Whitman, J. D. | bioRxiv Science

bioRxiv2020

SARS-CoV-2 infection of human iPSC-derived cardiac cells predicts novel cytopathic features in hearts of COVID-19 patients

Although COVID-19 causes cardiac dysfunction in up to 25% of patients, its pathogenesis remains unclear. Exposure of human iPSC-derived heart cells to SARS-CoV-2 revealed productive infection and robust transcriptomic and morphological signatures of damage, particularly in cardiomyocytes. Transcriptomic disruption of structural proteins corroborated adverse morphologic features, which included a distinct pattern of myofibrillar fragmentation and numerous iPSC-cardiomyocytes lacking nuclear DNA. Human autopsy specimens from COVID-19 patients displayed similar sarcomeric disruption, as well as cardiomyocytes without DNA staining. These striking cytopathic features provide new insights into SARS-CoV-2 induced cardiac damage, offer a platform for discovery of potential therapeutics, and raise serious concerns about the long-term consequences of COVID-19.

cell biology↗

bioRxiv2019

Chagas disease serological test performance in United States blood donor specimens

BackgroundChagas disease affects an estimated 300,000 individuals in the US. Diagnosis in the chronic phase requires positive results by two different IgG serological tests. Three ELISAs (Hemagen, Ortho, Wiener) and one rapid test (InBios) are FDA-cleared, but comparative data in US populations are sparse.\n\nMethodsWe evaluated 500 seropositive and 300 seronegative blood donor plasma samples. Country of birth was known for 255 seropositive specimens and grouped into regions: Mexico (n=94), Central America (n=88) and South America (n=73). Specimens were tested by the four FDA-cleared IgG serological assays. Test performance was evaluated by two comparators and latent class analysis.\n\nResultsInBios had the highest sensitivity (97.4-99.3%), but lowest specificity (87.5-92.3%). Hemagen had the lowest sensitivity (88.0-92.0%), but high specificity (99.0-100.0%). Sensitivity was intermediate for Ortho (92.4-96.5%) and Wiener (94.0-97.1%); both had high specificity (98.8-100.0% and 96.7-99.3%, respectively). Antibody reactivity and clinical sensitivity was lowest in donors from Mexico, intermediate in those from Central America and highest in those from South America.\n\nConclusionsOur findings provide an initial evidence base to improve laboratory diagnosis of Chagas disease in the US. The best current testing algorithm would employ a high sensitivity screening test followed by a high specificity confirmatory test.

microbiology↗