November 2, 2023

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COVID

Nirmatrelvir/ritonavir Use in Pregnant Women with SARS-CoV-2 Omicron Infection: A Target Trial Emulation
To date, there is a lack of randomized trial data examining the use of the antiviral nirmatrelvir/ritonavir in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected pregnant persons. This target trial emulation study aimed to address this gap by evaluating the use of nirmatrelvir/ritonavir in nonhospitalized pregnant women with symptomatic SARS-CoV-2 Omicron variant infection. Among patients diagnosed between 16 March 2022 and 5 February 2023, exposure was defined as outpatient nirmatrelvir/ritonavir treatment within 5 days of symptom onset or coronavirus disease 2019 (COVID-19) diagnosis. Primary outcomes were maternal morbidity and mortality index (MMMI), all-cause maternal death and COVID-19-related hospitalization, while secondary outcomes were individual components of MMMI, preterm birth, stillbirth, neonatal death and cesarean section. One-to-ten propensity-score matching was conducted between nirmatrelvir/ritonavir users and nonusers, followed by cloning, censoring and weighting. Overall, 211 pregnant women on nirmatrelvir/ritonavir and 1,998 nonusers were included. Nirmatrelvir/ritonavir treatment was associated with reduced 28-day MMMI risk (absolute risk reduction (ARR) = 1.47%, 95% confidence interval (CI) = 0.21–2.34%) but not 28-days COVID-19-related hospitalization (ARR = −0.09%, 95% CI = −1.08% to 0.71%). Nirmatrelvir/ritonavir treatment was also associated with reduced risks of cesarean section (ARR = 1.58%, 95% CI = 0.85–2.39%) and preterm birth (ARR = 2.70%, 95% CI = 0.98–5.31%). No events of maternal or neonatal death or stillbirth were recorded. The findings suggest that nirmatrelvir/ritonavir is an effective treatment in symptomatic pregnant women with SARS-CoV-2 Omicron variant infection.
Outcomes of SARS-CoV-2 Variant Infections Compared with Seasonal Influenza and Respiratory Syncytial Omicron Virus Infections in Adults Attending the Emergency Department: A Multicentre Cohort Study
Here are the results of a retrospective multicentre cohort study including adults attending the ED in six acute care hospitals in Stockholm County, Sweden, with an Omicron, influenza, or RSV infection during 2021-22 and 2015-19. During 2021-22, patients were tested for all three viruses by multiplex PCR testing. The primary outcome was 30-day all-cause mortality. Secondary outcomes were 90-day all-cause mortality, hospitalization, and intensive care unit (ICU) admission. A total of 6,385 patients from 2021-22 were included in the main analyses: 4,833 Omicron, 1,099 influenza, and 453 RSV. So for starters, COVID is about 5x as likely to be the reason for hospitalization compared to flu and 10x compared to RSV. The 30-day mortality was 7.9% for Omicron, 2.5% for influenza, and 6.0% for RSV. Among unvaccinated Omicron patients, stronger associations were observed compared with both influenza (OR 5.51 [95% CI 3.41-9.18]) and RSV (OR 3.29 [95% CI 2.01-5.56]). Findings were consistent in comparisons with 5,709 pre-pandemic influenza 995 RSV patients. In patients attending the ED, infections with Omicron were both more common and associated with more severe outcomes compared with influenza and RSV, in particular among unvaccinated patients.
Remdesivir Is Associated with Reduced Mortality in COVID-19 Patients Requiring Supplemental Oxygen Including Invasive Mechanical Ventilation Across SARS-CoV-2 Variants
Here the authors examined the comparative effectiveness study on the effect of remdesivir on in-hospital mortality among patients hospitalized for coronavirus disease 2019 (COVID-19) requiring supplemental oxygen, including low-flow oxygen (LFO), high-flow oxygen/noninvasive ventilation (HFO/NIV), or invasive mechanical ventilation/extracorporeal membrane oxygenation (IMV/ECMO) across variant of concern (VOC) periods. Patients hospitalized for COVID-19 between December 2020 and April 2022 and administered remdesivir upon admission were 1:1 propensity score matched to patients not administered remdesivir during their COVID-19 hospitalization. Remdesivir treatment was associated with a statistically significant reduction in in-hospital mortality at 14 days (LFO: aHR, 0.72; 95% CI, 0.66–0.79; HFO/NIV: aHR, 0.83; 95% CI, 0.77–0.89; IMV/ECMO: aHR, 0.73; 95% CI, 0.65–0.82) and 28 days (LFO: aHR, 0.79; 95% CI, 0.73–0.85; HFO/NIV: aHR, 0.88; 95% CI, 0.82–0.93; IMV/ECMO: aHR, 0.74; 95% CI, 0.67–0.82) compared with non-remdesivir treatment. Lower risk of mortality among remdesivir-treated patients was observed across VOC periods.

PASC/Long COVID

Effectiveness of Nirmatrelvir–Ritonavir Against the Development of Post–COVID-19 Conditions Among U.S. Veterans. A Target Trial Emulation
These results are from a retrospective target trial emulation study comparing matched cohorts receiving nirmatrelvir–ritonavir versus no treatment. The participants were nonhospitalized veterans in VHA care who were at risk for severe COVID-19 and tested positive for SARS-CoV-2 during January through July 2022. They executed 5 nested sequential trials with a 1-day period to account for all possible eligibility dates. Persons treated on day 0/1 (both days were considered as a single unit) were matched to persons who remained untreated on days 0 or 1, persons treated on day 2 were matched to persons who remained untreated on days 0 to 2, persons treated on day 3 were matched to persons who remained untreated on days 0 to 3, persons treated on day 4 were matched to persons who remained untreated on days 0 to 4, and persons treated on day 5 were matched to persons who remained untreated on days 0 to 5. Then they looked for 31 potential incident PCCs as captured by ICD-10 codes. No differences were observed between participants treated with nirmatrelvir–ritonavir (n = 9593) and their matched untreated comparators in the incidence of most PCCs examined individually or grouped by organ system, except for lower combined risk for venous thromboembolism and pulmonary embolism (subhazard ratio, 0.65 [95% CI, 0.44 to 0.97]; cumulative incidence difference, −0.29 percentage points [CI, −0.52 to −0.05 percentage points]). Some limitations that the authors discuss. The biggest is that they were just looking at diagnoses that were coded so they did not do any kind of survey or individual assessment. They excluded some of the people who ended up getting hospitalized. They failed to show a statistically significant difference. Even though we seem to have a large number being studied when you look at 31 variables you end up with small numbers in each comparator. Also, mostly an older male population of veterans so not clear that this is generalizable. They also reference a number of studies that have showed benefit.