There was radiological improvements within 7?days and viremia was undetectable in seven (70%) patients.45 However, the recovery was faster in those receiving convalescent plasma before 14?days after onset of illness compared to those who received the therapy after that time.45 In a systematic evaluate, five studies were included with 27 patients and all studies were with associated with a high risk of bias, and were nonrandomized with confounders, poor methodology, different dosage, and variable duration of therapy.80 Currently, convalescent plasma is being considered in clinical trial. fact that these were observational in nature. A single double-blind randomized controlled trial exhibited that hyperimmune intravenous immunoglobulin treatment resulted in a lower viral weight and reduced mortality in a subgroup who received treatment within 5?days of symptom onset of H1N1 contamination.52 The use of hyperimmune immunoglobulin in a double-blind, randomized, placebo-controlled trial resulted in no difference in the primary outcome measured by a 6-point ordinal level of clinical status on Day 7, although there were favorable antiviral and clinical responses in the subgroup of patients with influenza B.53 A third study of severe influenza, high-titer anti-influenza plasma transfusion did Verbascoside not result in a significant benefit in comparison with nonimmune plasma.54 Two meta-analysis of convalescent plasma in patients with viral pneumonia revealed reduction in mortality.48,51 The second meta-analysis included 1703 patients with pneumonia secondary to the 1918 influenza and showed 21% absolute reduction of the crude mortality rate.48 Advantage and disadvantage of convalescent plasma The transfusion of convalescent plasma has certain advantages and disadvantages. Convalescent plasma transfusion is usually potentially associate with a short-lived immunity and provide a fast and immediate therapy. Theoretically, convalescent plasma would work especially in moderately or severe contamination when given early. Potential risks of convalescent plasma transfusion include: risks of the transfusion of infectious brokers, transfusion-associated circulatory overload (TACO), transfusion-associated acute lung injury (TRALI) which is usually of particular concern in SARS, Verbascoside SARS-CoV-2 and MERS-CoV patients, and antibody-dependent enhancement (ADE). ADE is usually a possible concern that leads to worse immune-mediated tissue damage due to the presence of non-neutralizing antibodies and even in the presence of neutralizing SARS-CoV antibodies.55 In Rhesus macaques model of infection, vaccination with SARS-CoV spike protein and the development of neutralizing antispike antibodies before inoculation with SARS-CoV experienced resulted in severe lung disease despite develop lower viral loads.56 Convalescent plasma in the SARS and MERS-CoV Era During SARS-CoV infection, it was thought that convalescent plasma improve the outcome of infected patients.57 Previous studies including a meta-analysis of 27 studies of patients with SARS-CoV infection51 suggest that convalescent plasma may be used for patients with SARS as convalescent plasma showed improvements in survival and resulted in a shorter hospital stay.58,59 However, most of the studies were of low or very low quality, lacked control groups, and experienced risk of bias.51 The analysis included 6 case studies, 20 case series, 2 case-comparison studies, MMP16 and 1 prospective cohort study.51 A protocol for the use of convalescent plasma as a Verbascoside therapeutic option for MERS was suggested.60 Plasma donors were identified as those with anti-MERS-CoV indirect immunofluorescence assay (IFA) antibodies (titer of 1 1:160) with no evidence of active MERS-CoV infection.60 However, of 443 tested samples for MERS-CoV antibodies, only 12 (2.7%) had a reactive ELISA, and 9 of the 12 had reactive indirect fluorescent antibody and microneutralization assay titers. The study proved that clinical trial using such interventions is usually challenging due to the small pool of potential donors with sufficient high antibody titers.61 In nine confirmed survivors of Verbascoside MERS-CoV infection, 55%, 33%, and 22% of them experienced positive MERS antibodies by IFA at 3, 10, and 18?months, respectively.62 The two patients who had long lasting antibodies as tested by ELISA and IFA had severe disease; however, the actual Verbascoside titer of the antibodies was not reported in the study.62 In a larger study, MERS-CoV neutralizing antibodies were produced at low levels and were short-lived after mild or subclinical contamination.63,64 Further studies of the kinetics of the MERS-CoV antibodies showed that all surviving patients and 50% of fatal cases produced IgG and neutralizing antibodies during the first 2?weeks after diagnosis.65 However, these antibodies did not eliminate the virus from lower respiratory tract.65 In 12 patients from South Korea, nine (75%) patients experienced PRNT50 titers 1:320 by day 21 and two experienced titers 1:320 by day 28.66 Convalescent plasma in COVID-19 therapy The FDA recently approved convalescent plasma for the use in patients with COVID-19 as a new investigational drug on an emergency basis.67 The use of convalescent plasma is contingent upon the presence of an adequate level of neutralizing antibodies in the donor plasma before transfusion.68C70 At the present time, limited data are available about the efficacy of convalescent plasma for COVID-19 patients. The presence of IgM antibodies were weakly detected by ELISA and high IgG titers were observed in five samples.71 A summary of the use of convalescent plasma in COVID-19 patients is.