Hospital Admission and Hospital Course Predictors of Severity of Post-covid-19 Condition (preprint)

BACKGROUND Prediction of severity of Post-COVID-19 condition is not clear. We determined whether hospital course variables correlated with objective and subjective outcomes 3- and 6-months post-COVID-19 onset.METHODS Adults admitted to hospital with acute COVID-19 were recruited (Feb 15, 2020-April 1, 2021) from two tertiary hospitals in Vancouver, Canada. We recorded baseline characteristics, COVID severity score, organ function, ICU and hospital length of stay. Survivors were evaluated at 3- and 6-months post- COVID-19 onset: subjective: University of California San Diego Shortness of Breath Score, EuroQol 5D Visual Analogue Scale, Frailty Index; Objective: functional capacity (6-minute walk test), pulmonary (pulmonary function tests), cardiac (echocardiography, BNP), renal (creatinine), hepatic (AST, ALT, bilirubin), and coagulation (aPTT, INR, D-dimers, fibrinogen).RESULTS In 133 post-COVID-19 patients (age 62 ± 14 years, 65% male with frequent comorbidities [hypertension (42%), diabetes (29%), chronic cardiac (22%)), 42% were admitted to Intensive Care Unit: 23%, 23% and 2% required ventilation, vasopressors or renal support, respectively. One-third had restrictive lung function (< 80% predicted FVC %, TLC%, or DLCO%) at 3 months. Novel findings were correlations of (1) acute hepatic dysfunction with restrictive lung function at 3 months post COVID-19 onset; (2) more severe acute COVID-19 with later pro-thrombotic phenotype and (3) greater acute organ dysfunction with later objective organ dysfunction at 3- and 6-months. No hospital course variables were associated with subjective outcomes at 3- and 6-months.CONCLUSIONS Early organ dysfunction predicts later objective pathology especially restrictive lung disease and a pro-coagulant state. These hypothesis-generating findings require further validation in additional patients.

Sustained Dysregulation of the Plasma Renin-angiotensin System in Acute COVID-19 (preprint)

SARS-CoV-2 enters cells by binding to angiotensin-converting enzyme 2 (ACE2), and COVID-19 infection may therefore induce changes in the renin-angiotensin system (RAS). To determine the effects of COVID-19 on plasma RAS components, we measured plasma ACE, ACE2, and angiotensins I, (1-7), and II in 46 adults with COVID-19 at hospital admission and on days 2, 4, 7 and 14, compared to 50 blood donors (controls). We compared survivors vs. non-survivors, males vs. females, ventilated vs. not ventilated, and angiotensin receptor blocker (ARB) and angiotensin-converting enzyme (ACE) inhibitor-exposed vs. not exposed. At admission, COVID-19 patients had higher plasma levels of ACE (p=0.012), ACE2 (p=0.001) and angiotensin-(1-7) (p<0.001) than controls. Plasma ACE and ACE2 remained elevated for 14 days in COVID-19 patients, while plasma angiotensin-(1-7) decreased after 7 days. In adjusted analyses, plasma ACE was higher in males vs. females (p=0.042), and plasma angiotensin I was significantly lower in ventilated vs. non-ventilated patients (p=0.001). In summary, plasma ACE and ACE2 are increased for at least 14 days in patients with COVID-19 infection. Angiotensin-(1-7) levels are also elevated, but decline after 7 days. The results indicate dysregulation of the RAS with COVID-19, with increased circulating ACE2 throughout the course of infection.Clinical Trial Registration: https://clinicaltrials.gov/ Unique Identifier: NCT04510623