key: cord-1042121-vyue7kc0
authors: Zhao, Qian; He, Yong
title: Challenges of Convalescent Plasma Therapy on COVID-19
date: 2020-04-10
journal: J Clin Virol
DOI: 10.1016/j.jcv.2020.104358
sha: 904944c276ca288c35aea9bb3dcf333701514d27
doc_id: 1042121
cord_uid: vyue7kc0

nan

To the Editor, There are only a few available antiviral treatments, which have limited efficacy on COVID-19 at present. The latest Chinese guideline emphasized that convalescent plasma(CP) therapy was an emergent treatment for serious COVID-19 cases [1] .

Generally, CP has been applied to improve the survival rate of patients with a variety of viral epidemics, including SARS, MERS, influenza, Ebola virus disease, etc [2] . More recently, COVID-19 cases have also shown improvement to a certain degree after CP therapy in China [3] . In order to take full advantage of this promising treatment, there are still several critical problems need to be clarified.

Studies have shown that viremia, such as SARS, usually peaks in the first week of infection [4] . In the second week after symptom onset, patients usually develop an immune response which is more likely to cause cytokine storm that could be lethal [4, 5] .

Although there is one study which has indicated that CP therapy could reduce serum cytokine response with uncertain implementing time [6] , CP infusion still has its latent risk such as aggravating hyperimmune attacks, based on the foundation that CP therapy is passive immunity with administering pathogen-specific antibodies to patients [2] . This implies that CP therapy is more effective in earlier stage of disease and researches on SARS have confirmed it [4, 7] . Therefore, the optimal timing of administering CP on COVID-19 needs to be carefully considered.

In fact, the therapeutic effect of CP on COVID-19 is determined by the level of SARS-CoV-2 neutralizing antibody titer (NAT). A research on SARS demonstrated that the specific IgG began to increase around week 3 after onset, and peaked at week 12 [8] .

Besides, another study on influenza suggested that CP with a NAT level of ≥1:160 reduced mortality [6] . Thus, CP from donors who have recovered and who are at week 12 after onset with a NAT level of not less than 1:160 is expected to be more effective.

Moreover, due to various limitations of acquiring CP such as age, weight, state of health, informed consent, the amount of CP required, the ratio of recovered patients to those who J o u r n a l P r e -p r o o f 4 need plasma causes the shortage of CP. As a result, the source of CP limits its wide application, especially in countries which are in the acceleration stage and late accumulation stage of COVID-19 development.

In addition, the most common adverse reaction of CP therapy are transfusion-related events, involving chills, fever, anaphylactic reactions, transfusion-related acute lung injury, circulatory overload and hemolysis, etc [9, 10] . Meanwhile, the risk of transfusion-transmitted infections, such as human immunodeficiency virus, hepatitis B virus, hepatitis C virus and syphilis, should not be neglected [11] . Hence, how to use CP therapy properly becomes an issue which we need pay attention to.

In conclusion, CP therapy as a potential treatment for COVID-19, there are still some challenges to be dealt with. But considering the absence of specific treatment, we recommend that CP therapy could be an alternative option in emergent situation of COVID-19.

Declarations of interest: none J o u r n a l P r e -p r o o f

Department of General Administration of National Health Commission, Prevention and control plan for COVID-19

Convalescent plasma: new evidence for an old therapeutic tool?

The Joint Prevention and Control Mechanism of the State Council, Introduce the situation of prevention and treatment of COVID-19

Use of convalescent plasma therapy in SARS patients in Hong Kong

Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study

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

Retrospective comparison of convalescent plasma with continuing high-dose methylprednisolone treatment in SARS patients

Profile of specific antibodies to the SARS-associated coronavirus

Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment

Risks and side effects of therapy with plasma and plasma fractions

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