key: cord-323656-bzefn894
authors: Yoo, Jin-Hong
title: Convalescent Plasma Therapy for Corona Virus Disease 2019: a Long Way to Go but Worth Trying
date: 2020-04-06
journal: J Korean Med Sci
DOI: 10.3346/jkms.2020.35.e150
sha: 
doc_id: 323656
cord_uid: bzefn894

nan

dosage and administration protocols have not been standardized yet. In both cases, plasma was administered when antiviral drugs and steroids were given. It is hard to tell that the successful treatment is not necessarily due to plasma, and it cannot be refuted even if it is interpreted as an effect of antiviral agent or steroid. Or it is possible that these three elements were combined to create a synergistic effect.

But I'm going to change the way of interpretation. Given the mechanism of convalescent plasma therapy, I think this combination is rather worth being recommended.

The targets of COVID-19 treatment should be largely divided into two categories. First, it is aimed at the virus itself. The first thing you can think of is destroying the body of the virus. However, destroying the virus itself is a concept of disinfection and is too dangerous for humans to apply. As a therapeutic agent, there are drugs that inhibit RNA-dependent RNA polymerase by inhibiting the replication of viruses (e.g., remdesivir), or drugs that inhibit protease (e.g., lopinavir/ritonavir). 1,13 Another target is angiotensin converting enzyme 2 (ACE2), a gatekeeper and receptor for viruses to enter human cells. By raising the intracellular pH, glycosylation of ACE2 can be prevented to block the entry of the virus (e.g., chloroquine), 13,14 or it can be prevented from binding to ACE2 in advance by sticking to the spike protein of the virus. 15, 16 The latter, not the former, is the antibody.

Considering the above treatment mechanisms, it can be seen that it is difficult to succeed with only one mechanism to treat COVID-19. Blocking a virus with antibodies is not enough to win the battle. We must also suppress the replication of the virus, and prepare for a cytokine storm that occurs during treatment. 17 In conclusion, it makes no sense as to which of these treatment methods was a decisive factor in the successful treatment. Rather, it is necessary to combine all of these to engage in treatment.

We need to examine another important problem in plasma treatment.

Plasma therapy itself has important complications. Examples are transfusion-related acute lung injury (TRALI), circulatory overload, or anaphylaxis. 18 Fortunately, no adverse events have been reported. Nevertheless, these complications should always be a concern.

There is also the possibility of side effects that have been raised recently. It is the antibodydependent enhancement of entry (ADE). Neutralizing antibodies, once bound to the spike protein of the virus, cause a conformational change of the spike and, consequently, could trigger the paradoxical result of better entry into human cells through the IgFc receptor. 19 -21 This side effect has not yet been realized, but should be kept in mind in the future of plasma treatment and vaccine development.

Convalescent plasma therapy gives us a lot of hope, but there are challenges to overcome. In the implementation, thorough ethical verification is required, and donor selection criteria should be strictly enforced. And it needs further extensive research to see if it really works. To this end, I think that institutional support is required to approve every attempt as quickly as possible.

Again, it is time to focus all of our capabilities on treatment.

Drug treatment options for the 2019-new coronavirus (2019-nCoV)

Convalescent plasma: new evidence for an old therapeutic tool?

Convalescent plasma as a potential therapy for COVID-19

Use of convalescent plasma therapy in two COVID-19 patients with ARDS in Korea

Treatment of 5 critically ill patients with COVID-19 with convalescent plasma

The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis

Use of convalescent plasma therapy in SARS patients in Hong Kong

Experience of using convalescent plasma for severe acute respiratory syndrome among healthcare workers in a Taiwan hospital

Treatment with convalescent plasma for influenza A (H5N1) infection

Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection

Use of convalescent whole blood or plasma collected from patients recovered from Ebola virus disease for transfusion, as an empirical treatment during outbreaks

Viral load kinetics of SARS-CoV-2 infection in first two patients in Korea

Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro

Chloroquine is a potent inhibitor of SARS coronavirus infection and spread

Perspectives on monoclonal antibody therapy as potential therapeutic intervention for Coronavirus disease-19 (COVID-19)

Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody

Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology

Adverse effects of plasma transfusion

Molecular mechanism for antibody-dependent enhancement of coronavirus entry

Anti-severe acute respiratory syndrome coronavirus spike antibodies trigger infection of human immune cells via a pH-and cysteine proteaseindependent FcγR pathway

Antibody-dependent SARS coronavirus infection is mediated by antibodies against spike proteins


