Countermeasures to Coronavirus Disease 2019: Are Immunomodulators Rational Treatment Options—A Critical Review of the Evidence

Chastain, Daniel B; Stitt, Tia M; Ly, Phong T; Henao‐Martínez, Andrés F.; Franco‐Paredes, Carlos; Osae, Sharmon P.

doi:10.1093/ofid/ofaa219

Cited by 11 publications

(21 citation statements)

References 68 publications

(94 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Caution is also recommended for immunocompromised patients due to a higher susceptibility of bacterial infection, neutropenia, and thrombocytopenia following TCZ therapy. 13,17 Interestingly, we did not observe any side effects that required stopping TCZ therapy that could be attributed to the short course of the therapy.…”

Section: Discussionmentioning

confidence: 65%

Early use of tocilizumab in the prevention of adult respiratory failure in SARS‐CoV‐2 infections and the utilization of interleukin‐6 levels in the management

Antony

Davis²,

Davis³

et al. 2020

Journal of Medical Virology

View full text Add to dashboard Cite

Background Respiratory failure in severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection appears related to cytokine release syndrome (CRS) that often results in mechanical ventilation (MV). We investigated the role of tocilizumab (TCZ) on interleukin‐6 (IL‐6) trends and MV in SARS‐CoV‐2 patients. Methods In this longitudinal observational study, 112 patients were evaluated from 2/1/2020 ‐ 5/31/2020. TCZ was administered followed by methylprednisolone to patients with > 3L oxygen (O2) requirement and pneumonia severity index (PSI) score ≤ 130 with CT scan changes. IL‐6, C‐reactive protein (CRP), ferritin, lactate dehydrogenase (LDH), D‐dimer, and procalcitonin were monitored on days 0, 3, and 6 of therapy. Statistical analyses were performed with significance ≤ 0.05. Results 80/112 SARS‐CoV‐2‐positive patients (45 males, 56.96%; 34 females, 43.04%) were included in this study. Seven patients expired (8.75%) and nine patients required MV (11.25%). Median IL‐6 levels pre‐administration of TCZ was 342.50 (78.25 ‐ 666.25) pg/mL compared to post‐administration on day 3 (563; 162 ‐ 783) pg/mL ( P < 0.00001). On day 6, the median dropped to 545 (333.50 ‐ 678.50) pg/mL compared to day 3 ( P = 0.709). CRP, ferritin, LDH, and D‐dimer levels were reduced following TCZ therapy. Conclusions Early use of TCZ may reduce the need for MV and decrease CRP, ferritin, LDH, and D‐dimer levels. The sequential use of methylprednisolone for 72 hours seems to potentiate the effect and prolong the suppression of the cytokine storm. IL‐6 levels may be helpful as a prognostic tool. This article is protected by copyright. All rights reserved.

show abstract

Section: Discussionmentioning

confidence: 65%

Early use of tocilizumab in the prevention of adult respiratory failure in SARS‐CoV‐2 infections and the utilization of interleukin‐6 levels in the management

Antony

Davis²,

Davis³

et al. 2020

Journal of Medical Virology

View full text Add to dashboard Cite

show abstract

“…Janus kinase (JAK) mediates the release of proinflammatory cytokines leading to increased inflammatory processes [ 157 ]. The mechanism of JAK inhibitors, sunitinib, erlotinib, ruxolitinib, fedratinib, and baricitinib, is inhibition of cytokine signaling, thereby downregulating the immune response.…”

Section: Pharmacological Management Of Covid-19mentioning

confidence: 99%

“…The mechanism of JAK inhibitors, sunitinib, erlotinib, ruxolitinib, fedratinib, and baricitinib, is inhibition of cytokine signaling, thereby downregulating the immune response. The doses of sunitinib and erlotinib needed to inhibit AP2-associated kinase 1 and cyclin G-associated kinase are significantly higher than those used for anticancer treatment, which may result in unbearable adverse effects [ 157 ].…”

Section: Pharmacological Management Of Covid-19mentioning

confidence: 99%

See 1 more Smart Citation

Pharmacological considerations for the treatment of COVID-19 in people living with HIV (PLWH)

Gutierrez

Mur

Mateo

et al. 2021

Expert Opinion on Pharmacotherapy

View full text Add to dashboard Cite

Introduction When coronavirus infectious disease-2019 (COVID-19) blew up, ill-fated auguries on the collision between COVID-19 and the human immunodeficiency virus (HIV) epidemics loomed. Areas covered Data from observational studies suggest similar incidence attacks of SARS-CoV-2 infection in people living with HIV (PLWH) and HIV-uninfected populations. The mortality rate of COVID-19 is similar in both populations too. The authors discuss the role of combination antiretroviral therapy (cART) in preventing infection or reducing COVID-19 severity. They also discuss the pharmacological interventions for COVID-19 in PLWH. Expert opinion Management of COVID-19 in PLWH is no different from the general population. It should be based on careful supportive care, emphasizing lung-protective ventilation, and wise pharmacological interventions. The antiviral drug remdesivir and dexamethasone are the only pharmacological interventions with clinical benefit for COVID-19, whereas anticoagulation may prevent thrombotic complications. The experience with using these drugs in PLWH is limited, which prevents from rendering well-founded conclusions. Until more data on COVID-19 in PLWH become available, the best weapons within our reach are sound supportive care and sensible use of RDV and dexamethasone, bearing in mind the potential for drug–drug interactions of most corticosteroids and antiretroviral drugs.

show abstract

“…To date, public health agency efforts to combat the pandemic level of infection and resultant Coronavirus disease 2019 (COVID- 19) have relied mostly upon effective quarantine measures 2,3 . To further protect at-risk populations, a worldwide effort has been undertaken to develop additional countermeasures, such as antiviral compounds, immunomodulatory agents, vaccines, and neutralizing antibodies (nAbs) 4,5,6 .…”

Section: Introductionmentioning

confidence: 99%

Discovery and Development of Human SARS-CoV-2 Neutralizing Antibodies using an Unbiased Phage Display Library Approach

Cao

Maruyama

Zhou

et al. 2020

Preprint

View full text Add to dashboard Cite

SARS-CoV-2 neutralizing antibodies represent an important component of the ongoing search for effective treatment of and protection against COVID-19. We report here on the use of a naïve phage display antibody library to identify a panel of fully human SARS-CoV-2 neutralizing antibodies. Following functional profiling in vitro against an early pandemic isolate as well as a recently emerged isolate bearing the D614G Spike mutation, the clinical candidate antibody, STI-1499, and the affinity-engineered variant, STI-2020, were evaluated for in vivo efficacy in the Syrian golden hamster model of COVID-19. Both antibodies demonstrated potent protection against the pathogenic effects of the disease and a dose-dependent reduction of virus load in the lungs, reaching undetectable levels following a single dose of 500 micrograms of STI-2020. These data support continued development of these antibodies as therapeutics against COVID-19 and future use of this approach to address novel emerging pandemic disease threats.

show abstract

Countermeasures to Coronavirus Disease 2019: Are Immunomodulators Rational Treatment Options—A Critical Review of the Evidence

Cited by 11 publications

References 68 publications

Early use of tocilizumab in the prevention of adult respiratory failure in SARS‐CoV‐2 infections and the utilization of interleukin‐6 levels in the management

Early use of tocilizumab in the prevention of adult respiratory failure in SARS‐CoV‐2 infections and the utilization of interleukin‐6 levels in the management

Pharmacological considerations for the treatment of COVID-19 in people living with HIV (PLWH)

Discovery and Development of Human SARS-CoV-2 Neutralizing Antibodies using an Unbiased Phage Display Library Approach

Contact Info

Product

Resources

About