Immunomodulatory therapies for COVID-19

Abstract

PurposeAs COVID-19 disease progresses, the host inflammatory response contributes to hypoxemia and severe and critical illness. In these latter stages of disease, patients may benefit from immunomodulatory therapies to control the aberrant host inflammatory response. In this review, we provide an overview of these therapies and provide summaries of the studies that led to issuance of FDA Emergency Use Authorization or recommendation by the Infectious Diseases Society of America (IDSA).Materials and methodsWe reviewed English-language studies, Emergency Use Authorizations (EUAs), and guidelines from March 2020 to present.Conclusion and relevanceThere are several therapies with proposed benefit in severe and critical COVID-19 disease. Few have been issued FDA EUA or recommendation by the Infectious Diseases Society of America (IDSA). Physicians should be familiar with the evidence supporting use of these therapies and the patient populations most likely to benefit from each.

Hemophagocytic Syndrome and COVID-19: A Comprehensive Review

“…and the amplification of the anti-inflammatory process. Furthermore, TLRs activation results in the release of type I interferon, which has a direct antiviral activity and activates the adaptive immune system [46][47][48]. Additionally, the NOD-like receptors (NLRs) sense the damage-associated molecular pattern (DAMP), released from dying and damaged cells, resulting in high levels of IL-1β, one of the main activators of IL-6 [46,49].…”

“…Cytokine targeting and suppression could result in decreased proinflammatory signaling and improved clinical status [57]. Inhibition of IL-6, a key mediator of the inflammatory process in CS and a prognostic marker in COVID-19, with IL-6 receptor inhibitors including tocilizumab and sarilumab has shown its efficacy in the severe COVID-19 stages [1,48]. Earlier studies on tocilizumab had varying results and effectiveness was demonstrated in multiple studies [62][63][64], while others failed to show any clinical improvement in patients using tocilizumab compared to standard care [65].…”

“…An impaired NK cell cytolytic activity as well as reduced counts were linked to the hyperinflammation seen in severe COVID-19 patients [ 52 ]. The high levels of IL-6, being associated with severe COVID-19, have been shown to reduce the expression of perforin and granzyme B in NK cells, subsequently reducing their cytolytic activity [ 48 , 53 ]. Mazzoni et al found an inverse correlation between NK cells’ cytotoxic potential and high levels of IL-6 [ 54 ].…”

“…Although, only the anti-inflammatory approaches, using immunomodulators, have shown to improve survival in these patients [ 59 ]. Corticosteroids including dexamethasone have an anti-inflammatory activity against various cytokines (IFN-δ, TNF-α, IL-1, IL-2), and have been shown to reduce mortality in patients requiring respiratory support [ 48 , 57 ]. Appropriate timing and dosing for corticosteroids are important and should only be administered to patients presenting with clinical, radiological, and laboratory markers suggestive of a CS [ 60 ].…”

“…At present, the Infectious Diseases Society of America (IDSA) recommends the use of tocilizumab in critically ill COVID-19 patients with systematic inflammation in combination with standard of care, including steroids. If not available, sarilumab can be used instead of tocilizumab [ 48 ]. IL-1, a cytokine generated by macrophages, activating neutrophils that become uncontrolled and result in severe lung injury, ARDS, and multiorgan failure, was studied as a target for inhibition with the monoclonal antibody anakinra [ 48 , 70 ].…”