key: cord-0923428-1h28p93r authors: Rabelo-da-Ponte, Francisco Diego; Silvello, Daiane; Scherer, Juliana Nichterwitz; Ayala, Alejandro Raul; Klamt, Fábio title: Convalescent Plasma Therapy on Patients with Severe or Life-Threatening COVID-19: A Metadata Analysis date: 2020-08-10 journal: J Infect Dis DOI: 10.1093/infdis/jiaa509 sha: 131e933cf616f393b442c36667aab0f68d8b70a0 doc_id: 923428 cord_uid: 1h28p93r nan A c c e p t e d M a n u s c r i p t 3 Dear Editor, Current therapeutic options to mitigate severe COVID-19 cases remain limited. Prior experience with convalescent plasma (CP) to treat SARS, H1N1, and Ebola patients suggested that passive immunization by plasma transfusion suppresses viremia and improves clinical outcomes, reducing the number of deaths and length of stay in the intensive care unit (ICU) with minimal side effects. These findings are not universal, as Zeng et al. described discouraging effects of convalescent plasma therapy on survival in COVID-19 patients [1] , and a recent COVID-19 study stratified by disease severity (n = 103 participants) did not show significant improvement following CP administration, when compared to standard care alone [2] . However, a sub-analysis suggested a potential CP therapeutic benefit in those with advanced disease, including patients with COVID-19 suffering from severe disease (respiratory distress and/or hypoxemia) but not in patients with life-threatening disease (shock, organ failure, or requiring mechanical ventilation) [2] . In order to add more information whether CP administration is effective as a treatment over the continuum of care of COVID-19 patients, we performed a metadata analysis, including random-effects meta-analysis and meta-regression, based on available data [1] [2] [3] [4] [5] [6] [7] [8] [9] . The following measures, before and after CP transfusions, were checked: i) viral load A c c e p t e d M a n u s c r i p t Figure 1 . Summary of pooled results of convalescent plasma use in COVID-19 patients. The inverse variance weighted method was used to combine summary measures using randomeffects models to minimize the effects of heterogeneity between studies [1] [2] [3] [4] [5] [6] [7] [8] [9] and sensitivity analyses using fixed-effects models. Negative viral load rates were expressed as the Risk Ratio (RR) and clinical disease severity and C-reactive protein level were expressed as the ratio of mean (ROM). Risk ratios and ratio of mean less than one (1) indicate a positive effect of the intervention. Meta-regression analyses were performed to investigate the influence of other concurrently administered agents and patient age on the outcomes examined. All tests were two-tailed; P ≤0.05 was considered statistically significant. All analyses were performed using the "meta" package in R and RStudio software. A c c e p t e d M a n u s c r i p t Effect of Convalescent Plasma Therapy on Viral Shedding and Survival in Patients with Coronavirus Disease Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients with Severe and Life-threatening COVID-19: A Randomized Clinical Trial Use of Convalescent Plasma Therapy in Two COVID-19 Patients with Acute Respiratory Distress Syndrome in Korea Treatment of 5 Critical Ill Patients With With Convalescent Plasma Effectiveness of convalescent plasm therapy in severe COVID-19 patients Treatment with Convalescent Plasma for Critically ILL Patients with Severe Acute Respiratory Syndrome Coronavirus 2 Infection Treatment with convalescent plasma for COVID-19 patients in Wuhan Treatment of COVID-19 Patients with Convalescent Plasma Convalescent plasma treatment of severe COVID-19: A matched control study Convalescent Plasma in 5,000 Patients A c c e p t e d M a n u s c r i p t