Early High-Titer Plasma Therapy to Prevent Severe Covid-19in Older Adults

Excerpts from The New England Journal of Medicine

India

healthysoch

New Delhi, January 08, 2021 :

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.

Salient Features :

• Convalescent plasma administered to Hospitalized patients has been unsuccessful, perhaps because antibodies should be administered earlier in the course of illness.
• In a randomized, placebo controlled trial published today,(NEJM) patients who were 75 years of age or older, or above 65 with Comorbidities (Hypertension, Heart disease, Obesity, Diabetes, Chronic Kidney disease, COPD received Convalescent plasma (80 patients) or placebo (80 patient) within 72 hours of 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.
• 16 % patients in plasma group developed severe disease as compared to 31% in placebo group(p = < 0.03) with relative risk reduction of 48%
• 5% in plasma group and 12% in placebo group had life threatening disease
• 2 patients in plasma group and 4 patients in placebo group died

According to Dr. G C Khilnani Chairman, PSRI Institute of Pulmonary, Critical care and Sleep Medicine, “There has been untiring effort at reducing the severity of Covid disease in order to minimize suffering, reduce health care cost and most importantly mortality. Also, there has been consistent reduction in mortality with covid despite lac of Randomized trials showing statistically significant benefit. Exceptions are Corticosteroids, Remdesivir (No mortality benefit so far)”

Convalescent plasma is not a new therapy, As much a century back, it was used for treating Diphtheria. As far as Covid infection is concerned, it is proven beyond doubt that presence of IgG antibodies gives protection in the form of reducing the rate of infection and also severity of disease (Trial with Moderna and Pfizer vaccine). The safety of convalescent plasma therapy is well established by Mayo clinic study in which more than twenty thousand patients received plasma therapy without adverse effects. However, none of the studies provided evidence of benefit when plasma therapy was used in moderately severe disease.

We know that after Covid infection IgM antibodies form on 7th day and IgG antibodies start on 14th day and peak at 29th day. Therefore, in first week there are no antibodies to combat virus. In this study conducted in elderly (and susceptible population) early administration Convalescent plasma with high titre of antibodies showed significant (p <0.03) reduction in severity of disease. This indeed is encouraging in the ever evolving intricacies of Covid treatment.

Dr Khilani said, “I think that we should identify susceptible patient (Elderly >75 years without comorbidity) and those above 65 with Comorbidities (Hypertension, heart disease, obesity diabetics, chronic kidney disease, post organ transplant patients, COPD, immunosuppressed etc) ” and manage by following steps :

• Admit in hospital
• early investigations in the form of biomarkers (CBC, CRP, D dimer, Ferritin, LDH, IL6 ), done on alternate days
• Consider administering plasma therapy early (Preferably within 72 hours of onset of symptoms irrespective of severity)
• Do a HRCT on 5th day (or earlier if symptoms of cough and breathlessness are there) and administer Remdesivir if pneumonia is present (irrespective of oxygen levels and biomarkers)
• Corticosteroids for Covid are double edged Sword so should be administered in case of pneumonia with high level of biomarkers /reduction in oxygen saturation and NEVER without concomitant administration of antiviral drug.
• Of course supportive management with oxygen and optimum intensive care is most important.
• Consider Tociluzimab in case of most severe, life threatening disease.

There is a case of reducing number of severe cases by following this strategy which, would reduce the number of patients requiring ICU care and mortality. It is very difficult to statistically prove mortality benefit with a single strategy. Therefore, these studies help us to formulate management of this disease which has shattered our lives and many have lost their dear ones.

Author : Dr. G C Khilnani Chairman, PSRI Institute of Pulmonary, Critical care and Sleep Medicine, PSRI Hospital, New Delhi. Formerly, Professor and Head Dept of Pulmonary Critical care and Sleep Medicine, AIIMS, New Delhi-110029 gckhil@gmail.com 9810353696 NB: Please circulate to disseminate information