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Preprint in English | bioRxiv | ID: ppbiorxiv-472112


Severe COVID-19 is associated with epithelial and endothelial barrier dysfunction within the lung as well as in distal organs. While it is appreciated that an exaggerated inflammatory response is associated with barrier dysfunction, the triggers of this pathology are unclear. Here, we report that cell-intrinsic interactions between the Spike (S) glycoprotein of SARS-CoV-2 and epithelial/endothelial cells are sufficient to trigger barrier dysfunction in vitro and vascular leak in vivo, independently of viral replication and the ACE2 receptor. We identify an S-triggered transcriptional response associated with extracellular matrix reorganization and TGF-{beta} signaling. Using genetic knockouts and specific inhibitors, we demonstrate that glycosaminoglycans, integrins, and the TGF-{beta} signaling axis are required for S-mediated barrier dysfunction. Our findings suggest that S interactions with barrier cells are a contributing factor to COVID-19 disease severity and offer mechanistic insight into SARS-CoV-2 triggered vascular leak, providing a starting point for development of therapies targeting COVID-19 pathogenesis.

Preprint in English | medRxiv | ID: ppmedrxiv-21266786


Serological surveillance studies of infectious diseases provide population-level estimates of infection and antibody prevalence, generating crucial insight into population-level immunity, risk factors leading to infection, and effectiveness of public health measures. These studies traditionally rely on detection of pathogen-specific antibodies in samples derived from venipuncture, an expensive and logistically challenging aspect of serological surveillance. During the COVID-19 pandemic, guidelines implemented to prevent the spread of SARS-CoV-2 infection made collection of venous blood logistically difficult at a time when SARS-CoV-2 serosurveillance was urgently needed. Dried blood spots (DBS) have generated interest as an alternative to venous blood for SARS-CoV-2 serological applications due to their stability, low cost, and ease of collection; DBS samples can be self-generated via fingerprick by community members and mailed at ambient temperatures. Here, we detail the development of four DBS-based SARS-CoV-2 serological methods and demonstrate their implementation in a large serological survey of community members from 12 cities in the East Bay region of the San Francisco metropolitan area using at- home DBS collection. We find that DBS perform similarly to plasma/serum in enzyme-linked immunosorbent assays and commercial SARS-CoV-2 serological assays. In addition, we show that DBS samples can reliably detect antibody responses months post-infection and track antibody kinetics after vaccination. Implementation of DBS enabled collection of valuable serological data from our study population to investigate changes in seroprevalence over an eight-month period. Our work makes a strong argument for the implementation of DBS in serological studies, not just for SARS-CoV-2, but any situation where phlebotomy is inaccessible.

Preprint in English | medRxiv | ID: ppmedrxiv-20248894


As essential personnel, United States farmworkers have continued working in-person throughout the COVID-19 pandemic. We undertook prospective surveillance of SARS-CoV-2 infection and antibody prevalence among farmworkers in Californias Salinas Valley from 15 June to 30 November, 2020. Over this period, we observed 22.1% (1514/6864) positivity for current SARS-CoV-2 by nucleic acid detection among farmworkers tested at federally-qualified migrant and community health clinics, as compared to 17.2% (1255/7305) among other adults from the same communities (risk ratio, 1.29; 95% confidence interval, 1.20-1.37). In a nested study enrolling 1,115 farmworkers, prevalence of current infection was 27.7% among farmworkers reporting [≥]1 potential COVID-19 symptom, and 7.2% among farmworkers without symptoms (adjusted odds ratio 4.17; 2.86-6.09). Prevalence of anti-SARS-CoV-2 IgG antibodies increased from 10.5% (6.0-18.4%) between 16 July-31 August to 21.2% (16.6-27.4%) between 1-30 November. The high observed prevalence of infection among farmworkers underscores the need for vaccination and other preventive interventions.