The impact of vitamin D administration on mortality in COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Vitamin D, known for its role in bone health, is now being explored for its immunomodulatory effects. This study aimed to evaluate the impact of vitamin D supplementation on mortality in coronavirus disease 2019 (COVID-19) patients through a systematic review and meta-analysis of randomized controlled trials. METHODS: A comprehensive search was conducted across PubMed, Scopus, Web of Science, and preprint servers for eligible trials up to July 8, 2024. Two investigators independently screened the records and assessed the risk of bias using the Cochrane Risk of Bias Tool. Trials were eligible if they compared vitamin D with control interventions in adults with COVID-19. Data extraction and analysis were carried out independently, employing a random-effects model to estimate pooled odds ratios for mortality. RESULTS: Nineteen randomized controlled trials with 2495 participants were included. The meta-analysis showed a significant reduction in all-cause mortality with vitamin D supplementation (pooled OR 0.72, 95% CI 0.53-0.98; I2 = 20%). Subgroup analysis for severe COVID-19 cases also indicated significant mortality reduction (pooled OR 0.57, 95% CI 0.35-0.92; I2 = 18%). CONCLUSION: Vitamin D supplementation appears to reduce mortality in COVID-19 patients, especially in severe cases. These findings highlight the potential benefits of vitamin D as an adjunct treatment in COVID-19, though further large-scale trials are needed to confirm these effects and determine optimal dosing.

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.

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.

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 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.

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.

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.

Preadmission use of inhaled corticosteroids and risk of fatal or severe COVID-19: a meta-analysis.

Objective: With emerging of observational evidence, we aimed to perform a meta-analysis to summarize the overall effect of the chronic use of inhaled corticosteroids on the clinical outcomes in patients with coronavirus disease 2019 (COVID-19). Methods:Systematic literature search in electronic databases was performed to identify observational studies that investigated the preadmission use of inhaled corticosteroids on the risk of a fatal or severe course of illness in patients with COVID-19 and reported adjusted measures of association. Adjusted odds ratios or relative risks and the corresponding 95% confidence intervals from each study were pooled to produce pooled odds ratio and 95% confidence interval. Results: The meta-analysis revealed no significant difference in the risk for the development of a fatal course of COVID-19 with preadmission use of inhaled corticosteroids in patients with COVID-19 relative to non-use of inhaled corticosteroids (pooled odds ratio=1.28; 95% confidence interval 0.73-2.26). Similarly, the meta-analysis observed no significant difference in the risk for the development of a severe course of COVID-19 with preadmission use of inhaled corticosteroids in patients with COVID-19 relative to non-use of inhaled corticosteroids (pooled odds ratio=1.45; 95% confidence interval 0.96-2.20).Conclusions: Our findings assured the safety of continued use of inhaled corticosteroids during the COVID-19 pandemic.

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.

The effect of tocilizumab on mortality in hospitalized patients with COVID-19: a meta-analysis of randomized controlled trials.

OBJECTIVE: We aimed to perform a meta-analysis of randomized controlled trials (RCTs) to summarize the overall effect of tocilizumab on the risk of mortality among patients with coronavirus disease 2019 (COVID-19). METHODS: We systematically searched PubMed, Cochrane Central Register of Controlled Trials, Google Scholar, and medRxiv (preprint repository) databases (up to 7 January 2021). Pooled effect sizes with 95% confidence interval (CI) were generated using random-effects and inverse variance heterogeneity models. The risk of bias of the included RCTs was appraised using version 2 of the Cochrane risk-of-bias tool for randomized trials. RESULTS: Six RCTs were included: two trials with an overall low risk of bias and four trials had some concerns regarding the overall risk of bias. Our meta-analysis did not find significant mortality benefits with the use of tocilizumab among patients with COVID-19 relative to non-use of tocilizumab (pooled hazard ratio = 0.83; 95% CI 0.66-1.05, n = 2,057). Interestingly, the estimated effect of tocilizumab on the composite endpoint of requirement for mechanical ventilation and/or all-cause mortality indicated clinical benefits, with some evidence against our model hypothesis of no significant effect at the current sample size (pooled hazard ratio = 0.62; 95% CI 0.42-0.91, n = 749). CONCLUSION: Despite no clear mortality benefits in hospitalized patients with COVID-19, tocilizumab appears to reduce the likelihood of progression to mechanical ventilation.

Concordance of recommendations across clinical practice guidelines for the management of hypertension in Southeast Asia with internationally reputable sources.

OBJECTIVES: This study aimed to assess the rate of concordance, and to investigate sources of non-concordance of recommendations in the management of hypertension across CPGs in Southeast Asia, with internationally reputable clinical practice guidelines (CPGs). METHODS: CPGs for the management of hypertension in Southeast Asia were retrieved from the websites of the Ministry of Health or cardiovascular specialty societies of the individual countries of Southeast Asia during November to December 2020. The recommendations for the management of hypertension specified in the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guideline and the 2018 European Society of Cardiology (ESC)/European Society of Hypertension (ESH) guideline were selected to be the reference standards; the recommendations concerning the management of hypertension in the included CPGs in Southeast Asia were assessed if they were concordant with the reference recommendations generated from both the 2017 ACC/AHA guideline and the 2018 ESC/ESH guideline, using the population (P)-intervention (I)-comparison (C) combinations approach. RESULTS: A total of 59 reference recommendations with unique and unambiguous P-I-C specifications was generated from the 2017 ACC/AHA guideline. In addition, a total of 51 reference recommendations with unique and unambiguous P-I-C specifications was generated from the 2018 ESC/ESH guideline. Considering the six included CPGs from Southeast Asia, concordance was observed for 30 reference recommendations (50.8%) out of 59 reference recommendations generated from the 2017 ACC/AHA guideline and for 31 reference recommendations (69.8%) out of 51 reference recommendations derived from the 2018 ESC/ESH guideline. CONCLUSIONS: Hypertension represents a significant issue that places health and economic strains in Southeast Asia and demands guideline-based care, yet CPGs in Southeast Asia have a high rate of non-concordance with internationally reputable CPGs. Concordant recommendations could perhaps be considered a standard of care for hypertension management in the Southeast Asia region.

Use of potentially inappropriate medications among older outpatients and inpatients in a tertiary care hospital in Malaysia.

BACKGROUND: Older individuals are seemingly having more medical conditions, which predispose them to a greater risk of polypharmacy. Potentially inappropriate medications (PIMs), including those having anticholinergic and sedative properties, are common in their prescriptions, often associated with functional decline and negative health outcomes. Thus, this study reports proportions of inappropriate drugs and drug burden exposures and its correlation with patient-reported outcomes (PROs) among cognitively intact older adults admitted to a ward or visiting the outpatient clinic at a tertiary care hospital in Malaysia. METHODS: This cross-sectional study included data from 344 older (173 inpatients and 171 outpatients) patients, aged 60 years and above, through validated questionnaires. Medication appropriateness was assessed via Medication Appropriateness Index (MAI) tool, whereas Beers and Screening Tool of Older Person's Potentially Inappropriate Prescribing (STOPP) criteria were used to evaluate PIMs and potentially inappropriate prescribing (PIP), respectively. The Drug Burden Index (DBI) and polypharmacy, as well as PROs, included Groningen Frailty Indicator (GFI), Katz Index of Independence in Activities of Daily Living (Katz ADL) and Older People's Quality of Life (OPQOL) were also evaluated. RESULTS: Overall, inpatients received significantly higher medications (6.90 ± 2.70 vs 4.49 ± 3.20) than outpatients. A significantly higher proportion of inpatients received at least one PIM (65% vs 57%) or PIP (57.4% vs 17.0%) and higher mean MAI score (1.76 ± 1.08 and 1.10 ± 0.34) and DBI score (2.67 ± 1.28 vs 1.49 ± 1.17) than outpatients. Inpatients had significantly higher total OPQOL (118.53 vs 79.95) and GFI score (5.44 vs 3.78) than outpatients. We only found significant correlations between GFI and DBI and total OPQOL and the number of PIMs. CONCLUSIONS: Proportions of PIMs and DBI exposure were significantly higher in an inpatient setting. No significant correlations between exposures to inappropriate medications or drug burden and PROs were observed.

Quality of clinical practice guidelines for the management of hypertension in six Southeast Asian countries.

Background: The endemic of hypertension along with high prevalence of uncontrolled hypertension in Southeast Asia indicates an important role for high-quality clinical practice guidelines (CPGs) to optimize the management of hypertension. However, there was no reported quality appraisal of the CPGs for the management of hypertension in Southeast Asia.Objective: This study aimed to evaluate methodological quality across the CPGs for the management of hypertension in Southeast Asia with a validated quality appraisal tool.Methods: The CPGs for the management of hypertension in Southeast Asia were retrieved from the websites of the Ministry of Health or cardiovascular specialty societies of the individual countries of Southeast Asia. Two reviewers with academic backgrounds independently appraised the methodological quality of all the included CPGs using the Appraisal of Guideline ResEarch and Evaluation (AGREE II) instrument.Results: Six CPGs were identified, each of them from Thailand, Malaysia, Indonesia, Brunei, Singapore, and Vietnam. The highest-scoring quality domain was 'clarity of presentation' (mean=78.7 ± 14.6%), whereas the lowest-scoring quality domains were 'applicability' and 'editorial independence' (mean=8.4 ± 6.0% and mean=8.3 ± 18.6%, respectively). Except for the CPG originated from Malaysia which was "recommended" for use in practice (standardized score for three domains was ≥50.0%), the remaining five CPGs were "weakly recommended" for use in practice (standardized score for one to two domains was ≥50%).Conclusion: More efforts are needed to improve the quality of the developed CPGs for the management of hypertension in Southeast Asia.

Insulin Treatment May Not Be Associated with Increased Mortality in Patients with COVID-19 and Concurrent Diabetes.

Previous study reported that preadmission insulin treatment in patients with coronavirus disease 2019 (COVID-19) and concurrent diabetes was associated with a significantly increased odds of mortality. However, such association may be modified by possible baseline differences in glycemic control between insulin users and non-insulin users. Misinterpretation of the association between insulin treatment and mortality could lead to confusion in clinical practice and hospitalized patients with COVID-19 for whom insulin treatment is appropriately indicated may be omitted from such treatment. However, requirement for insulin during hospitalization for COVID-19 may be a marker of poor prognosis and as such could be used to identify patient population who require more aggressive treatments to prevent mortality.

The risk of mortality in patients with COVID-19 with pre-diagnosis use of NSAIDs: a meta-analysis.

The notion that the use of non-steroidal anti-inflammatory drugs (NSAIDs) may lead to adverse outcomes upon acquisition of coronavirus disease 2019 (COVID-19) should be discredited with a review of the real-life evidence. We aimed to perform a meta-analysis to summarize the risk of mortality with the preadmission/pre-diagnosis use of NSAIDs in patients with COVID-19. A systematic literature search was performed to identify eligible studies in electronic databases. The outcome of interest was the development of a fatal course of COVID-19. Adjusted hazard ratio or odds ratio/relative risk and the corresponding 95% confidence interval from each study were pooled using a random-effects model to produce pooled hazard ratio and pooled odds ratio, along with 95% confidence interval. The meta-analysis of 3 studies with a total of 2414 patients with COVID-19 revealed no difference in the hazard for the development of a fatal course of COVID-19 between NSAID users and non-NSAID users (pooled hazard ratio = 0.86; 95% confidence interval 0.49-1.51). Therefore, NSAIDs should not be avoided in patients who are appropriately indicated during the COVID-19 pandemic.

Real-world effectiveness of BNT162b2 mRNA vaccine: a meta-analysis of large observational studies.

This paper aims to summarize through meta-analyses the overall vaccine effectiveness of the BNT162b2 mRNA vaccine from observational studies. A systematic literature search with no language restriction was performed in electronic databases to identify eligible observational studies which reported the adjusted effectiveness of the BNT162b2 mRNA vaccine to prevent RT-PCR confirmed COVID-19. Meta-analyses with the random-effects model were used to calculate the pooled hazard ratio (HR) and pooled incidence rate ratio (IRR) at 95% confidence intervals, and the vaccine effectiveness was indicated as (pooled HR - 1)/HR or (pooled IRR - 1)/IRR. Nineteen studies were included for this meta-analysis. The meta-analysis revealed significant protective effect against RT-PCR confirmed COVID-19 ≥ 14 days after the first dose, with vaccine effectiveness of 53% (95% confidence interval 32-68%), and ≥ 7 days after the second dose, with vaccine effectiveness of 95% (95% confidence interval: 96-97%). Despite its effectiveness, reporting vaccine safety data by relevant stakeholders should be encouraged as BNT162b2 mRNA is a new vaccine that has not gained full approval. There have been limited data about vaccine effectiveness among immunocompromised patients; thus, the vaccine should be used cautiously in this patient population.

Venous thromboembolism in critically ill COVID-19 patients receiving prophylactic or therapeutic anticoagulation: a systematic review and meta-analysis.

Many aspects of care such as management of hypercoagulable state in COVID-19 patients, especially those admitted to intensive care units is challenging in the rapidly evolving pandemic of novel coronavirus disease 2019 (COVID-19). We seek to systematically review the available evidence regarding the anticoagulation approach to prevent venous thromboembolism (VTE) among COVID-19 patients admitted to intensive care units. Electronic databases were searched for studies reporting venous thromboembolic events in patients admitted to the intensive care unit receiving any type of anticoagulation (prophylactic or therapeutic). The pooled prevalence (and 95% confidence interval [CI]) of VTE among patients receiving anticoagulant were calculated using the random-effects model. Subgroup pooled analyses were performed with studies reported prophylactic anticoagulation alone and with studies reported mixed prophylactic and therapeutic anticoagulation. We included twelve studies (8 Europe; 2 UK; 1 each from the US and China) in our systematic review and meta-analysis. All studies utilized LMWH or unfractionated heparin as their pharmacologic thromboprophylaxis, either prophylactic doses or therapeutic doses. Seven studies reported on the proportion of patients with the previous history of VTE (range 0-10%). The pooled prevalence of VTE among ICU patients receiving prophylactic or therapeutic anticoagulation across all studies was 31% (95% CI 20-43%). Subgroup pooled analysis limited to studies reported prophylactic anticoagulation alone and mixed (therapeutic and prophylactic anticoagulation) reported pooled prevalences of VTE of 38% (95% CI 10-70%) and 27% (95% CI 17-40%) respectively. With a high prevalence of thromboprophylaxis failure among COVID-19 patients admitted to intensive care units, individualised rather than protocolised VTE thromboprophylaxis would appear prudent at interim.

Pharmacotherapeutic considerations for systemic rheumatic diseases amid the COVID-19 pandemic: more questions than answers.

Thus far, associations between the presence of systemic rheumatic disease and an increased risk of novel coronavirus disease 2019 (COVID-19) acquisition or a worse prognosis from COVID-19 have not been conclusive. It is not known for certain if there is an association between any pharmacological agent used for rheumatologic treatment, including biological and non-biological disease-modifying antirheumatic drugs (DMARDs), and an increased risk of COVID-19 acquisition or adverse outcomes from COVID-19, although these agents have been associated with an overall higher risk of infections. The pharmacological management of patients with a rheumatic disease without COVID-19 should currently follow usual treatment approaches. Individualized approaches to adjusting DMARD regimens in patients with documented COVID-19 seems prudent, with specific attention paid to the severity of the infection. Patients receiving antimalarials (hydroxychloroquine/chloroquine) may continue treatment with these agents. Treatment with sulfasalazine, methotrexate, leflunomide, immunosuppressants and biological agents other than interluekin-6 receptor inhibitors and JAK inhibitors should be stopped or withheld. It should be reasonable to resume DMARD treatment when patients are no longer symptomatic and at least 2 weeks after documentation of COVID-19, although the decision should be individualized, preferably based on infection severity.