May 9, 2024

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COVID: Early Viral Phase

Favorable Antiviral Effect of Metformin on Severe Acute Respiratory Syndrome Coronavirus 2 Viral Load in a Randomized, Placebo-Controlled Clinical Trial of Coronavirus Disease 2019
The COVID-OUT trial was a 2 × 3 randomized, placebo-controlled, double-blind trial that assessed metformin, fluvoxamine, and ivermectin; 999 participants self-collected anterior nasal swabs on day 1 (n = 945), day 5 (n = 871), and day 10 (n = 775). Viral load was quantified using reverse-transcription quantitative polymerase chain reaction. The mean SARS-CoV-2 viral load was reduced 3.6-fold with metformin relative to placebo (-0.56 log10 copies/mL; 95% confidence interval [CI], -1.05 to -.06; P = .027). Those who received metformin were less likely to have a detectable viral load than placebo at day 5 or day 10 (odds ratio [OR], 0.72; 95% CI, .55 to .94). The metformin effect was consistent across subgroups and increased over time. Neither ivermectin nor fluvoxamine showed effect over placebo.
Association of Nirmatrelvir–ritonavir with Post-acute Sequelae and Mortality in Patients Admitted to Hospital with COVID-19: A Retrospective Cohort Study
These are the results of a retrospective cohort study that used real-world, territory-wide inpatient records, vaccination records, and confirmed COVID-19 case data from the Hong Kong Hospital Authority and Department of Health, The Government of the Hong Kong Special Administrative Region. The treatment group included patients prescribed nirmatrelvir–ritonavir within 5 days of symptom onset, excluding those prescribed molnupiravir within 21 days, and the control group had no exposure to either nirmatrelvir–ritonavir or molnupiravir. The outcomes were post-acute inpatient death and 13 sequelae (congestive heart failure, atrial fibrillation, coronary artery disease, deep vein thrombosis, chronic pulmonary disease, acute respiratory distress syndrome, interstitial lung disease, seizure, anxiety, post-traumatic stress disorder, end-stage renal disease, acute kidney injury, and pancreatitis). These outcomes were evaluated starting at 21 days after the positive RT-PCR date in each respective cohort constructed for the outcome. The study showed extended benefits of nirmatrelvir–ritonavir for reducing the risk of post-acute inpatient death as well as cardiovascular and respiratory complications among patients admitted to hospital with COVID-19. The authors state that further research is essential to uncover the underlying mechanisms responsible for these observed negative associations and to devise effective strategies for preventing the onset of post-acute sequelae.
Effectiveness of Nirmatrelvir-Ritonavir for the Prevention of COVID-19–Related Hospitalization and Mortality: A Systematic Literature Review
The article begins with an introduction that highlights the tremendous experience we now have had using this medication, with over 12.7 million treatment courses prescribed since it became available at the end of 2021. The article also points out that NMV/r is recommended as the preferred outpatient COVID-19 treatment for individuals at high risk of progression to severe disease. They mention the pivotal randomized double-blind placebo-controlled multinational trial “Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients,” which resulted in an 86% reduction in the combined end point of COVID-19–related hospitalization or death from any cause when patients were treated within five days of the symptom onset. They also comment on the “Evaluation of Protease Inhibition for COVID-19 in Standard-Risk Patients” that looked at vaccinated adults and reported a 62% decrease in COVD-19–related medical visits relative to placebo. They ultimately included 18 studies, with a total of 343,197 receiving NMV/r treatment, that reported on NMV/r effectiveness for prevention of hospitalization or mortality. The analysis revealed an NMV/r effectiveness of 21%–89% for the prevention of all-cause hospitalization and 24%–60% for COVID-related hospitalization. Their analysis revealed that this impact was regardless of vaccination status. Two studies reported NMV/r effectiveness of 66% and 85% against all-cause mortality.

COVID: The Late Phase/PASC/Long COVID

Cognitive Profile in Multiple Sclerosis and Post-COVID Condition: A Comparative Study Using a Unified Taxonomy
This is a cross-sectional study that included 218 patients with PCC and 218 with MS matched by age, sex, and years of education. Patients were evaluated with a comprehensive neuropsychological protocol. Fatigue and depression were also assessed. They report that cognitive profiles of post-COVID condition (PCC) and MS largely overlapped, with a greater impairment in episodic memory in MS. The most salient deficits in both disorders were in attention and processing speed. The severity of fatigue was greater in patients with PCC, but, the correlations between fatigue severity and neuropsychological tests were more prominent in the case of MS. Ultimately they report that this study found similar cognitive profiles in PCC and MS. Fatigue was more severe in PCC, but was more associated with cognitive performance in MS.
Unravelling the Mechanisms Behind Exercise Intolerance and Recovery in Long COVID
This study investigated the relationship between heart rate recovery at the first minute (HRR1), a proxy for autonomic imbalance, and exercise intolerance in patients with Long COVID. Additionally, the study aimed to assess the effects of a 12-week home-based inspiratory muscle training program on autonomic modulation in this patient population. These are the results from the InsCOVID trial which was a single-center randomized clinical trial with blinded assessors, that enrolled 26 Long COVID patients. It aimed to investigate the effects of a 12-week home-based inspiratory muscle training program, compared to usual care in a 1:1 ratio. The heart rate was evaluated at rest, peak effort, and the first minute of the recovery phase. HRR1 was defined as the difference between maximal exercise heart rate and heart rate at the first minute into recovery. First off, their results revealed a significant association between baseline HRR1 and exercise tolerance. They suggest that HRR1 is a practical, cost-effective, and easily collected surrogate for assessing autonomic nervous system function, exercise tolerance and guiding simple therapeutic interventions to improve exercise capacity in this specific patient population. They also report a significant association between baseline HRR1 and responsiveness to an inspiratory muscle training program which they make a point of contrasting with other exercise training approaches. They suggest that this diaphragmatic breathing and strengthening through inspiratory muscle training could modulate arterial baroreflex sensitivity, consequently improving sympathovagal balance.

COVID: Low- and Middle-Income Countries

Epidemiology of SARS-CoV-2 in Kakuma Refugee Camp Complex, Kenya, 2020-2021
The United Nations High Commissioner for Refugees (UNHCR) estimated that as of December 2020, there were 20 million refugees and 4.1 million asylum seekers globally, most of whom were living in low- and middle-income countries. As of December 2021, Kenya hosted over half a million refugees in urban and camp settings. The number of refugees into Kenya increased steadily during 2019‒2022. During the COVID-19 pandemic, the Kakuma Refugee Camp Complex (KRCC) was home to almost half of all the refugees in Kenya. This camp is located in Turkana West subcounty which is located in Turkana County in northwestern Kenya. It shares international boundaries with Uganda to the west and South Sudan to the northwest and is ≈600 km from Nairobi. Here these investigators conducted a descriptive analysis of routinely collected data from March 2020‒December 31, 2021, on demographics, SARS-CoV-2 testing results, and clinical outcomes of COVID-19 in KRCC. The first positive SARS-CoV-2 case from KRCC was detected on May 22, 2020, in a refugee camp two months after the first case of SARS-CoV-2 was reported in Kenya. From there, the number of confirmed cases only increased. In general this is a young population with the median patient age being 25 (1–102) years and (51.0%) of the patients were male. The overall CFRs were 2.25% (95% CI 1.29%–3.20%) for KRCC and 1.83% (95% CI 1.78%–1.87%) for Kenya. Of the deaths in KRCC, (CFR 2.86%, 95% CI 1.52%–4.20%) were reported among refugees, and (CFR 1.11%, 95% CI 0.00%–2.33%) among the host community.