COVID-19 Mortality in California Based on Death Certificates: Disproportionate Impacts Across Racial/Ethnic Groups and Nativity (preprint)

ABSTRACT Purpose To examine characteristics of coronavirus disease 2019 (COVID-19) decedents in California (CA) and evaluate for disproportionate mortality across race/ethnicity and ethnicity/nativity. Methods COVID-19 deaths were identified from death certificates. Age-adjusted mortality rate ratios (MRR) were compared across race/ethnicity. Proportionate mortality rates (PMR) were compared across race/ethnicity and by ethnicity/nativity. Results We identified 10,200 COVID-19 deaths in CA occurring February 1 through July 31, 2020. Decedents tended to be older, male, Hispanic, foreign-born, and have lower educational attainment. MRR indicated elevated COVID-19 morality rates among Asian/Pacific Islander, Black, and Hispanic groups compared with the White group, with Black and Hispanic groups having the highest MRR at 2.75 (95%CI:2.54-2.97) and 4.18 (95%CI: 3.99-4.37), respectively. Disparities were larger at younger ages. Similar results were observed with PMR, which remained in analyses stratified by education. Elevated PMR were observed in all ethnicity/nativity groups, especially foreign-born Hispanic individuals, relative to U.S.-born non-Hispanic individuals, were generally larger at younger ages, and persisted after stratifying by education. Conclusions Differential COVID-19 mortality was observed in California across racial/ethnic groups and by ethnicity/nativity groups with evidence of greater disparities among younger age groups. Identifying COVID-19 disparities is an initial step towards mitigating disease impacts in vulnerable communities.

Therapeutic effects of dipyridamole on COVID-19 patients with coagulation dysfunction (preprint)

The human coronavirus HCoV-19 infection can cause acute respiratory distress syndrome (ARDS), hypercoagulability, hypertension, extrapulmonary multiorgan dysfunction. Effective antiviral and anti-coagulation agents with safe clinical profiles are urgently needed to improve the overall prognosis. We screened an FDA approved drug library and found that an anticoagulant agent dipyridamole (DIP) suppressed HCoV-19 replication at an EC50 of 100 nM in vitro. It also elicited potent type I interferon responses and ameliorated lung pathology in a viral pneumonia model. In analysis of twelve HCoV-19 infected patients with prophylactic anti-coagulation therapy, we found that DIP supplementation was associated with significantly increased platelet and lymphocyte counts and decreased D-dimer levels in comparison to control patients. Two weeks after initiation of DIP treatment, 3 of the 6 severe cases (60%) and all 4 of the mild cases (100%) were discharged from the hospital. One critically ill patient with extremely high levels of D-dimer and lymphopenia at the time of receiving DIP passed away. All other patients were in clinical remission. In summary, HCoV-19 infected patients could potentially benefit from DIP adjunctive therapy by reducing viral replication, suppressing hypercoagulability and enhancing immune recovery. Larger scale clinical trials of DIP are needed to validate these therapeutic effects.

ACE2 expression by colonic epithelial cells is associated with viral infection, immunity and energy metabolism (preprint)

Respiratory disease caused by the 2019 novel coronavirus (2019-nCoV) pneumonia first emerged in Wuhan, Hubei Province, China, in December 2019 and spread rapidly to other provinces and other countries. Angiotensin-converting enzyme 2 (ACE2) is the receptor for SARS-CoV and has been suggested to be also the receptor for 2019-nCoV. Paradoxically, ACE2 expression in the lung protects mice from SARS-CoV spike protein induced lung injury by attenuating the renin-angiotensin system. In the intestine, ACE2 also suppresses intestinal inflammation by maintaining amino acid homeostasis, antimicrobial peptide expression and ecology of the gut microbiome. Upon analysis of single cell-RNA sequencing data from control subjects and those with colitis or inflammatory bowel disease (IBD), we found that ACE2 expression in the colonocytes was positively associated with genes regulating viral infection, innate and cellular immunity, but was negatively associated with viral transcription, protein translation, humoral immunity, phagocytosis and complement activation. In summary, we suggest that ACE2 may play dual roles in mediating the susceptibility and immunity of 2019-nCoV infection.