Combination of Baricitinib plus Remdesivir and Dexamethasone improves time to recovery and mortality among hospitalized patients with severe COVID-19 infection (preprint)

Background There seems to be a gap in the therapeutic options for severe Covid-19 pneumonia. Though the beneficial effect of combination treatment with baricitnib and remdesivir in accelerating clinical status improvement is described, the impact of the triple therapy with baricitinib + remdesivir/dexamethasone is not known. Methods A retrospective observational study comparing the effect of baricitinib plus standard treatment (remdesivir and dexamethasone) with standard therapy in patients requiring ≥ 5 L/min O2 was conducted. The primary outcome was to compared time to recovery in both groups, and the secondary outcomes was to determine mortality rate at discharge. Results Of 457 patients hospitalized during the study period, 51 patients received standard treatment while 88 patients received baricitinib plus standard treatment. In baricitinib group, the rate ratio of recovery was 1.28 (95%CI 0.84-1.94, p=0.24) with a reduction in median time to recovery of 3 days compared to standard treatment group. Subgroup analysis based on Ordinal Scale showed reduction in median time to recovery by 4 and 2 days with rate ratio of recovery of 2.95 (1.03-8.42, p =0.04) and 1.80 (1.09-2.98, p=0.02) in Ordinal Scale 5 and 6 respectively. No benefit was found in the Ordinal Scale 7 subgroup. An overall decrease in rate (15.9% vs 31.4% p=0.03) a likelihood (OR 0.41, 95%CI 0.18-0.94, p=0.03) of mortality was observed in the baricitinib group. Bacteremia and thrombosis were noted in the Baricitinib group, but comparable with the Standard of care group. Conclusion Baricitinib with standard therapy reduced time to recovery and offer mortality benefit in patients with severe COVID-19 pneumonia.”

Comparison of clinical course and outcomes of critically ill patients with SARS-CoV2 infection managed in traditional ICU and "Flex" ICU during the surge of the pandemic in the Bronx. (preprint)

BACKGROUND: As part of the response to increasing critical care capacity during the unprecedented surge of COVID-19 infections, NYC Health + Hospital systems identified and resourced areas in the hospital that could deliver critical care as "Flex" ICUs to complement the traditional ICUs to manage the rapid influx of critically ill patients. OBJECTIVE: Comparison of clinical features and outcomes of mechanically ventilated COVID-19 patients admitted to the traditional and "Flex" ICUs during the surge of the pandemic. METHODS: Retrospective comparative cohort study of patients with confirmed SARS-CoV-2 infection on mechanical ventilation admitted to traditional ICU and 'Flex' ICU. Univariate and multivariate analyses were conducted to detect factors associated with death from COVID-19 patients in mechanical ventilation by the Cox proportional hazards regression model. RESULTS: Out of the 312 patients on mechanical ventilation, 111(35.6%) were admitted to the traditional ICU, and 201(64.4%) to the 'Flex' ICU. The mortality rate was higher in the 'Flex' ICU compared with the traditional ICU (H.R., 1.37, 95% CI, 1.05-1.81, p<0.05), but the adjusted risk model was not significantly associated with increased mortality (adjusted, H.R., 1.29, 95% CI, 0.97-1.71, p=0.078). CONCLUSION "Flex" ICUs played a crucial role in critically ill patients' management during the pandemic. The mortality risk of patients in the "Flex" ICU was comparable to traditional ICUs in the adjusted analysis. While there is enough evidence for Intensivist managed ICUs to have better outcomes, our study demonstrates the feasibility of non-intensivist leading "Flex" ICUs during a crisis.

High Initial Titres of Anti-Spike Antibodies following SARS-CoV-2 Infection is Associated with Faster Decay Rates at Four Months Follow-Up (preprint)

Background Dynamics of humoral immune responses to SARS-CoV-2 antigens following infection suggests an initial decay of antibody followed by subsequent stabilization. We aim to understand the longitudinal humoral responses to SARS-CoV-2 nucleocapsid (N) protein and spike (S) protein and to evaluate their correlation to clinical symptoms among healthcare workers (HCW). Methods In this cross-sectional longitudinal cohort study done in two phases over four months, HCW underwent serial qualitative serology testing for anti-N antibody, quantitative MSH-ELISA to detect Receptor Binding Domain and full-length S reactive antibodies and completed online surveys about COVID-19 related symptoms and healthcare/community exposure. Results Anti-N antibody positivity was 27% and anti-S positivity was 28% in Phase 1. In Phase 2 anti-S titres were higher in symptomatic than in asymptomatic positive subjects in Phase 1. Marginally higher titers were seen in asymptomatic compared to the symptomatic positive subgroup in Phase 2. A positive correlation was noted between age, number and duration of symptoms, and Phase 1 anti-S antibody titre. A strong correlation was observed between Phase 1 titers and decay of anti-S antibody titres between the two phases. Significant correlation with rate of decay was also noted with fever, GI symptoms, and total number and duration of COVID-19 symptoms. Conclusions Higher initial anti-S antibody titres were associated with larger number and longer duration of symptoms as well as faster decay during the two time points.

Impact of Residential Neighborhood and Race/Ethnicity on Outcomes of Hospitalized Patients with COVID-19 in the Bronx (preprint)

The socially vulnerable have been most affected due to the COVID-19 pandemic, similar to the aftermath of any major disaster. Racial and social minorities are experiencing a disproportionate burden of morbidity and mortality. The aim of this study was to evaluate the impact of residential location/community and race/ethnicity on outcomes of COVID-19 infection among hospitalized patients within the Bronx. This was a single center retrospective observational cohort study that included SARS-CoV2 positive adult residents of the Bronx (stratified as residents of South Bronx vs Rest of Bronx) hospitalized between March-May 2020. Data extracted from hospital electronic medical records included residential addresses, race, comorbidities, and insurance details. Comorbidity burden other clinical and laboratory details were also assessed to determine their correlation to COVID-19 severity of illness and outcomes of mortality and length of stay. As expected, the COVID-19 pandemic differentially affected outcomes in those in the more socially disadvantaged area of the South Bronx versus the rest of the Bronx borough. Residents of the South Bronx had a significantly higher comorbidity burden and had public insurance to access medical care in comparison to the remainder of the Bronx. Interestingly, for the patient population studied there was no observed difference in 30-day mortality by race/ethnicity among those infected with COVID-19 in spite of the increased disease burden observed. This adds an interesting perspective to the current literature, and highlights the need to address the social/economic factors contributing to health access disparity to reduce the adverse impact of COVID-19 in these communities.