Latest COVID-19 trials show convalescent plasma worked, vitamin C did not

Two recent studies looked at treatments for hospitalized patients with COVID-19. The first, published by the New England Journal of Medicine on Oct. 25, found that convalescent plasma reduced mortality among COVID-19 patients on mechanical ventilation. It randomized 475 patients in Belgium to either standard care or convalescent plasma with a neutralizing antibody titer of at least 1:320 (except that, due to a shortage, plasma with a titer of 1:160 was administered to 17.7% of the patients). The mortality rate at day 28 was 35.4% in the convalescent-plasma group versus 45.0% in the standard-care group (P=0.03), with greater effect in patients who underwent randomization 48 hours or less after the initiation of mechanical ventilation.

The study authors noted several differences between their trial and previous ones of convalescent plasma, including their focus on patients who were more severely ill with acute respiratory distress syndrome. They also used plasma with high neutralizing antibody titers and treated patients as early as possible after the initiation of mechanical ventilation. Limitations include that the study was not blinded, that SARS-CoV-2 variants have changed since the study period, and that the trial ended prematurely because of a lack of patients. The authors suggested that the success of their intervention might be due to the convalescent plasma reducing the quantity of virus alive in the lungs of patients who continued to shed the virus, which in turn might reduce inflammation.

The other study, published by JAMA on Oct. 25, found that IV vitamin C did not reduce mortality in hospitalized COVID-19 patients. It harmonized two trials that randomized patients to IV vitamin C or control (placebo or no vitamin C) every six hours for 96 hours (maximum of 16 doses). Enrollment ended early because statistical triggers for harm and futility were met in one trial. Among 1,568 critically ill patients (1,037 on vitamin C and 531 controls), the median number of organ support-free days was 7 versus 10, respectively; survival to hospital discharge was 61.9% for the vitamin C group versus 64.6% for the control group, for a posterior probability of 24.0% for efficacy. Of the 1,022 patients who were not critically ill (456 on vitamin C and 566 controls), the median number of organ support-free days was 22 in each group, and survival to hospital discharge was 85.1% versus 86.6%, with a posterior probability of 17.8% for efficacy.

The study authors concluded that vitamin C did not improve the studied outcomes. “On the contrary, there were high posterior probabilities (>90% for organ support–free days and >75% for hospital survival) that vitamin C worsened both outcomes in critically ill patients and those not critically ill,” they wrote. An accompanying editorial also expressed concern about the risk of harm. “This study represents another in a growing list of randomized clinical trials failing to demonstrate a benefit with vitamin C for treating infection or sepsis wherein the high probability of futility convincingly supports the null hypothesis that vitamin C is not superior to placebo or no treatment,” it said. “Although the allure of vitamin C may continue to tempt clinicians, the results from the harmonized LOVIT-COVID and REMAP-CAP trials should lead clinicians to use therapies that have been demonstrated to be beneficial in patients with COVID-19 as opposed to one that is almost certainly ineffective and potentially harmful.”