In a recent study published in PLOS ONE, researchers investigated whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection severity could increase the risk of chronic pain.

Study: COVID-19 symptom load as a risk factor for chronic pain: A national cross-sectional study. Image Credit: fizkes/
Study: COVID-19 symptom load as a risk factor for chronic pain: A national cross-sectional study. Image Credit: fizkes/


The long-term impact of SARS-CoV-2 infections continues to be a growing population health concern. Studies have reported that the severity of the coronavirus disease 2019 (COVID-19) might be related to lingering long COVID symptoms persisting beyond three months of acute infection and not experienced before contracting SARS-CoV-2, including chronic pain.

Chronic-type pain has been linked to anxiety, sleep disturbances, and depression. In addition, it can affect routine activities, decrease social participation, and have considerable financial implications due to higher medical expenditures and lowered work productivity.

Moreover, chronic pain is complicated to manage. However, population-level data on the association between the severity of SARS-CoV-2 infections and pain development are limited, warranting further research.

About the study

In the present nationwide cross-sectional study, researchers investigated SARS-CoV-2 infection severity as a novel determinant of chronic pain among United States (US) residents.

The team analyzed data obtained from the National Health Interview Survey (NHIS, 15,335 adult individuals) study conducted in 2021 that evaluated the adjusted probability of frequent pain development in the previous three months for individuals reporting none or mild COVID-19 symptoms and those experiencing moderate-severe COVID-19 symptoms in comparison to uninfected individuals.

The NHIS survey was conducted by the National Center for Health Statistics (NCHS) for the Centers for Disease Control and Prevention (CDC). The participants were interviewed in person and propensity score-matched (PSM) in a 1.0:1.0:1.0 ratio to assess the prime study outcome of pain frequency among matched individuals.

Multivariate logistic regression analysis was performed to determine the odds ratios (OR) by adjusting for covariates such as age, sex, body mass index (BMI), ethnicity or race, educational attainment, poverty income ratios (PIRs), and comorbidities such as diabetes, walking difficulties, and chronic inflammatory disorders (including gout, rheumatoid arthritis, fibromyalgia, and lupus).

In addition, the team performed sensitivity analyses by examining covariate distribution and pain scores for asymptomatic COVID-19 patients vs. mild COVID-19 patients and between the mild COVID-19 group and severe COVID-19 group participants. Individuals with inadequate pain-related data and those who had never undergone SARS-CoV-2 testing were excluded from the analysis.


Among the study participants, 12,131 never tested SARS-CoV-2-positive (77%), 1,440 experienced none or mild COVID-19 symptoms (11%), whereas 1,764 experienced moderate-to-severe COVID-19 symptoms (13%). While 11,965 participants reported no or infrequent pain (80%), 3370 (20%) experienced chronic pain.

Pain prevalence was significantly higher among moderate-to-severe COVID-19 patients (26%) than uninfected individuals (19%). Adjusted (OR 1.3) and matched modeling (OR 1.5) estimates indicated individuals with moderate-to-severe SARS-CoV-2 infections were more likely to experience chronic pain than uninfected ones.

Of interest, asymptomatic and mild COVID-19 patients showed a lesser likelihood of reporting pain in the previous three months than uninfected individuals (OR 0.8). The adjusted odds of experiencing chronic pain were 4.0 percent higher among COVID-19 patients with higher symptom loads (20%) than uninfected participants (16%).

The covariates were independently associated with SARS-CoV-2 infection status and chronic pain. Before matching, compared to participants testing SARS-CoV-2-negative, those with positive COVID-19 results showed an increased likelihood of being of working age, non-white, with a lower level of education, a lower household income, and an increased prevalence of comorbidities.

After matching, the adjusted pain probability was 6.0 percent higher among individuals with higher symptom loads (22%) than uninfected individuals (16%). The likelihood of pain among asymptomatic and mild COVID-19 patients compared to uninfected individuals became non-significant (OR 0.9).


Overall, the study findings showed that COVID-19 severity could enhance chronic pain risk. With a continual increase in the prevalence of severe SARS-CoV-2 infections, chronic duration pain may be more frequently experienced by individuals. Health policies and measures are required to mitigate COVID-19, prevent severe infections, and lower the global burden on health and healthcare facilities.

However, causality cannot be established due to the cross-sectional study design. COVID-19 may have been underdiagnosed since all individuals infected by SARS-CoV-2 may not necessarily undergo SARS-CoV-2 testing due to social stigmas related to SARS-CoV-2 tests and infections and inequalities in access to health services. Further research must include objectively obtained data and account for SARS-CoV-2 vaccination status and the history of anti-SARS-CoV-2 therapies.

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