Effect of Tocilizumab on P/F Ratio in Patients with Covid 19 Pneumonia

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus -2 (SARS-CoV-2). The incubation period of covid-19 is about 14 days with the average of 4 to 5 days from exposure to symptoms onset [1]. The signs and symptoms of covid-19 include fever, dry cough, sore throat, shortness of breath on exertion, myalgia, headache, nasal congestion, diarrhea, loss of taste and loss of smell [2,3]. The severity of illness ranges from mild to critical, mild to moderate disease including mild pneumonia with oxygen saturation ranging from 90-94% found in 81 %, severe disease includes hypoxia or more than 50% lung involvement on imaging in 14% and critical disease includes respiratory failure, shock or multi-organ system dysfunction in 5 % of the patients [4].


Introduction
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus -2 (SARS-CoV-2). The incubation period of covid-19 is about 14 days with the average of 4 to 5 days from exposure to symptoms onset [1]. The signs and symptoms of covid-19 include fever, dry cough, sore throat, shortness of breath on exertion, myalgia, headache, nasal congestion, diarrhea, loss of taste and loss of smell [2,3]. The severity of illness ranges from mild to critical, mild to moderate disease including mild pneumonia with oxygen saturation ranging from 90-94% found in 81 %, severe disease includes hypoxia or more than 50% lung involvement on imaging in 14% and critical disease includes respiratory failure, shock or multi-organ system dysfunction in 5 % of the patients [4].
The mainstay of management of patients with covid-19 is oxygen therapy; it can be given by face mask or nasal cannula [5]. All patients requiring oxygen therapy are also given steroids including dexamethasone or methylprednisolone, 6mg/day of dexamethasone or 0.5-1mg/kg/day of methylprednisolone.
Anticoagulation also plays an important role as COVID-19 may be hypercoaguable. Enoxaparin is given in dose of 1mg/kg every 12 hourly for 1 to 3 months. One of the main complications of COVID-19 disease is "CYTOKINE RELEASE SYNDROME". Following criteria is applied for CRS. i.
Ferritin >1000mcg/L and rising in last 24 hours.
ii. Ferritin >2000mcg/L in patient requiring high flow oxygen or ventilation.

Methods
This is a retrospective study; data was retrieved and analyzed retrospectively from March 2020 to June 2020. 40 patients were included in study. The study was done in Liaquat National Hospital

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Karachi. Patients more than 18 years of age with positive Covid-19 PCR, those with oxygen saturation less than 88% and those who met the criteria of CRS as described earlier, were included in study.
All the patients with age below 18 years, deranged liver function test and proclacitonin value greater than 0.5 were excluded from the study.

Data collection procedure
Data of the patients meeting the inclusion criteria presented to the Covid ICU/HDU from April 2020 to July 2020 were enrolled in the study. After taking approval from the institutional ethical committee, detailed history documented by researcher including presenting complaints of fever, cough, shortness of breath and altered level of consciousness. Laboratory investigations including CRP, Ferritin, LDH, N/L ratio, IL -6 levels, D-Dimer, P/F ratio will be monitored. Sofa score will be calculated. Patients meeting the inclusion criteria will be given Tocilizumab (8mg/kg), I/V and clinical outcome will be assessed as whether patients improved or deteriorated/expired.

Data analysis
SPSS version 22 will be used for data analysis. Frequencies and percentages will be computed for categorical variables like gender, either one or two doses of Tocilizumab given. Variables will be presented as mean± standard deviation for continuous variables like age, P/F ratio before and after the administration of Tocilizumab. Chi square will be used to check association between categorical variables while mean comparison will be done by using independent t-test and AVONA as appropriate. P value <0.05 will be considered as significant. two between 41 to 60 years and group three with patients more than 6 years. We have selected the patients for administering the drug Tocilizumab. 8 doses were given to 8 patients and they did not require second dose because either they improved, or they expired. 32 patients were given two doses as shown in (Table2).   the chart that is representing the deterioration of P/F ratio after the drug therapy or no response to the therapy as discussed previously. But majority of the patients responded well, and they had good clinical response.

Discussion
This study describes the effect of Tocilizumab in the patients with covid-19 that were admitted an Intensive Care unit of a tertiary care hospital. These patients received Tocilizumab as a treatment of covid pneumonia and ARDS. This drug improved the P/F ratio of the patients and increases the clinical recovery.
Tocilizumab is a monoclonal antibody that target IL-6 receptors. It is approved by FDA for the treatment of rheumatoid arthritis, giant cell arthritis and juvenile arthritis [8]. Recently it is being used for the cytokine release syndrome in patients with covid-19 pneumonia [9]. As described earlier that CRS is due to release of certain inflammatory cytokines and chemokines [10]. It was observed that patients with Covid-19 pneumonia developed CRS and their timely intubation and starting of Tocilizumab therapy is clinically effective for these patients [11].
Also, some studies suggested the effect of Tocilizumab has a limited role in clinical improvement of patients with CRS.
Other case series suggested the significant role of Tocilizumab in treatment of patients with Covid-19 pneumonia [12][13][14]. In

Conclusion
Tocilizumab is an Interleukin receptor blocker. It has a promising role in clinical recovery of the Covid-19 infected patients. It decreases oxygen requirement, improves weaning off from ventilators and also decreases the morbidity.