Impact of cytokine storm on severity of COVID-19 disease in a private hospital in West Jakarta prior to vaccination
Authors: Ramatillah Diana Laila , Gan Siew Hua , Pratiwy Ika , Syed Sulaiman Syed Azhar , Jaber Ammar Ali Saleh , Jusnita Nina , Lukas Stefanus , Abu Bakar Usman 
Published: January 2022

Background and aim
Coronavirus Disease 2019 (COVID-19) has become a worldwide pandemic and is a threat to global health. Patients who experienced cytokine storms tend to have a high mortality rate. However, to date, no study has investigated the impact of cytokine storms.

Materials and methods
This retrospective cohort study included only COVID-19 positive patients hospitalized in a Private Hospital in West Jakarta between March and September 2020. All patients were not vaccinated during this period and treatment was based on the guidelines by the Ministry of Health Indonesia. A convenience sampling method was used and all patients who met the inclusion criteria were enrolled.

Results
The clinical outcome of COVID-19 patients following medical therapy was either cured (85.7%) or died (14.3%), with 14.3% patients reported to have cytokine storm, from which 23.1% led to fatalities. A plasma immunoglobulin (Gammaraas®) and/or tocilizumab (interleukin-6 receptor antagonist; Actemra®) injection was utilised to treat the cytokine storm while remdesivir and oseltamivir were administered to ameliorate COVID-19. Most (61.5%) patients who experienced the cytokine storm were male; mean age 60 years. Interestingly, all patients who experienced the cytokine storm had hypertension or/ and diabetes complication (100%). Fever, cough and shortness of breath were also the common symptoms (100.0%). Almost all (92.3%) patients with cytokine storm had to be treated in the intensive care unit (ICU). Most (76.9%) patients who had cytokine storm received hydroxychloroquine and all had antibiotics [1) azithromycin + levofloxacin or 2) meropenam for critically ill patients] and vitamins such as vitamins C and B-complex as well as mineral. Unfortunately, from this group, 23.1% patients died while the remaining 70% of patients recovered. A significant (p<0.05) correlation was established between cytokine storms and age, the presence of comorbidity, diabetes, hypertension, fever, shortness of breath, having oxygen saturation (SPO2) less than 93%, cold, fatigue, ward of admission, the severity of COVID-19 disease, duration of treatment as well as the use of remdesivir, Actemra® and Gammaraas®. Most patients recovered after receiving a combination treatment (oseltamivir + remdesivir + Antibiotics + Vitamin/Mineral) for approximately 11 days with a 90% survival rate. On the contrary, patients who received oseltamivir + hydroxychloroquine + Gammaraas® + antibiotics +Vitamin/Mineral, had a 83% survival rate after being admitted to the hospital for about ten days.

Conclusion
Factors influencing the development of a cytokine storm include age, duration of treatment, comorbidity, symptoms, type of admission ward and severity of infection. Most patients (76.92%) with cytokine storm who received Gammaraas®/Actemra®, survived although they were in the severe and critical levels (87.17%). Overall, based on the treatment duration and survival rate, the most effective therapy was a combination of oseltamivir + favipiravir + hydroxychloroquine + antibiotics + vitamins/minerals.