Treatment of severe COVID-19: an evolving paradigm

ABSTRACT

Introduction

The pathogenesis of severe COVID-19 is due, in part, to dysregulation of the human immune system in response to SARS-CoV-2 infection. Immune cells infected with SARS-CoV-2 can trigger a hyperinflammatory response of both the adaptive and innate immune system that has been associated with severe disease, hospitalization, and death, and better treatment options are urgently needed.

Areas covered

A mainstay of therapy for COVID-19 involves an antiviral agent, remdesivir, in combination with a systemic corticosteroid, dexamethasone.

Expert opinion

The addition of a second immunomodulator, such as an interleukin-6 inhibitor or a Janus kinase inhibitor, has been associated with clinical benefit in a subset of patients with moderate-to-severe disease, but their use remains controversial. This manuscript reviews what is known about the approach to treatment of severe COVID-19 and examines how immunomodulators such as infliximab and abatacept may alter clinical management and COVID-19 research in the years ahead based on the results of randomized, controlled trials.

KEYWORDS:

• SARS-CoV-2
• COVID-19
• infliximab
• abatacept
• IL-6
• Janus Kinase

Article highlights

• Severe COVID-19 is associated with advanced age as well as a variety of comorbid conditions, including cardiovascular disease, chronic obstructive pulmonary disease, diabetes, hypertension, and immunocompromising conditions.

• Hyperinflammation is a hallmark of severe COVID-19 and strategies targeting the immune system hold therapeutic promise.

• Interleukin-6 inhibitors and Janus kinase inhibitors have shown a clinical benefit in some patients hospitalized with COVID-19.

• ACTIV-1 is a randomized, double-blinded, placebo-controlled, multicenter platform study evaluating immunomodulators for the treatment of patients hospitalized with COVID-19

• In ACTIV-1, the immunomodulators infliximab and abatacept demonstrated a mortality benefit in patients hospitalized with COVID-19.

Declaration of interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.