Embracing Imatinib: a novel approach to safeguarding the endothelial barrier in patients with COVID-19.

Imatinib, an ABL tyrosine-kinase inhibitor, shows promise in restoring endothelial barrier function in patients with COVID-19, thus, preventing cytokine leakage from the alveolar compartment to the systemic compartment. COVID-19 is characterized by an alveolar cytokine storm, and imatinib has been shown to strengthen the endothelial barrier and mitigate alveolar inflammatory responses by modulating NF-κB signaling. Incorporating imatinib into COVID-19 treatment strategies offers a novel approach to safeguard the endothelial barrier and address the complex pathophysiology of the disease, including its potential implications in long COVID. Given that endothelial dysfunction plays a central role in COVID-19 progression and long COVID development, protecting the endothelial barrier during acute infection is crucial in preventing the persistent endothelial dysfunction associated with long COVID.

Intermediate- to high-dose dexamethasone versus low-dose dexamethasone in patients with COVID-19 requiring respiratory support: a systematic review and meta-analysis of randomized trials.

The present review critically appraised the randomized clinical trials that compared mortality outcomes between intermediate- to high-dose dexamethasone and low-dose dexamethasonein patients with COVID-19 and reported pooled mortality risk estimates associated with these two dosing regimens of dexamethasone. The systematic searching of electronic databases was limited to randomized clinical trials that compared mortality outcomes between intermediate- to high-dose dexamethasone with low-dose dexamethasone in patients with COVID-19 requiring respiratory support. The primary outcome of interest in this review was all-cause mortality. A total of eight trials with 1800 patients randomized to receive intermediate to high-dose dexamethasone and 1715 patients randomized to low-dose dexamethasone were included. The meta-analysis of six trials revealed no significant difference in the risk of 28-day all-cause mortality between intermediate- to high-dose dexamethasone and low-dose dexamethasone (odds ratio 1.16, 95% confidence interval, 0.77-1.74). Similarly, the meta-analysis of five trials revealed no significant difference between the two doses regarding 60-day all-cause mortality (odds ratio 0.96, 95% confidence interval 0.74-1.26). The results suggest intermediate- to high-dose dexamethasone to be as effective as low-dose dexamethasone in reducing the risk of mortality among patients with COVID-19 requiring respiratory support. However, higher dexamethasone doses could expose patients with COVID-19 to an increased risk of adverse events, such as hyperglycemia.

The effect of vitamin C on the risk of mortality in patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Vitamin C appears to be a viable treatment option for patients with COVID-19. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) of vitamin C versus comparative interventions in patients with COVID-19. The outcome of interest was all-cause mortality. RESULTS: The meta-analysis of eleven trials using a random-effects model revealed significant reduction in the risk of all-cause mortality with the administration of vitamin C among patients with COVID-19 relative to no vitamin C (pooled odds ratio = 0.53; 95% confidence interval 0.30-0.92). Subgroup analysis of studies that included patients with severe COVID-19 also produced findings of significant mortality reduction with the administration of vitamin C relative to no vitamin C (pooled odds ratio = 0.47; 95% confidence interval 0.26-0.84). CONCLUSION: Overall, evidence from RCTs suggests a survival benefit for vitamin C in patients with severe COVID-19. However, we should await data from large-scale randomized trials to affirm its mortality benefits.

Systematic review and meta-analysis of anti-CD20 treatments in patients with COVID-19: an assessment of severe illness and mortality outcomes.

BACKGROUND: The use of anti-CD20 monoclonal antibodies, such as rituximab and ocrelizumab, has emerged as a matter of concern, in patients with coronavirus disease 2019 (COVID-19). OBJECTIVE: We aimed to summarize the overall evidence on the pre-admission/pre-diagnosis use of anti-CD20 among patients with COVID-19 with regards to mortality and severe illness outcomes. METHODS: A systematic literature search with no language restriction was performed in electronic databases, including PubMed, Google Scholar, Scopus, and preprint servers (medRxiv, Research Square, SSRN), to identify eligible studies published up to June 13, 2023. The outcomes of interest were the development of severe illness and all-cause mortality. A random-effects model was used to estimate the pooled odds ratio for outcomes of interest using anti-CD20 monoclonal antibodies relative to non-use of anti-CD20 monoclonal antibodies, at 95% confidence intervals. RESULTS: Our systematic review and meta-analysis revealed significantly increased odds for development of severe illness (pooled odds ratio 2.95; 95% confidence interval 2.30, 3.78; n = 534,349) and significantly increased odds for mortality (pooled odds ratio 2.14; 95% confidence interval 1.37, 3.35; n = 333,462) with the use of anti-CD20 monoclonal antibodies, relative to non-use of anti-CD20 monoclonal antibodies, in patients with COVID-19. CONCLUSION: Healthcare practitioners should exercise caution when prescribing these anti-CD20 monoclonal antibodies during the COVID-19 pandemic to patients who are indicated for these agents, particularly those with underlying conditions like multiple sclerosis or rheumatoid arthritis.

The effect of probiotics on the risk of mortality in patients with COVID-19: systematic review and meta-analysis of randomized trials.

Probiotics have been hypothesized to play a beneficial role in modulating immune responses and gut microbiota in various clinical settings. This systematic review and meta-analysis aimed to assess the effectiveness of probiotics in reducing all-cause mortality among patients diagnosed with COVID-19. We conducted a comprehensive search of the following databases: PubMed, Scopus, and Web of Science for published studies, and medRxiv, Research Square, and SSRN for preprints. The search spanned from the inception of these databases to April 4, 2023. We included studies that investigated the use of probiotics as an intervention and their impact on all-cause mortality in patients with COVID-19. A random-effects model meta-analysis was employed to estimate the pooled odds ratio, along with 95% confidence interval, to quantify the outcomes associated with probiotic use compared to other interventions. Our systematic review comprised six studies, encompassing a total of 642 patients. The meta-analysis, employing a random-effects model, demonstrated a statistically significant reduction in the risk of all-cause mortality when probiotics were administered to patients with COVID-19, compared to those not receiving probiotics (pooled odds ratio = 0.44; 95% confidence interval 0.24-0.82). In conclusion, evidence derived from randomized controlled trials (RCTs) indicates a survival benefit associated with the use of probiotics among COVID-19 patients. However, it is essential to exercise caution and await data from large-scale randomized trials to definitively confirm the mortality benefits of probiotics in this patient population.

The effectiveness of mRNA-1273 vaccine against COVID-19 caused by Delta variant: A systematic review and meta-analysis.

We aimed to perform meta-analyses to summarize the overall effectiveness of the mRNA-1273 vaccine against COVID-19 caused by the Delta variant from real-world studies. A systematic literature search with no language restriction was performed in electronic databases to identify eligible observational studies that reported the effectiveness of the mRNA-1273 vaccine to prevent reverse transcription-polymerase chain reaction (RT-PCR) confirmed COVID-19 caused by Delta variant of SARS-CoV-2 (B.1.617.2). A random-effects meta-analysis model was used to estimate the pooled odds ratio (OR) at a 95% confidence interval (CI), and the vaccine effectiveness was indicated as (pooled OR - 1)/OR. Five studies were included for this systematic review and meta-analysis. The meta-analysis revealed that the administration of mRNA-1273 vaccine protected against RT-PCR confirmed COVID-19 caused by Delta variant ≥21 days post first dose, with pooled vaccine effectiveness of 66% (95% CI: 65%-67%), as well as ≥14 days after the second dose, with pooled vaccine effectiveness of 91% (95% CI: 84%-95%). In conclusion, the mRNA-1273 vaccine offers a substantial protection rate against RT-PCR confirmed COVID-19 caused by the Delta variant upon full vaccination, although with slightly reduced effectiveness relative to other strains of SARS-CoV-2.

Use of Calcium Channel Blockers and the Risk of All-cause Mortality and Severe Illness in Patients With COVID-19: A Systematic Review and Meta-analysis.

ABSTRACT: Owing to the reported safety concerns, we aimed to perform a systematic review and meta-analysis to determine the effect of preadmission/prediagnosis use of calcium channel blockers (CCBs) on the clinical outcomes in patients with COVID-19. A systematic literature search with no language restriction was conducted in electronic databases in July 2021 to identify eligible studies. The outcomes of interest were all-cause mortality and severe illness. A random-effects model was used to estimate the pooled summary measure for outcomes of interest with the preadmission/prediagnosis use of CCBs relative to nonuse CCBs, at 95% confidence intervals (CIs). The meta-analyses revealed no significant difference in the odds of all-cause mortality [pooled odds ratio (OR) = 0.82; 95% CI 0.68-1.00; n = 58,355] and in the odds of severe illness (pooled OR = 0.83; 95% CI 0.61-1.15; n = 46,091) respectively, with preadmission/prediagnosis use of CCBs relative to nonuse of CCBs. Nevertheless, subgroup analysis of studies originated from East Asia reported a significant reduction in the odds of all-cause mortality (pooled OR = 0.50; 95% CI 0.37-0.68) and the odds of severe illness (pooled OR = 0.51; 95% CI 0.33-0.78). There may not be safety concerns with the use of CCBs in patients with COVID-19, but their potential protective effects in the East Asian patients merit further investigations.

The effect of higher-intensity dosing of anticoagulation on the clinical outcomes in hospitalized patients with COVID-19: A meta-analysis of randomized controlled trials.

OBJECTIVE: We aimed to perform a meta-analysis to summarize the overall evidence from randomized controlled trials related to higher-intensity anticoagulation in hospitalized patients with COVID-19. METHODS: A systematic literature search was performed in electronic databases to identify randomized controlled trials comparing the clinical outcomes between intermediate/ therapeutic anticoagulation and prophylactic anticoagulation. Meta-analyses with random-effects models were used to estimate the pooled odds ratio (OR) for outcomes of interest at a 95% confidence interval (CI). RESULTS: Eight randomized controlled trials were included, with a total of 5405 hospitalized patients with COVID-19. The meta-analysis revealed no statistically significant difference in the odds of mortality (pooled OR = 0.92; 95% CI 0.71-1.19) but a statistically significant reduction in the odds of development of thrombotic events (pooled OR = 0.55; 95% CI 0.42-0.72), and significantly increased odds of development of major bleeding (pooled OR = 1.81; 95% CI 1.20-2.72) with the use of intermediate/therapeutic anticoagulation, relative to prophylactic anticoagulation. Subgroup analysis in patients with a severe course of COVID-19 observed a statistically significant reduction in the odds of development of thrombotic events (pooled OR = 0.66; 95% CI 0.45-0.98) but no significant difference in the odds of development of major bleeding events (pooled OR = 1.37; 95% CI 0.74-2.56), with the use of intermediate/therapeutic anticoagulation, relative to prophylactic anticoagulation. CONCLUSION: There could be net clinical benefits with higher-intensity dosing of anticoagulation relative to prophylactic-dosing of anticoagulation among hospitalized patients with severe COVID-19.

The use of neutralizing monoclonal antibodies and risk of hospital admission and mortality in patients with COVID-19: a systematic review and meta-analysis of randomized trials.

AIM: Several randomized trials have evaluated the effect of neutralizing monoclonal antibodies on the risk of hospital admission and risk of mortality in patients with COVID-19. We aimed to summarize the overall evidence in the form of a systematic review and meta-analysis. METHODS: A systematic literature search with no language restriction was performed in electronic databases and preprint repositories to identify eligible studies published up to 29 June 2021. The outcomes of interest were hospital admission and all-cause mortality. A random-effects model was used to estimate the pooled odds ratio (OR) for outcomes of interest with the use of neutralizing monoclonal antibodies relative to nonuse of neutralizing monoclonal antibodies, at 95% confidence intervals (CI). RESULTS: Our systematic literature search identified nine randomized controlled trials. Three trials had an overall low risk of bias, while four trials had some concerns in the overall risk of bias. The meta-analysis revealed no statistically significant difference in the odds of mortality (pooled OR = 0.69; 95% CI 0.33-1.47), but a statistically significant reduction in the odds of hospital admission (pooled OR = 0.29; 95% CI 0.21-0.42), with the administration of a neutralizing monoclonal antibody among patients with COVID-19, relative to non-administration of a neutralizing monoclonal antibody, at the current sample size. CONCLUSION: The reduced risk of hospital admission with neutralizing monoclonal antibodies use suggests that the timing of neutralizing antibodies administration is key in preventing hospital admission and, ultimately, death. Future randomized trials should aim to determine if the clinical outcomes with neutralizing monoclonal antibodies differ based on serostatus.

The effectiveness of BNT162b2 mRNA vaccine against COVID-19 caused by Delta variant of SARS-CoV-2: a systematic review and meta-analysis.

Meta-analyses were utilized to determine the overall effectiveness of BNT162b2 mRNA vaccine (Pfizer vaccine) against COVID-19 caused by Delta variant from large real-world studies. A systematic literature search with no language restriction was performed in electronic databases to identify eligible observational studies that reported the effectiveness of the BNT162b2 mRNA vaccine to prevent reverse transcription-polymerase chain reaction (RT-PCR) confirmed COVID-19 caused by Delta variant of SARS-CoV-2 (B.1.617.2). Random-effects meta-analysis model was used to estimate the pooled odds ratio (OR) at a 95% confidence interval, and the vaccine effectiveness was indicated as (pooled OR - 1)/OR. Seven studies were included for this meta-analysis. The meta-analysis revealed that the administration of BNT162b2 mRNA vaccine protected against RT-PCR confirmed COVID-19 caused by Delta variant ≥ 21 days after the first dose, with vaccine effectiveness of 55% (95% confidence interval 46-63%), as well as ≥ 14 days after the second dose, with vaccine effectiveness of 81% (95% confidence interval 69-88%). In conclusion, the BNT162b2 mRNA vaccine offers a substantial protection rate against RT-PCR confirmed COVID-19 caused by the Delta variant upon full vaccination, albeit with slightly reduced effectiveness relative to other strains of SARS-CoV-2.

Kratom and Pain Tolerance: A Randomized, Placebo-Controlled, Double-Blind Study.

Background: Kratom has a long history of traditional medicine use in Southeast Asia. Consumption of kratom products has also been reported in the US and other regions of the world. Pain relief is among many self-reported kratom effects but have not been evaluated in controlled human subject research. Methods: Kratom effects on pain tolerance were assessed in a randomized, placebo-controlled, double-blind study. During a 1-day inpatient stay, participants received a randomized sequence of kratom and placebo decoctions matched for taste and appearance. Pain tolerance was measured objectively in a cold pressor task (CPT) as time (seconds) between the pain onset and the hand withdrawal from the ice bath. Health status, vital signs, objective, and subjective indicators of withdrawal symptoms, self-reported data on lifetime kratom use patterns, and assessments of blinding procedures were also evaluated. Results: Twenty-six males with the mean (SD) age 24.3 (3.4) years were enrolled. They reported the mean (SD) 6.1 (3.2) years of daily kratom consumption. Pain tolerance increased significantly 1 hour after kratom ingestion from the mean (SD) 11.2 (6.7) seconds immediately before to 24.9 (39.4) seconds 1 hour after kratom consumption (F(2,53.7)=4.33, p=0.02). Pain tolerance was unchanged after consuming placebo drinks: 15.0 (19.0) seconds immediately before and 12.0 (8.1) seconds 1 hour after consumption of placebo (F(2,52.8)=0.93, p=0.40). No discomfort or signs of withdrawal were reported or observed during 10-20 hours of kratom discontinuation. Conclusions: Kratom decoction demonstrated a substantial and statistically significant increase in pain tolerance. Further rigorous research on kratom pain-relieving properties and a safety profile is needed.