April 27,2023

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Clinical Reports

SARS-CoV-2 Reinfection and Severity of the Disease: A Systematic Review and Meta-Analysis
- Since the discovery of SARS-CoV-2, changes in genotype and reinfection with different variants have been observed in COVID-19-recovered patients, raising questions around the clinical pattern and severity of primary infection and reinfection. In this systematic review, researchers summarize the results of 23 studies addressing SARS-CoV-2 reinfections. A total of 23,231 reinfected patients were included, with pooled estimated reinfection rates ranging from 0.1 to 6.8%. Reinfections were more prevalent during the Omicron variant period. The most common symptoms during the first and second infection were fever (41.1%), cough (35.7% and 44.6%), myalgia (34.5% and 33.3%), fatigue (23.8% and 25.6%), and headaches (24.4% and 21.4%). No significant differences of clinical pattern were observed between primary infection and reinfection. No significant differences in the severity of infection were observed between primary infection and reinfection. Being female, being a patient with comorbidities, lacking anti-nucleocapsid IgG after the first infection, being infected during the Delta and Omicron wave, and being unvaccinated were associated with a higher risk of reinfection. Conflicting age-related findings were found in two studies. Reinfection with SARS-CoV-2 suggests that natural immunity is not long-lasting in COVID-19 patients.
Completeness and Spin of medRxiv Preprint and Associated Published Abstracts of COVID-19 Randomized Clinical Trials
- Preprints are increasingly important in medical research communication. In rapidly evolving areas such as COVID-19, preprints, which by definition have not been peer reviewed, can influence practice and potentially cause harm. Researchers examined publication timelines, completeness, and spin in the abstracts of all randomized clinical trials (RCTs) related to COVID-19 posted to medRxiv during the first 2 years of the pandemic and compared the latter 2 with their published counterparts.
Risk of new-onset Long Covid following reinfection with SARS-CoV-2: community-based cohort study
- Long Covid was reported by those ≥16 years after 4.0% and 2.4% of first and second infections, respectively; the corresponding estimates among those <16 years were 1.0% and 0.6%. The aOR for Long Covid after second compared to first infections was 0.72 (95% confidence interval: 0.63–0.81) for those ≥16 years and 0.93 (0.57–1.53) for those <16 years. The risk of new-onset Long Covid after a second SARS-CoV-2 infection is lower than that after a first infection for those ≥16 years, though there is no evidence of a difference in risk for those <16 years. However, there remains some risk of new-onset Long Covid after a second infection, with around 1 in 40 of those ≥16 years and 1 in 165 of those <16 years reporting Long Covid after a second infection.

Low vitamin D levels are associated with Long COVID syndrome in COVID-19 survivors
- Researchers observed lower 25(OH)vitamin D levels, evaluated at follow-up, in subjects with Long-COVID than those without. Regarding the affected health-areas evaluated in the entire cohort, researchers observed lower 25(OH)vitamin D levels in those with neurocognitive symptoms at follow-up as compared to those without. In patients presenting vitamin D deficiency both at admission and at follow-up, those affected by Long-COVID presented lower 25(OH)vitamin D levels, at follow-up, compared to those not affected. In multiple-regression analyses, lower 25(OH)vitamin D levels, at follow-up, resulted as the only variable significantly associated with Long-COVID in this cohort. COVID-19 survivors with Long-COVID have lower 25(OH)vitamin D levels as compared to matched-patients without Long-COVID. This data suggests that vitamin D levels should be evaluated in COVID-19 patients after hospital-discharge. Role of vitamin D supplementation as preventive strategy of COVID-19 sequelae should be tested in randomized-controlled trials.

Antiviral Therapeutics and Vaccines

Effectiveness of Coronavirus Disease 2019 (COVID-19) Bivalent Vaccine
- Among 51017 employees, COVID-19 occurred in 4424 (8.7%) during the study. In multivariable analysis, the bivalent vaccinated state was associated with lower risk of COVID-19 during the BA.4/5 dominant (HR, .71; 95% C.I., .63-.79) and the BQ dominant (HR, .80; 95% C.I., .69-.94) phases, but decreased risk was not found during the XBB dominant phase (HR, .96; 95% C.I., .82-.1.12). Estimated vaccine effectiveness (VE) was 29% (95% C.I., 21%-37%), 20% (95% C.I., 6%-31%), and 4% (95% C.I., -12%-18%), during the BA.4/5, BQ, and XBB dominant phases, respectively. Risk of COVID19 also increased with time since most recent prior COVID-19 episode and with the number of vaccine doses previously received. Conclusions. The bivalent COVID-19 vaccine given to working-aged adults afforded modest protection overall against COVID-19 while the BA.4/5 lineages were the dominant circulating strains, afforded less protection when the BQ lineages were dominant, and effectiveness was not demonstrated when the XBB lineages were dominant.
Molnupiravir and risk of post-acute sequelae of COVID-19:
- In people with SARS-CoV-2 infection and at least one risk factor for progression to severe covid-19, compared with no treatment, molnupiravir use within five days of infection was associated with reduced risk of PASC in people who had not received a covid-19 vaccine, had received one or two vaccine doses, and had received a booster dose, and in those with primary SARS-CoV-2 infection and reinfection. Among people at high risk of progression to severe covid-19, molnupiravir use within five days of SARS-CoV-2 infection may be a viable approach to reduce the risk of PASC.
Clinical experience with the α2A-adrenoceptor agonist, guanfacine, and N-acetylcysteine for the treatment of cognitive deficits in “Long-COVID19”
- Prolonged cognitive deficits (“brain fog”) following COVID19 infection (long-COVID) are common and debilitating, yet there are currently no approved treatments. Cognitive impairment particularly targets the working memory and executive functions of the prefrontal cortex (PFC). The PFC has unusual neurotransmission and neuromodulation that render it vulnerable to stressors, and basic research has identified mechanisms that protect PFC connections. Based on the basic neuroscience data, researchers tried a combined open label treatment to bolster prefrontal function: the α2A-adrenoceptor agonist, guanfacine, which strengthens prefrontal connectivity, and the anti-oxidant, N- acetylcysteine (NAC), which protects mitochondria and reduces kynurenic acid blockade of NMDA receptors. Twelve patients with “brain fog” including difficulties in executive functions were treated with guanfacine (1mg, PO bedtime for the first month, increased to 2mg after 1 month, if well-tolerated) and 600 mg NAC daily. Guanfacine+NAC improved cognitive abilities in eight of the twelve patients; four patients discontinued therapy, two for unspecified reasons and two due to hypotension and/or dizziness, common side effects of guanfacine. Those who stayed on guanfacine+NAC reported improved working memory, concentration, and executive functions, including a resumption of normal workloads. One patient briefly stopped taking guanfacine due to a hypotensive episode and reported a return of cognitive deficits that abated with resumed guanfacine treatment. Although placebo-controlled trials will be needed to more rigorously demonstrate efficacy, as these agents have established safety, they may be immediately helpful in treating the large number of patients suffering from prolonged cognitive deficits following COVID19 infection.

Diagnostics

Lessons Learned From a COVID-19 Dog Screening Pilot in California K-12 Schools
- Studies have demonstrated dogs’ impressive ability for detecting VOCs associated with COVID-19 infection using specimens collected from SARS-CoV-2–infected and uninfected individuals. After training in the laboratory, this study’s dogs were field tested and, in more than 3500 screenings, correctly determined COVID-19 status in most instances. Unlike most other studies, this study’s dogs directly screened people in the field, rather than specimens. This study’s method was associated with improved testing efficiency but had a modest decrease in sensitivity and specificity compared with laboratory results. Dog screening for COVID-19 infection can be completed in a matter of seconds. However, dog screening directly on individuals introduced variables, such as distractions (eg, noises, young children) and environmental factors (eg, wind, smells), that likely contributed to decreased sensitivity and specificity. Researchers considered other options, including a sample collection strategy used by other investigator, however, those options would sacrifice cost and time efficiency. Study limitations included the low prevalence of SARS-CoV-2 during the study period and the consequently low number of COVID-19 infections. The goal is for dogs to perform large-scale VOC screening with antigen testing being performed only on persons with positive dog screening results, thereby reducing antigen tests performed by approximately 85%. While modifications are needed before widespread implementation, this study supports use of dogs for efficient and noninvasive COVID-19 screening and could be used for other pathogens.