Early Convalescent Plasma for COVID-19 Does Not Result in Faster Symptom Resolution

No significant differences in time to symptom resolution or symptom prevalence were found between patients with COVID-19 infection who received early treatment with convalescent vs control plasma.

Patients infected with COVID-19 who received early treatment with convalescent plasma did not experience faster symptom resolution compared with those who received control plasma. These study results were published in The Journal of Infectious Diseases.

The Convalescent Plasma to Limit SARS-CoV-2 Associated Complications (CSSC-004) trial was a randomized, controlled, double-masked trial comprising 1070 patients with COVID-19 infection. The primary outcome was the difference in time to symptom resolution by day 14 between patients randomly assigned to receive early outpatient treatment with either convalescent plasma (n=538) or control plasma (n=532). Self-reported data on patients’ symptoms were collected via telephone (days 1, 3, 5, 7, and 10) and via in-person visits (days 0 and 14). Researchers used chi-squared and Wilcoxon rank sum testing to compare differences between the cohorts.

Among patients in the convalescent plasma and control cohorts, the majority were women (54.1% vs 59.8%, respectively), the median age was 43.0 (IQR, 33-54) and 44.5 (IQR, 33-55) years, and 12.8% and 31.2% were fully vaccinated against COVID-19 infection, respectively. In both cohorts, approximately 80% of the patients received treatment during the pre-Alpha and Alpha waves, and the median time between symptom onset and transfusion was 6 (IQR, 4-7) days.

At day 14 more than 70% of patients in both cohorts reported symptomatic infection, indicating a median of 2 (IQR, 0-4) ongoing symptoms. The most commonly reported symptoms among patients in the convalescent in plasma vs control cohorts were cough (39.0% vs 41.5%), fatigue (38.5% vs 40.4%), and loss of smell (32.7% vs 34.4%) or taste (27.9% vs 27.4%). There were no statistically significant between-group differences noted in regard to the prevalence of each of these symptoms.

Our results highlight the need for future trials to assess symptoms in the acute illness phase to understand impact on one’s ability to return to work.

Changes in the severity of cough, shortness of breath, fatigue, and headache from baseline to day 14 did not significantly differ between patients who received convalescent vs control plasma.

Subgroup analyses among patients with diabetes, men, and those who received treatment within 5 days of symptom onset all showed no significant differences in the time to symptom resolution between those in the convalescent plasma and control cohorts.

Limitations of this study were the inclusion of relatively few patients who were fully vaccinated, as well as potentially limited generalizability among patients infected with variants other than Alpha or Delta.  

According to the researchers, “Our results highlight the need for future trials to assess symptoms in the acute illness phase to understand impact on one’s ability to return to work.”

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Baksh SN, Heath SL, Fukuta Y, et al. Symptom duration and resolution with early outpatient treatment of convalescent plasma for coronavirus disease 2019: a randomized trial. J Infect Dis. Published online January 31, 2023. doi:10.1093/infdis/jiad023