May 31,2023

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Clinical Reports

Association between SARS-CoV-2 variants and frequency of acute symptoms: Analysis of a multi-institutional prospective cohort study - December 20, 2020 – June 20, 2022
- While prior work examining SARS-CoV-2 variants of concern focused on hospitalization and death, less is known about differences in clinical presentation. Researchers compared the prevalence of acute symptoms across pre-Delta, Delta, and Omicron. Researchers conducted an analysis of the INSPIRE Registry, a cohort study enrolling symptomatic SARS-CoV-2 positive participants. Researchers determined the association between pre-Delta, Delta, and Omicron time periods and the prevalence of 21 COVID-19 acute symptoms. Study authors enrolled 4,113 participants from December 2020 – June 2022. Pre-Delta vs Delta vs Omicron participants had increasing sore throat (40.9%, 54.6%, 70.6%; p < .001), cough (50.9%, 63.3%, 66.7%; p < .001), and runny noses (48.9%, 71.3%, 72.9%; p < .001). We observed reductions during Omicron in chest pain (31.1%, 24.2%, 20.9%; p < .001), shortness of breath (42.7%, 29.5%, 27.5%; p < .001), loss of taste (47.1%, 61.8%, 19.2%; p < .001), and loss of smell (47.5%, 55.6%, 20.0%; p < .001). Participants infected during Omicron were more likely to report symptoms of common respiratory viruses, such as sore throat, and less likely to report loss of smell and taste.
Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection
- A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 were PASC positive at 6 months. A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.

Antiviral Therapeutics and Vaccines

Pfizer’s PAXLOVID™ Receiving FDA Approval for Adult Patients at High Risk of Progression to Severe COVID-19.
- PAXLOVID is the first FDA-approved oral treatment for COVID-19; has been authorized for emergency use since December 2021. Approval is based on the totality of scientific evidence submitted, including efficacy data from the Phase 2/3 EPIC-HR study showing an 86% reduction in risk of COVID-19-related hospitalization or death from any cause in patients who took PAXLOVID within five days of symptom onset. PAXLOVID remains available to eligible patients via prescription at no charge.

Epidemiology

Potential for Recurrent Mpox Outbreaks Among Gay, Bisexual, and Other Men Who Have Sex with Men — United States, 2023
- Monkeypox (mpox) has disproportionately affected gay, bisexual, and other men who have sex with men (MSM); the percentage of MSM with immunity due to vaccination or infection varies among jurisdictions. What is added by this report? Mathematical modeling suggests that the risk for future outbreaks depends linearly on the level of immunity in the population at risk; cumulative incidence, on the other hand, has multiple thresholds. More than 592,000 MSM live in jurisdictions with risk for mpox recurrences capable of sustained transmission if a cluster of infectious cases were reintroduced. What are the implications for public health practice? Increasing vaccination coverage among MSM at risk and in jurisdictions with low immunity has the potential to reduce the risk for and potential size of future mpox outbreaks.
A Prospective Study of Key Correlates for Household Transmission of SARS-CoV-2
- Randomized controlled trials evaluated monoclonal antibodies for the treatment (Study 2067) and prevention (Study 2069) of COVID-19. Household contacts of the infected index case in Study 2067 were enrolled in Study 2069 and prospectively followed; these cohorts provided a unique opportunity to evaluate correlates of transmission, specifically viral load. This post-hoc analysis was designed to identify and evaluate correlates of SARS-CoV-2 transmission, adjusting for potential confounding factors related to source SARS-CoV-2 viral load and risk of SARS-CoV-2 acquisition in this population. Correlates of transmission were evaluated in potential transmission pairs (any infected household member plus susceptible household contact). In total, 943 participants were included. In multivariable regression, two potential correlates were determined to have a statistically significant (P < .05) association with transmission risk. A 10-fold increase in viral load was associated with a 40% increase in odds of transmission; sharing a bedroom with the index participant was associated with a 199% increase in odds of transmission. In this prospective, post-hoc analysis that controlled for confounders, the two key correlates for transmission of SARS-CoV-2 within a household are sharing a bedroom and increased viral load, consistent with increased exposure to the infected individual.
Efficacy and safety of antimicrobial stewardship prospective audit and feedback in patients hospitalized with COVID-19 (COVASP): a pragmatic, cluster-randomized, non-inferiority trial
- Between March 1 and Oct 29, 2021, 1411 patients were screened and 886 were enrolled: 457 into the prospective audit and feedback plus standard of care group, of whom 429 completed the study, and 429 into the standard of care group, of whom 404 completed the study. Baseline characteristics were similar for both groups, with an overall mean age of 56·7 years (SD 17·3) and a median baseline ordinal scale of 4·0 (IQR 4·0–5·0). 301 audit and feedback events were recorded in the intervention group and 215 recommendations were made, of which 181 (84%) were accepted. Despite lower antibiotic use in the intervention group than in the control group (length of therapy 364·9 vs 384·2 days per 1000 patient days), clinical status at postadmission day 15 was non-inferior (median ordinal score 2·0 [IQR 2·0–3·0] vs 2·0 [IQR 2·0–4·0]; p=0·37, Mann-Whitney U test). Neutropenia was uncommon in both the intervention group (13 [3%] of 420 patients) and the control group (20 [5%] of 396 patients), and acute kidney injury occurred at a similar rate in both groups (74 [18%] of 421 patients in the intervention group and 76 [19%] of 399 patients in the control group). No intervention-related deaths were recorded. This cluster-randomized clinical trial shows that prospective audit and feedback is safe and effective in optimizing and reducing antibiotic use in adults admitted to hospital with COVID-19. Despite many competing priorities during the COVID-19 pandemic, antimicrobial stewardship should remain a priority to mitigate the overuse of antibiotics in this population.
COVID-19 and Risk for Mental Disorders Among Adults in Denmark
- Risk of new-onset mental disorders and redeemed psychotropic medication was estimated through survival analysis using a Cox proportional hazards model, with a hierarchical time-varying exposure, reporting hazard rate ratios (HRR) with 95% CIs. All outcomes were adjusted for age, sex, parental history of mental illness, Charlson Comorbidity Index, educational level, income, and job status. A total of 526 749 individuals had positive test results for SARS-CoV-2 (50.2% men; mean [SD] age, 41.18 [17.06] years), while 3 124 933 had negative test results (50.6% women; mean [SD] age, 49.36 [19.00] years), and 501 110 had no tests performed (54.6% men; mean [SD] age, 60.71 [19.78] years). Follow-up time was 1.83 years for 93.4% of the population. The risk of mental disorders was increased in individuals with positive (HRR, 1.24 [95% CI, 1.17-1.31]) and negative (HRR, 1.42 [95% CI, 1.38-1.46]) test results for SARS-CoV-2 compared with those never tested. Compared with individuals with negative test results, the risk of new-onset mental disorders in SARS-CoV-2–positive individuals was lower in the group aged 18 to 29 years (HRR, 0.75 [95% CI, 0.69-0.81]), whereas individuals 70 years or older had an increased risk (HRR, 1.25 [95% CI, 1.05-1.50]). A similar pattern was seen regarding psychotropic medication use, with a decreased risk in the group aged 18 to 29 years (HRR, 0.81 [95% CI, 0.76-0.85]) and elevated risk in those 70 years or older (HRR, 1.57 [95% CI, 1.45-1.70]). The risk for new-onset mental disorders was substantially elevated in hospitalized patients with COVID-19 compared with the general population (HRR, 2.54 [95% CI, 2.06-3.14]); however, no significant difference in risk was seen when compared with hospitalization for non–COVID-19 respiratory tract infections (HRR, 1.03 [95% CI, 0.82-1.29]). In this Danish nationwide cohort study, overall risk of new-onset mental disorders in SARS-CoV-2–positive individuals did not exceed the risk among individuals with negative test results (except for those aged ≥70 years). However, when hospitalized, patients with COVID-19 had markedly increased risk compared with the general population, but comparable to risk among patients hospitalized for non–COVID-19 infections. Future studies should include even longer follow-up time and preferentially include immunological biomarkers to further investigate the impact of infection severity on postinfectious mental disorder sequelae.