Friday, April 17, 2020


Dr K K Aggarwal
President Confederation of Medical Associations of Asia and Oceania, HCFI and Past National President IMA

India has started convalescent plasma therapy in COVID 19 patients. ILBS, Kerala, TN and many other centers have started it. Its time
1.      For a central website of the donors
2.      Indian Red Cross to become the nodal agency
3.      Expedite permissions to hospitals

634: What is Convalescent plasma 

In the United States, the Food and Drug Administration (FDA) is accepting investigational new drug applications for use of convalescent plasma for patients with severe or life-threatening COVID-19 pathways for use through these applications include clinical trials, expanded access programs, and emergency individual use.

635: Is there any study

One case series described administration of plasma from donors who had completely recovered from COVID-19 to five patients with severe COVID-19 on mechanical ventilation and persistently high viral titers despite investigational antiviral treatment.

The patients had decreased nasopharyngeal viral load, decreased disease severity score, and improved oxygenation by 12 days after transfusion. [Shen C, Wang Z, Zhao F, et al. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA 2020.]

636: Does these findings establish a causal effect.


637 : Will there by any logistic issues

Finding appropriate donors and establishing testing to confirm the neutralizing activity of plasma may be logistical challenges.

638: What is the solution addressed by the USA

In the United States, the American Red Cross is helping to collect and distribute convalescent plasma throughout the country

639: What is Convalescent plasma

It refers to plasma from an individual who has recovered from an infection. It is a means of antibody transfer to provide passive immunity (neutralizing antibodies against the infectious pathogen) until the individual can develop an active immune response, with the hope that clinical outcomes can be improved in the recipient.

640: When its use is allowed

Convalescent plasma is not routinely available, nor is it a licensed product; instead, it has been made available for specific agents at times of disease epidemics or pandemics. Once an epidemic has subsided, convalescent plasma is likely to become unavailable.

641: What are related products

Related products include convalescent serum (contains antibodies but not clotting factors) and hyperimmune globulin (a manufactured concentrated product containing a high titer of antibodies).

Monoclonal antibodies with neutralizing potential are another approach, although this requires additional development and manufacturing steps.

642: What are the Indications

Convalescent plasma (or hyperimmune globulin) could in principle be used to improve the clinical course of disease in affected individuals or to reduce the risk of developing disease (eg, postexposure prophylaxis).

643: Can it be risky

The risk of transfusion reactions or disease worsening must be considered in the risk-benefit analysis.

644: Is there any evidence

Prior to SARS-CoV-2 – A 2015 systematic review and meta-analysis of the use of convalescent plasma for treating severe acute respiratory syndromes summarized results from clinical studies as follows (this analysis preceded the emergence of the 2019 novel coronavirus [SARS-CoV-2])

645: Is there any evidence in SARS

SARS-CoV (2003 SARS epidemic) – There was reduced mortality (on the order of 7 to 23 percent lower mortality). There was a reduced hospital length of stay, especially when convalescent plasma was administered within two weeks of symptom onset. No major complications were reported.

646: Is there any evidence in MERS

MERS-CoV (2012 outbreak) – No clinical studies were identified, although animal models suggested there might be a benefit.

647: Is there any evidence in Influenza viruses

H1N1-pdm09 (2009 pandemic) – One study reported an 80 percent reduction in mortality, especially with early treatment. There was a reduced length of intensive care unit (ICU) stay. No major complications were reported.

H5N1 (avian influenza; several outbreaks) – Nonsignificant benefits (one study).

H1N1 (1918-1919 flu epidemic) – There was reduced mortality (approximately 20 percent reduction) according to another meta-analysis. These studies used convalescent blood rather than plasma; chills, fever, and sweats were reported following the infusions.

647: Is the evidence strong

The reviewed studies were generally considered of low quality due to high risk of bias and lack of control groups. The observed lower mortality with convalescent plasma could reflect selection bias (therapy only given to patients who were well enough to be treated) or publication bias (only positive studies reported).

648: Is it effective in  Ebola

A separate study found no evidence of benefit in Ebola virus disease, although some case reports described good outcomes.

649: When it is most useful

Thus, convalescent plasma is generally most appropriate for individuals who are severely ill and do not have access to better alternatives.

650: Criteria for optimal preparation of plasma (or hyperimmune globulin) include

High enough titer of neutralizing antibody to be effective

Lack of infectious particles (either the target pathogen or others)

Blood type compatible (ABO; Rh in women of reproductive potential)

Evidence for efficacy and lack of harm, ideally from randomized trials or prospective studies

Informed consent with discussion of the risk of disease and risks and benefits of therapy

The FDA has released guidance to assist with obtaining convalescent plasma during the SARS-CoV-2 coronavirus pandemic of 2019-2020 for individuals who do not have access to a clinical trial.

651: How much plasma can be donated

400 ml (for two to three patients)

652: After how many days plasma can be donated

2 weeks

653: What is the Mayo clinic protocol

Only hospitalized COVID-19 patients who meet certain criteria and who are referred by their health care provider will participate in this protocol. Mayo Clinic is serving as the lead institution for the protocol, working collaboratively with industry, academic, and government partners

654: How many people have donated plasm in USA

Thousands of COVID-19 survivors in the US are lining up to donate convalescent plasma to leading universities, which are pushing forward with clinical trials in the race for solutions against the coronavirus pandemic until there's a vaccine to go around.

655: How often can one donate

A single COVID-19 survivor could provide enough plasma in one sitting to treat two or three other patients. If they donate every seven days, as some in New York have begun doing, one person could donate 10 to 12 units of plasma in a month.

656: When should we administer plasma

Viraemia peaks in the first week of infection in most viral illnesses.

The patient usually develops a primary immune response by days 10–14, which is followed by virus clearance.

Therefore, theoretically, it should be more effective to administer the convalescent plasma at the early stage of the disease.

However, other treatments might have an effect on the relationship between convalescent plasma and antibody level, including antiviral drugs, steroids, and intravenous immunoglobulin.

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