Convalescent Plasma Therapy for Critically ill Covid-19 Patients

INTRODUCTION: Recent emergence of coronavirus disease 2019 ( COVID-19 ) PANDEMIC has reassessed usefulness of historic convalescent plasma therapy ( CPT ).

On March 11, 2020, WHO declared COVID-19 as PANDEMIC. The current treatment of COVID-19 caused by novel coronavirus SARS COV-2, Is limited to supportive care with critical care as NO APPROVED therapies or vaccines are available. Data from studies of COVID-19 is still scarce and limited to data from China, Spain, the United States of America, Germany, France. This will be a problem when predicting treatment outcomes. This COVID-19 PANDEMIC has demonstrated the fragility of our health systems in tackling emergency situations related to spreading of NEW infectious agents that require rapid development of care strategies.

What is Plasma?

Plasma is the protein-rich fluid part of your blood, it helps protect your body against illness and infections and controls excessive bleeding. Donated plasma is used for medical treatment it can help with bleeding disorders, weakened immune system and much more. Plasma is collected either by whole blood donation or plasma donation. Osmolality is the number of osmoles per kg of solvent. It does not change with temperature, so it is most commonly used.

The osmolality of plasma is mainly contributed by Na+, Glucose, Urea, Proteins, K+. There are 3 major plasma proteins: Albumin, Globulin, Fibrinogen. Most are synthesized in the Liver, but antibodies (Ab) are synthesized from lymphocytes. Plasma proteins contribute only 2 mosmol per litre to Plasma, because of high concentration and low molecular weight. Most abundant plasma protein is Albumin. Fibrinogen contributes to the viscosity of blood. Acute phase reactants are a class of proteins whose plasma concentration increase in response to inflammation or tissue damage. Eg: C-Reactive protein (CRP).

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How Convalescent Plasma Therapy Works for Coronavirus?

Convalescent means recovering from any kind of disease. Plasma is part of blood responsible maintaining PH of blood and it contains proteins and among proteins mainly Antibodies (Abs). Ab is produced against Antigen (Ag). Ag is part of the virus/bacteria/protozoa body, also known as PATHOGENS. A healthy person is capable of developing Abs in 10-14 days after infection, 2 types of Abs generated IgG and IgM. IgM is produced 1st, that is specific for nCOV. By day 21 PATHOGEN is completely removed from the body , but there is increased concentration of IgG mainly and also IgM. So, if this pathogen again infects healthy person body is cured in 2-3 days easily.

These Abs produced naturally in a NOW healthy person, completely cured of SARS COV-2, is donated to the critically infected patient of SARS COV-2. The IgG, IgM Abs are isolated from donor plasma and received by the recipient to fight against SARS COV-2, this recipient can recover faster as he/she is now receiving preformed Abs from the donor. Unfortunately, we need more Recovered healthy patients to be Donors to save the life of Critically ill COVID patients but all of the recovered patients are NOT willing to Donate their plasma. If we can find out the sequence of Abs and if we can produce same Abs by Monoclonal Ab production or Hybridoma technology, then we can have sufficient amount of Abs to SAVE LIVES of Critically ill COVID patients.

Benefits of Plasma Therapy :

Convalescent plasma therapy (CPT) has been used since the early 1900s to treat emerging infectious diseases. Recent large outbreaks of viral diseases for which Antivirals or Vaccines are still lacking have RENEWED interest in CPT as life-saving treatment. Benefits :

1. Polyclonal Abs in CPT can benefit patient with humoral immune deficiencies, and
2. Benefit patients with hemorrhagic Diathesis by clotting factors.
3. It is likely to contain Abs against other common betacoronavirus associated with a common cold which has shown cross-reaction with SARS COV-2 Ags in IVIG (Intravenous Immunoglobulin) preparations.
4. IVIG has led to a recovery in Chinese patients with severe Critically ill COVID patient.
5. Blood group O is less likely to become infected with SARS COV-2.
6. 1 dose of 200 ml CP transfusion significantly improves COVID-19 Patients with Increase in Oxyhemoglobin saturation within 3 days, by Rapid neutralization of viremia.
7. All symptoms especially fever, cough, shortness of breath, chest pain disappeared / largely improved within 1-3 days upon CP transfusion.
8. After CP treatment patients were weaned from mechanical ventilation.

So, CPT might be a promising treatment option for COVID-19 RESCUE.

Risks of Convalescent Plasma Therapy?

The potential clinical benefit and risk of Convalescent blood products in COVID-19 remains UNCERTAIN.

1. One of risk of plasma transfusion is the transmission of the potential organism.
2. Transfusion-related Acute Lung Injury (TRALI) can be life-threatening in patients already suffering from Acute Lung Injury (ALI).
3. TRALI was reported in an Ebola virus disease woman who received CP therapy, that is although UNCOMMON, But this specific adverse effect is worth noting, especially among Critically ill patients experiencing a significant pulmonary injury.
4. Another Rare risk is Antibody-dependent infection enhancement occurring at sub-neutralizing concentrations, which could suppress the Innate growth of the virus.
5. A last COVID-19 specific concern is worsening of underlying coagulopathy from clotting factors in transfused plasma since it has not been reported till date, it remains a theoretical concern.

CONCLUSION :

The compelling need to control global health crisis by COVID-19 outbreak.

Currently, there are NO Reliable therapeutic options for CRITICALLY ill COVID-19 patients. CPT ( convalescent plasma therapy ) can be an effective therapeutic option with promising evidence on Safety, Improvement of clinical symptoms and Reduced mortality. A definitive conclusion can not be drawn on optimal doses and treatment time point for CPT to COVID-19, large Multi-center clinical trials are needed to tackle this PANDEMIC.

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