key: cord-1036689-du26c7l1
authors: Jiang, Weijun; Li, Weiwei; Xiong, Lei; Wu, Qiuyue; Wu, Jian; He, Bangshun; Shen, Jiawei; Pang, Rongrong; Luo, Tao; Guo, Yanju; Yang, Yang; Han, Ying; Dai, Wei; Zhu, Peiran; Xia, Xinyi
title: Clinical efficacy of convalescent plasma therapy on treating COVID‐19 patients: Evidence from matched study and a meta‐analysis
date: 2020-12-21
journal: Clin Transl Med
DOI: 10.1002/ctm2.259
sha: 922533890d3f09144c359c6920b0b76143e896ad
doc_id: 1036689
cord_uid: du26c7l1

nan

are relatively serious and nucleic acid test repeated positive. In addition, we also found the rate of male in case with CPT groups were significantly higher than matched control group (P < 0.0001). However, no significant differences in age, disease severity, discharge condition, basic disease, and the number in the ICU between case with CPT groups and matched control group were found. The demographic and clinical characteristics of all patients are show in Table S1 .

We performed a meta-analysis of 12 observational studies (1019 cases and 954 controls) that a significant reduction in mortality (odds ratio [OR] = 0.66, 95% confidence interval [CI] = 0.50-0.86, P = 0.002) was found in the CPT group compared with the standard treatment group, and a true positive result was also found in trial sequential analysis (TSA). Our analyses also suggest that CPT may have a clinically relevant impact in reducing the rate of mortality in COVID-19 (4.91% vs. 9.20%). In subgroup analysis, we revealed significant associations within the Caucasian subgroup (OR = 0.71, 95% CI = 0.52-0.98, P = 0.037), matched study subgroup (OR = 0.49, 95% CI = 0.32-0.77, P = 0.002), severe subgroup (OR = 0.63, 95% CI = 0.40-1.00, P = 0.049), critical subgroup (OR = 0.24, 95% CI = 0.06-0.92, P = 0.037), severity of MIX subgroup (OR = 0.53, 95% CI = 0.33-0.86, P = 0.010), dose of 250-300 subgroup (OR = 0.41, 95% CI = 0.22-0.77, P = 0.006), no specific dose subgroup (OR = 0.24, 95% CI = 0.06-0.92, P = 0.037), journal of unpublished subgroup (OR = 0.42, 95% CI = 0.26-0.68, P = 0.000), and case size of <50 subgroup (OR = 0.37, 95% CI = 0.21-0.65, P = 0.001), but not the remaining subgroups. In addition, an edge effect may exist in the race of MIX subgroup. Specific data are summarized in Figure 1 , Table 1 , Figure S1 , and Table S2 .

We found no evidence of serious adverse events or complications due to CPT, but four participants reported slight transfusion-related adverse events (clinical symptoms include red, itchy, and inflamed skin) following CPT. TSA found a false positive, although our pooled meta-analysis found a significant increase in the incidence of adverse events in patients treated with CPT compared to the control group (OR = 2.63, 95% CI = 1.40-4.94, P = 0.003).

In subgroup analysis, we revealed significant associations with in the Caucasian subgroup (OR = 2.40, 95% CI = 1.21-4.79, P = 0.013), RCT subgroup (OR = 2.42 95% CI = 1.19-4.91, P = 0.014), severe subgroup (OR = 3.88, 95% CI = 1.24-12.12, P = 0.019), journal of published subgroup (OR = 3.43, 95% CI = 1.23-9.57, P = 0.018), and case size of >50 subgroup (OR = 4.51, 95% CI = 1.58-12.88, P = 0.005), but not the remaining subgroups. In addition, we also found an edge effect in the Asian subgroup, matched study, dose of 200 subgroup, dose of 400 subgroup, and unpublished subgroup. Data on the association between CPT and adverse event risk are summarized in Figure 2 , Table 1 , Figure S1 , and Table S2 . No differences between the two groups in terms of hospital stay, improvement of clinical symptoms, and discharge were found (Figures S2-S5 and Tables S3-S5 ). Begg's funnel plot and Egger's test were performed to assess publication bias. We additionally conducted sensitivity analyses by omitting one study at a time in the calculation of a summary outcome. Although the sample sizes for cases and controls in all eligible studies varied, corresponding pooled ORs, SMD, and 95%CIs were not qualitatively altered with or without studies on small samples. No other single study influenced pooled OR, SMD, and 95% CI qualitatively.

John Mair-Jenkins et al 10 analyzed 32 studies of CPT and SARS coronavirus infection. They revealed consistent evidence for a statistically significant reduction in mortality (OR = 0.25; 95% CI = 0.14-0.45), especially when convalescent plasma is administered early after symptom onset. However, Li et al, 4 Agarwal et al 7 , and Simonovich et al reported that CPT was not associated with a reduction in progression to severe COVID-19 or all-cause mortality. Our analyses and pooled meta-analysis suggest that CPT significantly decreased the mortality in COVID-19 patients.

To the best of our knowledge, it is a systematically review and meta-analysis of the efficacy and security of CPT to COVID-19 patients in the largest sample size. We found that CPT significantly decreased the rate of mortality in COVID-19 patients in our matched control study and meta-analysis. Our results showed that CPT could significantly reduce the mortality in COVID-19 patients, and there was no significant increase the incidence of adverse events. These data provide evidence favoring the efficacy and safety of CPT as a therapeutic agent in COVID-19 patients and provide comprehensive reference for COVID-19 treatment. 

The authors declare that there is no conflict of interest.

WJJ, XYX, and WWL conceived and designed the experiments. WJJ, QYW, and JW performed publication searches and selection. WJJ, LX, and BSH analyzed the data. JWS, YY, YH, and RRP prepared the figures. WD, TL, PRZ, and YJG contributed materials/analysis tools. WJJ wrote and revised the paper. All authors reviewed the manuscript.

Weijun Jiang 1,# Weiwei Li 1,# Lei Xiong 1,# Qiuyue Wu 1,# Jian Wu 1 Bangshun He 1, 2 Jiawei Shen 1 Rongrong Pang 1, 3 Tao Luo 1 Yanju Guo 1

Clinical characteristics of coronavirus disease 2019 in China

Use of convalescent plasma in hospitalized patients with COVID-19: case series

Convalescent plasma treatment of severe COVID-19: a matched control study. medRxiv

Effect of convalescent plasma therapy on time to clinical improvement in patients with severe and life-threatening COVID-19: a randomized clinical trial

Clinical efficacy of convalescent plasma for treatment of COVID-19 infections: results of a multicenter clinical study

Convalescent Plasma for COVID-19. A randomized clinical trial

Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial (PLACID Trial)

Mortality reduction in 46 severe Covid-19 patients treated with hyperimmune plasma. A proof of concept single arm multicenter interventional trial. medRxiv

The therapeutic effectiveness of Convalescent plasma therapy on treating COVID-19 patients residing in respiratory care units in hospitals in Baghdad

The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis

# These authors contributed equally to this work and should be considered as joint first authors.

Jiang https://orcid.org/0000-0001-7552-3170 Xinyi Xia https://orcid.org/0000-0002-7178-0505