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

JAMA. 2020 Apr 28;323(16):1582-1589. doi: 10.1001/jama.2020.4783.

Abstract

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Neutralizing / therapeutic use*
  • Antibodies, Viral / blood
  • Antibodies, Viral / therapeutic use*
  • Antiviral Agents / therapeutic use
  • Betacoronavirus / immunology*
  • Blood Donors
  • Coronavirus Infections / drug therapy
  • Coronavirus Infections / physiopathology
  • Coronavirus Infections / therapy*
  • Critical Illness
  • Female
  • Glucocorticoids / therapeutic use
  • Humans
  • Immunization, Passive
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Male
  • Methylprednisolone / therapeutic use
  • Middle Aged
  • Organ Dysfunction Scores
  • Pandemics
  • Pneumonia, Viral / drug therapy
  • Pneumonia, Viral / physiopathology
  • Pneumonia, Viral / therapy*
  • Respiratory Distress Syndrome, Adult / therapy*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antiviral Agents
  • Glucocorticoids
  • Immunoglobulin G
  • Immunoglobulin M
  • Methylprednisolone

Supplementary concepts

  • COVID-19
  • COVID-19 serotherapy
  • severe acute respiratory syndrome coronavirus 2