ABSTRACT
Background: There is limited information on effectiveness of COVID-19 therapies in immunocompromised patients, who are at higher risk of hospitalizations, complications, and mortality due to COVID-19. We examined hospital all-cause mortality for early RDV use vs. no RDV use among immunocompromised COVID-19 patients across several distinct dominant variants of concern (VOC) periods: pre-Delta (Dec'20-Apr'21), Delta (May-Nov'21) and Omicron (Dec'21-Apr'22). Method(s): Using the Premier Healthcare Database, we identified adults with an immunocompromised condition (cancer, solid organ and hematopoietic stem cell transplant, hematologic malignancies, primary immunodeficiencies, asplenia, bone marrow failure/aplastic anemia, severe combined immunodeficiencies or HIV), hospitalized with a primary diagnosis of COVID-19. Patients treated with RDV in first 2 days of admission vs. those not treated with RDV during the hospitalization were matched using 1:1 preferential withinhospital propensity matching with replacement. Patients were excluded if discharged within 3 days of RDV initiation. Cox Proportional Hazards Model was used to examine time to 14-and 28-day mortality. Result(s): Overall (Dec'20-Apr'22), 14,169 RDV-treated patients were matched to 5,341 unique non-RDV patients. Post-matching balance was achieved with 59% being 65+ years, 40.5% with no supplementary oxygen charges, 39% received low-flow oxygen, 19% on high-flow oxygen/non-invasive ventilation and 1.5% on invasive mechanical ventilation/ECMO at baseline. During the study period, unadjusted mortality rate was significantly lower for RDV patients at 14 days (11% [95% CI: 11%-12%] vs 15% [15%-16%];p< .0001) and 28 days (18% [17%-18%];p< .0001 vs 22% [22%-23%];p< .0001) as compared to patients that did not receive RDV. After adjusting for baseline and clinical covariates, 14-day results showed that RDV had significantly lower mortality risk compared to non-RDV across all VOC periods [overall (30% lower risk), pre-delta (41%), Delta (23%), Omicron (25%)]. Similarly, 28-day results showed that RDV had significantly lower mortality risk compared to non-RDV across all VOC periods [overall (25%), pre-delta (35%), Delta (21%), Omicron (16%)] (Fig). Conclusion(s): Timely initiation of RDV in first two days of hospital admission demonstrated significant mortality reduction in immunocompromised patients hospitalized with primary diagnosis of COVID-19. RDV demonstrated consistent benefit in an immunocompromised cohort across all variant periods of the pandemic.
ABSTRACT
Background: Clinical management of COVID-19 based on oxygenation requirements continues to change over time as variants of concern (VOC) evolve. We examine hospital all-cause mortality for early hospital RDV use vs. no RDV use across dominant VOC periods: pre-Delta (Dec'20-Apr'21), Delta (May-Nov'21) and Omicron (Dec'21-Apr'22). Method(s): We examined adults with a primary discharge diagnosis of COVID-19 (ICD-10: U07.1) using the Premier Healthcare Database. Patients treated with RDV in the first 2 days of admission vs. those not treated with RDV during the hospitalization were matched using a 1:1 preferential within-hospital propensity matching with replacement. Patients were excluded if discharged within 3 days of RDV initiation. Time to mortality at 14-and 28-days was examined for patients with no supplemental oxygen charges (NSOc), low-flow oxygen (LFO), high-flow oxygen/non-invasive ventilation (HFO/NIV) and invasive mechanical ventilation/ECMO (IMV/ECMO) at baseline. Baseline was defined as first 2 days of hospitalization. Result(s): 164,791 RDV-treated patients were matched to 48,473 unique non-RDV patients. Post-matching balance was achieved across groups with different baseline oxygenation levels and VOC periods. In the matched weighted cohort, 35% required NSOc, 41% LFO, 21% HFO/NIV and 3% IMV/ECMO. During the overall study period (Dec'20-Apr'22), unadjusted mortality rate was significantly lower for RDV patients across all oxygenation levels at 14 days (NSOc: 5.4% vs. 7.3%, LFO: 6.4% vs. 8.8%, HFO/NIV: 16.8% vs. 19.4%, IMV/ECMO: 27.8% vs. 35.3%) and 28 days (NSOc: 8.0% vs. 9.8%, LFO: 9.8% vs. 12.3%, HFO/ NIV: 25.8% vs. 28.3%, IMV/ECMO: 41.4% vs. 50.6%). After adjusting for baseline and clinical covariates, 14-day mortality results showed that RDV significantly lower risk compared to non-RDV across all oxygenation levels at baseline [NSO (26%), LFO (28%), HFO/NIV (17%), IMV/ ECMO (27%)]. Similarly, 28-day mortality results showed that RDV significantly lower risk compared to non-RDV across all oxygenation levels at baseline [NSO (19%), LFO (21%), HFO/NIV (12%), IMV/ECMO (26%)]. This lower mortality risk associated with RDV was consistently observed across all variant periods (Figure). Conclusion(s): Timely initiation of RDV within first two days of hospital admission demonstrated significant mortality reduction in patients hospitalized for a primary diagnosis of COVID-19 across all oxygenation levels. Remdesivir demonstrated consistent benefit across all variant periods of the pandemic to-date.
ABSTRACT
Background: There is limited data on the association between COVID-19 therapy and hospital readmissions, including during evolution of the pandemic over time. We examine all cause 30-day readmissions after a COVID-19 hospitalization among remdesivir (RDV)-treated vs non-RDV treated patients across different dominant variants of concern (VOC) periods: pre-Delta (May'20-Apr'21), Delta (May-Nov'21) and Omicron (Dec'21-Apr'22). Method(s): Using the Premier Healthcare Database, we examined adults hospitalized with a primary diagnosis of COVID-19 (ICD-10:U07.1) who were discharged alive from the COVID-19 hospitalization. All-cause readmission to the same hospital was examined using multivariate logistic regression. The model adjusted for: age, corticosteroids use, VOC period, Charlson comorbidity index, maximum oxygenation requirements and ICU admission during COVID-19 hospitalization. Result(s): In the study period (May'20-Apr'22), 440,601 patients with a primary diagnosis of COVID-19 were discharged alive, of which 53% received RDV. As compared to non-RDV, RDV patients were younger (median[IQR]: 62[51-73] vs 64[52-76]), with a lower proportion with no supplementary oxygen charges (30% vs 52%), a higher proportion with low-flow oxygen (46% vs 36%), highflow oxygen/non-invasive ventilation (20% vs 10%), and invasive mechanical ventilation/ECMO (4% vs 2%). Among RDV-treated, the all-cause 30-day readmission was 6.3% compared to 9.1% (p< .0001) in non-RDV treated. Lower readmission for RDV vs non-RDV was seen in Pre-delta (6.3% vs 9.3%;p< .0001), Delta (5.1% vs 7.8%;p< .0001), and Omicron (8.7% vs 9.9%;p< .0001) (Fig). After adjusting for age and characteristics at index hospitalization including corticosteroid, RDV patients had significantly lower likelihood of all-cause 30-day readmission (OR[95% CI]:0.73[0.72-0.75]) as compared to non-RDV. Significantly Lower odds of 30-day readmission for RDV vs non-RDV patients were observed in Pre-delta (0.69[0.67-0.71]), Delta (0.72[0.68-0.76]) and Omicron-(0.87[0.83-0.92]) (Fig). Similarly, RDV-related reduction in readmissions was also seen for COVID-19 related readmissions. Conclusion(s): RDV use during the COVID-19 hospitalization was associated with significantly lower likelihood of all-cause 30-day readmission across the VOC periods of the pandemic May 2020 till April 2022. The lower rate of hospital re-admission for RDV-treated patients was observed despite the RDV group having higher supplemental oxygen requirement during their index COVID-19 hospitalization.
ABSTRACT
The optimal time to initiate research on emergencies is before they occur. However, timely initiation of high quality research may launch during an emergency under the right conditions. These include an appropriate context, clarity in scientific aims, preexisting resources, strong operational and research structures that are facile, and good governance. Here, Nebraskan rapid research efforts early during the 2020 coronavirus disease pandemic, while participating in the firstuse of U.S. federal quarantine in 50 years, are described from these aspects, as the global experience with this severe emerging infection grew apace. The experience has lessons in purpose, structure, function, and performance of research in any emergency, when facing any threat.