Persistent Long-COVID Pain Symptoms Frequently Occur, Warrant Further Study

Long-COVID-related pain symptoms were more common among women, those with preexisting comorbidities, and those who smoked.

A “non-negligible” proportion of patients post-COVID-19 acute infection experience persistent chest-, gastrointestinal-, musculoskeletal-, general body-, and/or nervous system-related long-term pain symptoms, according to the authors of a meta-analysis published in Pain Practice.

The study authors conducted a systematic review and meta-analysis to assess the proportion of patients who had experienced consistent long-term pain and symptoms after COVID-19 acute infection, including joint pain, cardiovascular & respiratory pain, muscle pain, nervous system pain, gastrointestinal pain, and general body pain. Secondary outcomes included functional outcomes, quality of life (QoL), and inflammatory markers for varying pain symptoms.

The reviewers searched PubMed/MEDLINE and Embase, from database inception until the end of March 2022, for studies published in English reporting on persisting pain symptoms and inflammatory and/or functional outcomes in individuals post acute COVID-19 infection. Of the 611 studies identified by reviewers, 26 were included for meta-analysis: 10 prospective studies, 6 cross-sectional studies, 6 retrospective cohort studies, 3 case control studies, and 1 case series. Sample sizes ranged from 33 to 273,618 participants, with studies conducted in multiple countries (including Spain, Turkey, the US, Italy, Switzerland, France, Nigeria, China, Iran, India, South Africa, Egypt, Ecuador, Bangladesh, Germany, and Poland). The quality of evidence was rated as moderate to low based on the Newcastle-Ottawa Scale.

Using a random-effects-restricted maximum-likelihood model, the researchers determined that the percentages of patients experiencing persisting pain symptoms for up to a year post-acute COVID-19 infection in the 6 pain domains investigated were as follows: 

  • chest pain, 8% (95% CI, 0.06, 0.13; P <.01; n=286,330);
  • gastrointestinal pain, 6% (95% CI, 0.03, 0.10; P <.01; n=8222);
  • joint pain, 18% (95% CI, 0.11, 0.25; P <.01; n=6522);
  • muscle pain, 18% (95% CI, 0.13, 0.26; P <.01; n=287,027);
  • nervous system pain, 12% (95% CI, 0.08, 0.16; P <.01; n=286, 318); and
  • general body pain, 17% (95% CI, 0.07, 0.36; P <.01; n=276,098).
[L]ong-COVID pain symptoms are being experienced by non-negligible proportions of those recovering from acute COVID-19 episodes, thus highlighting the importance of future research efforts to focus on this aspect.

Quality of life and/or functional outcomes were reported in 13 studies of long COVID, with varying percentages of mild to moderate impairments reported relating to overall quality of life, breathlessness, cognition, fatigue, mobility, and physical endurance. In 4 studies, breathlessness was experienced by 11.7% to 34.25% of patients who scored at least 1 on the modified Medical Research Council (mMRC) dyspnea scale during follow-up periods ranging from 2 months to 1 year; in 2 studies,  20.7% to 34.5% of patients reported fatigue or restriction in strenuous activity (as measured by the Eastern Cooperative Oncology Group [ECOG] performance scale) during follow-up periods ranging from 2 months to 1 year; in 2 studies using the 6-minute walking test, 79% of patients performed below normal levels 6 weeks post-acute-COVID-19 infection and 12% underperformed at the 1-year follow up.

The relationship between inflammatory markers and pain domains were assessed in 4 studies. Among the findings: muscle and joint pain persistence were associated with elevated levels of D-dimer and interleukin (IL)-6 and decreased lymphocytes during COVID-19 acute phase; chest pain symptoms were associated with increased fibrinogen values, as well as myalgia; and long-COVID-19 arthritis and pulmonary sequelae were both associated with elevated CRP or erythrocyte sedimentation rate (ESR) and D-dimer, respectively.

In examining risk factors for long-COVID-related pain symptoms, the researchers found that: (1) women were more likely to experience such symptoms, especially headache; (2) long-COVID symptom development was associated with preexisting comorbidities including autoimmune diseases, depression, hypertension, chronic kidney disease, depression or anxiety, and hypothyroidism; and (3) smoking status at the time of infection and recovery were both associated with long-COVID symptoms.

Limitations for this review include the large number of studies that were not prospective, underrepresentation of specific populations, variation in follow-up periods, and the lack of standardized assessments for evaluating the persistence of symptoms.

“This study’s findings suggest that although not well characterized, long-COVID pain symptoms are being experienced by non-negligible proportions of those recovering from acute COVID-19 episodes, thus highlighting the importance of future research efforts to focus on this aspect,” the researchers concluded.

This article originally appeared on Pulmonology Advisor


Kerzhner O, Berla E, Har-Even M, Ratmansky M, Goor-Aryeh I. Consistency of inconsistency in long-COVID-19 pain symptoms persistency: a systematic review and meta-analysis. Pain Pract. Published online July 21, 2023. doi:10.1111/papr.13277