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

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.

Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

Figure 1.. Temporal Changes of Cycle Threshold Value, Pao2/Fio2, SOFA Score, and Body Temperature in Patients Receiving Convalescent Plasma Transfusion

A, Change in cycle threshold (Ct) value in nasopharyngeal swabs of infected patients at day 0, day 3, day 7, and day 12 after the plasma transfusion. A Ct value of 40 was defined as undetectable. B, Change in Sequential Organ Failure Assessment (SOFA) score of the patients with convalescent plasma treatment (range 0-24, with higher scores indicating more severe illness; see footnote to Table 2 for more complete definition). C, Change in Pao2/Fio2 ratio of the treated patients from day 0 to day 12 after treatment. D, Change in body temperature of the 5 patients following plasma transfusion.

Figure 2.. Changes of Receptor Binding Domain–Specific IgG and IgM ELISA and Neutralizing Antibody Titers Before and After Convalescent Plasma Transfusion in Patients

Higher titer values indicate greater protection. A, Variation of RBD-specific IgG ELISA titer. B, Variation of RBD-specific IgM ELISA titer. C, Variation of neutralizing antibody titer against SARS-CoV-2 in recipients in day 0, day 1, day 3, and day 7 following transfusion. The identical line segments were adjusted slightly to avoid superimposition. RBD indicates receptor binding domain.