Excess burden of respiratory and abdominal conditions following COVID-19 infections during the ancestral and Delta variant periods in the United States: An EHR-based cohort study from the RECOVER Program

ImportanceThe frequency and characteristics of post-acute sequelae of SARS-CoV-2 infection (PASC) may vary by SARS-CoV-2 variant. ObjectiveTo characterize PASC-related conditions among individuals likely infected by the ancestral strain in 2020 and individuals likely infected by the Delta variant in 2021. DesignRetrospective cohort study of electronic medical record data for approximately 27 million patients from March 1, 2020-November 30, 2021. SettingHealthcare facilities in New York and Florida. ParticipantsPatients who were at least 20 years old and had diagnosis codes that included at least one SARS-CoV-2 viral test during the study period. ExposureLaboratory-confirmed COVID-19 infection, classified by the most common variant prevalent in those regions at the time. Main Outcome(s) and Measure(s)Relative risk (estimated by adjusted hazard ratio [aHR]) and absolute risk difference (estimated by adjusted excess burden) of new conditions, defined as new documentation of symptoms or diagnoses, in persons between 31-180 days after a positive COVID-19 test compared to persons with only negative tests during the 31-180 days after the last negative test. ResultsWe analyzed data from 560,752 patients. The median age was 57 years; 60.3% were female, 20.0% non-Hispanic Black, and 19.6% Hispanic. During the study period, 57,616 patients had a positive SARS-CoV-2 test; 503,136 did not. For infections during the ancestral strain period, pulmonary fibrosis, edema (excess fluid), and inflammation had the largest aHR, comparing those with a positive test to those with a negative test, (aHR 2.32 [95% CI 2.09 2.57]), and dyspnea (shortness of breath) carried the largest excess burden (47.6 more cases per 1,000 persons). For infections during the Delta period, pulmonary embolism had the largest aHR comparing those with a positive test to a negative test (aHR 2.18 [95% CI 1.57, 3.01]), and abdominal pain carried the largest excess burden (85.3 more cases per 1,000 persons). Conclusions and RelevanceWe documented a substantial relative risk of pulmonary embolism and large absolute risk difference of abdomen-related symptoms after SARS-CoV-2 infection during the Delta variant period. As new SARS-CoV-2 variants emerge, researchers and clinicians should monitor patients for changing symptoms and conditions that develop after infection. STATEMENTS AND ACKNOWLEDGEMENTSO_LIAuthorship has been determined by ICJME recommendation C_LIO_LIDisclosures to be obtained at time of submission C_LIO_LIThe content is solely the responsibility of the authors and does not necessarily represent the official views of the RECOVER Program, the NIH or other funders C_LIO_LIWe would like to thank the National Community Engagement Group (NCEG), all patient, caregiver and community Representatives, and all the participants enrolled in the RECOVER Initiative. C_LI