Anakinra in hospitalized patients with severe COVID-19 pneumonia requiring oxygen therapy: Results of a prospective, open-label, interventional study

A Balkhair¹, I Al-Zakwani², M Al Busaidi³, A Al-Khirbash⁴, S Al Mubaihsi⁵, H BaTaher⁶, J Al Aghbari⁷, I Al Busaidi⁸, M Al Kindi⁹, S Baawain¹⁰, A Al Alawi¹¹, A Al Lawati¹², B Al Rawahi¹³, K Al-Baimani¹⁴, K Al Zidi¹⁵, N Elfatih¹⁶, B Dawud¹⁷, B John¹⁸, F Rehman¹⁹, F Yousif²⁰, G Al Khadouri²¹, I Saber²², J Lal²³, M Gargouri²⁴, M Al-Ward²⁵, N AbuDraz²⁶, S Al Ruqeishi²⁷, S Kumar²⁸, W Abdelmottaleb²⁹, Z Al-Naamani³⁰, Z Bin Nazar³¹, O Balkhair³²

Affiliations

¹ Department of Medicine, Infectious Diseases Unit, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: balkhair2020@gmail.com.
² Department of Pharmacology & Clinical Pharmacy, College of Medicine & Health Sciences, Sultan Qaboos University, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: azakwani@squ.edu.om.
³ Department of Medicine, Intensive Care, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: mujahid@squ.edu.om.
⁴ Department of Pharmacology & Clinical Pharmacy, College of Medicine & Health Sciences, Sultan Qaboos University, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: athar_sk2@hotmail.com.
⁵ Department of Medicine, Pulmonology, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: alsaif1010@squ.edu.om.
⁶ Department of Medicine, Infectious Diseases Unit, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: Bataher84@gmail.com.
⁷ Department of Medicine, Pulmonology, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: j-alaghbari83@hotmail.com.
⁸ Department of Medicine, Infectious Diseases Unit, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: ibrahimbusaidi@gmail.com.
⁹ Department of Microbiology and Immunology, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: dralkindi@squ.edu.om.
¹⁰ Department of Radiology and Molecular Imaging, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: salehbaawain@gmail.com.
¹¹ Department of Medicine, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: dr.abdullahalalawi@gmail.com.
¹² Department of Medicine, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: alii.allawati@gmail.com.
¹³ Department of Hematology, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: bass@squ.edu.om.
¹⁴ Department of Medicine, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: khalidbimani@gmail.com.
¹⁵ Department of Medicine, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: khalfanalzidii@gmail.com.
¹⁶ Department of Medicine, Pulmonology, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: nasreenelfatih@hotmail.com.
¹⁷ Department of Surgery, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: Bashardawud@gmail.com.
¹⁸ Department of Surgery, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: bassinj@gmail.com.
¹⁹ Department of Medicine, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: dr_farooq03@yahoo.com.
²⁰ Department of Medicine, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: Faroug118@gmail.com.
²¹ Department of Hematology, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: ghalibsa@squ.edu.om.
²² Department of Surgery, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: islam.ss@squ.edu.om.
²³ Department of Medicine, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: Jawahirlal@squ.edu.om.
²⁴ Department of Surgery, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: gargourimourad@yahoo.fr.
²⁵ Department of Surgery, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: Mustafa.m.alward@gmail.com.
²⁶ Department of Surgery, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: najeeb_draz@hotmail.com.
²⁷ Department of Hematology, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: salimruq@squ.edu.om.
²⁸ Department of Medicine, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: seet.sunil@gmail.com.
²⁹ Department of Medicine, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: Dr.wam1@yahoo.com.
³⁰ Department of Medicine, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: zakriya2006@hotmail.com.
³¹ Faculty of Biological Sciences, University of Leeds, UK. Electronic address: drzuhail@gmail.com.
³² Faculty of Biological Sciences, University of Leeds, UK. Electronic address: balkhair2012@gmail.com.

PMID: 33217576
PMCID: PMC7670920
DOI: 10.1016/j.ijid.2020.11.149

Anakinra in hospitalized patients with severe COVID-19 pneumonia requiring oxygen therapy: Results of a prospective, open-label, interventional study

A Balkhair et al. Int J Infect Dis. 2021 Feb.

. 2021 Feb:103:288-296.

doi: 10.1016/j.ijid.2020.11.149. Epub 2020 Nov 17.

Authors

Affiliations

¹ Department of Medicine, Infectious Diseases Unit, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: balkhair2020@gmail.com.
² Department of Pharmacology & Clinical Pharmacy, College of Medicine & Health Sciences, Sultan Qaboos University, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: azakwani@squ.edu.om.
³ Department of Medicine, Intensive Care, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: mujahid@squ.edu.om.
⁴ Department of Pharmacology & Clinical Pharmacy, College of Medicine & Health Sciences, Sultan Qaboos University, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: athar_sk2@hotmail.com.
⁵ Department of Medicine, Pulmonology, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: alsaif1010@squ.edu.om.
⁶ Department of Medicine, Infectious Diseases Unit, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: Bataher84@gmail.com.
⁷ Department of Medicine, Pulmonology, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: j-alaghbari83@hotmail.com.
⁸ Department of Medicine, Infectious Diseases Unit, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: ibrahimbusaidi@gmail.com.
⁹ Department of Microbiology and Immunology, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: dralkindi@squ.edu.om.
¹⁰ Department of Radiology and Molecular Imaging, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: salehbaawain@gmail.com.
¹¹ Department of Medicine, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: dr.abdullahalalawi@gmail.com.
¹² Department of Medicine, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: alii.allawati@gmail.com.
¹³ Department of Hematology, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: bass@squ.edu.om.
¹⁴ Department of Medicine, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: khalidbimani@gmail.com.
¹⁵ Department of Medicine, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: khalfanalzidii@gmail.com.
¹⁶ Department of Medicine, Pulmonology, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: nasreenelfatih@hotmail.com.
¹⁷ Department of Surgery, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: Bashardawud@gmail.com.
¹⁸ Department of Surgery, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: bassinj@gmail.com.
¹⁹ Department of Medicine, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: dr_farooq03@yahoo.com.
²⁰ Department of Medicine, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: Faroug118@gmail.com.
²¹ Department of Hematology, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: ghalibsa@squ.edu.om.
²² Department of Surgery, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: islam.ss@squ.edu.om.
²³ Department of Medicine, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: Jawahirlal@squ.edu.om.
²⁴ Department of Surgery, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: gargourimourad@yahoo.fr.
²⁵ Department of Surgery, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: Mustafa.m.alward@gmail.com.
²⁶ Department of Surgery, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: najeeb_draz@hotmail.com.
²⁷ Department of Hematology, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: salimruq@squ.edu.om.
²⁸ Department of Medicine, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: seet.sunil@gmail.com.
²⁹ Department of Medicine, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: Dr.wam1@yahoo.com.
³⁰ Department of Medicine, Sultan Qaboos University Hospital, PO Box 35, Alkoudh 123, Muscat, Oman. Electronic address: zakriya2006@hotmail.com.
³¹ Faculty of Biological Sciences, University of Leeds, UK. Electronic address: drzuhail@gmail.com.
³² Faculty of Biological Sciences, University of Leeds, UK. Electronic address: balkhair2012@gmail.com.

PMID: 33217576
PMCID: PMC7670920
DOI: 10.1016/j.ijid.2020.11.149

Abstract

Objective: The aim of this study was to evaluate the efficacy of anakinra in patients who were admitted to hospital for severe COVID-19 pneumonia requiring oxygen therapy.

Methods: A prospective, open-label, interventional study in adults hospitalized with severe COVID-19 pneumonia was conducted. Patients in the interventional arm received subcutaneous anakinra (100 mg twice daily for 3 days, followed by 100 mg daily for 7 days) in addition to standard treatment. Main outcomes were the need for mechanical ventilation and in-hospital death. Secondary outcomes included successful weaning from supplemental oxygen and change in inflammatory biomarkers. Outcomes were compared with those of historical controls who had received standard treatment and supportive care.

Results: A total of 69 patients were included: 45 treated with anakinra and 24 historical controls. A need for mechanical ventilation occurred in 14 (31%) of the anakinra-treated group and 18 (75%) of the historical cohort (p < 0.001). In-hospital death occurred in 13 (29%) of the anakinra-treated group and 11 (46%) of the historical cohort (p = 0.082). Successful weaning from supplemental oxygen to ambient air was attained in 25 (63%) of the anakinra-treated group compared with 6 (27%) of the historical cohort (p = 0.008). Patients who received anakinra showed a significant reduction in inflammatory biomarkers.

Conclusion: In patients with severe COVID-19 pneumonia and high oxygen requirement, anakinra could represent an effective treatment option and may confer clinical benefit.

Trial registration number: ISRCTN74727214.

Keywords: Anakinra; COVID-19; COVID-19 pneumonia; Hyperinflammation; Mechanical ventilation.

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Figures

**Figure 1**
Change in oxygen requirement over time. (a) Graphic depiction of change in oxygen requirement over time (to maintain SpO₂ >93%) for each patient in the anakinra-treated group. Day 0 refers to the day of initiation of anakinra (day of enrolment). Each number represents a single patient. (b) Graphic depiction of change in oxygen requirement over time (to maintain SpO₂ >93%) for each patient in the historical control group. Day 0 refers to the day of enrolment equivalence. Each number represents a single patient.

**Figure 2**
The effect of anakinra on inflammatory biomarkers. (a) Changes in IL-6 concentrations between D0 (day 0) and D14 (day 14) among patients in the anakinra group (*comparison data available for 33 patients*). (b) Changes in CRP concentrations between D0 (day 0) and D14 (day 14) among patients in the anakinra group (*comparison data available for 40 patients*). (c) Changes in LDH concentrations between D0 (day 0) and D14 (day 14) among patients in the anakinra group (*comparison data available for 28 patients*).

See this image and copyright information in PMC

References

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Anakinra in hospitalized patients with severe COVID-19 pneumonia requiring oxygen therapy: Results of a prospective, open-label, interventional study

Affiliations

Anakinra in hospitalized patients with severe COVID-19 pneumonia requiring oxygen therapy: Results of a prospective, open-label, interventional study

Authors

Affiliations

Abstract

Figures

References

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Substances

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical