COVID-19

The 2024 National Academies of Sciences, Engineering, and Medicine Long COVID Definition: What Clinicians Need to Know

Author/s: 
Lily Chu, Karyn Bishof, Abigail A Dumes, E Wesley Ely, Paule V Joseph, Andrea B Troxel

Millions of Americans affected by Long COVID (LC) report difficulty accessing care and support. One barrier is obtaining a diagnosis. In response, US federal agencies commissioned a National Academies of Sciences, Engineering, and Medicine (NASEM) committee to re-examine the existing federal definitions for LC. The Committee concluded that LC is "an infection-associated chronic condition (IACC) occurring after SARS-CoV-2 infection that is present for at least 3 months as a continuous, relapsing and remitting, or progressive disease state that can present as singular or multiple symptoms and/or diagnosable conditions." The full report was released in June 2024. We briefly highlight features and aspects of the definition that may help clinicians identify those who remain undiagnosed and improve care for all LC patients.

Personal protective effect of wearing surgical face masks in public spaces on self-reported respiratory symptoms in adults: pragmatic randomised superiority trial

Author/s: 
Runar Barstad Solberg, Atle Fretheim, Ingeborg Hess Elgersma, Mette Fagernes, Bjørn Gunnar Iversen, Lars G Hemkens, Christopher James Rose, Petter Elstrøm

Objective: To evaluate the personal protective effects of wearing versus not wearing surgical face masks in public spaces on self-reported respiratory symptoms over a 14 day period.

Design: Pragmatic randomised superiority trial.

Setting: Norway.

Participants: 4647 adults aged ≥18 years: 2371 were assigned to the intervention arm and 2276 to the control arm.

Interventions: Participants in the intervention arm were assigned to wear a surgical face mask in public spaces (eg, shopping centres, streets, public transport) over a 14 day period (mask wearing at home or work was not mentioned). Participants in the control arm were assigned to not wear a surgical face mask in public places.

Main outcome measures: The primary outcome was self-reported respiratory symptoms consistent with a respiratory infection. Secondary outcomes included self-reported and registered covid-19 infection.

Results: Between 10 February 2023 and 27 April 2023, 4647 participants were randomised of whom 4575 (2788 women (60.9%); mean age 51.0 (standard deviation 15.0) years) were included in the intention-to-treat analysis: 2313 (50.6%) in the intervention arm and 2262 (49.4%) in the control arm. 163 events (8.9%) of self-reported symptoms consistent with respiratory infection were reported in the intervention arm and 239 (12.2%) in the control arm. The marginal odds ratio was 0.71 (95% confidence interval (CI) 0.58 to 0.87; P=0.001) favouring the face mask intervention. The absolute risk difference was -3.2% (95% CI -5.2% to -1.3%; P<0.001). No statistically significant effect was found on self- reported (marginal odds ratio 1.07, 95% CI 0.58 to 1.98; P=0.82) or registered covid-19 infection (effect estimate and 95% CI not estimable owing to lack of events in the intervention arm).

Conclusion: Wearing a surgical face mask in public spaces over 14 days reduces the risk of self-reported symptoms consistent with a respiratory infection, compared with not wearing a surgical face mask.

Trial registration: ClinicalTrials.gov NCT05690516.

Olgotrelvir as a Single-Agent Treatment of Nonhospitalized Patients with Covid-19

Author/s: 
Rongmeng Jiang, Bing Han, Wanhong Xu, Xiaoying Zhang, Chunxian Peng, Qiang Dang, Wei Sun, Ling Lin

Background: Olgotrelvir is an oral antiviral with dual mechanisms of action targeting severe acute respiratory syndrome coronavirus 2 main protease (i.e., Mpro) and human cathepsin L. It has potential to serve as a single-agent treatment of coronavirus disease 2019 (Covid-19).

Methods: We conducted a phase 3, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of olgotrelvir in 1212 nonhospitalized adult participants with mild to moderate Covid-19, irrespective of risk factors, who were randomly assigned to receive orally either 600 mg of olgotrelvir or placebo twice daily for 5 days. The primary and key secondary end points were time to sustained recovery of a panel of 11 Covid-19-related symptoms and the viral ribonucleic acid (RNA) load. The safety end point was incidence of treatment-emergent adverse events.

Results: The baseline characteristics of 1212 participants were similar in the two groups. In the modified intention-to-treat population (567 patients in the placebo group and 558 in the olgotrelvir group), the median time to symptom recovery was 205 hours in the olgotrelvir group versus 264 hours in the placebo group (hazard ratio, 1.29; 95% confidence interval [CI], 1.13 to 1.46; P<0.001). The least squares mean (95% CI) changes of viral RNA load from baseline were -2.20 (-2.59 to -1.81) log10 copies/ml in olgotrelvir-treated participants and -1.40 (-1.79 to -1.01) in participants receiving placebo at day 4. Skin rash (3.3%) and nausea (1.5%) were more frequent in the olgotrelvir group than in the placebo group; there were no treatment-related serious adverse events, and no deaths were reported.

Conclusions: Olgotrelvir as a single-agent treatment significantly improved symptom recovery. Adverse effects were not dose limiting. (Funded by Sorrento Therapeutics, a parent company of ACEA Therapeutics; ClinicalTrials.gov number, NCT05716425.).

Keywords 

Tilt Table Testing

Author/s: 
Chesire, W.P., Dudenkov, D.V., Munipalli, B.

A 43-year-old woman presented with a 1-year history of recurring symptoms of sudden onset of fatigue, palpitations, dyspnea, chest pain, lightheadedness, and nausea that were associated with standing and resolved with sitting. These symptoms began 1 month after mild COVID-19 infection. At presentation, while supine, blood pressure (BP) was 123/70 mm Hg and heart rate (HR) was 90/min; while seated, BP was 120/80 and HR was 93/min; after standing for 1 minute, BP was 124/80 and HR was 119/min. Physical examination results were normal. Oxygen saturation was 98% at rest while breathing room air. She had no oxygen desaturation during a 6-minute walk test but walked only 282 m (45% predicted). Complete blood cell count, morning cortisol, and thyrotropin blood levels were normal. Electrocardiogram (ECG), chest computed tomography, pulmonary function testing, methacholine challenge, bronchoscopy, echocardiography, and cardiac catheterization findings were normal. During tilt table testing, the patient experienced lightheadedness and nausea when moved from horizontal to the upright position. Results of the tilt table test are shown in the Table and Figure.

Tilt Table Testing

Author/s: 
Chesire, W.P., Dudenkov, D.V., Munipalli, B.

A 43-year-old woman presented with a 1-year history of recurring symptoms of sudden onset of fatigue, palpitations, dyspnea, chest pain, lightheadedness, and nausea that were associated with standing and resolved with sitting. These symptoms began 1 month after mild COVID-19 infection. At presentation, while supine, blood pressure (BP) was 123/70 mm Hg and heart rate (HR) was 90/min; while seated, BP was 120/80 and HR was 93/min; after standing for 1 minute, BP was 124/80 and HR was 119/min. Physical examination results were normal. Oxygen saturation was 98% at rest while breathing room air. She had no oxygen desaturation during a 6-minute walk test but walked only 282 m (45% predicted). Complete blood cell count, morning cortisol, and thyrotropin blood levels were normal. Electrocardiogram (ECG), chest computed tomography, pulmonary function testing, methacholine challenge, bronchoscopy, echocardiography, and cardiac catheterization findings were normal. During tilt table testing, the patient experienced lightheadedness and nausea when moved from horizontal to the upright position. Results of the tilt table test are shown in the Table and Figure.

Outpatient randomized controlled trials to reduce COVID-19 hospitalization: Systematic review and meta-analysis

Author/s: 
Daniele Focosi, David J. Sullivan, Daniel F. Hanley, Mario Cruciani, Massimo Franchini, Jiangda Ou, Arturo Casadevall, Nigel Paneth

This COVID-19 outpatient randomized controlled trials (RCTs) systematic review compares hospitalization outcomes amongst four treatment classes over pandemic period, geography, variants, and vaccine status. Outpatient RCTs with hospitalization endpoint were identified in Pubmed searches through May 2023, excluding RCTs <30 participants (PROSPERO-CRD42022369181). Risk of bias was extracted from COVID-19-NMA, with odds ratio utilized for pooled comparison. Searches identified 281 studies with 61 published RCTs for 33 diverse interventions analyzed. RCTs were largely unvaccinated cohorts with at least one COVID-19 hospitalization risk factor. Grouping by class, monoclonal antibodies (mAbs) (OR = 0.31 [95% CI = 0.24-0.40]) had highest hospital reduction efficacy, followed by COVID-19 convalescent plasma (CCP) (OR = 0.69 [95% CI = 0.53-0.90]), small molecule antivirals (OR = 0.78 [95% CI = 0.48-1.33]), and repurposed drugs (OR = 0.82 [95% CI: 0.72-0.93]). Earlier in disease onset interventions performed better than later. This meta-analysis allows approximate head-to-head comparisons of diverse outpatient interventions. Omicron sublineages (XBB and BQ.1.1) are resistant to mAbs Despite trial heterogeneity, this pooled comparison by intervention class indicated oral antivirals are the preferred outpatient treatment where available, but intravenous interventions from convalescent plasma to remdesivir are also effective and necessary in constrained medical resource settings or for acute and chronic COVID-19 in the immunocompromised.

Nirmatrelvir or Molnupiravir Use and Severe Outcomes From Omicron Infections

Author/s: 
Lin, Dan-Yu, Huang, Shuaiqi, Abi Fadel, Francois

Question: What outcomes are associated with ritonavir-boosted nirmatrelvir or molnupiravir use for outpatient treatment of SARS-CoV-2 Omicron subvariants, particularly BQ.1.1 and XBB.1.5, in high-risk individuals?

Findings: In a cohort study of 68 867 patients who received a diagnosis of COVID-19 at Cleveland Clinic from April 1, 2022, to February 20, 2023, and who were at high risk of progressing to severe COVID-19, both nirmatrelvir and molnupiravir use were significantly associated with reductions in hospitalization and death. The association was observed across subgroups defined by age, race and ethnicity, date of diagnosis, vaccination status, previous infection status, and coexisting conditions.

Meaning: These findings suggest that both nirmatrelvir and molnupiravir can be used to treat nonhospitalized patients who are at high risk of progressing to severe COVID-19.

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