Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults

Libster, Romina; Marc, Gonzalo Pérez; Wappner, Diego; Coviello, Silvina; Bianchi, Alejandra; Braem, Virginia; Esteban, Ignacio; Caballero, Mauricio T.; Wood, Cristian; Berrueta, Mabel; Rondan, Aníbal; Lescano, Gabriela; Cruz, Pablo Jordão Alcântara; Ritou, Yvonne; Viña, Valeria Fernández; Paggi, D; Esperante, Sebastián; Ferreti, Adrián; Ofman, Gastón; Ciganda, Álvaro; Rodriǵuez, Rocío Serrano; Lantos, Jorge; Valentini, Ricardo; Itcovici, Nicolás; Hintze, Alejandra; Oyarvide, M Laura; Etchegaray, Candela; Neira, Alejandra; Name, Ivonne; Alfonso, Julieta; Castelo, Rocío López; Caruso, Gisela; Rapelius, Sofía; Arenzana-Seisdedos, Fernando; Etchenique, Federico Cesar; Dimase, Federico; Alvarez, Dario Raul; Aranda, Sofia Sol; Yanotti, Clara Sánchez; Luca, Julián De; Baglivo, Sofía Jares; Laudanno, Sofia Lujan; Nowogrodzki, Florencia; Larrea, Ramiro Manuel; Silveyra, María Dolores; Leberzstein, Gabriel; Debonis, Alejandra; Molinos, Juan; Gonzalez, Marco A.; Pérez, Eduardo García; Kreplak, Nicolás; Argüello, Susana Pastor; Gibbons, Luz; Althabe, Fernando; Bergel, Eduardo; Polack, Fernando P.

doi:10.1056/nejmoa2033700

Cited by 809 publications

(1,032 citation statements)

References 16 publications

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“…As such, the current paucity of supportive evidence for CP make it less widely utilized (141). Distinctively, there may be differences amongst patients' subgroups and at what stage initiation of therapy is most beneficial as reflected in the positive data with CP from an RCT of 160 elderly patients with early symptomatic disease, suggesting that the benefits of CP in term of reducing disease progression are linked to waning of the immune response with age (142).…”

Section: Humoral Immunitymentioning

confidence: 99%

A Comprehensive Review of Viral Characteristics, Transmission, Pathophysiology, Immune Response, and Management of SARS-CoV-2 and COVID-19 as a Basis for Controlling the Pandemic

et al. 2021

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COVID-19 emerged from China in December 2019 and during 2020 spread to every continent including Antarctica. The coronavirus, SARS-CoV-2, has been identified as the causative pathogen, and its spread has stretched the capacities of healthcare systems and negatively affected the global economy. This review provides an update on the virus, including the genome, the risks associated with the emergence of variants, mode of transmission, immune response, COVID-19 in children and the elderly, and advances made to contain, prevent and manage the disease. Although our knowledge of the mechanics of virus transmission and the immune response has been substantially demystified, concerns over reinfection, susceptibility of the elderly and whether asymptomatic children promote transmission remain unanswered. There are also uncertainties about the pathophysiology of COVID-19 and why there are variations in clinical presentations and why some patients suffer from long lasting symptoms—“the long haulers.” To date, there are no significantly effective curative drugs for COVID-19, especially after failure of hydroxychloroquine trials to produce positive results. The RNA polymerase inhibitor, remdesivir, facilitates recovery of severely infected cases but, unlike the anti-inflammatory drug, dexamethasone, does not reduce mortality. However, vaccine development witnessed substantial progress with several being approved in countries around the globe.

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Section: Humoral Immunitymentioning

confidence: 99%

A Comprehensive Review of Viral Characteristics, Transmission, Pathophysiology, Immune Response, and Management of SARS-CoV-2 and COVID-19 as a Basis for Controlling the Pandemic

et al. 2021

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“…Another example of the necessity of the temporal principle is that antibody therapy against rabies is effective only when it is administered shortly after infection. This principle has also been reinforced in studies showing that administration of either mAbs or convalescent plasma to newly symptomatic COVID-19 in the outpatient setting can reduce disease progression (19,20). Notably, COVID-19 is a biphasic disease in which an initial phase of viral replication may progress to a life-threatening inflammatory phase with lung damage; while the former phase is likely to respond to antibody therapy, the latter is more likely to respond to anti-inflammatory agents (21).…”

mentioning

confidence: 97%

“…Adding to the complexity of dosing are the pharmacokinetics of immunoglobulins, which vary as a function of isotype and antigen load. Nonetheless, effective doses of mAbs (20) and convalescent plasma (CP) (19,30,31) for COVID-19 have been arrived at based on clinical experience and the fundamental principles of immunoglobulin pharmacokinetics.…”

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confidence: 99%

“…A randomized trial of convalescent plasma compared to standard of care in hospitalized patients with COVID-19 showed that it was associated with earlier recovery in patients with severe, but not life-threatening, disease (65). Two randomized controlled trials from Argentina provide strong support for the requirement of early therapy since one found a large beneficial effect when treatment was given within 3 days of symptoms in outpatients (19), while another found no effect in severe disease in hospitalized patients (6). The findings of several case-control and open label studies associate convalescent plasma therapy with reduced mortality in hospitalized patients, especially when given earlier in the course of illness and before mechanical ventilation (45,47,65).…”

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confidence: 99%

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The Principles of Antibody Therapy for Infectious Diseases with Relevance for COVID-19

Casadevall

Pirofski

Joyner

2021

mBio

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Antibody therapies such as convalescent plasma and monoclonal antibodies have emerged as major potential therapeutics for coronavirus disease 2019 (COVID-19). Immunoglobulins differ from conventional antimicrobial agents in that they mediate direct and indirect antimicrobial effects that work in concert with other components of the immune system. The field of infectious diseases pioneered antibody therapies in the first half of the 20th century but largely abandoned them with the arrival of conventional antimicrobial therapy. Consequently, much of the knowledge gained from the historical development and use of immunoglobulins such as serum and convalescent antibody therapies was forgotten; principles and practice governing their use were not taught to new generations of medical practitioners, and further development of this modality stalled. This became apparent during the COVID-19 pandemic in the spring of 2020 when convalescent plasma was initially deployed as salvage therapy in patients with severe disease. In retrospect, this was a stage of disease when it was less likely to be effective. Lessons of the past tell us that antibody therapy is most likely to be effective when used early in respiratory diseases. This article puts forth three principles of antibody therapy, namely, specificity, temporal, and quantitative principles, connoting that antibody efficacy requires the administration of specific antibody, given early in course of disease in sufficient amount. These principles are traced to the history of serum therapy for infectious diseases. The application of the specificity, temporal, and quantitative principles to COVID-19 is discussed in the context of current use of antibody therapy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

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“…Recent trials involving convalescent plasma in the treatment of COVID-19 have had variable results. These variable results have led the IDSA to only recommend the use of convalescent plasma in the context of a clinical trial [34][35][36][37]. As an investigational agent, this approach should be used with caution as the safety of convalescent plasma therapy has not been fully studied, and its use may be associated with risks that could worsen the disease [38].…”

Section: Proposed Conventional Treatment Strategies For Covid-19mentioning

confidence: 99%

Adjunctive Nutraceutical Therapies for COVID-19

Subedi

Tchen

Gaire

et al. 2021

IJMS

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The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19), is a worldwide pandemic, as declared by the World Health Organization (WHO). It is a respiratory virus that infects people of all ages. Although it may present with mild to no symptoms in most patients, those who are older, immunocompromised, or with multiple comorbidities may present with severe and life-threatening infections. Throughout history, nutraceuticals, such as a variety of phytochemicals from medicinal plants and dietary supplements, have been used as adjunct therapies for many disease conditions, including viral infections. Appropriate use of these adjunct therapies with antiviral proprieties may be beneficial in the treatment and/or prophylaxis of COVID-19. In this review, we provide a comprehensive summary of nutraceuticals, such as vitamins C, D, E, zinc, melatonin, and other phytochemicals and function foods. These nutraceuticals may have potential therapeutic efficacies in fighting the threat of the SARS-CoV-2/COVID-19 pandemic.

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Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults

Cited by 809 publications

References 16 publications

A Comprehensive Review of Viral Characteristics, Transmission, Pathophysiology, Immune Response, and Management of SARS-CoV-2 and COVID-19 as a Basis for Controlling the Pandemic

A Comprehensive Review of Viral Characteristics, Transmission, Pathophysiology, Immune Response, and Management of SARS-CoV-2 and COVID-19 as a Basis for Controlling the Pandemic

The Principles of Antibody Therapy for Infectious Diseases with Relevance for COVID-19

Adjunctive Nutraceutical Therapies for COVID-19

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