A study in JAMA Network Open in June 2024 investigates different variables associated with time to recovery from SARS-CoV-2 infection. The authors describe persistent symptoms and disability after SARS-CoV-2 infection, also known “post-COVID-19 condition”, as a “major public health concern”. Their report covers the epidemiologic features of recovery from SARS-CoV-2 during the first 3 years of the US pandemic period through 14 longstanding cohort studies.
The study
The authors use data from the Collaborative Cohort of Cohorts for COVID-19 Research (C4R), which comprises 14 established prospective, National Institutes of Health-funded cohort studies. The C4R study determined SARS-CoV-2 infection through 2 waves of questionnaires administered across the C4R population via telephone interview, mailed pamphlet, electronic survey, and/or in-person examinations. To assess recovery, participants were asked “following your COVID-19 infection, would you say you are completely recovered from COVID-19 now?” and participants who responded yes were asked “how long did it take for you to recover?”.
Out of 53,143 eligible participants, 49,319 responded to at least 1 C4R questionnaire. Among them, 6,980 (14.2%) reported a history of first nonfatal SARS-CoV-2 infection and 5,036 of these (72.1%) provided information on time to recovery. Excluding asymptomatic and fatal cases there were 4,708 participants in the main analysis. Vaccination prior to infection was reported by 966 participants (20.5%), of whom 57 (5.9%) had received only 1 mRNA vaccine dose.
What does the study find?
The study reports that at the time of questionnaire completion, 3,656 participants (77.6%) reported a complete recovery. Median time to recovery was 20 days and decreased over time; participants who were vaccinated at the time of infection had “shorter median time to recovery”. Restricted mean recovery time was 35.4 days and was associated with “sociodemographic, clinical, lifestyle, and infection-related factors”. “More than 1 in 5” participants did not recover from infection by 90 days after infection.
“Self-reported recovery by 90 days was less likely in women than men and in participants with vs without prepandemic clinical CVD. Recovery was favourably associated with vaccination prior to infection and infection during the Omicron wave, and these associations were partially mediated by reduced severity of acute infection.”
The researchers suggest that their findings are “consistent with a substantial US population burden of PCC”. However, they state the importance of examining longer-term trajectories of recovery and distinguishing COVID-19-related from non-COVID-19 causes of PCC-like symptoms. They indicate that the observation of a reduction in the burden of PCC over time is “consistent with other reports” and could be due to “reductions in the risk of severe SARS-CoV-2 illness over the course of the pandemic”.
The authors recognise that vaccination status at the time of infection was “not confirmed to modify associations of recovery with any of the factors”, the effect estimate for clinical CVD was “substantially attenuated among vaccinated vs unvaccinated participants”.
“Our findings support the use of vaccines to reduce the risk of long COVID, particularly in high-risk groups.”
Prepandemic health conditions were associated with longer recovery times. Unfavourable recovery outcomes were also “observed in American Indian or Alaska Native participants in models that did not account for cohort”, who reported a “higher burden of severe infection and nonrecovery at 90 days”. Another observation is that “women experienced worse recovery despite a lower rate of severe acute illness”.
The authors highlight a need for further investigation on the “longer-term prognosis and mechanisms” of PCC, which should include comparisons of multiorgan structure and function before and after infection to “inform treatment and prevention”.
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