key: cord-0705850-p73gwrl2
authors: Franchini, Massimo
title: Why should we use convalescent plasma for COVID-19?
date: 2020-05-16
journal: Eur J Intern Med
DOI: 10.1016/j.ejim.2020.05.019
sha: 4e5eae720ebcfc865316e12548ec82b34f3157c8
doc_id: 705850
cord_uid: p73gwrl2

nan

Coronavirus, an enveloped virus belonging to the family of Coronaviridae which initially caused enzootic infections, has shown in the last decades to be capable of crossing the species barrier causing severe epidemics in humans. A novel flu-like coronavirus, emerging towards the end of 2019 and subsequently named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2 , the virus that causes Coronavirus Disease 2019 ) has been associated with an epidemic initially focused in Wuhan, China [1] . From there, SARS-CoV-2 has spread quickly throughout China, infecting many thousands of people and causing more than 4,500 deaths [2] . However, in a globalize world, it immediately became well clear that this fearsome infection could not be confined to China only, but soon it spread to neighboring Asian countries and immediately after to more than 201 countries around the world, where more than 3,200,000 individuals have contracted SARS-CoV-2 and more than 230,000 of them have deceased (data updated on May 3, 2020) [2]. On march 11, WHO declared the rapidly spreading coronavirus outbreak a pandemic and Italy is currently the country with the highest number of cases of SARS-CoV-2 infection after USA and this has generated an unprecedented health and social emergency. Unfortunately, no standardized therapy does exist for COVID-19 and a number drugs for the use in patients with life-threatening COVID-19 are currently being investigated in a number of non-randomized or randomized trials. These agents includes steroids, chloroquine, antiviral and anti-inflammatory agents [3] . In addition, experiences from previous coronavirus epidemics indicate that convalescent plasma collected from recovered COVID-19 patients, containing antibodies specific against SARS-CoV-2 that can be delivered from donors to patients, could be a potentially effective therapeutic weapon [4] . [6] . In the pooled analysis of the data, the review revealed the evidence for a consistent reduction in mortality in the group treated with plasma therapy compared with that receiving placebo or no therapy (odds ratio, 0.25; 95% CI:0.14-0.45 with a low degree of heterogeneity: I 2 = 0%) [6] . Only few reports have been plasma ranging from day 11 to day 18 of admission [9] . All the patients (including a pregnant woman) recovered from the SARS-CoV-2 infection. Finally, Zeng and colleagues tested the role of convalescent plasma in 6 critically end-stage COVID-19 patients [10] . Although the blood component, which was transfused at a median of 21.5 days after first detection of viral shedding, led to the discontinuation of the SARS-CoV-2 shedding by 3 days after infusion, it was not able to improve the survival in these patients with advanced disease (5/6 and 14/15 deaths in the convalescent plasma group and control group, respectively). Based on the results of this trial, the authors concluded the convalescent plasma should be used in an early phase of the disease to obtain the best effect [10] . University of Pavia, has given a contribute to this research. Indeed, considering the dramatic situation and the high lethality rate of COVID-19 in Italy, we have planned an interventional singlearm trial (NCT04321421) to produce hyperimmune plasma for treating critical patients with COVID-19. The results of these numerous trials are greatly awaited as they will permit to respond to the many still unanswered issues regarding convalescent plasma, including donors' selection (i.e., age, gender, diagnosis of SARS-Cov-2 infection and of recovery, anti-SARS-CoV-2 antibody titer required for plasma donation), plasma collection and biologic qualification (number, volume and frequency of donations, infectious disease markers and pathogen inactivation) and treatment and disease characteristics (i.e., dose and timing of convalescent plasma infused and stage of the disease at which to start convalescent plasma treatment).

There is currently great interest towards the use of passive immunotherapy by means of transfusion of convalescent plasma from recovered COVID-19 patients documented the high number of ongoing trials and of reviews/perspectives/commentaries published every day. The results of such trials will help us to elucidate the still unanswered issues related listed above and related to convalescent plasma collection, biologic validation and treatment modalities. Meanwhile, the data arising from previous coronaviruses epidemics and from COVID-19 case series, although limited, strongly encourage clinicians and investigators to treat COVID-19 patients, particularly at an early stage of the disease, also with convalescent plasma in the frame of registered protocols.

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COVID-19) epidemics, the newest and biggest global health threats: what lessons have we learned?

World Health Organization. Coronavirus disease (COVID-19) outbreak

The epidemiology, diagnosis and treatment of COVID-19

Convalescent plasma as a potential therapy for COVID-19

Pivotal role of convalescent plasma in managing emerging infectious diseases

Convalescent Plasma Study Group. 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

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

Effectiveness of convalescent plasma therapy in severe COVID-19 patients

Treatment With Convalescent Plasma for Critically Ill Patients With SARS-CoV-2 Infection

Effect of Convalescent Plasma Therapy on Viral Shedding and Survival in COVID-19 Patients