key: cord-0835702-rirftuu9
authors: Hammarström, Lennart; Abolhassani, Hassan; Baldanti, Fausto; Marcotte, Harold; Pan-Hammarström, Qiang
title: Development of passive immunity against SARS-CoV-2 for management of immunodeficient patients - a perspective
date: 2020-05-12
journal: J Allergy Clin Immunol
DOI: 10.1016/j.jaci.2020.04.043
sha: 775e23a4a1d481ba5575dc82814fa65ccd0e32d3
doc_id: 835702
cord_uid: rirftuu9

nan

potential prophylaxis and therapy in a naïve population, particularly in patients with primary 26 or secondary immunodeficiencies. The former mainly includes patients with defects in T cell-27 mediated immunity and, to a lesser extent, those with antibody deficiencies and immune 28 dysregulation. The latter includes patients undergoing therapy with immunosuppressive drugs, 29 such as stem cell transplanted patients. In addition, patients with B cell malignancies and 30 autoimmune disorders treated with selected forms of targeted therapy (such as anti-CD20) 31 may also develop secondary immunodeficiency characterized by hypogammaglobulinemia. 32

Although many drug candidates have been identified through in vitro viral neutralization 33 experiments or based on clinical observations, thus far, there are no specific therapeutic 34 agents to treat COVID-19. The anti-viral drug Remdesivir has shown some effects during 35 compassionate use in COVID-19 patients 1 , however, randomized, placebo-controlled clinical 36

trials have yet to prove its value. Another combination of anti-viral drugs (Lopinavir-37 Ritonavir) did not provide any benefit for hospitalized COVID-19 patients with severe disease 38 in a randomized, controlled, open-label trial 2 . The anti-malaria drug 39 chloroquine/hydroxychloroquine has also been reported to show positive clinical results. 40

However, recent studies showed no beneficial effects but rather a negative influence on 41 cardiac function, with an increased mortality in the high dose group 3 . 42

As immunodeficient individuals are unlikely to respond to active vaccination, there is an 44 urgent need for additional forms of therapy. Many of these patients are currently receiving 45 substitution with intravenously or subcutaneously administered gammaglobulin preparations. 46

However, as the available lots were manufactured before the appearance of severe acute 47 respiratory syndrome coronavirus 2 (SARS-CoV-2), they are unlikely to provide protection as 48 they do not contain any specific antibodies against this new virus. Low levels of cross-reactive antibodies may exist due to previous exposure to other types of coronavirus, but at 50 non-neutralizing titers. Thus, preparations enriched in specific antibodies against SARS-CoV-51 2 are needed for these patients. 52 53 Passive immunotherapy, using preformed antibodies, is a century-old treatment modality, 54 which is still used today for selected infections using polyclonal antibodies, preferably as a 55 hyperimmune preparation from convalescent donors. In order to identify individuals, who 56 have recovered from COVID-19, novel tests are currently entering the market and used for 57

analyzing the presence of antibodies against the virus. These antibodies are initially of the 58 Immunoglobulin M (IgM) class, followed by IgG (preferentially IgG3, a subclass usually 59 associated with viral infections) and IgA 4 . The target antigen chosen for serological assays is 60 most often the spike protein or subunits thereof (S1). The RBD (Receptor Binding Domain), 61 which confers binding to the angiotensin-converting enzyme 2, may be of particular interest 62 in this context. Yet, even antibodies that interfere with the fusion process (and which will not 63 directly interfere with binding) may also be of therapeutic interest and should therefore be 64 investigated. To date, no systematic study has been made to address which antigen would be 65 optimal for screening of convalescent donors for therapeutic antibodies. concerns such as antibody-dependent enhancement. The highly effective monoclonal 118 antibodies, however, usually take a longer time to develop, as substantial testing in 119 appropriate animal models is required before being used clinically. 120 121 In summary, passive immunotherapy is a promising tool for management of immunodeficient 122 patients during the COVID-19 pandemic. Before a specific anti-viral therapy or an effective 123 vaccine is available, polyclonal and monoclonal antibodies may also provide protection for 6 the high-risk group of individuals such as elderly persons and healthcare workers as well as a 125 therapy for severely ill COVID-19 patients. Different approaches of passive immunotherapy 126 have their own risk and benefit issues that need to be considered ( Table 2) and their safety  127 and efficacy beyond standard care should be tested in controlled, randomized clinical trials. 128

Use of Remdesivir for Patients with Severe Covid-19

Adults Hospitalized with Severe Covid-19

Effect 137 of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for 138

Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 139 (SARS-CoV-2) Infection: A Randomized Clinical Trial

A 142 serological assay to detect SARS-CoV-2 seroconversion in humans

Use of convalescent 145 plasma therapy in SARS patients in Hong Kong

The potential danger of suboptimal antibody responses in 148 COVID-19

Potent binding of 2019 novel 150 coronavirus spike protein by a SARS coronavirus-specific human monoclonal

Patients With COVID-19 With Convalescent Plasma. JAMA 2020

Treatment with 156 convalescent plasma for critically ill patients with SARS-CoV-2 infection

Effectiveness of convalescent 159 plasma therapy in severe COVID-19 patients