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Early high-titer convalescent plasma prevents 75% of extreme COVID-19 in aged

The ongoing COVID-19 pandemic has caused over 1.39 million deaths worldwide. Many of these deaths occurred in the elderly, with disproportionate rates of serious illness, hospitalization, and death, especially those with underlying chronic conditions such as diabetes, high blood pressure, and kidney disease.

A promising new clinical study published on the preprint server medRxiv * reports that the risk of serious illness is reduced by 73% if convalescent plasma with a high antibody titer is administered early in the course of COVID-19 in older patients. This could encourage the use of this safe, inexpensive prophylactic intervention to prevent hospital overload and save lives in a variety of ways.

So far, only a few effective drugs against COVID-19 have been approved. Therapies showing promise include the use of convalescent plasma (CP), which uses serum obtained from the blood of people who have had SARS-CoV-2 infection, typically mildly, and have recovered. Your blood is therefore rich in antibodies that specifically target the virus and prevent it from entering and infecting host cells.

CP has previously been used to treat a number of diseases, but is highly dependent on the time of administration and the titer of specific antibodies. Several previous studies have shown no convincing evidence of clinical benefit in COVID-19 patients.

Several early studies cast doubts on the role of convalescent plasma (CP) in COVID-19. However, this could well be due to the late management of this modality. The current study aimed to test the ability of CP to prevent the progression of COVID-19 into serious illness when administered in the first 72 hours after symptoms appeared.

The researchers conducted a randomized, double-blind controlled trial of high-titered anti-SARS-CoV-2 antibody CP in elderly patients within this period after the onset of mild symptoms between June 4 and October 25, 2020. Their aim was to evaluate the reduction in severe respiratory illnesses defined by a respiratory rate ≥ 30 or an oxygen saturation below 93% in the room air.

While 210 patients were originally to be examined, the number of severe cases rose sharply in late July, pulling both doctors and hospital capacity out of the study. Coupled with a dramatic decrease in the number of patients available for screening towards the latter part of the study, it meant that it would have been difficult to achieve the original goal without unduly extending the study period. The study was therefore terminated prematurely in order to analyze the data obtained so far.

The study group finally comprised 160 patients, every 75 years or older or between 65 and 74 years old, but with one or more comorbid illnesses. The median age was 77 years and ~ 63% were female.

All had at least one symptom from each of the two categories for at least 48 hours when tested for the virus by reverse transcriptase polymerase chain reaction (RT-PCR).

The first category included non-specific symptoms such as fever, sweating, and chills, while the second included more suspicious symptoms such as fatigue, shortness of breath, dry cough, sore throat, changes in taste or smell, and muscle pain. None of the patients already had severe respiratory disease.

After diagnosis, the patients were hospitalized and randomly assigned CP with anti-SARS-CoV-2 spike IgG titers of over 1: 1,000 or placebo over 1.5 to 2 hours. Thus 80 received plasma and 80 received a placebo. The minimum clinically significant reduction in the risk of severe respiratory distress was set at 40%, which meant that the expected risk had to be reduced from 50% in the control group to 30% in the intervention group for the CP infusion to be seen as effective.

The researchers found that only ~ 16% of the plasma recipient group had progressive disease, compared to ~ 31% of the placebo group. The early use of CP thus reduced the risk by 48%. The time to development of severe illness in the CP group was delayed compared to the control group. In the age group over 75 years, the relative risk was reduced by 65%.

However, when 6 of the participants who developed severe dyspnoea after randomization but before receiving CP were excluded from the analysis, the reduction in risk of severe outcomes was even higher for the remaining members of the group at 60%, which confirms the effectiveness of this intervention.

The researchers also found a dose-dependent response to CP, with the dividing line at 1: 3,200 (the mean IgG titer). If the CP used contained IgG in high doses above this titer, it resulted in better responses, reducing the risk of severe results by 73%. For each patient who recovered without developing serious illness, four patients would need to be infused.

The scientists suggest that encouraging local donation from a community effort and selecting super donors with IgG titers above 1: 12,800 could help each donor provide CP to over 20 sick patients with only 750 ml of donated blood each. Repeat donations could be made as IgG levels have been shown to have remained high for months. Most of the high-titer CP donors in this study had a history of COVID-19 disease that required hospitalization.

The researchers comment, “Raising awareness of early symptoms in seniors will be critical as time-limited effective intervention is available. Plasma against COVID-19 is conceptually like health insurance. It should be in hand when it seems intuitively unnecessary. “

This intervention is simple and inexpensive, but can be life-saving in most high-risk cases. This would reduce mortality from COVID-19 while preventing health care overload and allowing some degree of control until other effective drugs or a vaccine become widely available.

* Important NOTE

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behavior, or be treated as established information.

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