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

Abstract

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.

Tocilizumab use in COVID‐19‐associated pneumonia

“…First, we compared patients who were treated with TCB early in their course to patients receiving it either before or after intubation; our data showed a similar observation to that reported by other authors 10,11 . There was a significant effect of TCB on mortality where 22% of patients receiving the drug late died versus 9% receiving it early.…”

“…First, we compared patients who were treated with TCB early in their course to patients receiving it either before or after intubation; our data showed a similar observation to that reported by other authors. 10,11 There was a significant effect of TCB on mortality Our study has several limitations; the study is a retrospective analysis done in a single medical center and therefore results may not be generalizable to other centers. The study carries the limitations of retrospective analysis, specifically as it pertains to patients selected to receive TCB.…”

Organ-specific manifestations of COVID-19 infection

“…This "cytokine storm" results from an inflammatory over-reaction as a response to SARS-CoV-2 infection that ultimately leads to endothelial cell dysfunction, damage of the vascular barrier, capillary leak and diffuse alveolar damage [35]. In this context, anti-IL-6 inhibitors, such as the monoclonal antibody tocilizumab, inhibitors of JAK kinases, such as baricitinib, and corticosteroids, especially dexamethasone, have been evaluated in patients with severe COVID-19 and have shown promising preliminary results [36][37][38][39].…”

Beneficial and harmful outcomes of tocilizumab in severe COVID-19: a systematic review and meta-analysis

“…The majority of included studies were carried out in different hospitals in high-income countries in America and Europe, such as the US [13, 18, 22, 28, 31, 34, 35, 48, 49, 53-60, 66], Italy [14, 15, 17, 19, 20, 41, 44-47, 50, 51, 63, 65], Spain [21, 26, 27, 32, 33, 39, 40, 42, 43], and France [25, 29, 30, 61, 62, 64]. A lesser number were conducted in China [11, 12].…”