January 19, 2023

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Clinical Reports

Long COVID: major findings, mechanisms and recommendations
Long COVID is an often debilitating illness that occurs in at least 10% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. More than 200 symptoms have been identified with impacts on multiple organ systems. At least 65 million individuals worldwide are estimated to have long COVID, with cases increasing daily. Biomedical research has made substantial progress in identifying various pathophysiological changes and risk factors and in characterizing the illness; further, similarities with other viral-onset illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome have laid the groundwork for research in the field. In this Review, researchers explore the current literature and highlight key findings, the overlap with other conditions, the variable onset of symptoms, long COVID in children and the impact of vaccinations. Although these key findings are critical to understanding long COVID, current diagnostic and treatment options are insufficient, and clinical trials must be prioritized that address leading hypotheses. Additionally, to strengthen long COVID research, future studies must account for biases and SARS-CoV-2 testing issues, build on viral-onset research, be inclusive of marginalized populations and meaningfully engage patients throughout the research process.
Effect of using a structured pacing protocol on post-exertional symptom exacerbation and health status in a longitudinal cohort with the post-COVID-19 syndrome
The WHO Borg CR-10 is a structured pacing protocol shown for the first time in the current literature to substantially reduce PESE episodes whilst increasing activity levels even in a cohort of individuals with long-standing PCS symptoms. This approach to pacing has the potential to be an effective rehabilitation intervention in PCS. The study also demonstrated that PESE episodes could be triggered by physical, cognitive, or emotional exertion and each episode comprises several symptoms with variable duration of each episode. Future research should investigate a longer pacing program in a clinical trial setting for both post-acute and chronic stages of PCS and must explore the potential of this intervention to prevent the development of a chronic PCS state in these individuals.

Antiviral Therapeutics and Vaccines

Detection of SARS-CoV-2 IgA and IgG in human milk and breastfeeding infant stool 6 months after maternal COVID-19 vaccination
Thirty-seven mothers and 25 infants were enrolled between December 2020 and November 2021 for this prospective observational study. All mothers were vaccinated during lactation except three, which were vaccinated during pregnancy. Milk, maternal plasma, and infants’ stool was collected pre-vaccination and at periods up to 6 months following COVID-19 vaccine series initiation/completion. SARS-CoV-2 antibody levels and their neutralization capacities were assessed. SARS-CoV-2-specific IgA and IgG levels were higher in infant stool post-maternal vaccination amongst milk-fed compared to controls. Maternal SARS-CoV-2-specific IgA and IgG concentrations decreased over 6 months post-vaccination but remained higher than pre-vaccination levels. We observed improved neutralization capacity in milk and plasma after COVID-19 vaccination. The presence of SARS-CoV-2-specific antibodies in infant stool following maternal vaccination offers further evidence of the lasting transfer of these antibodies through breastfeeding.
Effect of Fluvoxamine vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19
In this platform randomized clinical trial conducted during a period of predominance for the Delta and Omicron variants in the US, including 1288 adult outpatients with COVID-19 treated with fluvoxamine vs placebo, the hazard ratio was 0.96 (95% credible interval, 0.86-1.06) for time to sustained recovery with a posterior P = .21 for the probability of improvement. This did not meet the prespecified threshold of greater than 0.95 for posterior probability. Among outpatients with mild to moderate COVID-19, treatment with 50 mg of fluvoxamine twice daily for 10 days, compared with placebo, did not improve time to sustained recovery. These findings do not support the use of fluvoxamine at this dose and duration in patients with mild to moderate COVID-19.
Hyperimmune Globulin for Severely Immunocompromised Patients Hospitalized With Coronavirus Disease 2019
The aim of this randomized, controlled trial is to determine whether antisevere acute respiratory syndrome coronavirus 2 hyperimmune globulin (COVIG) protects against severe coronavirus disease 2019 (COVID-19) in severely immunocompromised, hospitalized, COVID-19 patients. Patients were randomly assigned to receive COVIG or intravenous immunoglobulin (IVIG) without SARS-CoV-2 antibodies. Severe COVID-19 was observed in 2 of 10 (20%) patients treated with COVIG compared to 7 of 8 (88%) in the IVIG control group (P= .015, Fisher’s exact test). Antisevere acute respiratory syndrome coronavirus 2 hyperimmune globulin may be a valuable treatment in severely immunocompromised, hospitalized, COVID-19 patients and should be considered when no monoclonal antibody therapies are available.
A Systematic Review of Trials Currently Investigating Therapeutic Modalities for Post-Acute COVID-19 Syndrome and Registered on World Health Organization International Clinical Trials Platform
Researchers identified 388 registered trials with a high degree of heterogeneity exploring 144 unique interventions for PACS. Most target general alleviation of symptoms. There is a need for further high-quality and methodologically robust PACS treatment trials conducted with standardization of outcomes while following WHO’s recommendation for uniform evaluation and treatment.

Epidemiology

Long covid outcomes at one year after mild SARS-CoV-2 infection: nationwide cohort study
Risk of an evidence based list of 70 reported long covid outcomes in unvaccinated patients infected with SARS-CoV-2 matched to uninfected people, adjusted for age and sex and stratified by SARS-CoV-2 variants, and risk in patients with a breakthrough SARS-CoV-2 infection compared with unvaccinated infected controls. Risks were compared using hazard ratios and risk differences per 10 000 patients measured during the early (30-180 days) and late (180-360 days) time periods after infection. Covid-19 infection was significantly associated with increased risks in early and late periods for anosmia and dysgeusia (hazard ratio 4.59 (95% confidence interval 3.63 to 5.80), risk difference 19.6 (95% confidence interval 16.9 to 22.4) in early period; 2.96 (2.29 to 3.82), 11.0 (8.5 to 13.6) in late period), cognitive impairment (1.85 (1.58 to 2.17), 12.8, (9.6 to 16.1); 1.69 (1.45 to 1.96), 13.3 (9.4 to 17.3)), dyspnoea (1.79 (1.68 to 1.90), 85.7 (76.9 to 94.5); 1.30 (1.22 to 1.38), 35.4 (26.3 to 44.6)), weakness (1.78 (1.69 to 1.88), 108.5, 98.4 to 118.6; 1.30 (1.22 to 1.37), 50.2 (39.4 to 61.1)), and palpitations (1.49 (1.35 to 1.64), 22.1 (16.8 to 27.4); 1.16 (1.05 to 1.27), 8.3 (2.4 to 14.1)) and with significant but lower excess risk for streptococcal tonsillitis and dizziness. Hair loss, chest pain, cough, myalgia, and respiratory disorders were significantly increased only during the early phase. Male and female patients showed minor differences, and children had fewer outcomes than adults during the early phase of covid-19, which mostly resolved in the late period. Findings remained consistent across SARS-CoV-2 variants. Vaccinated patients with a breakthrough SARS-CoV-2 infection had a lower risk for dyspnoea and similar risk for other outcomes compared with unvaccinated infected patients. This nationwide study suggests that patients with mild covid-19 are at risk for a small number of health outcomes, most of which are resolved within a year from diagnosis.