Virus World

The global spread of SARS-CoV-2/COVID-19 is devastating health systems and economies worldwide. Recombinant or vaccine-induced neutralizing antibodies are used to combat the COVID-19 pandemic. However, recently emerged SARS-CoV-2 variants B.1.1.7 (UK), B.1.351 (South Africa) and B.1.1.248 (Brazil) harbor mutations in the viral spike (S) protein that may alter virus-host cell interactions and confer resistance to inhibitors and antibodies. Here, using pseudoparticles, we show that entry of UK, South Africa and Brazil variant into human cells is susceptible to blockade by entry inhibitors. In contrast, entry of the South Africa and Brazil variant was partially (Casirivimab) or fully (Bamlanivimab) resistant to antibodies used for COVID-19 treatment and was less efficiently inhibited by serum/plasma from convalescent or BNT162b2 vaccinated individuals. These results suggest that SARS-CoV-2 may escape antibody responses, which has important implications for efforts to contain the pandemic.

Preprint available (Feb. 11. 2021):

https://doi.org/10.1101/2021.02.11.430787 

Jan. 15, 2021 -- Blood transfusions from recovered COVID-19 patients that contained high antibody levels reduced the number of COVID-19 deaths among other hospitalized patients, according to a new study by Mayo Clinic.  If given early to patients with mild COVID-19, the treatments slowed the progression of disease, they wrote in the New England Journal of Medicine. “I think it behooves the medical community to continue to innovate and test therapies for treatment. Realistically, we’re months away from having a substantial number of people vaccinated,” R. Scott Wright, MD, coordinator of the Mayo Clinic’s COVID-19 plasma therapy program, told the Minneapolis Star-Tribune.  Early in the pandemic, Mayo Clinic launched a nationwide program that linked hospitalized COVID-19 patients with donor plasma. The research team analyzed records for more than 3,000 patients to determine whether those who received blood with high levels of antibodies fared better than those who received blood with low antibody levels. Overall, patients who received antibody-rich plasma had a 25% lower chance of dying within 30 days. In addition, patients who received plasma within three days of their COVID-19 diagnosis had a lower risk of death than those who received transfusions later. Health outcomes were better for those who received plasma and didn’t need to be placed on a ventilator. “Patients who were on ventilator did not see a benefit,” Wright told the newspaper. “It was too late.” 

Hospitals should conserve their limited plasma supplies for patients who are most likely to benefit from a transfusion, Louis Katz, MD, the acting chief medical director of the Mississippi Valley Regional Blood Center in Iowa, wrote in an accompanying editorial in the New England Journal of Medicine. “Uncontrolled compassionate use of convalescent plasma…should be discouraged, even though clinicians recognize how difficult it can be to ‘just stand there’ at the bedside of a patient in the ICU,” he wrote. At his center, Katz said, about a fifth of plasma donations contain high enough antibodies to provide the benefits seen in the Mayo Clinic study. “Constraints on therapies for COVID-19 that are effective for limited patient populations are a powerful argument for continued consistent adherence to recommended nonpharmaceutical interventions and the rapid deployment and uptake of effective vaccines,” he wrote.

Original Findings Publishes in NEJM (Jan. 13, 2020):

https://doi.org/10.1056/NEJMoa2031893

Background: Therapies to interrupt the progression of early coronavirus disease 2019 (Covid-19) remain elusive. Among them, convalescent plasma administered to hospitalized patients has been unsuccessful, perhaps because antibodies should be administered earlier in the course of illness.

Methods: We conducted a randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older adult patients within 72 hours after the onset of mild Covid-19 symptoms. The primary end point was severe respiratory disease, defined as a respiratory rate of 30 breaths per minute or more, an oxygen saturation of less than 93% while the patient was breathing ambient air, or both. The trial was stopped early at 76% of its projected sample size because cases of Covid-19 in the trial region decreased considerably and steady enrollment of trial patients became virtually impossible.

Results: A total of 160 patients underwent randomization. In the intention-to-treat population, severe respiratory disease developed in 13 of 80 patients (16%) who received convalescent plasma and 25 of 80 patients (31%) who received placebo (relative risk, 0.52; 95% confidence interval [CI], 0.29 to 0.94; P=0.03), with a relative risk reduction of 48%. A modified intention-to-treat analysis that excluded 6 patients who had a primary end-point event before infusion of convalescent plasma or placebo showed a larger effect size (relative risk, 0.40; 95% CI, 0.20 to 0.81). No solicited adverse events were observed.

Conclusions: Early administration of high-titer convalescent plasma against SARS-CoV-2 to mildly ill infected older adults reduced the progression of Covid-19. (Funded by the Bill and Melinda Gates Foundation and the Fundación INFANT Pandemic Fund; Dirección de Sangre y Medicina Transfusional del Ministerio de Salud number, PAEPCC19, Plataforma de Registro Informatizado de Investigaciones en Salud number, 1421, and ClinicalTrials.gov number, NCT04479163. opens in new tab.)

Published in NEJM (Jan. 6, 2021):

https://doi.org/10.1056/NEJMoa2033700

To determine the effect of COVID-19 convalescent plasma on mortality, we aggregated patient outcome data from randomized clinical trials (RCT), matched-control, case series, and case report studies. Random-effects analyses of RCT data demonstrated that hospitalized COVID-19 patients transfused with convalescent plasma exhibited a lower mortality rate compared to patients receiving standard treatments. These data provide evidence favoring the efficacy of human convalescent plasma as a therapeutic agent in hospitalized COVID-19 patients.

Preprint in medRxiv (Oct. 29, 2020):

https://doi.org/10.1101/2020.07.29.20162917

Convalescent plasma taken from Covid-19 survivors should not be considered a standard of care for coronavirus, an NIH panel says. A National Institutes of Health panel said there's no evidence backing the use of convalescent plasma to treat coronavirus patients and that doctors should not treat it as a standard of care until more study has been done. "There are insufficient data to recommend either for or against the use of convalescent plasma for the treatment of COVID-19," the panel of more than three dozen experts said in a statement posted on the NIH website Tuesday. The statement, which was posted quietly, contradicts the Trump Administration's characterization of the treatment as "historic" and a "major advance" and directly refers to last week's emergency use authorization by the US Food and Drug Administration. "Convalescent plasma should not be considered standard of care for the treatment of patients with COVID-19," the committee, which evaluates treatments for coronavirus, said in the statement. "Prospective, well-controlled, adequately powered randomized trials are needed to determine whether convalescent plasma is effective and safe for the treatment of COVID-19. Members of the public and health care providers are encouraged to participate in these prospective clinical trials." 

Last week, President Trump declared that the FDA's emergency use authorization was historic. "Today I am pleased to make a truly historic announcement in our battle against the China virus that will save countless lives," Trump said at a White House news conference. "Today's action will dramatically increase access to this treatment." Health and Human Services Secretary Alex Azar was equally effusive. "This is a major advance in the treatment of patients. A major advance," he said at last week's briefing. The timing raised suspicions the White House had pressured FDA -- something FDA Commissioner Dr. Stephen Hahn denied several times. Trump had also said politics held up the FDA's EUA. But Hahn had also made misleading comments about the data supporting the use of convalescent plasma -- which is the antibody-rich serum taken from the blood of people who have recovered from an infection. The hope is infusing this plasma into new patients will kickstart their immune response. It's a treatment that dates back more than 100 years and has never been used broadly.

The NIH panel, led by Dr. Clifford Lane, the head of research at the National Institute of Allergy and Infectious Diseases; Dr. Roy Gulick, chief of the Division of Infectious Diseases at Weill Medical College of Cornell University; and Dr. Henry Masur, chief of the Critical Care Medicine Department at NIH, said much more research is needed into whether the treatment works. Data published so far don't really show whether it helps patients, they said. "The long-term risks of treatment with COVID-19 convalescent plasma and whether its use attenuates the immune response to SARS-CoV-2, making patients more susceptible to reinfection, have not been evaluated," the statement added. Plus, different patients have differing levels of antibodies, so the treatment is highly variable, they said....

A study by U.S. researchers from Pennsylvania State University, Houston Methodist Hospital, Weill Cornell Medical College, and the CCDC Army Research laboratory in Austin, has investigated what’s the best time-window to collect plasma from COVID-19 convalescent patients. The researchers evaluated the changes with time in the levels of neutralizing antibodies (nAbs) against the virus in samples collected from 175 donors. The short answer: within the first 60 days after symptom onset. During this time, 80% of the individuals with any virus neutralization titer, display levels of neutralization above 160. This is the FDA-recommended value for use in COVID-19 convalescent plasma therapy. However, after this period, and during the next two months, the titers declined rapidly, and at some point only 20% of the individuals still maintain the recommended levels of neutralization.

The researchers also confirmed that neutralization titers are greater if the patients have undergone severe COVID-19 disease, and when the individuals are older. Just the presence of dyspnea (shortness of breath) in the patients, increases the titer of nAbs. Similarly, plasma from individuals in the age interval 20-30, as compared to older than 60-year old patients, are significantly less likely to have the recommended levels of neutralization after 60 days from symptoms start.

The study also confirmed the use of a simple ELISA assay to determine the levels of total antibodies against the receptor binding domain (RBD) of the viral spike protein, as an easy surrogate method to select plasma samples that will neutralize the virus. Virus neutralization assays are more time consuming, require several days, and need laboratory access to biosafety level 3 facilities.

The study is available as preprint in bioRxiv (August 21, 2020): https://doi.org/10.1101/2020.08.21.261909

Scientists have identified a diverse group of antibodies that block the new coronavirus’s ability to infect cells — even when applied in low doses. The immune-system proteins called neutralizing antibodies interfere with hostile microbes trying to enter target cells. David Ho at Columbia University Vagelos College of Physicians and Surgeons in New York City and his colleagues studied neutralizing antibodies from the plasma of five people with severe cases of COVID-19 (L. Liu et al. Nature http://doi.org/d4md; 2020).

Nineteen antibodies proved highly effective at preventing SARS-CoV-2 infection of cell samples. A small dose of one of the antibodies protected golden Syrian hamsters (Mesocricetus auratus) from SARS-CoV-2 infection. The 19 antibodies attach to a variety of locations on the coronavirus spike protein. A therapy made from antibodies that fasten onto the spike protein at multiple sites could be difficult for the virus to evade through mutation..

Original Study Published in Nature (July 22, 2020):

https://doi.org/10.1038/s41586-020-2571-7

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

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 

A clinical trial in older adults with COVID-19 shows that an early dose of blood plasma from recovered people helps to prevent the progression to severe disease. The plasma of people who have recovered from COVID-19 contains antibodies against SARS-CoV-2. But treatment with such plasma has had mixed results, and some scientists have suggested that plasma needs to be given early in the disease course to be effective. Fernando Polack at Fundación INFANT in Buenos Aires and his colleagues conducted a rigorous clinical trial to assess the effect of treatment with plasma within 72 hours of symptom onset. Participants included people over the age of 75 and those between 65 and 74 with at least one pre-existing condition such as diabetes (R. Libster et al. N. Engl. J. Med. https://doi.org/10.1056/NEJMoa2033700; 2021). Severe COVID-19 developed in 16% of the 80 study participants who received plasma and 31% of the 80 participants in the placebo group. The team found that donor plasma containing higher concentrations of antibodies against SARS-CoV-2 was associated with a greater reduction in the risk of developing severe disease — providing evidence that the antibodies themselves are responsible for the therapeutic effect.

BACKGROUND

Convalescent plasma is frequently administered to patients with Covid-19 and has been reported, largely on the basis of observational data, to improve clinical outcomes. Minimal data are available from adequately powered randomized, controlled trials.

METHODS

We randomly assigned hospitalized adult patients with severe Covid-19 pneumonia in a 2:1 ratio to receive convalescent plasma or placebo. The primary outcome was the patient’s clinical status 30 days after the intervention, as measured on a six-point ordinal scale ranging from total recovery to death.

RESULTS

A total of 228 patients were assigned to receive convalescent plasma and 105 to receive placebo. The median time from the onset of symptoms to enrollment in the trial was 8 days (interquartile range, 5 to 10), and hypoxemia was the most frequent severity criterion for enrollment. The infused convalescent plasma had a median titer of 1:3200 of total SARS-CoV-2 antibodies (interquartile range, 1:800 to 1:3200]. No patients were lost to follow-up. At day 30 day, no significant difference was noted between the convalescent plasma group and the placebo group in the distribution of clinical outcomes according to the ordinal scale (odds ratio, 0.83 (95% confidence interval [CI], 0.52 to 1.35; P=0.46). Overall mortality was 10.96% in the convalescent plasma group and 11.43% in the placebo group, for a risk difference of −0.46 percentage points (95% CI, −7.8 to 6.8). Total SARS-CoV-2 antibody titers tended to be higher in the convalescent plasma group at day 2 after the intervention. Adverse events and serious adverse events were similar in the two groups.

CONCLUSIONS

No significant differences were observed in clinical status or overall mortality between patients treated with convalescent plasma and those who received placebo. (PlasmAr ClinicalTrials.gov number, NCT04383535. opens in new tab.)

Published in NEJM (November 24, 2020):

https://doi.org/10.1056/NEJMoa2031304

Using blood of recovered COVID-19 patients - or so-called convalescent plasma - as a potential treatment is of little benefit in helping hospitalised patients fight off the infection, according to results of a clinical trial in India. Published in the BMJ British Medical Journal on Friday, the results show that convalescent plasma, which delivers antibodies from COVID-19 survivors to infected people, failed to reduce death rates or halt progression to severe disease. The findings, from a study of more than 400 hospitalised COVID-19 patients, are a setback for a treatment that U.S. President Donald Trump touted in August as an “historic breakthrough”. The United States and India have authorised convalescent plasma for emergency use. Other countries, including Britain, are collecting donated plasma so that it could be widely rolled out if shown to be effective.

“The ... trial was able to show a small effect on the rate at which patients were able rid themselves of the virus, but this was not enough to improve their recovery from the disease,” said Simon Clarke, an expert cellular microbiology at the University of Reading. “In simple terms, there were no clinical benefits to the patients.” The Indian researchers enrolled 464 adults with confirmed moderate COVID-19 who were admitted to hospitals across India between April and July. They were randomly split into two groups - with one group receiving two transfusions of convalescent plasma, 24 hours apart, alongside best standard care, and the control group best standard care only. 

After 7 days, use of convalescent plasma seemed to improve some symptoms, such as shortness of breath and fatigue, the researchers said, and led to higher rates of something known as “negative conversion” - a sign that the virus is being neutralised by antibodies. But this did not translate into a reduction in deaths or progression to severe disease by 28 days.

“The poor performance of convalescent plasma in this trial is disappointing but not entirely surprising,” said Ian Jones, a professor of virology, also at Reading University. He said the plasma is more likely to work if given very swiftly after someone is contracts COVID-19. He urged these and other researchers to continue to conduct trials of convalescent plasma as a potential COVID-19 treatment, but to do so in newly diagnosed patients. “We still do not have enough treatments for the early stage of disease to prevent severe disease and until this becomes an option, avoiding being infected with the virus remains the key message,” he said.

Original study published in the British Medical Journal (Oct. 22, 2020):

https://doi.org/10.1136/bmj.m3939

The decision could generate intense controversy inside the administration and the broader scientific community because of a dearth of reliable data. The Food and Drug Administration announced Sunday that it has authorized the use of blood plasma from patients who have recovered from Covid-19 as a treatment for the disease. The decision to issue an emergency use authorization, which President Trump’s press secretary heralded ahead of time as a “major therapeutic breakthrough,” likely falls far short of that description — and could generate intense controversy inside the administration and the broader scientific community. So-called convalescent plasma is among a host of potential therapeutics that have been undergoing testing in clinical trials. The hope is that infusions of antibody-rich plasma from those who have recovered from Covid-19 can be injected into ill patients, kickstarting their immune system and allowing them to fight off the virus until they can generate their own antibodies. “Today’s action will dramatically expand access to this treatment,” Trump said at a White House news conference Sunday afternoon. He called the EUA a “truly historic announcement” and said that convalescent plasma has been proven to reduce mortality by 35%, which he called a “tremendous number.” Alex Azar, secretary of Health and Human Services, followed Trump. “We dream in drug development of something like a 35% mortality reduction,” he said. “This is a major advance in the treatment of patients.”

An FDA staffer who reviewed the data on convalescent plasma — and whose name was redacted from a memo released by the agency — was far less enthusiastic, writing that the data “support the conclusion that [convalescent plasma] to treat hospitalized patients with COVID-19 meets the ‘may be effective’ criteria for issuance of an EUA. Adequate and well-controlled randomized trials remain nonetheless necessary for a definitive demonstration of … efficacy and to determine the optimal product attributes and the appropriate patient populations for its use.” The announcement comes less than a week after officials at the National Institutes of Health staged a rare intervention to stop the FDA from issuing the emergency use authorization. NIH officials involved in the decision told the New York Times that more data, derived from randomized controlled trials, were needed.  The announcement also follows sustained pressure from the president on his own administration. Trump told reporters last week that U.S. officials were slow-walking clearance of blood plasma until after the November election. He also took to Twitter on Saturday to criticize the FDA for making it difficult to test vaccines and therapeutics, though he didn’t specifically mention plasma.

Trump thanked FDA Commissioner Stephen Hahn, who participated in the news conference, for issuing the EUA, adding, “The FDA really stepped up, and especially over the last few days in getting this done.” Asked by a reporter about the hold up in issuing the EUA, Trump said, “There are people in the FDA and actually in your larger department [HHS] that can see things being held up and wouldn’t mind so much — its my opinion, a very strong opinion — and that’s for political reasons.” He added, “We are being very strong and we are being very forthright, and we have some incredible answers, and we’re not going to be held up.”

The documents released by the FDA do not make clear where the 35% figure cited by Trump and Azar comes from. But it may be based on a study conducted by the Mayo Clinic and the NIH, which indicated that plasma treatments appeared to have a small but statistically significant impact on reducing mortality in hospitalized Covid-19 patients who received the infusions within three days of the onset of symptoms, compared with those who got plasma after four days or later. The death rate after seven days was 8.7% in patients treated early and 11.9% in those not treated until later. But that study, while it included more than 35,000 patients, did not include a placebo group and was not randomized, making it difficult to interpret the data. And it hasn’t been peer-reviewed by other scientists and published in a medical journal...

Passive antibody transfer is a longstanding treatment strategy for infectious diseases that involve the respiratory system. In this context, human convalescent plasma has been used to treat coronavirus disease 2019 (COVID-19), but the efficacy remains uncertain. Objective: To explore potential signals of efficacy of COVID-19 convalescent plasma. Design: Open-label, Expanded Access Program (EAP) for the treatment of COVID-19 patients with human convalescent plasma.

Multicenter, including 2,807 acute care facilities in the US and territories. Participants: Adult participants enrolled and transfused under the purview of the US Convalescent Plasma EAP program between April 4 and July 4, 2020 who were hospitalized with (or at risk of) severe or life threatening acute COVID-19 respiratory syndrome. Intervention: Transfusion of at least one unit of human COVID-19 convalescent plasma using standard transfusion guidelines at any time during hospitalization. Convalescent plasma was donated by recently-recovered COVID-19 survivors, and the antibody levels in the units collected were unknown at the time of transfusion. Main Outcomes and Measures: Seven and thirty-day mortality.

The 35,322 transfused patients had heterogeneous demographic and clinical characteristics. This cohort included a high proportion of critically-ill patients, with 52.3% in the intensive care unit (ICU) and 27.5% receiving mechanical ventilation at the time of plasma transfusion. The seven-day mortality rate was 8.7% [95% CI 8.3%-9.2%] in patients transfused within 3 days of COVID-19 diagnosis but 11.9% [11.4%-12.2%] in patients transfused 4 or more days after diagnosis (p<0.001). Similar findings were observed in 30-day mortality (21.6% vs. 26.7%, p<0.0001). Importantly, a gradient of mortality was seen in relation to IgG antibody levels in the transfused plasma. For patients who received high IgG plasma (>18.45 S/Co), seven-day mortality was 8.9% (6.8%, 11.7%); for recipients of medium IgG plasma (4.62 to 18.45 S/Co) mortality was 11.6% (10.3%, 13.1%); and for recipients of low IgG plasma (<4.62 S/Co) mortality was 13.7% (11.1%, 16.8%) (p=0.048). This unadjusted dose-response relationship with IgG was also observed in thirty-day mortality (p=0.021). The pooled relative risk of mortality among patients transfused with high antibody level plasma units was 0.65 [0.47-0.92] for 7 days and 0.77 [0.63-0.94] for 30 days compared to low antibody level plasma units. Conclusions and Relevance: The relationships between reduced mortality and both earlier time to transfusion and higher antibody levels provide signatures of efficacy for convalescent plasma in the treatment of hospitalized COVID-19 patients.

Preprint of the study in medRxiv (August 12, 2020):

https://doi.org/10.1101/2020.08.12.20169359 

The blood from seriously ill Covid-19 patients on ventilators was found by researchers to be highly inflammatory and harmful to the body. Antibodies  generated by the immune system to neutralise 

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