Virus World

Antibody treatment for COVID-19 seems to have spurred mutations in the SARS-CoV-2 that infected a man with a compromised immune system.In mid-2020, a man was admitted to hospital with COVID-19. He had been diagnosed with cancer in 2012; the illness and his treatment had probably weakened his immune system. The man’s COVID-19 was treated with two courses of the antiviral drug remdesivir and, later, two courses of convalescent plasma — antibody-laden blood from people who had recovered from COVID-19. He died 102 days after admission. Ravindra Gupta at the University of Cambridge, UK, and his colleagues analysed viral genomes obtained from the man during his illness (S. A. Kemp et al. Nature https://doi.org/10.1038/s41586-021-03291-y; 2021). The viral populations in his blood changed little after remdesivir treatment. But after each course of convalescent plasma, the samples were dominated by viruses with a particular pair of mutations in the SARS-CoV-2 spike protein, the main target of the immune system. Experiments showed that one of the mutations weakened the potency of the antibodies in the convalescent plasma, yet also reduced the virus’s infectivity. The second mutation restored infectivity. The potential for viral evolution means that convalescent plasma should be used cautiously when treating people with compromised immunity, the authors say.

Research published in Nature (Feb. 5, 2021):

https://doi.org/10.1038/s41586-021-03291-y 

Since December 2019, Coronavirus Disease 2019 (COVID-19) has become a global pandemic, causing mass morbidity and mortality. Prior studies in other respiratory infections suggest that convalescent plasma transfusion may offer benefit to some patients. Here, the outcomes of thirty-nine hospitalized patients with severe to life-threatening COVID-19 who received convalescent plasma transfusion were compared against a cohort of retrospectively matched controls.

Plasma recipients were selected based on supplemental oxygen needs at the time of enrollment and the time elapsed since the onset of symptoms. Recipients were transfused with convalescent plasma from donors with a SARS-CoV-2 (severe acute respiratory disease coronavirus 2) anti-spike antibody titer of ≥1:320 dilution. Matched control patients were retrospectively identified within the electronic health record database. Supplemental oxygen requirements and survival were compared between plasma recipients and controls.  Convalescent plasma recipients were more likely than control patients to remain the same or have improvements in their supplemental oxygen requirements by post-transfusion day 14, with an odds ratio of 0.86 (95% CI: 0.75~0.98; p=0.028). Plasma recipients also demonstrated improved survival, compared to control patients (log-rank test: p=0.039). In a covariates-adjusted Cox model, convalescent plasma transfusion improved survival for non-intubated patients (hazard ratio 0.19 (95% CI: 0.05 ~0.72); p=0.015), but not for intubated patients (1.24 (0.33~4.67); p=0.752). 

Convalescent plasma transfusion is a potentially efficacious treatment option for patients hospitalized with COVID-19; however, these data suggest that non-intubated patients may benefit more than those requiring mechanical ventilation.

Preprint available in medRxiv (May 22, 2020):

https://doi.org/10.1101/2020.05.20.20102236

Hospitalized patients with COVID-19 receiving convalescent plasma did not gain a statistically significant benefit in time to clinical improvement in a small randomized trial conducted in Wuhan, China. But that may have been because the trial was stopped early, leaving it underpowered for many of the intended analyses. Among the 103 patients treated in the study -- barely half of the originally planned 200 -- more patients receiving convalescent plasma in addition to standard treatment experienced clinical improvement within 28 days compare with a group getting standard care only (51.9% vs 43.1%, respectively; HR 1.40, 95% CI 0.79-2.49, P=0.26), reported Zhong Liu, MD, PhD, of Chinese Academy of Medical Sciences and Peking Union Medical College, and colleagues.

However, in a subgroup analysis of patients with severe, but not life-threatening, disease, there was a significant difference in clinical improvement in the plasma group compared to controls (HR 2.15, 95% CI 1.07-4.32, P=0.03), the authors wrote in JAMA. Liu and colleagues explained that they had to give up enrolling patients in late March, when the outbreak in Wuhan petered out. Beginning March 24, no new cases were reported in the city where, just a few weeks earlier, hundreds were diagnosed every day. Had they succeeded in recruiting 200 patients, they estimated that the trial would have had 80% power to detect a benefit from the intervention. 

The group recommended a new, larger trial of convalescent plasma in patients with severe COVID-19 where sufficient numbers can be enrolled. Previously, a five-patient case series in China found beneficial effects of convalescent plasma among hospitalized COVID-19 patients, but an editorial warned the therapy is difficult to scale.

In addition, Liu and colleagues noted its effects have been varied, likely due to "no standardization or evidence-based rationale for donor selection, quality control of convalescent plasma, or recipient transfusion indications for convalescent plasma."

Original Study Published in JAMA (June 3, 2020):

https://doi.org/10.1001/jama.2020.10044