Background: Studies from the Spanish influenza era reported that transfusion of influenza-convalescent human blood products reduced mortality in patients with influenza complicated by pneumonia. Treatments for H5N1 influenza are unsatisfactory, and convalescent human plasma containing H5N1 antibodies could be an effective therapy during outbreaks and pandemics. Purpose: To determine whether transfusion with influenza-convalescent human blood products reduced the risk for death in patients with Spanish influenza pneumonia. Data Sources: Manual search of English-language journals from 1918 to 1925. Citations from retrieved studies were also searched. Study Selection: Published English-language studies that had at least 10 patients in the treatment group, used convalescent blood products to treat Spanish influenza pneumonia in a hospital setting, and reported on a control or comparison group. Data Extraction: Two investigators independently extracted data on study characteristics, outcomes, adverse events, and quality. Data Synthesis: Eight relevant studies involving 1703 patients were found. Treated patients, who were often selected because of more severe illness, were compared with untreated controls with influenza pneumonia in the same hospital or ward. The overall crude case-fatality rate was 16% (54 of 336) among treated patients and 37% (452 of 1219) among controls. The range of absolute risk differences in mortality between the treatment and control groups was 8% to 26% (pooled risk difference, 21% [95% Cl, 15% to 27%]). The overall crude case-fatality rate was 19% (28 of 148) among patients who received early treatment (after <4 days of pneumonia complications) and 59% (49 of 83) among patients who received late treatment (after ≥4 days of pneumonia complications). The range of absolute risk differences in mortality between the early treatment group and the late treatment group was 26% to 50% (pooled risk difference, 41 % [Cl, 29% to 54%]). Adverse effects included chill reactions and possible exacerbations of symptoms in a few patients. Limitations: Studies were few and had many methodologic limitations. No study was a blinded, randomized, or placebo-controlled trial. Some pertinent studies may have been missed. Conclusions: Patients with Spanish influenza pneumonia who received influenza-convalescent human blood products may have experienced a clinically important reduction in the risk for death. Convalescent human H5N1 plasma could be an effective, timely, and widely available treatment that should be studied in clinical trials.

Meta-analysis: Convalescent blood products for spanish influenza pneumonia : A future H5N1 treatment? Commentary

In the current SARS-CoV-2 pandemic, there has been worldwide debate on the use of corticosteroids in COVID-19. In the recent RECOVERY trial, evaluating the effect of dexamethasone, a reduced 28-day mortality in patients requiring oxygen therapy or mechanical ventilation was shown. Their results have led to considering amendments in guidelines or actually already recommending corticosteroids in COVID-19. However, the effectiveness and safety of corticosteroids still remain uncertain, and reliable data to further shed light on the benefit and harm are needed. The aim of this systematic review and meta-analysis was to evaluate the effectiveness and safety of corticosteroids in COVID-19. A systematic literature search of RCTS and observational studies on adult patients was performed across Medline/PubMed, Embase and Web of Science from December 1, 2019, until October 1, 2020, according to the PRISMA guidelines. Primary outcomes were short-term mortality and viral clearance (based on RT-PCR in respiratory specimens). Secondary outcomes were: need for mechanical ventilation, need for other oxygen therapy, length of hospital stay and secondary infections. Forty-four studies were included, covering 20.197 patients. In twenty-two studies, the effect of corticosteroid use on mortality was quantified. The overall pooled estimate (observational studies and RCTs) showed a significant reduced mortality in the corticosteroid group (OR 0.72 (95%CI 0.57–0.87). Furthermore, viral clearance time ranged from 10 to 29 days in the corticosteroid group and from 8 to 24 days in the standard of care group. Fourteen studies reported a positive effect of corticosteroids on need for and duration of mechanical ventilation. A trend toward more infections and antibiotic use was present. Our findings from both observational studies and RCTs confirm a beneficial effect of corticosteroids on short-term mortality and a reduction in need for mechanical ventilation. And although data in the studies were too sparse to draw any firm conclusions, there might be a signal of delayed viral clearance and an increase in secondary infections.

/pdf/corticosteroid-use-in-covid-19-patients-a-systematic-review-3cp59vynvi.pdf

Corticosteroid use in COVID-19 patients: a systematic review and meta-analysis on clinical outcomes.

Treatment of the novel Coronavirus Disease 2019 (COVID-19) remains a complicated challenge, especially among patients with severe disease. In recent studies, immunosuppressive therapy has shown promising results for control of the cytokine storm syndrome (CSS) in severe cases of COVID-19. However, it is well documented that immunosuppressive agents (e.g., corticosteroids and cytokine blockers) increase the risk of opportunistic infections. On the other hand, several opportunistic infections were reported in COVID-19 patients, including Aspergillus spp., Candida spp., Cryptococcus neoformans, Pneumocystis jiroveci (carinii), mucormycosis, Cytomegalovirus (CMV), Herpes simplex virus (HSV), Strongyloides stercoralis, Mycobacterium tuberculosis, and Toxoplasma gondii. This review is a snapshot about the main opportunistic infections that reported among COVID-19 patients. As such, we summarized information about the main immunosuppressive agents that were used in recent clinical trials for COVID-19 patients and the risk of opportunistic infections following these treatments. We also discussed about the main challenges regarding diagnosis and treatment of COVID-19-associated opportunistic infections (CAOIs).

/pdf/covid-19-associated-opportunistic-infections-a-snapshot-on-19hvborbpa.pdf

COVID-19-associated opportunistic infections: a snapshot on the current reports.

A COVID-19 Vaccine: Big Strides Come with Big Challenges

BACKGROUND: The efficacy of convalescent plasma (CP) for the treatment of coronavirus disease 2019 (COVID-19) remains unclear. METHODS: In a matched cohort analysis of hospitalized patients with severe COVID-19, the impact of CP treatment on in-hospital mortality was evaluated using univariate and multivariate Cox proportional-hazards models, and the impact of CP treatment on time to hospital discharge was assessed using a stratified log-rank analysis. RESULTS: In total, 64 patients who received CP a median of 7 days after symptom onset were compared to a matched control group of 177 patients. The incidence of in-hospital mortality was 12.5% and 15.8% in the CP and control groups, respectively (Pâ=â.52). There was no significant difference in the risk of in-hospital mortality between the 2 groups (adjusted hazard ratio [aHR] 0.93, 95% confidence interval [CI] .39-2.20). The overall rate of hospital discharge was not significantly different between the 2 groups (rate ratio [RR] 1.28, 95% CI .91-1.81), although there was a significantly increased rate of hospital discharge among patients 65-years-old or greater who received CP (RR 1.86, 95% CI 1.03-3.36). There was a greater than expected frequency of transfusion reactions in the CP group (2.8% reaction rate observed per unit transfused). CONCLUSIONS: We did not demonstrate a significant difference in risk of mortality or rate of hospital discharge between the CP and control groups. There was a signal for improved outcomes among the elderly, and further adequately powered randomized studies should target this subgroup when assessing the efficacy of CP treatment.

/pdf/convalescent-plasma-for-patients-with-severe-coronavirus-2ti6yb3061.pdf

Convalescent Plasma for Patients With Severe Coronavirus Disease 2019 (COVID-19): A Matched Cohort Study.

The burden and impact of secondary superadded infections in critically ill coronavirus disease 2019 (COVID-19) patients is widely acknowledged. However, there is a dearth of information regarding the impact of COVID-19 in patients with tuberculosis, HIV, chronic hepatitis, and other concurrent infections. This review was conducted to evaluate the consequence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in patients with concurrent co-infections based on the publications reported to date. An extensive comprehensive screening was conducted using electronic databases up to 3rd September 2020 after obtaining registration with PROSPERO (CRD420202064800). The observational studies or interventional studies in English, evaluating the impact of SARS-CoV-2 in patients with concurrent infections are included for the meta-analyses. Our search retrieved 20 studies, with a total of 205,702 patients. Patients with tuberculosis (RR = 2.10; 95% CI, 1.75-2.51; I2 = 0%), influenza (RR = 2.04; 95% CI, 0.15-28.25, I2 = 99%) have an increased risk of mortality during a co-infection with SARS-CoV-2. No significant impact is found in people living with HIV (RR = 0.99; 95% CI, 0.82-1.19; I2 = 30%), Chronic hepatitis (RR = 1.15; 95% CI, 0.73-1.81; I2 = 10%). Several countries (Brazil, Paraguay, Argentina, Peru, Colombia, and Singapore) are on the verge of a dengue co epidemic (cumulative 878,496 and 5,028,380 cases of dengue and COVID-19 respectively). The impact of COVID-19 in patients of concurrent infections with either tuberculosis or influenza is detrimental. The clinical outcomes of COVID-19 in HIV or chronic hepatitis patients are comparable to COVID-19 patients without these concurrent infections.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jmv.26740

Impact of COVID-19 in patients with concurrent co-infections: A systematic review and meta-analyses.

In the absence of definitive therapy for coronavirus disease (COVID-19), convalescent plasma therapy (CPT) may be a critical therapeutic option. This review was conducted to evaluate the impact of CPT in COVID-19 patients based on the publications reported to date. A robust screening of electronic databases was conducted up to 10th July 2020. Randomized controlled trials (RCTs), cohort studies, and case series with a control group evaluating the effectiveness and safety of CPT in patients with COVID-19 are included for the meta-analyses. Our search retrieved seven studies, including two RCTs and five cohort studies, with a total of 5444 patients. In patients with COVID-19, the use of CPT reduces mortality (odd's ratio [OR] 0.44; 95% CI, 0.25-0.77), increases viral clearance (OR, 11.29; 95% CI, 4.9-25.9) and improves clinically (OR, 2.06; 95% CI, 0.8 to 4.9). However, the evidence is of low quality (mortality reduction, and viral clearance), and very low quality (clinical improvement). CPT may be beneficial for reducing mortality, viral shedding and improving clinical conditions in COVID-19 patients. However, further randomized control trials (RCT) are required to substantiate the safety margin, initiation, optimal dosage, titre and duration of CPT.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jmv.26408

Convalescent plasma is a clutch at straws in COVID-19 management! A systematic review and meta-analysis.

Steroids may play a critical role in the current pandemic of coronavirus disease-2019 (COVID-19), given the dearth of specific therapeutic options. This review was conducted to evaluate the impact of glucocorticoid therapy in patients with COVID-19 based on the publications reported to date. A comprehensive screening was conducted using electronic databases up to August 19, 2020. The randomized controlled trials (RCTs) and cohort studies evaluating the effectiveness and safety of steroids in patients with COVID-19 are included for the meta-analyses. Our search retrieved twelve studies, including two RCTs and 10 cohort studies, with a total of 15,754 patients. In patients with COVID-19, the use of systemic glucocorticoid neither reduce mortality (odds ratio [OR] = 1.94, 95% confidence interval [CI]: 1.11-3.4, I2 = 96%), nor the duration of hospital stay (mean difference [MD] = 1.18 days, 95% CI: -1.28 to 3.64, I2 = 93%) and period of viral shedding (MD = 1.42 days, 95% CI: -0.52 to 3.37, I2 = 0%). Systemic steroid therapy may not be effective for reducing mortality, duration of hospitalization, and period of viral shedding. Studies are mostly heterogeneous. Further RCTs are required.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jmv.26483

Are the steroids a blanket solution for COVID-19? A systematic review and meta-analysis.

Prognostic predictors are of paramount interest for prompt intervention and optimal utilization of the healthcare system in the ongoing context of the COVID-19 pandemic. The platelet-to-lymphocyte count ratio (PLR), has emerged as a potential tool for risk stratification of critically ill patients with sepsis. The current systematic review explores the utility of PLR as a prognostic predictor of COVID-19 patients. We screened the electronic databases until May 15, 2021 after enrolling in PROSPERO (CRD42021220269). Studies evaluating the association between PLR on admission and outcomes in terms of mortality and severity among COVID-19 patients were included. We retrieved 32 studies, with a total of 2768 and 3262 COVID-19 patients for mortality and disease severity outcomes. Deceased and critically ill patients had higher PLR levels on admission in comparison to survivors and non-severe patients (mean differences [MD] = 66.10; 95% confidence interval [CI]: 47.75-84.44; p < 0.00001 and MD = 86.74; 95% CI: 67.7-105.7; p < 0.00001, respectively). A higher level of PLR on admission in COVID-19 patients is associated with increased morbidity and mortality. However, the evidence is of low quality and further studies regarding the cut-off value of PLR are the need of the hour.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jmv.27297

Role of platelet-to-lymphocyte count ratio (PLR), as a prognostic indicator in COVID-19: A systematic review and meta-analysis.

Background: The neutrophil-lymphocyte count ratio (NLR) has emerged as a potential prognostic tool for different diseases. In the current coronavirus disease (COVID-19) pandemic, the NLR may be a useful tool for risk scarification and the optimal utilization of limited healthcare resources. However, there is no consensus regarding the optimal value of NLR, and the association with disease severity and mortality. Thus, this study aims to systematically analyze the current evidence of the utility of baseline NLR as a predictive tool for mortality, disease severity in COVID-19 patients. Methods: A compendious screening of electronic databases up to June 15, 2021, was done after enlisting the protocol in PROSPERO (CRD42020202659). Studies evaluating the utility of baseline NLR in COVID-19 are included for this review as per the PRISMA statement. Results: We retrieved a total of 13112 and 12986 COVID-19 patients for survivability and severity over 90 studies. The expired and critically sick patients had elevated baseline NLR on admission, in comparison to survivors and noncritical patients. (SMD = 3.82; 95% CI: 2.79-4.85; I2 = 100% and SMD = 1.42; 95% CI: 1.22-1.63; I2 = 95%, respectively). The summary receiver operating curve analysis for mortality (AUC = 0.87; 95% CI: 0.86-0.87; I2 = 94.7%), and severity (AUC = 0.82; 95% CI: 0.80-0.84; I2 = 79.7%) were also suggestive of its significant predictive value. Conclusions: The elevated NLR on admission in COVID-19 patients is associated with poor outcomes.

https://journals.sagepub.com/doi/pdf/10.1177/08850666211045626

Soumya Sarkar

Papers

Impact of COVID-19 in patients with concurrent co-infections: A systematic review and meta-analyses.

Convalescent plasma is a clutch at straws in COVID-19 management! A systematic review and meta-analysis.

Are the steroids a blanket solution for COVID-19? A systematic review and meta-analysis.

Role of platelet-to-lymphocyte count ratio (PLR), as a prognostic indicator in COVID-19: A systematic review and meta-analysis.

The Impact of Neutrophil-Lymphocyte Count Ratio in COVID-19: A Systematic Review and Meta-Analysis.