key: cord-295475-o3ns4cfn
authors: Dastan, Farzaneh; Nadji, Seyed Alireza; Saffaei, Ali; Tabarsi, Payam
title: Tocilizumab administration in a refractory case of COVID-19
date: 2020-06-02
journal: Int J Antimicrob Agents
DOI: 10.1016/j.ijantimicag.2020.106043
sha: 
doc_id: 295475
cord_uid: o3ns4cfn

Novel coronavirus (COVID-19) pneumonia as a pandemic disease leads to acute respiratory distress syndrome (ARDS), acute cardiac injury, multi organ failure, and shock. In the absence of specific treatment for COVID-19, there is an urgent need to find the alternative treatments to manage this pandemic. Pathophysiological studies have demonstrated the role of inflammatory mediators in COVID-19 pneumonia. It appears that imbalances between inflammatory and anti-inflammatory cytokines are the probable underlying mechanism. Since, there is no specific treatment for the inflammatory phase of COVID-19 pneumonia, consideration of treatments, such as tocilizumab, as salvage therapy is necessary. Here, we reported a challenging case of COVID-19 who was successfully treated with tocilizumab.

with an oxygen saturation of 85%. Fever and cough were persistent, and new chest X-ray imaging revealed progression of bilateral infiltration in the lower and upper lobes (Fig. 1b) .

We decided to initiate ribavirin at dose of 1200 mg p.o. b.i.d. and intravenous immunoglobulin at a dose of 20 mg i.v. daily. Meropenem and teicoplanin were also started to cover any probable bacterial sources. After 2 days, on March 10, 2020, the clinical condition of the patient worsened. Dyspnea continued with greater severity and an oxygen saturation of 83%. The ratio between the partial pressure of oxygen in arterial blood (PiO 2 ) and the fraction of inspired oxygen decreased to 103 mmHg. Chest X-ray imaging did not show significant changes compared with the previous images (Fig. 1c) , and the patient was a candidate for intubation and invasive mechanical ventilation but this procedure did not achieve. At this time, tocilizumab was considered as a last chance of therapy. The patient's IL-6 level was checked, and a value of over 200 pg/mL was found. QuantiFERON-TB testing was negative for Mycobacterium tuberculosis. Viral markers, including hepatitis B virus, hepatitis C virus, and human immunodeficiency virus, were reported negative. Hence, tocilizumab (Actemra Hoffmann-La Roche Limited), as a single dose of 400 mg was infused for him over 2 hours. The patient's vital signs were checked carefully during infusion to monitor any probable adverse effects. After 2 days, the patient's dyspnea improved gradually and his oxygen saturation increased to 90%. Chest X-ray imaging also showed less infiltration in comparison with previous imaging (Fig. 1d) . Recovery was observed over the next few days, and dyspnea and oxygen saturation improved significantly. IL-6 levels were checked and found to decrease from 29 pg/mL to 6 pg/mL within a few days. Lung infiltration remarkably recovered in subsequent chest X-ray imaging (Fig. 1e and Fig. 1f) . A swab specimen was tested negative for COVID-19 by RT-PCR on March 18, 2020. After 18 days of hospitalization, the patient was discharged with acceptable clinical condition. No bothersome dyspnea was noted, and oxygen saturation was 93% without supplemental oxygen. The timeline of vital signs, therapeutic regimens, and laboratory results are shown in Cytokine release syndrome may be the underlying pathophysiology of refractory cases of COVID-19. Tocilizumab is a recombinant humanized monoclonal antibody developed against soluble and membrane-bound IL-6 receptors. Tocilizumab prevents the binding of IL-6 to its receptors and reduces the activity of the cytokine by competing with both the soluble and membrane-bound forms of its receptors [2] . In the current case, we faced a refractory COVID-19 case who did not respond to conventional therapeutic agents and tocilizumab administered as a salvage therapy. In contrast to hydroxychloroquine, tocilizumab may be a useful agent in severe cases who have not responded to conventional therapy (chloroquine/hydroxychloroquine and antivirals) and those patients with elevated levels of IL-6 [3] . Successful management of tocilizumab was reported in recent literature. Hammami MB et al., reported COVID-19 in a liver transplant recipient who responded to tocilizumab therapy [4] . The promising role of tocilizumab also reported in pilot studies. Improvement in respiratory and laboratory parameters were observed in those studies [5, 6] . However, while tocilizumab is a promising agent against COVID-19, it is not an appropriate agent in patients with active or latent tuberculosis, bacterial and fungal infections, multi-organ failure, and gastrointestinal perforation [7] . In conclusion, tocilizumab may be considered a salvage therapeutic agent in COVID-19 patients who did not respond to other agents. Clinicians should be aware of the precautions and contraindications of tocilizumab, such as latent infection, and administer the drug with caution.

Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro surveillance : bulletin Europeen sur les maladies transmissibles

The cytokine release syndrome (CRS) of severe COVID-19 and Interleukin-6 receptor (IL-6R) antagonist Tocilizumab may be the key to reduce the mortality

COVID-19 patients with at least a six-day follow up: A pilot observational study

Clinical Course of COVID-19 in a Liver Transplant Recipient on Hemodialysis and Response to Tocilizumab Therapy: A Case Report

Pilot prospective open, single-arm multicentre study on off-label use of tocilizumab in patients with severe COVID-19

Effective treatment of severe COVID-19 patients with tocilizumab

The risk of tuberculosis disease in rheumatoid arthritis patients on biologics and targeted therapy: A 15-year real world experience in Taiwan