BACKGROUND: Little is known about how symptoms or symptom clusters of Post-COVID Conditions (PCC) impact an individual's return to pre-COVID health. METHODS: We used four state-level COVID-19 case reporting systems and patient-reported survey data to identify patients with PCC and associations with an individual's return to pre-COVID health after laboratory-confirmed SARS-CoV-2 infection. Participants had a positive SARS-CoV-2 test between March-December 2020. Weighted regression models were used to 1) estimate prevalence of PCC; 2) identify risk factors associated with developing PCC; and 3) examine associations between PCC symptom clusters and return to pre-COVID health. Factor analysis was used to statistically identify post-COVID symptom clusters. FINDINGS: Prevalence of PCC in this population-based sample was 29·9% for persons with SARS-CoV-2 infection, during the pre-delta variant period (March-December 2020); 77·2% of persons experiencing PCC had not returned to pre-COVID health within 8-60 weeks after infection. Female sex, acute COVID-19 illness severity, and number of pre-existing comorbidities were significant risk factors associated with PCC. Myalgic encephalomyelitis/chronic fatigue syndrome-like symptoms, upper-respiratory symptoms, and gastrointestinal symptoms were significantly associated with not returning to pre-COVID health. INTERPRETATION: Understanding PCC symptom clustering may provide insight into pathophysiology, severity of PCC, and management for patients who have not returned to their usual state of health after SARS-CoV-2 infection. Tracking PCC can help measure the impact of COVID-19 vaccination and acute COVID-19-specific treatments on reducing PCC in the US.

Long-term symptoms often associated with COVID-19 (post-COVID conditions or long COVID) are an emerging public health concern that is not well understood. Prevalence of post-COVID conditions has been reported among persons who have had COVID-19 (range = 5%-80%), with differences possibly related to different study populations, case definitions, and data sources (1). Few studies of post-COVID conditions have comparisons with the general population of adults with negative test results for SARS-CoV-2, the virus that causes COVID-19, limiting ability to assess background symptom prevalence (1). CDC used a nonprobability-based Internet panel established by Porter Novelli Public Services* to administer a survey to a nationwide sample of U.S. adults aged ≥18 years to compare the prevalence of long-term symptoms (those lasting >4 weeks since onset) among persons who self-reported ever receiving a positive SARS-CoV-2 test result with the prevalence of similar symptoms among persons who reported always receiving a negative test result. The weighted prevalence of ever testing positive for SARS-CoV-2 was 22.2% (95% confidence interval [CI] = 20.6%-23.8%). Approximately two thirds of respondents who had received a positive test result experienced long-term symptoms often associated with SARS-CoV-2 infection. Compared with respondents who received a negative test result, those who received a positive test result reported a significantly higher prevalence of any long-term symptom (65.9% versus 42.9%), fatigue (22.5% versus 12.0%), change in sense of smell or taste (17.3% versus 1.7%), shortness of breath (15.5% versus 5.2%), cough (14.5% versus 4.9%), headache (13.8% versus 9.9%), and persistence (>4 weeks) of at least one initially occurring symptom (76.2% versus 69.6%). Compared with respondents who received a negative test result, a larger proportion of those who received a positive test result reported believing that receiving a COVID-19 vaccine made their long-term symptoms better (28.7% versus 15.7%). Efforts to address post-COVID conditions should include helping health care professionals recognize the most common post-COVID conditions and optimize care for patients with persisting symptoms, including messaging on potential benefits of COVID-19 vaccination.