Early immune responses have long-term associations with clinical, virologic, and immunologic outcomes in patients with COVID-19 (preprint)

The great majority of SARS-CoV-2 infections are mild and uncomplicated, but some individuals with initially mild COVID-19 progressively develop more severe symptoms. Furthermore, there is substantial heterogeneity in SARS-CoV-2-specific memory immune responses following infection. There remains a critical need to identify host immune biomarkers predictive of clinical and immunologic outcomes in SARS-CoV-2-infected patients. Leveraging longitudinal samples and data from a clinical trial in SARS-CoV-2 infected outpatients, we used host proteomics and transcriptomics to characterize the trajectory of the immune response in COVID-19 patients within the first 2 weeks of symptom onset. We identify early immune signatures, including plasma RIG-I levels, early interferon signaling, and related cytokines (CXCL10, MCP1, MCP-2 and MCP-3) associated with subsequent disease progression, control of viral shedding, and the SARS-CoV-2 specific T cell and antibody response measured up to 7 months after enrollment. We found that several biomarkers for immunological outcomes are shared between individuals receiving BNT162b2 (Pfizer–BioNTech) vaccine and COVID-19 patients. Finally, we demonstrate that machine learning models using 7-10 plasma protein markers measured early within the course of infection are able to accurately predict disease progression, T cell memory, and the antibody response post-infection in a second, independent dataset.

Association of Chronic Acid Suppression and Social Determinants of Health with COVID-19 Infection (preprint)

Acid suppressants are a widely-used class of medications previously linked to an increased risk of aerodigestive infections. However, prior studies of these medications as potentially reversible risk factors for COVID-19 have been conflicting. We performed a case-control study involving clinician-abstracted data from 900 health records across 3 US medical centers. We incorporated sociobehavioral predictors of infectious exposure using geomapping to publicly-available data. We found no evidence for an association between chronic acid suppression and incident COVID-19 (adjusted odds ratio 1.04, 95% CI: 0.92-1.17, P =0.515). However, we identified several medical and social features as positive (Latinx ethnicity, BMI ≥ 30, dementia, public transportation use, month of the pandemic) and negative (female sex, concurrent solid tumor, alcohol use disorder) predictors of new-onset infection. These results place both medical and social factors on the same scale within the context of the COVID-19 pandemic, and underscore the importance of comprehensive models of disease.