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-day following a SARS-CoV-2 test among adults and children with positive and negative test results. METHODS: We conducted a retrospective cohort study using electronic health record (EHR) data from 43 PCORnet sites participating in a national COVID-19 surveillance program. 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 during March 1, 2020-May 31, 2021 documented in their EHR. We used logistic regression to calculate the odds of having a symptom and Cox models to calculate the risk of having a newly diagnosed condition associated with a SARS-CoV-2 positive test. RESULTS: 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]) or 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 or fatigue compared with those testing negative. The risks of being newly diagnosed with type 1 or type 2 diabetes (adjusted hazard ratio[aHR], 1.25[95% CI, 1.17-1.33]), hematologic disorders (aHR, 1.19[95% CI, 1.11-1.28]), or 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 test also had higher odds or increased risk of being diagnosed with certain symptoms or conditions. CONCLUSIONS: Patients with SARS-CoV-2 infection, especially those who were hospitalized, were at higher risk of being diagnosed with certain symptoms and conditions after acute infection.

Background: Prior studies have documented differences in the age, racial, and ethnic characteristics among patients with SARS-CoV-2 infection. However, little is known about how these characteristics changed over time during the pandemic and whether racial, ethnic, and age disparities evident early in the pandemic were persistent over time. This study reports on trends in SARS-CoV-2 infections among U.S. adults from March 1, 2020 to January, 31 2022, using data from electronic health records. Methods and Findings: We captured repeated cross-sectional information from 43 large healthcare systems in 52 U.S. States and territories, participating in PCORnet, the National Patient-Centered Clinical Research Network. Using distributed queries executed at each participating institution, we acquired information for all patients >= 20 years of age who were tested for SARS-CoV-2 (both positive and negative results), including care setting, age, sex, race, and ethnicity by month as well as comorbidities (assessed with diagnostic codes). During this time period, 1,325,563 patients had positive (13% inpatient) and 6,705,868 patients had negative (25% inpatient) viral tests for SARS-CoV-2. Disparities in testing positive were present across racial and ethnic groups, especially in the inpatient setting. Compared to White patients, Black or African American and other race patients had relative risks for testing positive of 1.5 or greater in the inpatient setting for 12 of the 23-month study period. Compared to non-Hispanic patients, Hispanic patients had relative risks for testing positive in the inpatient setting of 1.5 or greater for 16 of 23. Ethnic and racial differences were present in emergency department and ambulatory settings but were less common across time than in inpatient settings. Trends in infections by age group demonstrated higher test positivity for older patients in the inpatient setting only for most months, except for June and July of 2020, April to August 2021, and January 2022. Comorbidities were common, with much higher rates among those hospitalized; hypertension (38% of patients SARS-CoV-2 positive vs. 29% for those negative) and type 2 diabetes mellitus (22% vs. 13%) were the most common. Conclusion and Relevance: Racial and ethnic disparities changed over time among persons infected with SARS-CoV-2. These trends highlight potential underlying mechanisms, such as poor access to care and differential vaccination rates, that may have contributed to greater disparities, especially early in the pandemic. Monitoring data on characteristics of patients testing positive in real time could allow public health officials and policymakers to tailor interventions to ensure that patients and communities most in need are receiving adequate testing, mitigation strategies, and treatment. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Antigen-specific CD4 and CD8 T cells are important components of the immune response to Mycobacterium tuberculosis, yet little information is currently known regarding how the breadth, specificity, phenotype, and function of M. tuberculosis-specific T cells correlate with M. tuberculosis infection outcome in humans. To facilitate evaluation of human M. tuberculosis-specific T cell responses targeting multiple different Ags, we sought to develop a high throughput and reproducible T cell response spectrum assay requiring low blood sample volumes. We describe here the optimization and standardization of a microtiter plate-based, diluted whole blood stimulation assay utilizing overlapping peptide pools corresponding to a functionally diverse panel of 60 M. tuberculosis Ags. Using IFN-gamma production as a readout of Ag specificity, the assay can be conducted using 50 mul of blood per test condition and can be expanded to accommodate additional Ags. We evaluated the intra- and interassay variability, and implemented testing of the assay in diverse cohorts of M. tuberculosis-unexposed healthy adults, foreign-born adults with latent M. tuberculosis infection residing in the United States, and tuberculosis household contacts with latent M. tuberculosis infection in a tuberculosis-endemic setting in Kenya. The M. tuberculosis-specific T cell response spectrum assay further enhances the immunological toolkit available for evaluating M. tuberculosis-specific T cell responses across different states of M. tuberculosis infection, and can be readily implemented in resource-limited settings. Moreover, application of the assay to longitudinal cohorts will facilitate evaluation of treatment- or vaccine-induced changes in the breadth and specificity of Ag-specific T cell responses, as well as identification of M. tuberculosis-specific T cell responses associated with M. tuberculosis infection outcomes.