Hypoxia inducible factors regulate infectious SARS-CoV-2, epithelial damage and respiratory symptoms in a hamster COVID-19 model.

Understanding the host pathways that define susceptibility to SARS-CoV-2 infection and disease are essential for the design of new therapies. Oxygen levels in the microenvironment define the transcriptional landscape, however the influence of hypoxia on virus replication and disease in animal models is not well understood. In this study, we identify a role for the hypoxic inducible factor (HIF) signalling axis to inhibit SARS-CoV-2 infection, epithelial damage and respiratory symptoms in Syrian hamsters. Pharmacological activation of HIF with the prolyl-hydroxylase inhibitor FG-4592 significantly reduced the levels of infectious virus in the upper and lower respiratory tract. Nasal and lung epithelia showed a reduction in SARS-CoV-2 RNA and nucleocapsid expression in treated animals. Transcriptomic and pathological analysis showed reduced epithelial damage and increased expression of ciliated cells. Our study provides new insights on the intrinsic antiviral properties of the HIF signalling pathway in SARS-CoV-2 replication that may be applicable to other respiratory pathogens and identifies new therapeutic opportunities.

Patient-physician social concordance, medical visit communication and patients' perceptions of health care quality.

UNLABELLED: Social characteristics (e.g. race, gender, age, education) are associated with health care disparities. We introduce social concordance, a composite measure of shared social characteristics between patients and physicians. OBJECTIVE: To determine whether social concordance predicts differences in medical visit communication and patients' perceptions of care. METHODS: Regression analyses were used to determine the association of patient-provider social concordance with medical visit communication and patients' perceptions of care using data from two observational studies involving 64 primary care physicians and 489 of their patients from the Baltimore, MD/Washington, DC/Northern Virginia area. RESULTS: Lower patient-physician social concordance was associated with less positive patient perceptions of care and lower positive patient affect. Patient-physician dyads with low vs. high social concordance reported lower ratings of global satisfaction with office visits (OR=0.64 vs. OR=1.37, p=0.036) and were less likely to recommend their physician to a friend (OR=0.61 vs. OR=1.37, p=0.035). A graded-response was observed for social concordance with patient positive affect and patient perceptions of care. CONCLUSION: Patient-physician concordance across multiple social characteristics may have cumulative effects on patient-physician communication and perceptions of care. PRACTICE IMPLICATIONS: Research should move beyond one-dimensional measures of patient-physician concordance to understand how multiple social characteristics influence health care quality.