In a recent study published in JAMA Network Open, researchers identified factors related to PCC [post-COVID-19 (coronavirus disease 2019] symptoms and assessed changes in PCC medical visits.

Study: Persistent COVID-19 Symptoms at 6 Months After Onset and the Role of Vaccination Before or After SARS-CoV-2 Infection. Image Credit: CROCOTHERY/Shutterstock
Study: Persistent COVID-19 Symptoms at 6 Months After Onset and the Role of Vaccination Before or After SARS-CoV-2 Infection. Image Credit: CROCOTHERY/Shutterstock

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COVID-19 patients may present with symptoms persisting for several months post-infection, referred to as ‘long COVID’. Further research conducted to improve understanding of long COVID-associated factors could aid in policy-making and the development of preventive strategies. Previous studies have documented COVID-19 vaccines to protect against COVID-19 severity outcomes such as hospitalizations and deaths; however, the association between COVID-19 vaccination and long COVID is unclear.

About the study

The present study investigated PCC-associated risk factors and changes in PCC-associated medical consultations over time.

The study utilized EPICC (epidemiology, immunology, and clinical characteristics of emerging infectious diseases with pandemic potential) study data implemented by the United States (US) MHS (military health system). Adult MHS beneficiaries testing SARS-CoV-2-positive between 28 February 2020 and 31 December 2021 were included and followed up for one year.

The study outcomes comprised survey-documented symptoms of SARS-CoV-2 infections in six months post-acute COVID-19 and the international statistical classification of diseases and related health problems, 10th revision diagnostic codes documented in medical records after six months of acute COVID-19 versus three months before acute COVID-19. 

The MHS beneficiaries (dependents, retirees, and active individuals) were enrolled in the EPICC trial through online and offline pathways. EPICC study eligibility included SARS-CoV-2 testing, the presence of SARS-CoV-2 infection-like disease, and/or SARS-CoV-2 exposure from known contacts, which was expanded in 2021 to include COVID-19 vaccination.

For the present study, the date of the onset of symptoms or the first SARS-CoV-2-positive result was dated before 31 December 2021. COVID-19 status was based on reports of PCR (polymerase chain reaction) analysis, documented in the healthcare records, self-reported throat or nasal swab test results indicating COVID-19, as mentioned in the survey, or specimens obtained during the study. The team excluded 549 individuals with suspected re-infections (SARS-CoV-2-positive results >3.0 months apart).

Clinical and demographic details were obtained using case report forms (CRF) from individuals recruited at military treatment facilities beginning in November 2020. All individuals filled out web-based surveys quarterly, and additionally, individuals recruited prior to November 2020 filled out catch-up surveys. Individuals who documented SARS-CoV-2 infection symptoms were queried regarding the date for onset of symptoms, COVID-19 severity, and duration.

For analyzing the probable protective effects of COVID-19 vaccines, surveys filled out on dates nearest to 1.0 months, 3.0 months, 6.0 months, 9.0 months, and 12.0 months post-onset of symptoms were retained. Individuals who had received COVID-19 vaccines two weeks before the survey were excluded from the analysis. The CCI (Charlson comorbidity index) scores were calculated for comorbid conditions documented by the MDR (military health system data repository) in the calendar year before the onset of the symptoms of COVID-19. Poisson regression modeling was performed, and risk ratios (RR) were calculated.


A total of 1,832 individuals were analyzed, of which 1,226 (67%) were aged between 18 and 44. The mean participant age was 41 years, 61% (n=1,118) were men, 77% (n-1,1413) were non-vaccinated during the acute infection period, and 71% (n=1,290) had no comorbid conditions. COVID-19-associated hospitalizations were documented for 13% (n=236) of individuals. Among the participants, 40% (n=728) had an illness lasting for ≥28.0 days [28 days to 89 days of illness duration among 364 individuals (20%) and ≥90.0 days of illness in another set of 364 (20%) individuals].

The most frequently observed symptoms rated to be of moderate intensity or severe in intensity a month post-symptom onset comprised fatigue (7.0%, n=47), intolerance to exercise (6.0%, n=43), breathing difficulties (5.0%, n=34), taste and/or smell loss (5.0%, n=39), and cough (4.0%, n=28). Among individuals who completed the six-month surveys (62%, n=1,138), 111 (10%) reported experiencing a symptom associated with COVID-19.

Individuals who had not received COVID-19 vaccines before infection (RR of 1.4), documented moderate illness (RR of 1.8) or severe illness (RR of 2.3) during the initial COVID-19 period, had a longer duration of hospital admission (risk ratio of 1.1 per day in the hospital) and had CCI scores ≥5.0 (RR of 1.6) shows a greater likelihood of documenting ≥28.0 days of COVID-19 symptoms.

Among non-vaccinated individuals, post-COVID-19 vaccination was linked to a 41.0% lesser risk of experiencing symptoms at six months (risk ratio of 0.6). Individuals had a greater risk of respiratory symptoms-related medical visits (RR of 2.0), diabetes-related medical visits (RR of 1.5), neurological symptoms-related medical visits (RR of 1.3), and medical visits for mental well-being (RR of 1.3) at six months after the onset of symptoms in comparison to those before SARS-CoV-2 infection.

Overall, the study findings showed that severe COVID-19 during the initial period, greater CCI scores, and unvaccinated status were associated with an increased risk of documenting SARS-CoV-2 infection symptoms lasting ≥28.0 days. In addition, SARS-CoV-2-positive individuals showed a greater likelihood of seeking medical consultation for diabetes, neurological, mental well-being, and respiratory system-associated illness for ≥6.0 months post-onset compared to their pre-SARS-CoV-2 infection medical care utilization patterns. The findings underpin the administration of SARS-CoV-2 vaccinations.

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