Infliximab against severe COVID-19-induced cytokine storm syndrome with organ failure—a cautionary case series

Abstract

The severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic has prompted search for therapeutics tackling both the pathogen and the overwhelming host response, on an unprecedented scale. In a minority of patients, the disease may cause frequently lethal complications from acute respiratory distress syndrome to multisystem organ failure presumably driven by a cytokine storm [1]. Therefore, anti-cytokine therapies may be helpful to prevent tissue injury. However, these antiinflammatory drugs constitute double-edged swords; while they can prevent organ damage, they increase the risk of concomitant (super)infection. Recently, Neurath argued for a protective effect of tumor necrosis factor (TNF) inhibitors in severe COVID-19 [2]. Specifically, TNF may aggravate lymphopenia through direct killing via TNF/TNFR1 signaling in T cells [3], and T cell dysfunction reflects an important yet underestimated target for immunomodulatory interventions [4]. Thus, anti-TNF strategies may be an interesting option in severe COVID-19. This is supported by data from patients with inflammatory bowel disease (IBD) already on anti-TNF treatment. As of June 16, 2020, outcome data from 1511 IBD patients with COVID-19, among them, 433 patients on anti-TNF, are available from the SECURE-IBD registry [5]. Of these, 16% were hospitalized but only three patients (0.7%) died. Compared to other anti-inflammatory drugs such appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material.

Clinical characteristics and post-intensive care outcomes of COVID-19 pneumonia.

“…The mortality of patients requiring admission to Intensive Care Units (ICUs) is high, reported at between 26% and 50% worldwide (4,5,6,7). Prompted by this, numerous therapies have been used on a compassionate basis in the absence of robust evidence, including antivirals and immune modulators, with mixed results (8,9). Furthermore, it has been suggested that COVID-19 pneumonia represents a su ciently novel disease entity that standard evidence-based approaches to ARDS are not applicable or even deleterious (10,11,12).…”

Infliximab can reduce mortality from 35 to 14% in critically ill patients with COVID-19: perhaps some potential confounders to consider

“…We read with great interest the recent article by Stallmach et al who reported data from a small retrospective case series of patients with COVID-19 that received infliximab compared to a contemporaneous cohort that received supportive care alone [ 1 ]. Infliximab (anti-TNF) was used to target proinflammatory cytokines that are associated with deterioration of organ function and poor outcomes in patients with COVID-19 [ 1 , 2 ]. The authors reported that mortality was reduced from 35% in the control group to 14% in the infliximab group [ 1 ].…”

“…Infliximab (anti-TNF) was used to target proinflammatory cytokines that are associated with deterioration of organ function and poor outcomes in patients with COVID-19 [ 1 , 2 ]. The authors reported that mortality was reduced from 35% in the control group to 14% in the infliximab group [ 1 ]. We would like to make some comments.…”

“…We would like to make some comments. Looking at the baseline characteristics of the patients, we can see that ferritin levels in the infliximab group were almost double those in the control group (2777.4 vs 1453 μg/L) [ 1 ]. It is possible that the patients in the treated group may have had secondary hemophagocytic lymphohistiocytosis (sHLH) syndrome induced by SARS-CoV-2 [ 3 ].…”

“…In conclusion, on the basis of the difference in ferritin levels between the two groups and the potential diagnosis of sHLH, the two groups in this study are not well matched [ 3 ]. A diagnosis of sHLH could explain the enormous cytokine storm responding so well to infliximab [ 1 ] and may also explain why dexamethasone is so effective in patients with severe COVID-19 [ 4 ]. The sHLH-cytokine storm may be the main reason for the rapid deterioration seen in patients with COVID-19 [ 3 ].…”