Background There is limited data on outcomes of moderate to severe Coronavirus disease 2019 (COVID-19) among patients treated with remdesivir and dexamethasone in a real-world setting. Objective To compare the effectiveness of standard of care (SOC) alone vs SOC plus remdesivir and dexamethasone. Methods Two population-based nationwide cohorts of individuals hospitalized with COVID-19 during February through December 2020. Death within 30 days and need of mechanical ventilation (MV) were compared by inverse probability of treatment weighted (ITPW) logistic regression analysis and shown as odds ratio (OR) with 95% confidence interval (CI). Results The 30-d mortality rate of 1694 individuals treated with remdesivir and dexamethasone in addition to SOC was 12.6% compared to 19.7% for 1053 individuals receiving SOC alone. This corresponded to a weighted OR of 30-day mortality of 0.47 (95% CI, 0.38-0.57) for patients treated with remdesivir and dexamethasone compared to patients receiving SOC alone. Similarly, progression to MV was reduced (OR 0.36 (95% CI, 0.29-0.46)). Conclusions and relevance Treatment of moderate to severe COVID-19 during June through December that included remdesivir and dexamethasone was associated with reduced 30-day mortality and need of MV compared to treatment in February through May.

Background Venous thromboembolism (VTE) is a potentially fatal complication of SARS-CoV-2 infection and thromboprophylaxis should be balanced against risk of bleeding. This study aimed to examine risks of VTE and major bleeding in hospitalized and community-managed SARS-CoV-2 patients compared with control populations. Methods Using nationwide population-based registries, 30-day risks of VTE and major bleeding in SARS-CoV-2 positive patients were compared with those of SARS-CoV-2 test-negative patients and with an external cohort of influenza patients. Medical records of all COVID-19 patients at six departments of infectious diseases in Denmark were reviewed in detail. Results The overall 30-day risk of VTE was 0.4% (40/9,460) among SARS-CoV-2 patients (16% hospitalized), 0.3% (649/226,510) among SARS-CoV-2 negative subjects (12% hospitalized), and 1.0% (158/16,281) among influenza patients (59% hospitalized). VTE risks were higher and comparable in hospitalized SARS-CoV-2 positive (1.5%), SARS-CoV-2 negative (1.8%), and influenza patients (1.5%). Diagnosis of major bleeding was registered in 0.5% (47/9,460) of all SARS-CoV-2 positive individuals and in 2.3% of those hospitalized. Medical record review of 582 hospitalized SARS-CoV-2 patients observed VTE in 4% (19/450) and major bleeding in 0.4% (2/450) of ward patients, of whom 31% received thromboprophylaxis. Among intensive care patients (100% received thromboprophylaxis), risks were 7% (9/132) for VTE and 11% (15/132) for major bleeding. Conclusions Among people with SARS-CoV-2 infection in a population-based setting, VTE risks were low to moderate and were not substantially increased compared with SARS-CoV-2 test-negative and influenza patients. Risk of severe bleeding was low for ward patients, but mirrored VTE risk in the intensive care setting.

Background and aims Proton pump inhibitor (PPI) use has been associated with increased risk of SARS-CoV-2 infection and severe outcomes. However, meta-analyses show unclear results leading to uncertainty regarding the safety of PPI use during the ongoing COVID-19 pandemic. Methods We conducted a nationwide observational study including all SARS-CoV-2 cases (n=83,224) in Denmark as of December 1, 2020. The association of current PPI use with risk of infection was examined in a case-control design. We investigated the risk of severe outcomes, including mechanical ventilation, ICU admission or death, in current PPI users (n=4,473) compared to never users. Propensity score matching was applied to control for confounding. Finally, we performed an updated meta-analysis on risk of SARS-CoV-2 infection and COVID-19 mortality attributable to PPI use. Results Current PPI use was associated with increased risk of infection; adjusted odds ratio (OR) 1.08 (95% CI 1.03-1.13). Among SARS-CoV-2 cases, PPI use was associated with increased risk of hospital admission; adjusted relative risk (RR) 1.13 (1.03-1.24), but not with other severe outcomes. The updated meta-analysis showed no association between PPI use and risk of infection or mortality; pooled OR 1.00 (95% CI 0.75-1.32) and RR 1.33 (95% CI 0.71-2.48). Conclusion Current PPI use may be associated with an increased risk of SARS-CoV-2 infection and hospital admission, but these results with minimally elevated estimates are most likely subject to residual confounding. No association was found for severe outcomes. The results from the meta-analysis indicated no impact of current PPI use on COVID-19 outcomes.

Incretin‐based therapies, glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) and dipeptidyl peptidase‐4 inhibitors (DPP‐4i), have been hypothesized to exert beneficial effects on COVID‐19 outcomes due to anti‐inflammatory properties. In this population‐based cohort study, we retrieved data from nationwide registries on all individuals diagnosed with severe acute respiratory syndrome coronavirus 2 infection up to 1 November 2020. For individuals with diabetes, we examined the impact of use of GLP‐1 RAs (n = 370) and DPP‐4i (n = 284) compared with sodium‐glucose cotransporter‐2 inhibitors (SGLT‐2i) (n = 342) on risk of hospital admission and severe outcomes. Relative risks (RRs) were calculated after applying propensity score weighted methods to control for confounding. Current users of GLP‐1 RAs had an adjusted RR of 0.89 (95% confidence interval 0.34‐2.33), while users of DPP‐4i had an adjusted RR of 2.42 (95% confidence interval 0.99‐5.89) for 30‐day mortality compared with SGLT‐2i use. Further, use of GLP‐1 RAs or DPP‐4i compared with SGLT‐2i was not associated with decreased risk of hospital admission. Thus, use of incretin‐based therapies in individuals with diabetes and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) was not associated with improved clinical outcomes.