Criteria for the optimal use of interleukin-6 receptor blockers in patients with COVID-19

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Abstract

Aim. To determine the criteria for the optimal use of IL-6 receptor blockers in patients with COVID-19 community-acquired pneumonia based on predictors of adverse outcomes.

Materials and methods. The single-center, non-randomized prospective study included 190 patients with community-acquired pneumonia caused by coronavirus 2 between the beginning of March and the end of May 2020. Of these, 89 patients received tocilizumab and 101 patients received sarilumab. The study inclusion criterion for the patient was indications for initiating therapy with one of the inhibitors of IL-6 receptors (anti-IL-6R) according to the Interim guidelines (versions 4 and 5). The exclusion criterion was the need to re-prescribe genetically engineered biological therapy (GEBT). The severity of the patient's condition was assessed according to the early warning score (NEWS2), the volume of lung tissue lesions was assessed according to computed tomography (CT). Laboratory monitoring included counting the absolute (abs) number of lymphocytes, serum levels of C-reactive protein (CRP), interleukin 6 (IL-6), D-dimer, lactate dehydrogenase, fibrinogen. Statistical data processing was conducted by nonparametric methods using the IBM SPSS Statistics V-22 software.

Results. The phenotype of a patient with a negative outcome prognosis was described: a male patient over 50 years of age with aggravated premorbid background (with cardiovascular diseases, obesity and/or chronic renal disease), lung lesion CT 3–4, saturation less than 93% upon inhalation of atmospheric air, persisting for 24–48 hours after GEBT. According to the blood test, lymphopenia was below 1000 U/L and CRP levels were above 50 mg/L. The laboratory parameters and clinical picture of the patient progressively worsened after 9–11 days of illness, regardless of the use of Anti-IL-6R. The features of patients monitoring when administering IL-6 receptor blockers have been determined.

Conclusion. IL-6 receptor blockers should be administered to patients hospitalized with severe COVID-19 before the development of hyperinflammatory reactions. The optimal "therapeutic window" is 7–8 days of illness.

About the authors

Tatyana S. Kruglova

City Clinical Hospital №52

Email: surckova.t@yandex.ru
ORCID iD: 0000-0002-4949-9178

врач аллерголог-иммунолог, зав. отд-нием аллергологии и иммунологии ГБУЗ ГКБ №52

Russian Federation, Moscow

Darya S. Fomina

City Clinical Hospital №52; Sechenov First Moscow State Medical University (Sechenov University)

Email: surckova.t@yandex.ru
ORCID iD: 0000-0002-5083-6637

канд. мед. наук, врач аллерголог- иммунолог, рук. центра аллергологии и иммунологии ГБУЗ ГКБ №52; доц. каф. клинической иммунологии и аллергологии ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» (Сеченовский Университет)

Russian Federation, Moscow

Nataliya G. Poteshkina

City Clinical Hospital №52; Pirogov Russian National Research Medical University

Author for correspondence.
Email: surckova.t@yandex.ru
ORCID iD: 0000-0001-9803-2139

д-р мед. наук, проф., рук. университетской клиники ГБУЗ ГКБ №52; зав. каф. общей терапии фак-та ДПО ФГАОУ ВО «РНИМУ им. Н.И. Пирогова»

Russian Federation, Moscow

Nadija F. Frolova

City Clinical Hospital №52

Email: surckova.t@yandex.ru
ORCID iD: 0000-0003-3234-8266

канд. мед. наук, врач-нефролог, зам. глав. врача по нефрологической помощи ГБУЗ ГКБ №52

Russian Federation, Moscow

Irina P. Beloglazova

City Clinical Hospital №52; Pirogov Russian National Research Medical University

Email: surckova.t@yandex.ru
ORCID iD: 0000-0002-2266-1497

канд. мед. наук, врач терапевт-пульмонолог, зав. 4-м терапевтическим отд-нием ГБУЗ ГКБ №52; доц. каф. общей терапии фак-та ДПО ФГАОУ ВО «РНИМУ им. Н.И. Пирогова»

Russian Federation, Moscow

Zinaida Yu. Mutovina

City Clinical Hospital №52; Central State Medical Academy of the President of the Russian Federation

Email: surckova.t@yandex.ru
ORCID iD: 0000-0001-5809-6015

канд. мед. наук, доц. каф. общей терапии, кардиологии и функциональной диагностики ФГБУ ДПО ЦГМА УД Президента РФ; врач-ревматолог, зав. ревматологическим отд-нием ГБУЗ ГКБ №52

Russian Federation, Moscow

Inna V. Samsonova

City Clinical Hospital №52

Email: surckova.t@yandex.ru
ORCID iD: 0000-0002-1228-1765

канд. мед. наук, зам. глав. врача по медицинской части ГБУЗ ГКБ №52

Russian Federation, Moscow

Elena A. Kovalevskaja

City Clinical Hospital №52

Email: surckova.t@yandex.ru
ORCID iD: 0000-0002-0787-4347

канд. мед. наук, врач-кардиолог, зав. кардиологическим отд-нием ГБУЗ ГКБ №52

Russian Federation, Moscow

Alena I. Zagrebneva

City Clinical Hospital №52; Pirogov Russian National Research Medical University

Email: surckova.t@yandex.ru
ORCID iD: 0000-0002-3235-1425

канд. мед. наук, зав. консультативно-диагностическим отд-нием №2 ГБУЗ ГКБ №52; доц. каф. общей терапии фак-та ДПО ФГАОУ ВО «РНИМУ им. Н.И. Пирогова»

Russian Federation, Moscow

Sofya A. Serdotetckova

City Clinical Hospital №52

Email: surckova.t@yandex.ru
ORCID iD: 0000-0001-8472-1152

врач аллерголог-иммунолог консультативно-диагностического отд-ния центра аллергологии и иммунологии ГБУЗ ГКБ №52

Russian Federation, Moscow

Anton A. Chernov

City Clinical Hospital №52; Russian Medical Academy of Continuous Professional Education

Email: surckova.t@yandex.ru
ORCID iD: 0000-0001-6209-387X

врач-терапевт отд. клин. фармакологии ГБУЗ ГКБ №52; мл. науч. сотр. Научно-исследовательского института молекулярной и персонализированной медицины ФГБОУ ДПО РМАНПО

Russian Federation, Moscow

Maryana A. Lysenko

City Clinical Hospital №52; Pirogov Russian National Research Medical University

Email: surckova.t@yandex.ru
ORCID iD: 0000-0001-6010-7975

д-р мед. наук, глав. врач ГБУЗ ГКБ №52; проф. каф. общей терапии фак-та ДПО ФГАОУ ВО «РНИМУ им. Н.И. Пирогова»

Russian Federation, Moscow

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Supplementary files

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2. Fig. 1. Survival curve of patients with COVID-19 according to laboratory parameters (CRP, lymphocytes, lactate dehydrogenase – LDH).

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3. Fig. 2. Survival curve of patients with COVID-19 according to laboratory parameters (CRP50 mg/l, lymphocytes 1000 abs.).

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4. Fig. 3. Survival curve of patients with COVID-19 according to laboratory parameters (CRP>/<50 mg/l).

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5. Fig. 4. The incidence of comorbidities in patients who received GEBT (n=190).

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6. Fig. 5. The proportion of deaths/comorbid conditions in patients having received SAR (n=101).

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