ABSTRACT
Aim and background: Severe COVID-19 pneumonia can be lifethreatening with a high mortality, largely due to an uncontrolled systemic hyperinflammatory response, generally referred to as cytokine storm. Tempering the immune response with immunomodulators has been considered as a potential therapeutic option. Except for a few, data on the effectiveness of different immunomodulating drugs are scarce and are limited to a few case reports and retrospective observational-cohort studies. Additionally, in the pandemic due to shortages, various immunomodulators were used with limited data on their effectiveness. This study looks at various immunomodulators used in the 2nd wave of COVID-19, and their impact on outcomes. Materials and methods: Retrospective analysis of 124 patients with severe COVID-19 disease who were treated with immunomodulators. The study population included patients above 18 years of age with confirmed COVID-19 admitted to ICU with severe pneumonia. All patients received standard of care treatment at the time of hospital admission according to the hospital protocols and updated data on treatment of COVID-19. Patients were considered eligible for immunomodulatory treatment if they showed rapidly worsening hypoxia and elevated inflammatory markers, as per standard recommendations. Immunomodulators were administered depending on the availability of specific agents at time of treatment. The immunomodulators used were tocilizumab, itolizumab, bevacizumab, pulse dose steroid with methylprednisolone and baricitinib. Results: 124 patients were treated with immunomodulators, 45 (36.3%) of them survived, and 79 (63.7%) passed away. Mean age in survivors was 48.2, and in non-survivors was 54.8, which was statistically significant. Diabetes and hypertension were the most common comorbidities observed. 97/124 patients (78.2%) received immunomodulator therapy within 48 hours of ICU admission, out of which 41 (42.2%) recovered and 56 (57.7%) passed away. 21/124 (21.8%) patients received immunomodulators after 48 hours of admission, and had a high mortality with only 3 (14.2%) recovering and 18 (85.7%) dead. There was a significant reduction in CRP levels post immunomodulator therapy among survivors compared to nonsurvivors. The mean invasive ventilator days were 4.27 and there was a significant difference among survivors and non-survivors. Among survivors (45) in our study, we found that immunomodulator therapy was seen to avoid mechanical ventilation in severe COVID patients (33) who received immunomodulator therapy early within 48 hours of ICU admission as seen by the improvement on a 7-point ordinal scale. The mean ventilator days for patients who received immunomodulator therapy after intubation were also reduced. Most common adverse events were found with itolizumab administration. Secondary infections were more in non-survivors and secondary bacterial pneumonia was the commonest. Conclusion: Our descriptive study showed that the early administration(<48 hours) of various immunomodulators reduced the need for ventilation and the number of ventilator days, compared to administration after 48 hours. There was an increased incidence of secondary bacterial infections among the non-survivors.
ABSTRACT
Introduction: The 1st wave of COVID-19 spread rapidly affecting most countries globally in a short duration. Many countries suffered the 2nd wave of COVID-19 infection, months after the 1st wave, largely driven by viral mutants with high transmissibility and reduced susceptibility to neutralising antibodies (1-3). Despite COVID-19 being the common etiology, the two waves have significant differences impacting both current understanding and future planning of the impact of COVID-19. This study from a tertiary ICU is a comparative analysis focusing on the cardinal differences in COVID-19 ICU patients between the two waves, with respect to baseline demographics, clinical features, disease severity, and outcomes. Materials and methods: Retrospective data was collected from the medical records of all patients with COVID-19 disease admitted to the intensive care unit (ICU) in the 1st and 2nd wave of the pandemic. COVID-19 disease was confirmed by means of a positive RT-PCR or a rapid antigen test (RAT) on a nasopharyngeal swab or respiratory sample. Baseline demographic and clinical data, disease severity, and outcomes were analysed. Results: 419 patients (74.9% males) were admitted to the ICU between July and December 2020 and 206 (65% males) patients between April and June 2021. The mean age of patients admitted in the 1st wave was 59.84 ± 13.7 (mean ± SD) years and the 2nd wave was 55.31 ± 14.9 years (p = 0.038). The duration from symptom onset to admission (Median, IQR) was 5 days (3, 7) for the 1st wave and 5 days (3, 8) for the 2nd wave. 74.5% (312/419) of the patients in the 1st wave and 64.5% (129/206) in the 2nd wave had one or more comorbidities (p = 0.05). The median CRP values were 83.0 mg% (IQR 31.45, 159.7) for the 1st wave and 93.0 mg% (IQR 48.0, 141.0) for the 2nd wave, respectively, statistically not significant. 31.8% (131/412) of the ICU patients in the 1st wave and 52.3% (103/196) in the 2nd wave required mechanical ventilator support (p < 0.05). The overall ICU mortality was 32.1% (134/418) for the 1st and 52.5% (104/198) for the 2nd wave (p value?). Conclusion: There is a significant difference between the 2 waves in age, comorbidities, and mortality, likely related to viral mutants, vaccination policies, and social mobility dynamics.