Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma.

By Chenguang Shen, Zhaoqin Wang, Fang Zhao, Yang Yang, Jin-xiu Li, Jing Yuan, Fuxiang Wang, Delin Li, Minghui Yang, L. Xing and 17 more. Journal of the American Medical Association (JAMA), 2020

2,209 citations recorded by the source corpus.

Importance Coronavirus disease 2019 (COVID-19) is a pandemic with no specific therapeutic agents and substantial mortality. It is critical to find new treatments. Objective To determine whether convalescent plasma transfusion may be beneficial in the treatment of critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Design, Setting, and Participants Case series of 5 critically ill patients with laboratory-confirmed COVID-19 and acute respiratory distress syndrome (ARDS) who met the following criteria: severe pneumonia with rapid progression and continuously high viral load despite antiviral treatment; Pao2/Fio2 <300; and mechanical ventilation. All 5 were treated with convalescent plasma transfusion. The study was conducted at the infectious disease department, Shenzhen Third People's Hospital in Shenzhen, China, from January 20, 2020, to March 25, 2020; final date of follow-up was March 25, 2020. Clinical outcomes were compared before and after convalescent plasma transfusion. Exposures Patients received transfusion with convalescent plasma with a SARS-CoV-2-specific antibody (IgG) binding titer greater than 1:1000 (end point dilution titer, by enzyme-linked immunosorbent assay [ELISA]) and a neutralization titer greater than 40 (end point dilution titer) that had been obtained from 5 patients who recovered from COVID-19. Convalescent plasma was administered between 10 and 22 days after admission. Main Outcomes and Measures Changes of body temperature, Sequential Organ Failure Assessment (SOFA) score (range 0-24, with higher scores indicating more severe illness), Pao2/Fio2, viral load, serum antibody titer, routine blood biochemical index, ARDS, and ventilatory and extracorporeal membrane oxygenation (ECMO) supports before and after convalescent plasma transfusion. Results All 5 patients (age range, 36-65 years; 2 women) were receiving mechanical ventilation at the time of treatment and all had received antiviral agents and methylprednisolone. Following plasma transfusion, body temperature normalized within 3 days in 4 of 5 patients, the SOFA score decreased, and Pao2/Fio2 increased within 12 days (range, 172-276 before and 284-366 after). Viral loads also decreased and became negative within 12 days after the transfusion, and SARS-CoV-2-specific ELISA and neutralizing antibody titers increased following the transfusion (range, 40-60 before and 80-320 on day 7). ARDS resolved in 4 patients at 12 days after transfusion, and 3 patients were weaned from mechanical ventilation within 2 weeks of treatment. Of the 5 patients, 3 have been discharged from the hospital (length of stay: 53, 51, and 55 days), and 2 are in stable condition at 37 days after transfusion. Conclusions and Relevance In this preliminary uncontrolled case series of 5 critically ill patients with COVID-19 and ARDS, administration of convalescent plasma containing neutralizing antibody was followed by improvement in their clinical status. The limited sample size and study design preclude a definitive statement about the potential effectiveness of this treatment, and these observations require evaluation in clinical trials.

Subfields: Biochemistry, Hematology, Infectious Diseases

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Citations in the corpus

• Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial (2020, background): “10 An open-label RCT of oral lopinavir-ritonavir found no significant effect on the primary outcome measure of time to clinical improve ment and no evidence of reduction in viral RNA titres compared to control.”
• Aging in COVID-19: Vulnerability, immunity and intervention (2020, positive): “Observational findings suggest improved clinical outcomes in those who are transfused with COVID-19 convalescent plasma (CCP), including radiological resolution, reduction in viral loads, and improved survival (Duan et al., 2020; Harvala et al., 2020; Hegerova et al., 2020; Joyner et al., 2020; Li e”
• Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology (2020, positive): “…patients with convalescent plasma improved clinical outcomes and decreased viral loads (Duan et al., 2020; Li et al., 2020a; Liu et al., 2020b; Shen et al., 2020), highlighting the importance transfer of potently neutralizing human monoclonal Abs (mAbs) protected animals challenged with…”
• Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial. (2020, background): “6) Interval between symptom onset and admission, median (IQR), d 12 (5-20) [n = 49] 10 (6-16) [n = 48]”
• Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations (2020, neutral): “Phase 1 trial of human polyclonal immunoglobulin G (SAB-301) in healthy participants; 81 Might reduce mortality in severe acute respiratory infections due to SARS-CoV and influenza; 83 associated with reduction in viral load and improvement in fever, oxygenation, and chest imaging in a case series, ”