Association between SARS-CoV-2 Infection and Select Symptoms and Conditions 31 to 150 Days After Testing among Children and Adults

Abstract

Background An increasing number of studies have described new and persistent symptoms and conditions as potential post-acute sequelae of SARS-CoV-2 infection (PASC). However, it remains unclear whether certain symptoms or conditions occur more frequently among persons with SARS-CoV-2 infection compared with those never infected with SARS-CoV-2. We compared the occurrence of specific COVID-associated symptoms and conditions as potential PASC 31 to 150 days following a SARS-CoV-2 test among adults (≥20 years) and children (<20 years) with positive and negative test results documented in the electronic health records (EHRs) of institutions participating in PCORnet, the National Patient-Centered Clinical Research Network. Methods and Findings This study included 3,091,580 adults (316,249 SARS-CoV-2 positive; 2,775,331 negative) and 675,643 children (62,131 positive; 613,512 negative) who had a SARS-CoV-2 laboratory test (nucleic acid amplification or rapid antigen) during March 1, 2020–May 31, 2021 documented in their EHR. We identified hospitalization status in the day prior through the 16 days following the SARS-CoV-2 test as a proxy for the severity of COVID-19. We used logistic regression to calculate the odds of receiving a diagnostic code for each symptom outcome and Cox proportional hazard models to calculate the risk of being newly diagnosed with each condition outcome, comparing those with a SARS-CoV-2 positive test to those with a negative test. After adjustment for baseline covariates, hospitalized adults and children with a positive test had increased odds of being diagnosed with ≥1 symptom (adults: adjusted odds ratio[aOR], 1.17[95% CI, 1.11-1.23]; children: aOR, 1.18[95% CI, 1.08-1.28]) and shortness of breath (adults: aOR, 1.50[95% CI, 1.38-1.63]; children: aOR, 1.40[95% CI, 1.15-1.70]) 31-150 days following a SARS-CoV-2 test compared with hospitalized individuals with a negative test. Hospitalized adults with a positive test also had increased odds of being diagnosed with ≥3 symptoms (aOR, 1.16[95% CI, 1.08 – 1.26]) and fatigue (aOR, 1.12[95% CI, 1.05 – 1.18]) compared with those testing negative. The risks of being newly diagnosed with type 1 or type 2 diabetes (aHR, 1.25[95% CI, 1.17-1.33]), hematologic disorders (aHR, 1.19[95% CI, 1.11-1.28]), and respiratory disease (aHR, 1.44[95% CI, 1.30-1.60]) were higher among hospitalized adults with a positive test compared with those with a negative test. Non-hospitalized adults with a positive SARS-CoV-2 test had higher odds of being diagnosed with fatigue (aOR, 1.11[95% CI, 1.05-1.16]) and shortness of breath (aOR, 1.22[95% CI, 1.15-1.29]), and had an increased risk (aHR, 1.12[95% CI, 1.02-1.23]) of being newly diagnosed with hematologic disorders (i.e., venous thromboembolism and pulmonary embolism) 31-150 days following SARS-CoV-2 test compared with those testing negative. The risk of being newly diagnosed with certain conditions, such as mental health conditions and neurological disorders, was lower among patients with a positive viral test relative to those with a negative viral test. Conclusions Patients with SARS-CoV-2 infection were at higher risk of being diagnosed with certain symptoms and conditions, particularly fatigue, respiratory symptoms, and hematological abnormalities, after acute infection. The risk was highest among adults hospitalized after SARS-CoV-2 infection.