Case Report: Effectiveness of tocilizumab in obese patient for treatment of severe COVID-19 pneumonia

Introduction

The COVID-19 outbreak caused by SARS-Cov-2 is the leading cause of mortality and morbidity due to ARDS, pneumonia, hypercoagulability, and septic shock.¹ Furthermore, obesity is an independent risk factor for developing severe COVID-19 complications with a high mortality. Pro-inflammatory cytokine markers such as IL-6 are discovered to play an important role in the systemic inflammatory status of severe COVID-19 patients. Inhibiting IL-6 has shown promising results in terms of cytokine storm reduction.²

Tocilizumab is a monoclonal antibody that inhibits IL-6² production. It is now one of the therapeutic options for cytokine release syndrome management. We present a case of a 32-year-old obese patient who has severe COVID-19 pneumonia. With the addition of Tocilizumab to standard care, the patient experienced rapid clinical improvement.

Case study

A 32-year-old male from the Bhaktapur area of Nepal who was otherwise healthy was admitted to the COVID Ward with a week’s history of fever and one day of shortness of breath (SOB). He had no previous medical history other than a few virus illnesses in the past. Ten days prior, his wife tested positive for COVID. With a body mass index of 39.21 kg/m², he qualified as obese. His total weight was 120 kg. He worked as a businessman. He worked at a desk most of the day and led a sedentary lifestyle. His peripheral oxygen saturation (SPO₂) was 88% in room air, and his respiratory rate was 28 beats per minute. It increased to 94% when using a 10 L/min face mask.

On admission, a nasal swab confirmed SARS-CoV2 infection. Inflammatory markers such as ferritin, CRP, D-dimer, and IL-6 were significantly elevated at 94.5 (normal 7 pg/ml).

Despite O₂ supplementation via non-rebreather mask @15 l/min, his SPO₂ dropped from 94% to 80% several hours after admission, so he was kept on High Flow Nasal Cannula (HFNC) with a flow rate of 60L/min and FiO₂ of 100%. The patient was given TOCILIZUMAB 800 mg in 100 ml of 0.9% normal saline intravenously over 1 hour due to increasing O2 demands and impending respiratory distress. Despite all precautions, the patient developed severe ARDS. Following tocilizumab administration, the patient’s ABG revealed PH-7.48, PO₂-34, PCO₂-38, HCO₃-: 28, PO₂/FiO₂-87, and he was intubated in the ICU the same day. At the same time, the patient was given standard empirical antibiotics (piperacillin, tazobactam, and azithromycin), steroids (Dexamethasone 20 mg iv od for 5 days, followed by 10 mg iv od for another 5 days), subcutaneous low molecular weight heparin, and vitamin supplements such as Tab Vitamin C, Zinc, and Vitamin D. The patient was also kept in a prone position for 16–18 hours per day (Figure 1).

Figure 1. Chest X-ray showing left sided infiltrates.

The patient began to improve clinically 48 hours after receiving tocilizumab. All of the inflammatory markers, including IL-6, that were elevated two days ago began to return to normal (Table 1). The patient’s condition significantly improved on the 12th day of admission, meeting extubation criteria, and he was thus extubated. He was transferred to the medical ward on the 14th day and discharged home on the 23rd.

Discussion

SARS-Cov-2 causes COVID-19. The leading causes of death in severe COVID-19 are ARDS and pneumonia, both of which are caused by uncontrolled inflammatory processes and multi-organ failure. This process primarily involves the release of pro-inflammatory cytokines (IL-2, IL-6, IL-7, tumor necrosis factor alpha).³ Tocilizumab is critical in preventing cytokine storms and associated ARDS. It is a monoclonal antibody against IL-6 receptors that has been humanized.² A retrospective cohort study in Ohio, USA,¹ discovered that using tocilizumab shortens the time to clinical improvement and the duration of invasive ventilation.

In our case, the IL-6 level was extremely high (94.5 pg/ml), which could have coincided with the occurrence of a cytokine storm. This stage is associated with increased levels of other inflammatory mediators such as ferritin, LDH, CRP, and D-dimer. During this course, specific and timely intervention may result in better outcomes. On the same day, our patient received tocilizumab and was placed on mechanical ventilation. There was a significant improvement in the patient’s respiratory parameters after receiving tocilizumab and other standard care; Pao₂/FiO₂ ratio improved from 87 to 373 and FiO₂ gradually tapered from 100% to 40%; PEEP from 15 cm of H₂O to 5 cm of H₂O, respectively, which is comparable with the case reports by Gentile et al.⁴

Initial signs of an unfavourable prognosis include the severity of lung damage, clinical deterioration, and the need for mechanical ventilation. However, with an effective treatment protocol, the patient recovered completely.

The findings of our case report, like any other case report, cannot be generalized, so well-designed research with a large sample size is needed to validate the efficacy of tocilizumab in COVID-19 patients.

Conclusion

Our findings show that using Tocilizumab in conjunction with systemic corticosteroids as part of the standard of care for halting pro-inflammatory cytokine cascades in early disease courses and prone positioning improves the outcome of mechanically ventilated patients with high risk of complications, while also shortening ICU stay. With the use of Tocilizumab in conjunction with other standard care, we saw a regression in radiological changes and a rapid clinical improvement.

Data availability

All data underlying the results are available as part of the article and no additional source data are required.

Reporting guidelines

Figshare. CARE guidelines. DOI: https://doi.org/10.6084/m9.figshare.20690110.⁵

Consent for publication

Written informed consent for publication of their clinical details and/or clinical images was obtained from the patient.