Profiling COVID-19 pneumonia progressing into the cytokine storm syndrome: results from a single Italian Centre study on tocilizumab versus standard of care

Abstract

[250 words] Objective Approximately 5% of patients with coronavirus disease 2019 (COVID-19) develop a life-threatening pneumonia that often occurs in the setting of increased inflammation or "cytokine storm". Anti-cytokine treatments are being evaluated but optimal patient selection remains unclear, and the aim of our study is to address this point. Methods Between February 29 to April 6, 2020, 111 consecutive hospitalized patients with COVID-19 pneumonia were evaluated in a single centre retrospective study. Patients were divided in two groups: 42 severe cases (TOCI) with adverse prognostic features including raised CRP and IL-6 levels, who underwent anti-cytokine treatments, mostly tocilizumab, and 69 standard of care patients (SOC). Results In the TOCI group, all received anti-viral therapy and 40% also received glucocorticoids. In TOCI, 62% of cases were ventilated and there were 3 deaths (17.8+/-10.6 days, mean follow up) with 7/26 cases remaining on ventilators, without improvement, and 17/26 developed bacterial superinfection. One fatality occurred in the 15 TOCI cases treated on noninvasive ventilation and 1 serious bacterial superinfection. Of the 69 cases in SOC, there was no fatalities and no bacterial complications. The TOCI group had higher baseline CRP and IL-6 elevations (p<0.0001 for both) and higher neutrophils and lower lymphocyte levels (p= 0.04 and p=0.001, respectively) with the TOCI ventilated patients having higher markers than non-ventilated TOCI patients. Conclusion Higher inflammatory markers, more infections and worse outcomes characterized ventilated TOCI cases compared to ward based TOCI. Despite the confounding factors, this suggests that therapy time in anti-cytokine randomized trials will be key.

Efficacy of tocilizumab in COVID‐19: A systematic review and meta‐analysis

“…Using the search strategy, the literature search yielded a total of 412 unique articles. A total of 23 studies met the inclusion and exclusion and were finalized for data extraction 16‐38 (Figure 1). Of the included studies, eight studies were available as preprints and 15 studies were published as peer‐reviewed articles.…”

Impact of corticosteroids and immunosuppressive therapies on symptomatic SARS-CoV-2 infection in a large cohort of patients with chronic inflammatory arthritis

“…The improvement in knowledge on COVID-19-related ARDS pathogenesis has pointed out the central role of the abnormal immune response to SARS-CoV-2 leading to a massive release of pro-in ammatory mediators known as cytokine release storm (54,55). This has actually paved the way for the use of biological drugs and small molecules in the treatment of the most severe subsets of COVID-19 (13,(56)(57)(58)(59)(60)(61). Although the apparent bene cial therapeutic effects of immunomodulatory agents cannot be translated into any speculation on their prophylactic role, the possibility that chronic use of ts/bDMARDs may dampen exaggerated immune reactions, thus mitigating COVID-19 progression into more symptomatic patterns, deserves further investigation.…”

Influenza infection, SARS, MERS and COVID-19: Cytokine storm – The common denominator and the lessons to be learned

“…However, the experience with COVID-19 pandemic raised some questions regarding the best timing of initiation of the immunomodulatory therapy. Although that is the patients with severe COVID-19 who benefit most from IL6-directed agents, recent findings indicated that the therapy should not be postponed and used mainly for the treatment of those who require mechanical ventilation [ 87 ]. It is important to remember that the cytokine storm may start from the early course of disease to later stage and it may be rapidly progressive at any time [ 88 ].…”