Toculizimab and Steroid combination therapy in management of COVID 19 induced cytokine release syndrome

Background: Steroids are used to treat cytokine
release syndrome(CRS) and inflammatory lung damage in severe COVID-19.Immunomodulatory drugs such
as Toculizimab(TCZ) could be of incremental benefit.The aim of this
retrospective cohort study was to evaluate the efficacy and safety of
combination therapy of TCZ and steroid in management of COVID-19 associated CRS.

Methods: This retrospective cohort study was
conducted at Noble hospital and Research Centre (NHRC),Pune,India between 2nd April and 2nd November 2020.Patients having
rapidly worsening respiratory status, defined as
presence of hypoxia(room air oxygen saturation< 90%) and
tachypnea(respiratory rate >30 per minute) at rest or after minimal exertion
despite use of antivirals and intravenous steroids(Methylprednisolone or
Dexamethasone) were prescribed TCZ. It was given intravenously at a
dose of 8 mg/kg bodyweight.The primary outcome was incidence
of all-cause mortality during hospital admission.Secondary outcomes included need
for mechanical ventilation and incidence of
infectious complications.Baseline and time
dependent risk factors significantly associated with death were identified by Relative risk estimation.

Results: Of 2831 admitted patients,515 (24.3% females) were administered TCZ and
steroids. There
were 135 deaths(26.2%),while 380 patients(73.8%) had clinical recovery.Mechanical
ventilation was required in 242(47%) patients,of which 44.2%(107/242) recovered
and were weaned off the ventilator. 37% patients could be managed in wards without need for intensive care
while 53% patients needed only supplemental oxygen prior to recovery.Infectious complications like hospital acquired pneumonia,blood stream bacterial
and fungal infections were seen in 2.13%, 2.13% and 0.06% patients
respectively.Age ≥60
yrs(p=0.014), IL-6 ≥100
pg/ml(p = 0.002), D-dimer ≥1000 ng/ml(p< 0.0001),CT severity index ≥18(p< 0.0001) and systemic complications like lung fibrosis(p=0.019),cardiac
arrhythmia(p< 0.0001),hypotension(p <0.0001) and encephalopathy(p
<0.0001) were associated with increased risk of death on Relative risk
estimation.

Conclusions: This study illustrates
the robust efficacy of TCZ and steroids as an anti-inflammatory combination
therapy in tackling CRS and needs timely
administration to interrupt the cascade leading to irreversible lung damage and
death.