Remdesivir Reduces Mortality in Hospitalized Covid-19 Patients across Variant Eras

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.

Remdesivir Is Associated with Reduced Readmission after Covid-19 Hospitalization

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.

Incidence of Long Covid Symptoms in Patients Previously Hospitalized for Covid-19

Background: Long COVID, also known as post-acute sequelae of COVID (PASC), affects more than 144 million people globally. While there is no broadly accepted consensus on a definition for the term "long COVID," studies have found symptoms persist or begin weeks or months after the end of SARS-CoV-2 infection. This study assessed the incidence of codes found in medical claims and hospital chargemasters that were consistent with long COVID symptoms commonly found in the literature. Method(s): Using the HealthVerity database, which provides closed claims and linked hospital chargemaster data on more than 25 million US patients, we examined patients aged 12 and above hospitalized between May 1, 2020 and September 30, 2021 with a diagnosis of COVID-19 who had at least 365 days of closed medical claims enrollment prior to index hospitalization admission and 90 days after admission, and did not have a long COVID diagnosis (ICD-10- CM U09.9) prior to the index hospitalization. Patients were allowed to have symptoms prior to hospitalization. The assessment period for the outcomes, which included 10 symptoms, was 90 days to 270 days after the date of hospitalization. Incidence rate per 100 person-years was calculated as the number of patients with the outcome divided by total person-time contributed (90 days after admission to the minimum of the following: outcome, inpatient death, disenrollment, end of data (April 30, 2022), or 270 days after admission). Result(s): The dataset included 3,661,303 patients with an inpatient hospitalization during the study period. The final study cohort included 44,922 patients hospitalized with COVID-19, 20,627 of whom experienced at least one of the long COVID symptoms. Anosmia and dysgeusia were the rarest events captured in medical claims. More commonly found symptoms were joint pain, fatigue and breathlessness (see table). Conclusion(s): This study examined diagnosed symptoms commonly found posthospitalization among COVID-19 patients and reported the incidence of these symptoms in a representative population. The start period of long COVID used in this study (90 days post hospitalization) is consistent with the WHO definition of long COVID. In the absence of an understanding of the pathophysiology of long COVID, the use of diagnosed symptoms to define long COVID has the advantage of ease of use and availability of data. Further studies of additional symptoms and predictors of long COVID are needed. (Figure Presented).

Has the COVID-19 pandemic lead to an upshift in emergency presentation and stage migration of colorectal cancer in Uruguay?

Background: Effective Cancer screening is critical in reducing cancer related mortality in CRC by increasing the detection in earlier stages. Worldwide, practically all cancer pathways have been negatively affected by the implications of the COVID-19 pandemic. Oncological care has not escaped the effects of reprioritization of health care services to handle the surge of COVID-19 patients adequately. Cancer screening programs are no exception as many were temporarily halted to alleviate the pressure on overwhelmed health care systems. In Uruguay, the first covid patients were detected in March 2020, and since then, the country's Public Health policies have been marked by the covid-19 public health emergency. The aim of this study is to assess the impact of the COVID-19 pandemic on CRC diagnosis. We further aimed to analyze the effect on the clinical presentation and stage at diagnosis during 2020-2021 compared with previous years. Methods: This was a retrospective cohort study performed at a single tertiary center. Patients diagnosed and managed with colorectal adenocarcinoma during the years 2020-2021 were compared with patients from 2018-2019. Those enrolled in 2018- 2019 were classified as the “pre-pandemic group”, and those enrolled in 2020-2021 were classified as the “pandemic group”. The primary outcome was the rate of stage IV disease at the time of diagnosis. Mann-Whitney test was used in the comparison of quantitative variables and Fisher's exact test was used for qualitative variables. Results: A total of 370 patients were included in this study. From March 2018 to 2019 (pre-pandemic), 217 patients were considered, and from March 2020 to 2021 (pandemic), 153 patients. Median age of pre-pandemic and pandemic group was 64.4 and 65.6 years, respectively. There was no statistically significant difference in cancer obstruction or perforation at diagnosis. Patient demographics and tumor clinicopathological features were comparable. The percentage of surgical candidates was lower during the pandemic (69% vs 62%). There was a significant difference in TNM tumor distribution between pre-pandemic and pandemic subgroups with a higher incidence of advanced (cT4 or cN+ or M1) tumors. T4 tumors and node positive disease were equivalent in both groups but the incidence of disseminated disease (cM1) was significantly higher in the pandemic group (P < 0.001). Conclusions: Our study demonstrates how cancer diagnostic variables, mainly stage at diagnosis, have been affected by the impact of the COVID-19 pandemic on cancer screening programs. Therefore, it is of utmost importance that cancer diagnosis and treatment pathways be reinstalled in full to return to and build on pre-pandemic priority to ensure the benefits from earlier diagnosis and treatment. Future studies are needed to verify the tendency in stage migration and to optimize CRC care in the pandemic scenario.

The impact of a vaccine mandate and the COVID-19 pandemic on influenza vaccination uptake in Western Australian health care students.

Annual influenza vaccination of health care students and workers helps protect themselves and patients from influenza, which has a high disease burden during seasonal peaks in Australia. Health care students are an important cohort whose early attitudes and habits towards influenza vaccination may influence future behaviours. We explored the knowledge, attitudes, and behaviours towards influenza vaccination of health care students in two universities from 2018 to 2020 using convergent mixed methodology. We also assessed the impact of two external events - the introduction of mandatory influenza vaccination for select students in 2019, and the COVID-19 pandemic in 2020. We found a significant increase in self-reported vaccination uptake between 2018 (73.5%) and 2020 (89.6%), with the mandate and COVID-19 pandemic being likely drivers of increased uptake. Vaccine mandates are effective but must be supported by easy accessibility, adequately addressing concerns around effectiveness and safety, and promotion of voluntary acceptance and trust.

Has the COVID-19 pandemic lead to an upshift in emergency presentation and stage migration of colorectal cancer in Uruguay?

Background: Effective Cancer screening is critical in reducing cancer related mortality in CRC by increasing the detection in earlier stages. Worldwide, practically all cancer pathways have been negatively affected by the implications of the COVID-19 pandemic. Oncological care has not escaped the effects of reprioritization of health care services to handle the surge of COVID-19 patients adequately. Cancer screening programs are no exception as many were temporarily halted to alleviate the pressure on overwhelmed health care systems. In Uruguay, the first COVID patients were detected in March 2020, and since then, the country’s Public Health policies have been marked by the COVID-19 public health emergency. The aim of this study is to assess the impact of the COVID-19 pandemic on CRC diagnosis. We further aimed to analyze the effect on the clinical presentation and stage at diagnosis during 2020-2021 compared with previous years. Methods: This was a single center retrospective cohort study performed at a tertiary center. Patients diagnosed and managed with colorectal adenocarcinoma during the years 2020-2021 were compared with patients from 2018 and 2019. Those enrolled in 2018-2019 were classified as the “pre-pandemic group”, and those enrolled in 2020-2021 were classified as the “pandemic group”. The primary outcome was the rate of stage IV disease at the time of diagnosis. Mann-Whitney test was used in the comparison of quantitative variables and Fisher’s exact test was used for qualitative variables. Results: A total of 369 patients were included in this study. From March 2018 to 2019 (pre-pandemic), 217 patients were considered, and from March 2020 to 2021 (pandemic), 152 patients. Median age of pre-pandemic and pandemic group was 64.4 and 65.6 years, respectively. There was no statistically significant difference in cancer obstruction or perforation at diagnosis. Other patient demographics were comparable (p˃0.05). The percentage of surgical candidates was lower during the pandemic (69% vs 62%). There was a significant difference in TNM tumor distribution between pre-pandemic and pandemic subgroups with a higher incidence of advanced (cT4 or cN+ or M1) tumors. T4 tumors and node positive disease were equivalent in both groups but the incidence of disseminated disease (cM1) was significantly higher in the pandemic group (48% vs 36%, p < 0.001). Conclusions: Our study demonstrates how cancer diagnostic variables, mainly stage at diagnosis, have been affected by the impact of the COVID-19 pandemic on cancer screening programs. Therefore, it is of utmost importance that cancer diagnosis and treatment pathways be reinstalled in full to return to and build on pre-pandemic priority to ensure the Uruguayan population benefits from earlier diagnosis and treatment. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosures: All authors have declared no conflicts of interest.

COVID-19 infection in renal transplant patients

Background: The SARS CoV-2 pandemic has disproportionately affected vulnerable patient populations including kidney transplant recipients (KTR). Methods: Our transplant centre covers a large multi-ethnic urban population with high rates of co-morbidity and social deprivation, and provides follow-up care for approximately 1500 kidney transplant recipients. In line with national guidance, COVID-19 testing was largely restricted to those patients presenting to secondary care. Where COVID-19 was confirmed or suspected, anti-proliferative drugs were stopped, maintenance corticosteroids increased, and calcineurin inhibitor was stopped in patients requiring admission. We performed a retrospective analysis of clinical presentations and outcomes in kidney transplant recipients with confirmed COVID-19 between 20th March and 10th May 2020. Results: 25 patients (approximately 1.6%) had confirmed COVID-19. 11 (44%) were female and 14 (56%) male. The median age was 61 years (range 33 - 84 years). 11 (44%) were White - British, 12 (48%) Asian and 2 (8%) Afro-Caribbean. Median time posttransplant was 84 months (range 6 - 360), and more recently transplanted patients were not at increased risk. Respiratory symptoms were the predominant presenting complaint in 19 patients (76%) followed by GI symptoms in 4 (16%). Acute kidney injury (stages 1-3) occurred in 15 patients (60%) with 7 patients (28% of whole population 46% of patients with AKI) requiring renal replacement therapy. 6 patients (40%) recovered renal function at a median follow up period of 26 days (range 10 - 51). 4 (16%) were admitted to ITU for ventilation. 10 patients (40%) died (although one death was not related to COVID-19). Among the patients who died, median age was 65 years and 6 (60%) were male with ethnicity proportionate to the study population. Conclusions: The strategy of performing COVID-19 testing only in patients requiring secondary care likely i) underestimates the incidence and ii) overestimates the disease severity. However, our data show that COVID-19 confers significant morbidity and mortality in kidney transplant recipients despite prompt reduction of immunosuppression. These data will inform a revised consent process for those patients awaiting kidney transplantation. Follow up studies are required to assess longer term outcomes, and potential complications in KTRs who have recovered from COVID-19.