Neutralizing-Antibody-Based Treatments for COVID-19: Achievements and Lessons Learnt for Future Pandemics

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Epidemiology".

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 18817

Special Issue Editor

Special Issue Information

Dear Colleagues,

The ongoing COVID-19 pandemic has caused more than 2 million deaths worldwide, which are still counting. Small-chemical antivirals and immunosuppressive treatments are not always efficacious, but passive and active immunotherapies based on neutralizing antibodies show potential. Convalescent COVID-19 plasma is a pioneer in the field, with monoclonal antibodies now entering the market and hyperimmune serum on the horizon. The vaccines approved to date are based on the induction of anti-Spike antibodies. The emergence of Spike variants is affecting the entire field, so challenges will remain for the coming months. In this Special Issue, we will summarize the achievements to date for all treatments based on neutralizing antibodies against COVID-19, and lessons that could prevent errors in future pandemics.

Dr. Daniele Focosi
Guest Editor

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Keywords

  • COVID-19
  • SARS-CoV-2
  • convalescent plasma
  • COVID-19 convalescent plasma (CCP)
  • hyperimmune serum
  • polyclonal immunoglobulins

Published Papers (5 papers)

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Research

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22 pages, 1851 KiB  
Article
Use of Quantitative Dried Blood Spots to Evaluate the Post-Vaccination Level of Neutralizing Antibodies against SARS-CoV-2
by Alexandre Marchand, Ingrid Roulland, Florian Semence, Olof Beck and Magnus Ericsson
Life 2021, 11(11), 1125; https://doi.org/10.3390/life11111125 - 22 Oct 2021
Cited by 7 | Viewed by 2848
Abstract
To combat the COVID-19 pandemic, vaccines against SARS-CoV-2 are now given to protect populations worldwide. The level of neutralizing antibodies following the vaccination will evolve with time and vary between individuals. Immunoassays quantifying immunoglobulins against the viral spike (S) protein in serum/plasma have [...] Read more.
To combat the COVID-19 pandemic, vaccines against SARS-CoV-2 are now given to protect populations worldwide. The level of neutralizing antibodies following the vaccination will evolve with time and vary between individuals. Immunoassays quantifying immunoglobulins against the viral spike (S) protein in serum/plasma have been developed, but the need for venous blood samples could limit the frequency and scale of control in populations. The use of a quantitative dried blood spot (DBS) that can be self-collected would simplify this monitoring. The objective of this study was to determine whether a quantitative DBS device (Capitainer qDBS 10 µL) could be used in combination with an Elecsys anti-SARS-CoV-2 S immunoassay from Roche to follow the development and persistence of anti-S antibodies. This objective was carried out through two clinical studies. The first study investigated 14 volunteers who received two doses of the Comirnaty (Pfizer) vaccine. The levels of anti-S antibodies and the progression over time post-vaccination were studied for three months. The level of produced antibodies varied between subjects, but a similar trend was observed. The anti-S antibodies were highly stimulated by the second dose (×100) and peaked two weeks later. The antibody levels subsequently decreased and three months later were down to 65%. DBS proved to be sufficiently sensitive for use in evaluating the immune status against SARS-CoV-2 over a prolonged time. The second cohort was composed of 200 random patients from a clinical chemistry department in Stockholm. In this cohort, we had no information on previous COVID-19 infections or vaccination. Nevertheless, 87% of the subjects had anti-S immunoglobulins over 0.8 U/mL, and the bias between plasma and DBS proved to be variable, as was also seen in the first vaccination study. Full article
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9 pages, 500 KiB  
Article
Previous Humoral Immunity to the Endemic Seasonal Alphacoronaviruses NL63 and 229E Is Associated with Worse Clinical Outcome in COVID-19 and Suggests Original Antigenic Sin
by Daniele Focosi, Angelo Genoni, Ersilia Lucenteforte, Silvia Tillati, Antonio Tamborini, Pietro Giorgio Spezia, Lorenzo Azzi, Andreina Baj and Fabrizio Maggi
Life 2021, 11(4), 298; https://doi.org/10.3390/life11040298 - 01 Apr 2021
Cited by 22 | Viewed by 4888
Abstract
Antibody-dependent enhancement (ADE) of severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) infection has been hypothesized. However, to date, there has been no in vitro or in vivo evidence supporting this. Cross-reactivity exists between SARS CoV-2 and other Coronaviridae for both cellular and humoral [...] Read more.
Antibody-dependent enhancement (ADE) of severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) infection has been hypothesized. However, to date, there has been no in vitro or in vivo evidence supporting this. Cross-reactivity exists between SARS CoV-2 and other Coronaviridae for both cellular and humoral immunity. We show here that IgG against nucleocapsid protein of alphacoronavirus NL63 and 229E correlate with the World Health Organization’s (WHO) clinical severity score ≥ 5 (incidence rate ratios was 1.87 and 1.80, respectively, and 1.94 for the combination). These laboratory findings suggest possible ADE of SARS CoV-2 infection by previous alphacoronavirus immunity. Full article
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10 pages, 489 KiB  
Article
Effects and Safety of Convalescent Plasma Administration in a Group of Polish Pediatric Patients with COVID-19: A Case Series
by Paweł Małecki, Kamil Faltin, Anna Mania, Katarzyna Mazur-Melewska, Agnieszka Cwalińska, Anna Zawadzka, Alicja Bukowska, Katarzyna Lisowska, Katarzyna Graniczna and Magdalena Figlerowicz
Life 2021, 11(3), 247; https://doi.org/10.3390/life11030247 - 17 Mar 2021
Cited by 7 | Viewed by 2328
Abstract
Despite the enormous advances in knowledge about the SARS-CoV-2 infection, the optimal treatment for COVID-19 is still not well defined. The use of convalescent plasma seems to be a promising method of treatment but requires further evaluation. Although it is usually mild, in [...] Read more.
Despite the enormous advances in knowledge about the SARS-CoV-2 infection, the optimal treatment for COVID-19 is still not well defined. The use of convalescent plasma seems to be a promising method of treatment but requires further evaluation. Although it is usually mild, in children with underlying chronic diseases, the course of SARS-CoV-2 infection may be very severe. We described a series of 13 pediatric patients (mean age 10.4 years, median 12) treated with convalescent plasma as a method of COVID-19 therapy. Medical history, with particular emphasis on comorbidities, clinical course, laboratory parameters, supportive treatment and virus elimination time, were analyzed. The mean hospitalization time was 22.6 days (median 20). The most common abnormalities included increased levels of C-reactive protein, D-dimer, and lymphopenia. Median time from symptom onset to convalescent plasma transfusion was 10.6 days (median 7 days). Six patients (46.2%) had a viral clearance on RT-PCR method from a nasopharyngeal swab within 3 days of transfusion, while in the remaining patients the mean elimination time was 12.1 days (median 6 days). Clinical improvement was achieved in all patients; no adverse effects were found in any of the cases. Convalescent plasma may be a promising treatment for COVID-19 in children. Full article
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Review

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32 pages, 2121 KiB  
Review
The Rise of SARS-CoV-2 Variants and the Role of Convalescent Plasma Therapy for Management of Infections
by Mohamed Moubarak, Keneth Iceland Kasozi, Helal F. Hetta, Hazem M. Shaheen, Abdur Rauf, Hayder M. Al-kuraishy, Safaa Qusti, Eida M. Alshammari, Emmanuel Tiyo Ayikobua, Fred Ssempijja, Adam Moyosore Afodun, Ritah Kenganzi, Ibe Michael Usman, Juma John Ochieng, Lawrence Obado Osuwat, Kevin Matama, Ali I. Al-Gareeb, Emmanuel Kairania, Monica Musenero, Susan Christina Welburn and Gaber El-Saber Batihaadd Show full author list remove Hide full author list
Life 2021, 11(8), 734; https://doi.org/10.3390/life11080734 - 23 Jul 2021
Cited by 38 | Viewed by 4691
Abstract
Novel therapies for the treatment of COVID-19 are continuing to emerge as the SARS-Cov-2 pandemic progresses. PCR remains the standard benchmark for initial diagnosis of COVID-19 infection, while advances in immunological profiling are guiding clinical treatment. The SARS-Cov-2 virus has undergone multiple mutations [...] Read more.
Novel therapies for the treatment of COVID-19 are continuing to emerge as the SARS-Cov-2 pandemic progresses. PCR remains the standard benchmark for initial diagnosis of COVID-19 infection, while advances in immunological profiling are guiding clinical treatment. The SARS-Cov-2 virus has undergone multiple mutations since its emergence in 2019, resulting in changes in virulence that have impacted on disease severity globally. The emergence of more virulent variants of SARS-Cov-2 remains challenging for effective disease control during this pandemic. Major variants identified to date include B.1.1.7, B.1.351; P.1; B.1.617.2; B.1.427; P.2; P.3; B.1.525; and C.37. Globally, large unvaccinated populations increase the risk of more and more variants arising. With successive waves of COVID-19 emerging, strategies that mitigate against community transmission need to be implemented, including increased vaccination coverage. For treatment, convalescent plasma therapy, successfully deployed during recent Ebola outbreaks and for H1N1 influenza, can increase survival rates and improve host responses to viral challenge. Convalescent plasma is rich with cytokines (IL-1β, IL-2, IL-6, IL-17, and IL-8), CCL2, and TNFα, neutralizing antibodies, and clotting factors essential for the management of SARS-CoV-2 infection. Clinical trials can inform and guide treatment policy, leading to mainstream adoption of convalescent therapy. This review examines the limited number of clinical trials published, to date that have deployed this therapy and explores clinical trials in progress for the treatment of COVID-19. Full article
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7 pages, 5284 KiB  
Review
The Three Pillars of COVID-19 Convalescent Plasma Therapy
by Massimo Franchini, Giancarlo Maria Liumbruno, Giorgio Piacentini, Claudia Glingani and Marco Zaffanello
Life 2021, 11(4), 354; https://doi.org/10.3390/life11040354 - 18 Apr 2021
Cited by 16 | Viewed by 2851
Abstract
The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread rapidly around the world in the last year causing the coronavirus disease 2019 (COVID-19), which still is a severe threat for public health. The therapeutic management of COVID-19 is challenging as, [...] Read more.
The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread rapidly around the world in the last year causing the coronavirus disease 2019 (COVID-19), which still is a severe threat for public health. The therapeutic management of COVID-19 is challenging as, up until now, no specific and efficient pharmacological therapy has been validated. Translating the experience from previous viral epidemics, passive immunotherapy by means of plasma from individuals recovered from COVID-19 has been intensively investigated since the beginning of the pandemic. In this narrative review, we critically analyze the three factors, named “pillars”, that play a key role in determining the clinical effectiveness of this biologic therapy: the convalescent plasma, the disease (COVID-19), and the patients. Full article
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