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Background: Aberrant immune response is hallmark of severe COVID-19, irrespectively from viral replication. Immunomodulatory therapies such as interleukin-6 (IL-6) receptor inhibitors were proven to be beneficial in reducing in-hospital mortality 1 . Yet, it remains unclear which patients can benefit most from such therapy.
Objectives: To identify predictors of clinical response to tocilizumab (TCZ) added to dexamethasone in patients hospitalized with severe COVID-19.
Methods: We prospectively assessed clinical and laboratory details of 120 patients hospitalized due to severe COVID-19 treated with TCZ (two doses of 8 mg/kg 24h apart) in our ward between 1 st Feb 2021 and 31 st Dec 2021. Severe COVID-19 was defined as SpO 2 <94% on room air with ground glass opacities in chest computed tomography (CT). Clinical response was defined as respiratory improvement on day 5 after TCZ infusion compared to day of treatment initiation, no further deterioration and survival. Decision of adding TCZ to dexamethasone as emergency therapy was made collectively by rheumatologists experienced in COVID-19 treatment. Laboratory and clinical parameters from hospital admission day and from TCZ institution day were analyzed. Statistical analysis was conducted with PQStat v.1.8.2 and predictors were identified in univariate logistic regression.
Results: We identified 86 (71.7%) clinical responders and 34 (28.3%) non-responders. 20 (58.8%) of the second group needed ICU admission, 18 (52.9%) died on ICU and 2 patients (5.9%) died on the ward. Responders were significantly younger (mean age 56.1 vs. 63.5 years, p=0.006), had lesser comorbidity burden (median Charleson Comorbidity Index 2 vs. 3, p=0.005), lower median lung involvement (50 vs. 70%, p<0.001), higher median baseline PaO2/FiO2 index (203 vs. 106, p<0.001) and less of them needed high-flow oxygen therapy on TCZ initiation day (12.7% vs 32.4%, p=0.025).
Identified predictors of clinical response are shown in
Predictors of good response to TCZ therapy in severe COVID-19. Apart from PaO2/FiO2 all parameters identified as predictors were measured on TCZ initiation day.
| Predictor | OR | 95%CI | p value |
|---|---|---|---|
| LDH <447 U/l | 12.67 | 4.42-36.31 | <0.001 |
| <70% of lungs involved in CT | 6.76 | 2.63-17.36 | <0.001 |
| 9-12 days from symptoms onset | 6.43 | 1.82-22.73 | 0.004 |
| RR <20/min | 5.40 | 2.29-12.75 | <0.001 |
| hs-TnI <26 ng/l | 4.80 | 1.55-14.81 | 0.006 |
| BUN <22.2 mg/dl | 4.71 | 2.02-10.99 | <0.001 |
| SpO2/FiO2 >122 | 4.47 | 1.92-10.40 | <0.001 |
| fibrinogen ≥490 mg/dl | 4.46 | 1.86-10.72 | <0.001 |
| no history of asthma/COPD | 4.39 | 1.55-16.71 | 0.030 |
| no history of atrial fibrillation | 4.20 | 1.23-14.33 | 0.022 |
| baseline PaO2/FiO2 >200 mmHg | 4.04 | 1.59-10.27 | 0.003 |
| 25(OH)D 3 ≥30 ng/ml | 3.98 | 1.40-11.28 | 0.009 |
| age <65 years | 3.69 | 1.60-8.46 | 0.002 |
| no history of ischaemic heart disease | 3.56 | 1.29-9.79 | 0.014 |
| procalcitonin 0.06-0.12 ng/ml | 3.20 | 1.20-8.54 | 0.020 |
| D-Dimer ≤1.28 µg/ml | 3.12 | 1.37-7.09 | 0.006 |
| IL-6 47.4-137.0 pg/ml | 3.07 | 1.90-4.98 | <0.001 |
OR – odds ratio, 95%CI – 95% confidence interval, LDH – lactate dehydrogenase, RR – respiratory rate, hs-TnI – high sensitivity troponin I, BUN – blood urea nitrogen, COPD – chronic obstructive pulmonary disease, 25(OH)D 3 – 25-hydroxycholecalciferol, IL-6 – interleukin 6
Conclusion: Administration of TCZ early in severe disease, with moderate IL-6 concentration and low organ damage indices is most beneficial in patients with severe COVID-19, especially in younger patients without respiratory and cardiac comorbidities.
REFERENCES:
[1]RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet Lond Engl . 2021;397:1637-1645.
Disclosure of Interests: None declared