July 18, 2024

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COVID: Children, Pregnant Individuals, and other Vulnerable Populations

Post–Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) After Infection During Pregnancy
These results are from a multicenter cohort study (NIH RECOVER [Researching COVID to Enhance Recovery]-Pregnancy Cohort), individuals who were pregnant during their first SARS-CoV-2 infection were enrolled across the United States from December 2021 to September 2023, either within 30 days of their infection or at differential time points thereafter. The primary outcome was PASC, defined as score of 12 or higher based on symptoms and severity as previously published by the NIH RECOVER-Adult Cohort, at the first study visit at least six months after the participant's first SARS-CoV-2 infection. Risk factors for PASC were evaluated, including sociodemographic characteristics, clinical characteristics before SARS-CoV-2 infection (baseline comorbidities, trimester of infection, vaccination status), and acute infection severity (classified by need for oxygen therapy). Multivariable logistic regression models were fitted to estimate associations between these characteristics and presence of PASC. Of the 1,502 participants, 61.1% had their first SARS-CoV-2 infection on or after December 1, 2021 (ie, during Omicron variant dominance); 51.4% were fully vaccinated before infection; and 182 (12.1%) were enrolled within 30 days of their acute infection. The prevalence of PASC was 9.3% (95% CI, 7.9–10.9%) measured at a median of 10.3 months (interquartile range 6.1–21.5) after first infection. The most common symptoms among individuals with PASC were postexertional malaise (77.7%), fatigue (76.3%), and gastrointestinal symptoms (61.2%). In a multivariable model, the proportion PASC positive with vs without history of obesity (14.9% vs 7.5%, adjusted odds ratio [aOR] 1.65, 95% CI, 1.12–2.43), depression or anxiety disorder (14.4% vs 6.1%, aOR 2.64, 95% CI, 1.79–3.88) before first infection, economic hardship (self-reported difficulty covering expenses) (12.5% vs 6.9%, aOR 1.57, 95% CI, 1.05–2.34), and treatment with oxygen during acute SARS-CoV-2 infection (18.1% vs 8.7%, aOR 1.86, 95% CI, 1.00–3.44) were associated with increased prevalence of PASC. The most common Long-COVID symptoms reported were postexertional malaise (77.7%), fatigue (76.3%), and gastrointestinal symptoms (61.2%).

COVID: Ventilation/Transmission

Oral Nirmatrelvir–Ritonavir as Postexposure Prophylaxis for COVID-19
These are results of a phase 2–3 double-blind trial to assess the efficacy and safety of nirmatrelvir–ritonavir in asymptomatic, rapid antigen test–negative adults who had been exposed to a household contact with COVID-19 within 96 hours before randomization. The participants were randomly assigned in a 1:1:1 ratio to receive nirmatrelvir–ritonavir (300 mg of nirmatrelvir and 100 mg of ritonavir) every 12 hours for five days or for 10 days or matching placebo for five or 10 days. The primary end point was the development of symptomatic SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection, confirmed on (RT-PCR) or rapid antigen testing, through 14 days in participants who had a negative RT-PCR test at baseline. A total of 2736 participants were randomly assigned to a trial group — 921 to the vive-day nirmatrelvir–ritonavir group, 917 to the 10-day nirmatrelvir–ritonavir group, and 898 to the placebo group. Symptomatic, confirmed SARS-CoV-2 infection developed by day 14 in 2.6% of the participants in the five-day nirmatrelvir–ritonavir group, 2.4% of those in the 10-day nirmatrelvir–ritonavir group, and 3.9% of those in the placebo group. Basically trending in the right direction but minimal potential benefit not reaching statistical significance. We get risk reductions relative to placebo of 29.8% (95% confidence interval [CI], –16.7 to 57.8; P=0.17) in the five-day nirmatrelvir–ritonavir group and 35.5% (95% CI, –11.5 to 62.7; P=0.12) in the 10-day nirmatrelvir–ritonavir group. The incidence of adverse events was similar across the trial groups, with dysgeusia being the most frequently reported adverse event (in 5.9% and 6.8% of the participants in the 5-day and 10-day nirmatrelvir–ritonavir groups, respectively, and in 0.7% of those in the placebo group).

COVID: Early Viral Phase

Combined Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 Reduces Molnupiravir-Induced Mutagenicity and Prevents Selection for Nirmatrelvir/Ritonavir Resistance Mutations
For background, the present treatment approach for SARS-CoV-2 primarily relies on a five-day course of a single direct-acting antivirals (DAA), with NMV/r being the most frequently prescribed direct-acting antiviral in the United States. The combination of the oral direct-acting antivirals NMV/r and MOV may provide additional therapeutic benefit, but this approach has not been tested in clinical trials. In a previous study, this group compared the antiviral effect of MOV or NMV/r and the coadministration of both in a SARS-CoV-2 macaque model. Macaques received the oral treatment of MOV, NMV/r, combination therapy, or vehicle control 12 hours after exposure to SARS-CoV-2, and then were followed for four days before necropsy. The combination therapy resulted in milder disease progression, a greater reduction in virus titer, and reduced lung pathology compared to either single-agent treatment. This group shares data generated by using what they describe as a highly accurate viral RNA sequencing approach, multiplexed Primer ID next-generation sequencing (MPID-NGS) that has an error rate as low as 0.01%, to examine the SARS-CoV-2 mutation profiles from the different treatment groups. They found that NMV/r reduced MOV-induced mutagenicity of SARS-CoV-2 when coadministered, while still contributing benefit to dual therapy. The mutagenic property of MOV increased several mutations related to 3CLpro resistance, but these mutations were not further enriched in the combination therapy.
Real-World Effectiveness of Ensitrelvir in Reducing Severe Outcomes in Outpatients at High Risk for COVID-19
These results come from a retrospective study that used a large Japanese health insurance claims database. It included high-risk outpatients for severe symptoms who received their first COVID-19 diagnosis between November 2022 and July 2023. The study included outpatients aged ≥ 18 years. The primary endpoint was all-cause hospitalization during the four-week period from the date of outpatient diagnosis and medication, comparing the ensitrelvir group (n = 5177) and the no antiviral treatment group (n = 162,133). The risk ratio and risk difference were evaluated after adjusting patient background distribution by the inverse probability of treatment weight (IPTW) method. Secondary endpoints were incidence of respiratory and heart rate monitoring, oxygen therapy, ventilator use, intensive care admission, and all-cause death.The risk ratio for all-cause hospitalization between the ensitrelvir group (n = 167,385) and the no antiviral treatment group (n = 167,310) was 0.629 [95% confidence interval (CI) 0.420, 0.943]. So about a 30% reduction for all-cause hospitalization. The incidence of both respiratory and heart rate monitoring and oxygen therapy was lower in the ensitrelvir group.
Comparative Effectiveness of Combination Therapy with Nirmatrelvir–ritonavir and Remdesivir versus Monotherapy with Remdesivir or Nirmatrelvir–ritonavir in Patients Hospitalized with COVID-19: A Target Trial Emulation Study
These are the results of a target trial emulation study, where they used electronic health records of patients aged 18 years or older who received either combination treatment of nirmatrelvir–ritonavir and remdesivir or monotherapy of either drug between March 16 and Dec 31, 2022, within five days of hospitalization for COVID-19 in Hong Kong. The primary outcome was all-cause mortality. They compared the risk of all-cause mortality, intensive care unit (ICU) admission, or ventilatory support for 90 days of follow-up between groups. Between March 16 and Dec. 31, 2022, 18 196 participants were identified from electronic health records and assigned to receive remdesivir (n=4232), nirmatrelvir–ritonavir (n=13 656), or nirmatrelvir–ritonavir and remdesivir (n=308). After a median follow-up of 84 days (IQR 45–90), risk of mortality was lower in patients who received nirmatrelvir–ritonavir monotherapy (hazard ratio [HR] 0·18 [95% CI 0·15 to 0·20]; absolute risk reduction [ARR] –16·33% [95% CI –16·98 to –15·68]) or remdesivir and nirmatrelvir–ritonavir combination therapy (HR 0·66 [95% CI 0·49 to 0·89]; ARR –6·52% [95% CI –7·29 to –5·74]) than in patients who received remdesivir monotherapy. Similar results were observed for ICU admission or ventilatory support (nirmatrelvir–ritonavir monotherapy: HR 0·09 [95% CI 0·07 to 0·11]; ARR –10·04% [95% CI –10·53 to –9·56]; combination therapy: HR 0·68 [95% CI 0·42 to 1·12]; ARR –3·24% [95% CI –3·84 to –2·64]). Compared with combination therapy, nirmatrelvir–ritonavir monotherapy was associated with lower risk of mortality (HR 0·27 [95% CI 0·20 to 0·37]; ARR –9·81% [95% CI –10·39 to –9·24]) and ICU admission or ventilatory support (HR 0·13 [95% CI 0·08 to 0·22]; ARR –6·80% [95% CI –7·22 to –6·39]).

COVID: Late Phase, PASC/Long COVID

Postacute Sequelae of SARS-CoV-2 Infection in the Pre-Delta, Delta, and Omicron Eras
Here the authors used health records of the Department of Veterans Affairs to build a study population of 441,583 veterans with SARS-CoV-2 infection between March 1, 2020, and January 31, 2022, and 4,748,504 noninfected contemporaneous controls. We estimated the cumulative incidence of PASC at 1 year after SARS-CoV-2 infection during the pre-Delta, Delta, and Omicron eras of the COVID-19 pandemic. Among unvaccinated persons infected with SARS-CoV-2, the cumulative incidence of PASC during the first year after infection was 10.42 events per 100 persons (95% confidence interval [CI], 10.22 to 10.64) in the pre-Delta era, 9.51 events per 100 persons (95% CI, 9.26 to 9.75) in the Delta era, and 7.76 events per 100 persons (95% CI, 7.57 to 7.98). Among vaccinated persons, the cumulative incidence of PASC at one year was 5.34 events per 100 persons (95% CI, 5.10 to 5.58) during the Delta era and 3.50 events per 100 persons (95% CI, 3.31 to 3.71) during the Omicron era. Vaccinated persons had a lower cumulative incidence of PASC at one year than unvaccinated persons 71.89% (95% CI, 69.50 to 74.43) was attributable to vaccines; 28.11% of the decrease (95% CI, 25.57 to 30.50) was attributable to era-related effects
The Efficacy of Antivirals, Corticosteroids, and mAbs as Acute COVID Treatments in Reducing the Incidence of Long COVID: A Systematic Review and Meta-analysis
Investigators did a search for articles that reported Long COVID incidence post-acute COVID with a follow-up of at least 30 days. They identified 2,363 records. Effect size from 14 papers investigating acute COVID antiviral treatment concluded its protective efficacy against Long COVID (OR 0.61, 95% CI: 0.48-0.79, p = 0.0002); however, corticosteroid (OR 1.57, 95% CI: 0.80-3.09, p = 0.1913) and mAbs treatments (OR 0.94, 95% CI: 0.56-1.56, p = 0.8012) did not generate such effect. Subsequent subgroup analysis revealed that antivirals provided stronger protection in the aged, male, unvaccinated and non-diabetic populations. Furthermore, antivirals effectively reduced eight out of the 22 analyzed Long COVID symptoms.