Current and emerging immunomodulators for treatment of SARS-CoV2 infection (COVID-19)

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ABSTRACT

Introduction

SARS-CoV-2, the virus that causes COVID-19, elicits a variety of host responses ranging from asymptomatic or mild illness in most people, to severe disease and critical illness in a subset of patients with systemic inflammation and hypoxemic respiratory failure.

Areas Covered

Heterogeneous clinical presentations are often driven by disparate responses of the host immune system, with severe disease associated with aberrant interferon signaling or cytokine storm syndrome. This manuscript examines current therapeutic approaches, including the use of immunomodulators such as corticosteroids, interleukin inhibitors, kinase inhibitors, fluvoxamine, and ivermectin, and also explores the ways that these therapies and others may be used to treat COVID-19 in the future.

Expert opinion

Modulation of the immune response has become a mainstay of treatment of COVID-19, although the optimal mechanism has not yet been defined and there is considerable controversy regarding clinical management. As time progresses, the therapeutic approach to COVID-19 will undoubtedly change, particularly as we learn more about the pathophysiology of SARS-CoV-2 infection.

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Most cited references 60

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A Novel Coronavirus from Patients with Pneumonia in China, 2019

Na Zhu, Dingyu Zhang, Wenling Wang … (2020)

Summary In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.)

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Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report

Mark Peters (2020)

Abstract Background Coronavirus disease 2019 (Covid-19) is associated with diffuse lung damage. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death. Methods In this controlled, open-label trial comparing a range of possible treatments in patients who were hospitalized with Covid-19, we randomly assigned patients to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care alone. The primary outcome was 28-day mortality. Here, we report the preliminary results of this comparison. Results A total of 2104 patients were assigned to receive dexamethasone and 4321 to receive usual care. Overall, 482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization (age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.001). The proportional and absolute between-group differences in mortality varied considerably according to the level of respiratory support that the patients were receiving at the time of randomization. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those who were receiving no respiratory support at randomization (17.8% vs. 14.0%; rate ratio, 1.19; 95% CI, 0.91 to 1.55). Conclusions In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support. (Funded by the Medical Research Council and National Institute for Health Research and others; RECOVERY ClinicalTrials.gov number, NCT04381936; ISRCTN number, 50189673.)

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Repurposed Antiviral Drugs for Covid-19 — Interim WHO Solidarity Trial Results

Aldo Pietro Maggioni, Jonathan Sterne (2021)

Abstract Background World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs — remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a — in patients hospitalized with coronavirus disease 2019 (Covid-19). Methods We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry. Results At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan–Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P=0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P=0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P=0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P=0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration. Conclusions These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.)

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Author and article information

Journal

Journal ID (nlm-ta): Expert Opin Pharmacother

Journal ID (iso-abbrev): Expert Opin Pharmacother

Title: Expert Opinion on Pharmacotherapy

Publisher: Taylor & Francis

ISSN (Print): 1465-6566

ISSN (Electronic): 1744-7666

Publication date (Electronic, pub): 1 February 2022

Publication date (Electronic, collection): 2022

Publication date PMC-release: 1 February 2022

Pages: 1-6

Affiliations

[0001]Weill Cornell Medicine, Division of General Internal Medicine, New York, NY, USA

Author notes

CONTACT Matthew W. McCarthy mwm9004@ 123456med.cornell.edu Weill Cornell Medicine, Division of General Internal Medicine, 525 East 68th Street, New York, NY 10065, USA

Article

Publisher ID: 2035360

DOI: 10.1080/14656566.2022.2035360

PMC ID: 8862166

PubMed ID: 35103549

SO-VID: 376d6dd6-eb98-4b6b-9f7c-3f7dfc466c53

License:

This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

Current and emerging immunomodulators for treatment of SARS-CoV2 infection (COVID-19)

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ABSTRACT

Introduction

Areas Covered

Expert opinion

Related collections

Novel Coronavirus Disease COVID-19

Most cited references 60

A Novel Coronavirus from Patients with Pneumonia in China, 2019

Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report

Repurposed Antiviral Drugs for Covid-19 — Interim WHO Solidarity Trial Results

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