May 04, 2023

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Clinical Reports

Long COVID brain fog and muscle pain are associated with longer time to clearance of SARS-CoV-2 RNA from the upper respiratory tract during acute infection
- Self-reported brain fog and muscle pain at 90+ days after acute COVID-19 onset were negatively associated with viral RNA clearance within 28 days of acute COVID-19 onset with adjustment for age, sex, BMI ≥ 25, and COVID vaccination status prior to COVID-19. Participants reporting higher severity brain fog or muscle pain at 90+ days after acute COVID-19 onset were less likely to have cleared SARS-CoV-2 RNA within 28 days. The acute viral RNA decay trajectories of participants who did and did not later go on to experience brain fog 90+ days after acute COVID-19 onset were distinct. This work indicates that at least two long COVID symptoms - brain fog and muscle pain – at 90+ days from acute COVID-19 onset are specifically associated with prolonged time to clearance of SARS-CoV-2 RNA from the upper respiratory tract during acute COVID-19. This finding provides evidence that delayed immune clearance of SARS-CoV-2 antigen or greater amount or duration of viral antigen burden in the upper respiratory tract during acute COVID-19 are directly linked to long COVID. This work suggests that host-pathogen interactions during the first few weeks after acute COVID-19 onset have an impact on long COVID risk months later.

Antiviral Therapeutics and Vaccines

U.S. Food and Drug Administration approved Arexvy, the first respiratory syncytial virus (RSV) vaccine approved for use in the United States
- The U.S. Food and Drug Administration approved Arexvy, the first respiratory syncytial virus (RSV) vaccine approved for use in the United States. Arexvy is approved for the prevention of lower respiratory tract disease caused by RSV in individuals 60 years of age and older.

Diagnostics

Vaccination with BCG-Denmark did not result in a lower risk of Covid-19 among health care workers than placebo
- A total of 3988 participants underwent randomization; recruitment ceased before the planned sample size was reached owing to the availability of Covid-19 vaccines. The modified intention-to-treat population included 84.9% of the participants who underwent randomization: 1703 in the BCG group and 1683 in the placebo group. The estimated risk of symptomatic Covid-19 by 6 months was 14.7% in the BCG group and 12.3% in the placebo group (risk difference, 2.4 percentage points; 95% confidence interval [CI], −0.7 to 5.5; P=0.13). The risk of severe Covid-19 by 6 months was 7.6% in the BCG group and 6.5% in the placebo group (risk difference, 1.1 percentage points; 95% CI, −1.2 to 3.5; P=0.34); the majority of participants who met the trial definition of severe Covid-19 were not hospitalized but were unable to work for at least 3 consecutive days. In supplementary and sensitivity analyses that used less conservative censoring rules, the risk differences were similar but the confidence intervals were narrower. There were five hospitalizations due to Covid-19 in each group (including one death in the placebo group). The hazard ratio for any Covid-19 episode in the BCG group as compared with the placebo group was 1.23 (95% CI, 0.96 to 1.59). No safety concerns were identified.
NVX-CoV2373 vaccine efficacy against hospitalization: A post hoc analysis of the PREVENT-19 phase 3, randomized, placebo-controlled trial
- PREVENT-19, the pivotal phase 3 trial of the Novavax adjuvanted, recombinant spike protein COVID-19 vaccine (NVX-CoV2373), demonstrated that the vaccine was well tolerated and efficacious (vaccine efficacy, VE = 90%) for the prevention of symptomatic COVID-19. In the trial, participants were randomly assigned in a 2:1 ratio to receive 2 doses of NVX-CoV2373 or placebo 21 days apart. Throughout the study, the predominant SARS-CoV-2 variant was alpha, but additional variants were in circulation (i.e., beta, gamma, epsilon, and iota). VE among the per-protocol efficacy analysis population was calculated according to pre-specified disease severity (mild, moderate, or severe) criteria, but the impact on the risk of COVID-19–associated hospitalization was not specifically investigated. During this analysis period (January 25, 2021, to April 30, 2021 [95 days]), 4 hospitalizations occurred among the 77 events analyzed for the primary endpoint using the per-protocol population, 0 among vaccine recipients and 4 among placebo recipients, yielding a post hoc VE against hospitalization of 100% (95% CI: 28.8, 100). Among an expanded efficacy population, also identified post hoc, which included COVID-19–associated hospitalizations without a requirement for diagnostic polymerase chain reaction testing performed at the study central laboratory, 12 total hospitalizations were identified, 0 among vaccine recipients and 12 among placebo recipients, yielding a post hoc VE against hospitalization of 100% (95% CI: 83.1, 100). These additional data from the PREVENT-19 trial provide relevant public health information concerning the attributes of NVX-CoV2373.
Comparative effectiveness of the sars-CoV-2 vaccines during Delta dominance
- Among ∼6.5 million fully vaccinated individuals in the UHC Medicare Advantage and our commercially insured research database, mRNA-1273 performed better than BNT162b2 for infection, composite-hospitalization (hospitalization/ICU transfer/hospice transfer/death), and composite-ICU transfer (ICU transfer/hospice transfer/death) caused by B.1.612.7 (delta) variant infection. 26 CE.COV2.S performed worse than BNT162b2 for infection, composite-hospitalization, and composite-ICU transfers. The number needed to vaccinate (NNV) with mRNA1273 to prevent one hospitalization at 90 days was 3130 compared to 26 CE.COV2·S and 15,472 compared to BNT162b2. The NNV with mRNA1273 to prevent one ICU transfer at 90 days was 6358 compared to 26 CE.COV2·S and 34,279 compared to BNT162b2. For every one million individuals vaccinated with BNT162b compared to mRNA-1273, the approximate incremental inpatient cost would be $405,000 and the approximate incremental ICU cost would be $662,000.The two-dose mRNA vaccines' effectiveness significantly exceeded the single-dose Ad26.COV2·S vaccine's effectiveness from population health and cost-effectiveness perspectives. The mRNA1273 vaccine showed slightly more effectiveness than the BNT162b vaccine.
Clinical Outcomes Following Treatment for COVID-19 With Nirmatrelvir/Ritonavir and Molnupiravir Among Patients Living in Nursing Homes
- In this cohort study of 14 617 patients, both molnupiravir and nirmatrelvir/ritonavir treatment were associated with a lower risk of hospitalization and a lower risk of inpatient disease progression. These findings suggest that the use of oral antivirals to treat COVID-19 may benefit older patients living in nursing homes by decreasing risks of hospitalization and inpatient disease progression.
Real-life experience with remdesivir for treatment of COVID-19 among older adults: a multicentre retrospective study
- The effect of remdesivir on COVID-19 mortality remains conflicting. Elderly individuals are at risk for poor COVID-19 outcomes. Researchers aimed to assess the effect of remdesivir on COVID-19 mortality among elderly individuals, using real-world data. Retrospective multinational cohort of individuals aged ≥65 years, hospitalized with COVID-19 in six medical centres between January 2020 and May 2021. Associations with in-hospital mortality were evaluated using a multivariable logistic regression model with propensity score adjustment for remdesivir therapy and while implementing generalized estimating equations to control for centre effect. Sensitivity analysis was performed by stratification according to the degree of respiratory support. Of 3010 individuals included, 2788 individuals required either oxygen supplementation or non-invasive/invasive mechanical ventilation, 489 (16%) were treated with remdesivir, and 836 (28%) died. Median age was 77 (IQR 70–84) years and 42% were women. Remdesivir was the only therapeutic intervention associated with decreased mortality [adjusted OR (aOR) 0.49, 95% CI 0.37–0.66, P < 0.001]. This protective effect was shown for individuals requiring oxygen support and non-invasive mechanical ventilation, while no association was found among individuals necessitating invasive mechanical ventilation. Risk factors for mortality included invasive ventilation (aOR 5.18, 95% CI 2.46–10.91, P < 0.001), higher serum creatinine (aOR 1.25, 95% CI 1.09–1.43, P = 0.001) and dyspnoea (aOR 1.40, 95% CI 1.07–1.84, P = 0.015) on presentation, and other non-modifiable factors, such as comorbidities. Among elderly individuals hospitalized with COVID-19, remdesivir carries survival benefit for those with moderate to severe disease. Its role among individuals with critical illness should be further assessed.

Epidemiology

Association between SARS-CoV-2 and metagenomic content of samples from the Huanan Seafood Market
- The role of the Huanan Seafood Market in the early SARS-CoV-2 outbreak remains unclear. Recently the Chinese CDC released data from deep sequencing of environmental samples collected from the market after it was closed on January-1- 2020 (Liu et al. 2023a). Prior to this release, Crits-Christoph et al. (2023) analyzed data from a subset of the samples. Both studies concurred that the samples contained genetic material from a variety of species, including some like raccoon dogs that are susceptible to SARS-CoV-2. However, neither study systematically analyzed the relationship between the amount of genetic material from SARS-CoV-2 and different animal species. Here researchers implement a fully reproducible computational pipeline that jointly analyzes the number of reads mapping to SARS-CoV-2 and the mitochondrial genomes of chordate species across the full set of samples. This study validates the presence of genetic material from numerous species, and calculate mammalian mitochondrial compositions similar to those reported by Crits-Christoph et al. (2023). However, the number of SARS-CoV-2 reads is not consistently correlated with reads mapping to any non-human susceptible species. For instance, 14 samples have >20% of their chordate mitochondrial material from raccoon dogs, but only one of these samples contains any SARS-CoV-2 reads, and that sample only has 1 of ∼200,000,000 reads mapping to SARS-CoV-2. Instead, SARS-CoV-2 reads are most correlated with reads mapping to various fish, such as catfish and largemouth bass. These results suggest that while metagenomic analysis of the environmental samples is useful for identifying animals or animal products sold at the market, co-mingling of animal and viral genetic material is unlikely to reliably indicate whether any animals were infected by SARS-CoV-2.
Researchers disagree over how bad it is to be reinfected, and whether COVID-19 can cause lasting changes to the immune system
- The latest data from various countries suggest rates ranging from 5% to 15%, although this proportion is expected to increase as time passes. When reinfection does occur, the good news is that the immune system seems primed to respond. In a preprint posted in March, researchers examined reinfections in US National Basketball Association players, staff and their families. They found that people who became reinfected cleared the virus faster — in about five days, on average, compared with about seven days for a first infection. People who had a vaccine dose between their first and second infection cleared the virus the fastest, says Stephen Kissler, an infectious-disease researcher at the Harvard T.H. Chan School of Public Health in Boston, Massachusetts, and a co-author of the paper. Other studies have shown that people who experience mild symptoms with their first infection will probably have a mild subsequent infection. And two large studies suggest that reinfections tend to be less risky than the initial one. In one study, researchers compared two groups of unvaccinated people in Qatar — around 6,000 who had been infected once and 1,300 who had been reinfected. The odds of severe, critical or fatal disease at reinfection were almost 90% lower than that for a primary infection. The other study, which looked at 3.8 million first infections and 14,000 reinfections in England, found that people were 61% less likely to die in the month following reinfection than in the same period after a first infection, and 76% less likely to be admitted to an intensive care unit. But reinfection isn’t risk free. Those who are most vulnerable to severe disease during a first infection continue to be the most vulnerable, even if their risk of hospitalization or dying diminishes.
Virtual Care and Emergency Department Use During the COVID-19 Pandemic Among Patients of Family Physicians in Ontario, Canada
- In this cross-sectional study of 13 820 family physicians with 12 951 063 patients in Ontario, Canada, researchers found that patients of physicians who provided a high percentage of virtual care during the first years of the COVID-19 pandemic did not have higher ED visits than patients of physicians who provided the lowest levels of virtual care. This finding remained unchanged after adjusting for patient characteristics. Findings of this study suggest that more virtual care from family physicians during the pandemic did not result in more ED use.
Assessment of Gender-Specific COVID-19 Case Fatality Risk per Malignant Neoplasm Type
- In this cohort study of 1.6 million hospitalizations with COVID-19 identified in the National Inpatient Sample from April 1 to December 31, 2020, there were more types of malignant neoplasm associated with a COVID-19 in-house case fatality risk of greater than 2-fold in the group of female patients (5 types: anal cancer, Hodgkin lymphoma, non-Hodgkin lymphoma, lung cancer, and ovarian cancer) compared with the group of male patients (2 types: Kaposi sarcoma and small intestine cancer). The results of this study suggest that the association of a concurrent malignant neoplasm with COVID-19 mortality may be more substantial for women than men.
Timing of intubation and ICU mortality in COVID-19 patients: a retrospective analysis of 4198 critically ill patients during the first and second waves
- This is a secondary analysis of prospectively collected data from adult patients with ARF due to COVID-19 admitted to 73 intensive care units (ICUs) between February 2020 and March 2021. Intubation was classified according to the timing of intubation. To assess the relationship between early versus late intubation and mortality, Researchers excluded patients with ICU length of stay (LOS) < 7 days to avoid the immortal time bias and we did a propensity score and a cox regression analysis. Researchers included 4,198 patients [median age, 63 (54‒71) years; 71% male; median SOFA (Sequential Organ Failure Assessment) score, 4 (3‒7); median APACHE (Acute Physiology and Chronic Health Evaluation) score, 13 (10‒18)], and median PaO2/FiO2 (arterial oxygen pressure/ inspired oxygen fraction), 131 (100‒190)]; intubation was considered very early in 2024 (48%) patients, early in 928 (22%), and late in 441 (10%). ICU mortality was 30% and median ICU stay was 14 (7‒28) days. Mortality was higher in the “late group” than in the “early group” (37 vs. 32%, p < 0.05). The implementation of an early intubation approach was found to be an independent protective risk factor for mortality (HR 0.6; 95%CI 0.5‒0.7). Early intubation within the first 24 h of ICU admission in patients with COVID-19 pneumonia was found to be an independent protective risk factor of mortality.