in 349 participants six months post-discharge. It was biased toward adults with clinical symptoms of pulmonary issues. In addition, it should cover Dyspnoea Profile questionnaires that explore the multidimensional components of breathlessness. Clinicians must also consider cardiopulmonary exercise testing and more complex investigations, such as magnetic resonance imaging (MRI) in cases of diagnostic uncertainties related to breathlessness

In post-COVID-19 conditions, cardiopulmonary exercise testing identified dysfunctional breathing or an erratic breathing pattern in the absence of a respiratory limitation or impaired oxygen delivery and reported a lower peak oxygen uptake in individuals with persistent breathlessness compared with those who had a full recovery after COVID-19.

Small cohort studies documented altered breathing patterns in ~20% of people admitted to hospitals with acute COVID-19, and those not admitted to hospital were referred to specialist follow-up clinics. They attributed aberrant breathing patterns to changes in lung function and effects of sedation and mechanical ventilation on respiratory centers, etc.

The Nijmegen Questionnaire specifically accessed hyperventilation syndrome, and the Breathing Pattern Assessment Tool (BPAT) accessed all breathing pattern disorders with high sensitivity and specificity.

Likewise, mechanistic similarities between COVID-19-related pneumonia and idiopathic pulmonary fibrosis (IPF), raise the possibility of a potential global burden of long-term fibrosis arising post-COVID-19.

At present, rehabilitation programs for people with post-COVID-19 conditions are highly heterogeneous, but they should cover aerobic and resistance exercises and spread awareness on symptom management. A recent systematic review showed they improved dyspnoea, physical function, and QoL. However, patients should be selected per symptom profiles, and further research should focus on high-quality evidence, particularly for people not admitted to hospital for COVID-19.

Research evaluating the effectiveness of non-pharmacological interventions is ongoing. However, respiratory and rehabilitation specialists should be at the core of integrated multidisciplinary teams offering support to patients with post-COVID-19 conditions. Most importantly, these teams should use therapeutic and rehabilitative strategies tailored to each patient's symptom profiles and specific needs to ensure they give culturally appropriate, equitable access to the diverse set of affected populations.

Conclusions

Like other critical illnesses, severe COVID-19 leaves patients with long-term morbidity that affects their quality of life (QoL) and physical and mental well-being. As well-recognized, symptoms-like brain fog and cognitive deficits are common in patients with long COVID. These manifestations might be related to the disease, its treatment, or both; notably, doctors administer such treatments in the intensive care unit (ICU) to complement life-support therapies.

In the future, studies should target characterizing the long-term complications of pulmonary and extrapulmonary sequelae of COVID-19 in-depth, e.g., its mechanisms of causing insult. Further, these studies should determine optimal diagnostic and management approaches for this debilitating condition to improve outcomes in this population.

Other future research priorities should be as follows:

i) identifying mechanisms governing reduced asthma and COPD control after COVID-19

ii) extrapulmonary complications that give rise to or worsen breathlessness after COVID-19

iii) diagnostic modality for detection of post-COVID-19 pulmonary vascular disease

iv) strategies to prevent, mitigate, and treat pulmonary fibrosis

v) mechanisms driving symptoms of breathlessness post-COVID-19 and rehabilitation or breathing exercises that effectively reduce it.

Journal reference:

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FRIDAY, June 2, 2023 (HealthDay News) -- A group of symptoms has been identified that can define postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC), according to a study published online May 25 in the Journal of the American Medical Association.

Tanayott Thaweethai, Ph.D., from Massachusetts General Hospital in Boston, and colleagues used self-reported symptoms to develop a definition of PASC and describe PASC frequencies across cohorts in a prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 sites located in 33 states, Washington, D.C., and Puerto Rico. A total of 9,764 participants met the selection criteria (8,646 infected; 1,118 uninfected).

The researchers found that for 37 symptoms, the adjusted odds ratios were 1.5 or greater for infected versus uninfected participants. Postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements were included as symptoms contributing to the PASC score. Overall, 10 percent of the 2,231 participants first infected on or after Dec. 1, 2021, and enrolled within 30 days of infection were PASC-positive at six months.

"This study is an important step toward defining long COVID beyond any one individual symptom," a coauthor said in a statement. "This research definition -- which may evolve over time -- will serve as a foundation for scientific discovery and treatment design."

Several authors disclosed ties to the pharmaceutical industry.

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Metapneumovirus causes many of the same symptoms as COVID 19 such as a bad cough, fever and a possible lung infection.

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A mix of respiratory viruses continue to circulate in B.C., such as respiratory syncytial virus and the virus that cause COVID-19.

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But health experts say there’s another virus that may cause similar symptoms as COVID.

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It’s called the human metapneumovirus (HMPV,) and while for most people symptoms will be mild, it can also cause a lung infection, severe cough, sore throat and fever, much like the coronavirus. U.S. health authorities have said that hospitalized cases of HMPV spiked this spring, especially among children, seniors and those with weak immune systems.

But is that happening in B.C.? Here’s what health officials say:

What is human metapneumovirus?

HMPV is a respiratory syncytial virus and most people who are infected experience mild symptoms similar to a cold, according to the Centers for Disease Control and Prevention (CDC). The symptoms last a week, and go away without treatment in healthy individuals. More serious cases can lead to lung infection and severe cough. The CDC says it’s spread through close contact, coughing and sneezing, and is more common in winter and spring.

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It can cause upper and lower respiratory disease in people of all ages, especially young children, older adults and those with weakened immune systems.

HMPV is in the Pneumoviridae family along with respiratory syncytial virus (RSV), and was discovered in 2001, according to the B.C. CDC.

Symptoms include cough, fever, nasal congestion and shortness of breath. Clinical symptoms can progress to bronchitis or pneumonia.

Are there cases of it in B.C.?

Yes.

Since the start of March, 7,990 samples have been tested in B.C., with 510 detections of the virus, according to the B.C. CDC.

The positivity rate in early spring was about 10 per cent and has since declined to below five per cent as of Thursday. The agency said the rates are much lower than COVID.

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How do I treat it?

Currently, there’s no vaccine for HMPV or antiviral drugs so doctors focus on treating the patients’ symptoms. The B.C. CDC says people can help prevent the spread of the virus by washing hands, and avoiding contact with people who are sick.

What should people do if they think they have it?

People who have cold-like symptoms should practise respiratory etiquette (coughing and sneezing into a tissue or your elbow) and wash their hands frequently and properly. They’re asked to stay home from work or school, not to share cups and utensils, and to refrain from kissing.

Those who have difficulty breathing or a severe cough that won’t go away should see a doctor.

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SciCheck Digest

Ventilators can be lifesaving for critically ill COVID-19 patients. A social media claim that a new study shows ventilators killed “nearly all” COVID-19 patients is “quite wrong,” according to the study’s co-author. Ventilator-associated complications can contribute to deaths, but patients are typically put on ventilators when they would otherwise die.


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COVID-19 can cause lung damage and respiratory failure. In patients who are unable to breathe well enough to supply oxygen to their bodies, mechanical ventilators can be lifesaving and give them time to recover. Ventilators help people breathe by pushing air into their lungs via a tube inserted down their windpipe.

Yet, social media posts have shared an article from the People’s Voice with a false headline: “Official Report: Ventilators Killed Nearly ALL COVID Patients.” The People’s Voice, formerly News Punch, frequently publishes articles with false and inflammatory headlines.

The posts misrepresent the conclusions of a study published in April in the Journal of Clinical Investigation. The idea that ventilators — and not COVID-19 — killed nearly all COVID-19 patients is “quite wrong,” study co-author Dr. Benjamin Singer, a pulmonary and critical care physician at Northwestern Medicine, told us.

Rep. Thomas Massie, a Republican from Kentucky, also misrepresented the conclusions of the study, tweeting, “How many COVID patients died due to the use of ventilators? A recent examination of the data suggests quite a few.”

The idea that ventilators are dangerous, and not COVID-19, is a misinterpretation of his data, Singer said. “It’s not the ventilator that was the cause of death,” he said. “The ventilator was very much life support for these patients. It was ultimately COVID-19” that caused the deaths.

Singer’s study looked at 585 people put on ventilators due to respiratory failure between 2018 and 2022 at Northwestern Memorial Hospital. These people primarily had COVID-19 or some other infectious disease, such as another viral or bacterial illness.

Around half of these very sick patients who required mechanical ventilation — people who likely would have died without the intervention — went on to survive their illness. The survival rate was similar whether they had COVID-19 or another disease and was consistent with the survival rate for COVID-19 patients on ventilators found in another, larger study.

Singer’s study explored the degree to which a known ventilator-related complication called ventilator-associated pneumonia contributes to death, finding that the complication is more common in people with COVID-19 and, when unresolved, is linked to death. VAP is usually treated with antibiotics.

People with COVID-19 likely have an elevated risk of VAP because they stay on ventilators for longer-than-average periods. COVID-19 also affects the immune system and damages the surface of the lungs in unique ways, Singer said, which could potentially make the lungs more susceptible to secondary infections.

VAP contributes to death in some COVID-19 and other infectious disease patients, explained Dr. Mark Metersky, a pulmonary and critical care physician and professor at the University of Connecticut School of Medicine who was not involved in the study.

However, virtually all of these patients would have died if they had not been put on a ventilator, he said. “It’s not that the ventilator killed them, the ones who died. It’s that the ventilator failed to save them.”

A related claim in a popular post — that medical professionals put patients on ventilators due to financial incentives — is also unsupported by evidence, as we and other fact-checkers previously explained. It’s standard for hospitals to get more money for patients, such as those on ventilators, who require more care.

Study Explored Ventilator-Related Pneumonia

VAP typically occurs as a form of secondary pneumonia, which means it shows up in patients who already have another pneumonia diagnosis, such as pneumonia resulting from COVID-19, the flu or a bacterial infection.

People are diagnosed with pneumonia when their lungs become swollen with fluid from a respiratory infection. VAP typically arises from bacteria introduced to the lungs via the patient’s breathing tube.

Singer’s new paper finds that once very sick COVID-19 patients are on ventilators, they are at greater risk of VAP compared with other similarly ill pneumonia patients, he said.

Further, the paper found that “whether that ventilator-associated pneumonia was cured or not was a major determinant of whether patients went on to live or die in the ICU,” he said. However, just being diagnosed with VAP was not associated with a higher risk of death.

Based on these conclusions, the People’s Voice article makes a false claim, which was shared widely: “Nearly all COVID-19 patients who died in hospital during the early phase of the pandemic were killed as a direct result of being put on a ventilator, a disturbing new report has concluded.”

First, many hospitalized COVID-19 patients have died who never went on ventilators. And Singer’s study was not limited to “the early phase of the pandemic” but rather went through March 2022.

As we’ve said, this line of thinking is also misleading because it does not make it clear that the patients on ventilators would have typically died without them. It is also untrue that Singer’s study showed that ventilator-related complications killed “nearly all” ventilated patients who died.

The People’s Voice article explains its reasoning by saying that “most patients” put on ventilators because of COVID-19 developed VAP. “So while COVID-19 may have put these patients in the hospital, it was actually a secondary infection brought on by the use of a mechanical ventilator that caused their deaths,” the article says.

In reality, 57% of COVID-19 patients on ventilators in the study developed VAP and a quarter of other ventilated pneumonia patients did. Around half of all patients with VAP died, which was “not significantly different” from the death rate in patients on ventilators who didn’t have VAP, according to the study.

Singer and his colleagues did find that patients whose VAP was not successfully treated were more likely to die than patients whose VAP resolved, indicating a connection between VAP and poor outcomes. The study was not randomized, and the researchers write that they cannot definitively determine that unresolved VAP — and not some other factor associated with it — leads to poor outcomes.

Metersky was skeptical that VAP is that much of a contributor to mortality, pointing to other studies that show a lower rate of VAP in pneumonia patients than was found in Singer’s study.

“Yes, some patients who are put on a ventilator will develop a fatal complication,” Metersky said. “Probably 1 in 100” patients put on a ventilator develop fatal VAP, he said, based on data from before the pandemic. Since about twice as many COVID-19 patients develop VAP compared with other pneumonia patients on ventilators, he said that would indicate that around 2% of people with COVID-19 who go on a ventilator die of VAP.

“But there are other complications,” Metersky said. These can include damage to the lungs from high oxygen and the air pressure from the ventilator or side effects from drugs used to sedate people on ventilators, for instance. “That’s why we don’t put a patient on a ventilator unless they absolutely need it,” he said.

Regardless, “it’s ridiculous to go from that study to say that the ventilators are killing all these people,” Metersky said, referring to the claim that nearly all COVID-19 deaths were caused by ventilators.

Early Ventilation Did Not Cause Mass Deaths

Other false claims, reviewed previously by others, state that overuse of ventilators played a major role in the first wave of COVID-19 deaths.

There were some suggestions very early in the pandemic that doctors should put COVID-19 patients on ventilators earlier than other pneumonia patients, Singer and Metersky both said, out of concern that respiratory failure might progress very quickly. 

This was soon followed by calls for caution in ventilating patients early, and these practices quickly stopped, Singer said. “The standard indications for initiation of mechanical ventilation are really the same as they always have been” for patients with pneumonia, he said, regardless of whether they have COVID-19.

Multiple facts about the early ventilation recommendations are unclear. First, there was no standard definition of what experts meant when recommending “early” ventilation. Decisions on when patients require mechanical ventilation are based on the best judgment of their doctors as they monitor multiple indicators. Doctors want to be sure the ventilator is truly necessary — that the patient is headed toward death from respiratory failure without it. But they also don’t want to wait until the patient has organ damage from lack of oxygen.

Second, it’s unclear how widespread early ventilation was. Singer mentioned that his own recent paper showed that Northwestern Medicine put patients with COVID-19 on ventilators after a similar amount of time in the ICU as other pneumonia patients. Others have pointed out that some doctors at the beginning of the pandemic took measures to avoid putting patients on ventilators due to shortages.

Finally, it’s uncertain what impact early ventilation had on patients. The available research, recently reviewed in a blog post by epidemiologist Gideon Meyerowitz-Katz, a Ph.D. candidate at the University of Wollongong in Australia, indicates that early versus later ventilation did not appreciably affect COVID-19 deaths. For instance, a review study that pooled and analyzed data from multiple studies found that going on a ventilator within a day of entering the ICU versus later had no impact on mortality.

It is possible that people occasionally were put on ventilators who could have avoided them, but this is difficult to quantify.

“There were probably a small number of patients who got put on a ventilator who ultimately might not have needed it,” Metersky said. “As we learned more about the disease, we learned to recognize that some patients may not need the ventilator. But it wasn’t this big conspiracy that we put everyone on the ventilator even though they could have gone home instead.”

Editor’s note: SciCheck’s articles providing accurate health information and correcting health misinformation are made possible by a grant from the Robert Wood Johnson Foundation. The foundation has no control over FactCheck.org’s editorial decisions, and the views expressed in our articles do not necessarily reflect the views of the foundation.

Sources

Pulmonary Manifestations.” COVID-19 Real-Time Learning Network. Updated 22 Feb 2022.

Tobin, Martin and Manthous, Constantine. “Mechanical Ventilation.” American Journal of Respiratory and Critical Care Medicine. Published 15 Jul 2017. Updated April 2020.

Adl-Tabatabai, Sean. “Official Report: Ventilators Killed Nearly ALL COVID Patients.” The People’s Voice. 13 May 2023.

Jones, Brea. “Posts Fabricate Charge Against Bill Gates in Philippines.” FactCheck.org. 10 Mar 2023.

Spencer, Saranac Hale. “Hate Crimes Hotline Headline Is Wrong.” FactCheck.org. 30 Nov 2018.

Yandell, Kate. “Posts Share Fake Chelsea Clinton Quote About Global Childhood Vaccination Effort.” FactCheck.org. 10 May 2023.

Gao, Catherine A. et al. “Machine Learning Links Unresolving Secondary Pneumonia to Mortality in Patients with Severe Pneumonia, Including COVID-19.” The Journal of Clinical Investigation. 27 Apr 2023.

Massie, Thomas (@RepThomasMassie). “How many COVID patients died due to the use of ventilators? A recent examination of the data suggests quite a few. ‘The investigators found nearly half of patients with COVID-19 develop a secondary ventilator-associated bacterial pneumonia.’” Twitter. 15 May 2023.

Nolan, Margaret B. et al. “Mortality Rates by Age Group and Intubation Status in Hospitalized Adult Patients From 21 United States Hospital Systems During Three Surges of the COVID-19 Pandemic.” Chest. 29 Jan 2023.

Frequently Asked Questions about Ventilator-Associated Pneumonia.” CDC website. Updated 9 May 2019.

Adele – Conspiracy Queen ???? (@truth.bomb.mom). “Such a bummer that this happened ????.” Instagram. 21 May 2023.

Fichera, Angelo. “Hospital Payments and the COVID-19 Death Count.” FactCheck.org. 21 Apr 2020.

Kertscher, Tom. “Fact-Check: Hospitals and COVID-19 Payments.” PolitiFact. 21 Apr 2020.

Pneumonia – Causes and Risk Factors.” NIH website. Updated 24 March 2022.

Pneumonia – What Is Pneumonia?” NIH website. Updated 24 Mar 2022.

Kohbodi, GoleNaz A. et al. “Ventilator-Associated Pneumonia.” Updated 10 Sep 2022.

Metersky, Mark L. et al. “Trend in Ventilator-Associated Pneumonia Rates Between 2005 and 2013.” JAMA. 13 Dec 2016.

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In a recent study published in the journal Scientific Reports, researchers investigated whether the severity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was indicative of undiagnosed cancer.

Study: Severe SARS-CoV-2 infection as a marker of undiagnosed cancer: a population-based study. Image Credit: Tyler Olson / Shutterstock.com

Background

Studies conducted during the coronavirus disease 2019 (COVID-19) pandemic reported that male sex, older age, and comorbidities such as chronic diseases and active cancers increased the risk of hospitalization and mortality due to SARS-CoV-2 infection. Individuals with active cancers were also at a relatively higher risk of COVID-19-associated mortality, even if they were vaccinated.

The six factors that increased the morbidity and mortality risk of cancer patients to SARS-CoV-2 infections were age, increased expression of the angiotensin-converting enzyme 2 (ACE-2) receptor transmembrane serine protease 2 (TMPRSS2)immunosuppression due to cancer treatments, as well as a pro-coagulant state and inflammatory responses induced by cancer. Some of these factors could influence the susceptibility to severe SARS-CoV-2 infections in individuals with undiagnosed cancers.

About the study

In the present study, researchers used data from the French Système National des Données de Santé (SNDS) database. This database has been used for various pharmacological and epidemiological studies, as it comprises healthcare reimbursement data for the entire population of France.

The SNDS database consists of one section with information on ambulatory medical care reimbursements, including laboratory tests, ambulatory medical care, and prescription drugs, whereas the other section consists of information on hospital admissions, discharges, medical procedures, and diagnoses.

From anonymized data, specific medical algorithms were used to identify pathologies, causes for hospitalization, long-term illness diagnoses, and treatment reimbursements. The study included data on intensive care unit (ICU) admissions between February 15, 2020, and August 31, 2021, which covered the period between the onset of the COVID-19 pandemic and the end of the fourth wave in France. The follow-up was extended to the end of December 2021 to allow for a four-month follow-up for ICU-admitted patients.

The study included data on individuals above the age of 16 who had availed of at least one reimbursement in the two years before the index date and had no cancer diagnoses in the previous five years. Nursing home residents and twins below the age of 22 were excluded from the study.

Study participants were categorized into two groups, the first of which included those admitted into the ICU. The second group included age, sex, and French department-matched controls who were not hospitalized.

Information on sex, age, area of residence, and socio-economic status were determined, and co-variables such as existing comorbidities, COVID-19 vaccination status, treatment with corticosteroids or immunosuppressants, and addictive disorders were analyzed.

The examined outcome included the incidence of cancer during the follow-up period in either of the two groups. An incidence of cancer was defined as hospitalization due to any cancer or cancer-like condition requiring reimbursement.

Participants were excluded from the analysis after the initial inclusion in case of death in either of the groups. Additionally, individuals from the control group who were hospitalized due to SARS-CoV-2 infection were subsequently removed from the control group and added to the ICU-admission group.

COVID-19 hospitalization and increased risk of cancer

A total of 897 of the 41,302 individuals admitted to the ICU with SARS-CoV-2 infection were diagnosed with cancer during the follow-up months as compared to 10,944 of the 713,670 controls diagnosed with cancer. In fact, individuals who had been admitted to the ICU had a 1.31 times higher risk of a cancer diagnosis than those who did not require hospitalization for SARS-CoV-2 infection.

When the follow-up period was decreased to three months or if only the female population was considered, the association between ICU admission and cancer diagnosis was stronger. Furthermore, as compared to controls, individuals in the ICU group were more likely to be diagnosed with hematological, renal, lung, or colon cancers. Other types of cancers did not show significant differences between the two groups.

While the study did not discuss any causal effect between SARS-CoV-2 infection and the development of cancer during the follow-up period, the researchers speculated on the differences in the screening and diagnosis techniques between the two groups that could have led to a detection bias.

Individuals admitted to the ICU with SARS-CoV-2 infection might have been subjected to repetitive lung scans and blood tests, which may have led to the detection of lung or hematological cancers. Comparatively, prostate-specific antigen tests or mammograms might not have been a priority during the ICU admission, thereby resulting in lower detection of prostate or breast cancers, respectively.

In contrast, individuals in the control group might have been screened for other cancers, as they were in a better health condition to undergo these tests.

Conclusions

Individuals who experienced severe SARS-CoV-2 infection requiring ICU admission were at a greater risk of being diagnosed with cancer during the following months than individuals who did not require hospitalization for COVID-19. While there is a potential for detection bias, these results indicate that severe SARS-CoV-2 infection could be a marker for undiagnosed cancer.

Journal reference:

  • Dugerdil, A., Semenzato, L., Weill, A. et al. (2023). Severe SARS-CoV-2 infection as a marker of undiagnosed cancer: a population-based study. Scientific Reports 13(8729). doi:10.1038/s41598-023-36013-7

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