Pre-exposure prophylaxis of new COVID-19 coronavirus infection with tixagevimab/cilgavimab in adult Moscow patients with primary immunodeficiencies

Cover Page

Cite item

Full Text

Abstract

Background. Primary immunodeficiencies (PIDs), now known as inborn errors of immunity, are a group of inherited diseases caused by defects in the genes that control the immune response. Patients with PIDs have risks of developing a severe course and/or death in COVID-19. Passive immunization with long-acting monoclonal antibodies (MABs) to SARS-CoV-2 should be considered as pre-exposure prophylaxis in patients with PIDs. Tixagevimab/cilgavimab is a combination of MABs that bind to the SARS-CoV-2 spike protein.

Aim. To evaluate the efficacy and safety of pre-exposure prophylaxis of new SARS-CoV-2 infection in PIDs with the combination of tixagevimab/cilgavimab.

Materials and methods. Forty eight patients diagnosed with PIDs were included in the study. Median follow-up after drug administration was 174 days. The total number of confirmed coronavirus infections in patients with PIDs as well as 6 months before and after administration of MAT were assessed.

Results. In the analyzed cohort, the overall incidence of COVID-19 from pandemic onset to MABs administration was 75% (36/48), with 31% (11/36) of over-infected patients having had the infection more than once. The incidence of COVID-19 immediately 6 months before the introduction of tixagevimab/cilgavimab was 40%. All patients who had COVID-19 after pre-exposure prophylaxis had a mild infection. The incidence of COVID-19 6 months after tixagevimab/cilgavimab administration significantly decreased compared to the incidence 6 months before administration (7 and 40%, respectively; p<0.001).

Conclusion. The use of tixagevimab/cilgavimab in patients with PIDs is effective as pre-exposure prophylaxis and reduces the risk of severe COVID-19.

About the authors

Anna A. Roppelt

City Clinical Hospital №52; Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology

Author for correspondence.
Email: roppelt_anna@mail.ru
ORCID iD: 0000-0001-5132-1267

канд. мед. наук, врач аллерголог- иммунолог клинико-диагностического отд-ния; мл. науч. сотр. отд. оптимизации лечения иммунодефицитов

Russian Federation, Moscow; Moscow

Marina S. Lebedkina

City Clinical Hospital №52

Email: roppelt_anna@mail.ru
ORCID iD: 0000-0002-9545-4720

врач – аллерголог-иммунолог отд-ния аллергологии и иммунологии

Russian Federation, Moscow

Anton A. Chernov

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

Email: roppelt_anna@mail.ru
ORCID iD: 0000-0001-6209-387X

мл. науч. сотр. Научно-исследовательского института молекулярной и персонализированной медицины; врач-терапевт отд. клинической фармакологии

Russian Federation, Moscow; Moscow

Tatiana S. Kruglova

City Clinical Hospital №52

Email: roppelt_anna@mail.ru
ORCID iD: 0000-0002-4949-9178

врач – аллерголог-иммунолог, зав. отд-нием аллергологии и иммунологии

Russian Federation, Moscow

Olga A. Mukhina

City Clinical Hospital №52

Email: roppelt_anna@mail.ru
ORCID iD: 0000-0002-3794-4991

врач – аллерголог-иммунолог консультативно-диагностического отд-ния

Russian Federation, Moscow

Yulia D. Yukhnovskaya

Sechenov First Moscow State Medical University (Sechenov University)

Email: roppelt_anna@mail.ru
ORCID iD: 0000-0002-0928-2054

клин. ординатор каф. клинической иммунологии и аллергологии Института клинической медицины

Russian Federation, Moscow

Farida A. Samedova

Sechenov First Moscow State Medical University (Sechenov University)

Email: roppelt_anna@mail.ru
ORCID iD: 0000-0002-0852-7208

клин. ординатор каф. клин. иммунологии и аллергологии Института клинической медицины

Russian Federation, Moscow

Ulyana A. Mаrkina

City Clinical Hospital №52

Email: roppelt_anna@mail.ru
ORCID iD: 0000-0002-6646-4233

врач – аллерголог-иммунолог отд-ния аллергологии и иммунологии

Russian Federation, Moscow

Gerelma V. Andrenova

City Clinical Hospital №52

Email: roppelt_anna@mail.ru
ORCID iD: 0000-0001-7053-3900

врач – аллерголог-иммунолог отд-ния аллергологии и иммунологии

Russian Federation, Moscow

Alexander V. Karaulov

Sechenov First Moscow State Medical University (Sechenov University)

Email: roppelt_anna@mail.ru
ORCID iD: 0000-0002-1930-5424

акад. РАН, д-р мед. наук, проф., зав. лаб. иммунопатологии Института молекулярной медицины, зав. каф. клин. иммунологии и аллергологии Института клинической медицины им. Н.В. Склифосовского

Russian Federation, Moscow

Mariana A. Lysenko

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

Email: roppelt_anna@mail.ru
ORCID iD: 0000-0001-6010-7975

д-р мед. наук, проф. каф. общей терапии фак-та дополнительного профессионального образования; глав. врач

Russian Federation, Moscow; Moscow

Daria S. Fomina

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

Email: roppelt_anna@mail.ru
ORCID iD: 0000-0002-5083-6637

канд. мед. наук, доц., доц. каф. клин. иммунологии и аллергологии; рук. Московского городского научно-практического центра аллергологии и иммунологии

Russian Federation, Moscow; Moscow

References

  1. Tangye SG, Al-Herz W, Bousfiha A, et al. Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol. 2022;42(7):1473-507. doi: 10.1007/s10875-022-01289-3
  2. Кан Н.Ю., Мухина А.А., Родина Ю.А. и др. Течение инфекции COVID-19 у пациентов с первичными иммунодефицитными состояниями. Педиатрия им. Г.Н. Сперанского. 2020;99(6):83-90 [Kan NYu, Mukhina AA, Rodina YuA, et al. COVID-19 infection in patients with primary immunodeficiencies. Pediatria n.a. G.N. Speransky. 2020;99(6):83-90. (in Russian)]. doi: 10.24110/0031-403X-2020-99-6-83-90
  3. Meyts I, Bucciol G, Quinti I, et al. Coronavirus disease 2019 in patients with inborn errors of immunity: an international study. J Allergy Clin Immunol. 2021;147(2):520-31. doi: 10.1016/j.jaci.2020.09.010
  4. Delavari S, Abolhassani H, Abolnezhadian F, et al. A. Impact of SARS-CoV-2 Pandemic on Patients with Primary Immunodeficiency. J Clin Immunol. 2021;41(2):345-55. doi: 10.1007/s10875-020-00928-x
  5. Milota T, Sobotková M, Smetanova J, et al. Risk Factors for Severe COVID-19 and Hospital Admission in Patients With Inborn Errors of Immunity – Results From a Multicenter Nationwide Study. Front Immunol. 2022;13:835770. doi: 10.3389/fimmu.2022.835770
  6. Milito C, Lougaris V, Giardino G, et al. Clinical outcome, incidence, and SARS-CoV-2 infection-fatality rates in Italian patients with inborn errors of immunity. J Allergy Clin Immunol Pract. 2021;9(7):2904-6.e2. doi: 10.1016/j.jaip.2021.04.017
  7. Karakoc Aydiner E, Bilgic Eltan S, Babayeva R, et al. Adverse COVID-19 outcomes in immune deficiencies: Inequality exists between subclasses. Allergy. 2022;77(1):282-95. doi: 10.1111/all.15025
  8. Drzymalla E, Green RF, Knuth M, et al. A. COVID-19-related health outcomes in people with primary immunodeficiency: A systematic review. Clin Immunol. 2022;243:109097. doi: 10.1016/j.clim.2022.109097
  9. Durkee-Shock JR, Keller MD. Immunizing the imperfect immune system: Coronavirus disease 2019 vaccination in patients with inborn errors of immunity. Ann Allergy Asthma Immunol. 2022;129(5):562-71.e1. doi: 10.1016/j.anai.2022.06.009
  10. Временные методические рекомендации. Профилактика, диагностика и лечение новой коронавирусной инфекции (COVID-19). Версия 17 (14.12.2022). Режим доступа: https://static-0.minzdrav.gov.ru/system/attachments/attaches/000/061/254/original/%D0%92%D0%9C%D0%A0_COVID-19_V17.pdf?1671088207. Ссылка активна на 20.01.2023 [Temporary guidelines. Prevention, diagnosis, and treatment of novel coronavirus infection (COVID-19). Version 17 (12/14/2022). Available at: https://static-0.minzdrav.gov.ru/system/attachments/attaches/000/061/254/original/%D0%92%D0%9C%D0%A0_COVID-19_V17.pdf?1671088207. Accessed: 20.01.2023 (in Russian)].
  11. Liu C, Ginn HM, Dejnirattisai W, et al. Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum. Cell. 2021;184(16):4220-36.e13. doi: 10.1016/j.cell.2021.06.020
  12. Dong J, Zost SJ, Graney AJ, et al. Genetic and structural basis for SARS-CoV-2 variant neutralization by a two-antibody cocktail. Nat Microbiol. 2021;6(10):1233-44. doi: 10.1038/s41564-021-00972-2
  13. Touret F, Baronti C, Pastorino B, et al. In vitro activity of therapeutic antibodies against SARS-CoV-2 Omicron BA.1, BA.2 and BA.5. Sci Rep. 2022;12(1):12609. doi: 10.1038/s41598-022-16964-z
  14. Tuekprakhon A, Nutalai R, Dijokaite-Guraliuc A, et al. Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum. Cell. 2022;185(14):2422-33.e13. doi: 10.1016/j.cell.2022.06.005
  15. Loo YM, McTamney PM, Arends RH, et al. The SARS-CoV-2 monoclonal antibody combination, AZD7442, is protective in nonhuman primates and has an extended half-life in humans. Sci Transl Med. 2022;14(635):eabl8124. doi: 10.1126/scitranslmed.abl8124
  16. Levin MJ, Ustianowski A, De Wit S, et al. PROVENT Study Group. Intramuscular AZD7442 (Tixagevimab-Cilgavimab) for Prevention of Covid-19. N Engl J Med. 2022;386(23):2188-200. doi: 10.1056/NEJMoa2116620
  17. Alhumaid S, Al Mutair A, Alali J, et al. Efficacy and Safety of Tixagevimab/Cilgavimab to Prevent COVID-19 (Pre-Exposure Prophylaxis): A Systematic Review and Meta-Analysis. Diseases. 2022;10(4):118. doi: 10.3390/diseases10040118
  18. Информационный бюллетень для медицинских работников: разрешение на экстренное применение лекарственного препарата эвушелд™ (evusheld™) (тиксагевимаб + цилгавимаб [набор]). Режим доступа: https://www.evusheldpi.com/content/dam/microsites/evusheld-elabelling/russia/pdf/Clean-Fact%20Sheet-HCP-PI-Evusheld-%20UAE_rus%2BRussian%20PV%20details%2BLF%20comm%20resolved.pdf Ссылка активна на 20.01.2023 [Fact Sheet for Healthcare Professionals: Emergency Use Authorization for Evusheld™ (Tixagevimab + Cilgavimab [Kit]). Available at: https://www.evusheldpi.com/content/dam/microsites/evusheld-elabelling/russia/pdf/Clean-Fact%20Sheet-HCP-PI-Evusheld-%20UAE_rus%2BRussian%20PV%20details%2BLF%20comm%20resolved.pdf Accessed: 20.01.2023 (in Russian)].
  19. Nguyen Y, Flahault A, Chavarot N, et al. Pre-exposure prophylaxis with tixagevimab and cilgavimab (Evusheld) for COVID-19 among 1112 severely immunocompromised patients. Clin Microbiol Infect. 2022;28(12):1654.e1-e4. doi: 10.1016/j.cmi.2022.07.015
  20. Totschnig D, Augustin M, Niculescu Iu, et al. SARS-CoV-2 Pre-Exposure Prophylaxis with Sotrovimab and Tixagevimab/Cilgavimab in Immunocompromised Patients-A Single-Center Experience. Viruses. 2022;14(10):2278. doi: 10.3390/v14102278
  21. Calabrese C, Kirchner E, Villa-Forte A, et al. Early experience with tixagevimab/cilgavimab pre-exposure prophylaxis in patients with immune-mediated inflammatory disease undergoing B cell depleting therapy and those with inborn errors of humoral immunity. RMD Open. 2022;8(2):e002557. doi: 10.1136/rmdopen-2022-002557
  22. Johnson S, Fernandez J. Incidence of COVID-19 infections in adults with primary immunodeficiency after receiving tixagevimab and cilgavimab. Ann Allergy Asthma Immunol. 2022;129(5):S54. doi: 10.1016/j.anai.2022.08.652
  23. Jones JM, Faruqi AJ, Sullivan JK, et al. COVID-19 Outcomes in Patients Undergoing B Cell Depletion Therapy and Those with Humoral Immunodeficiency States: A Scoping Review. Pathog Immun. 2021;6(1):76-103. doi: 10.20411/pai.v6i1.435
  24. Cook C, Patel NJ, D`Silva KM, et al. Clinical characteristics and outcomes of COVID-19 breakthrough infections among vaccinated patients with systemic autoimmune rheumatic diseases. Ann Rheum Dis. 2022;81(2):289-91. doi: 10.1136/annrheumdis-2021-221326

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Distribution of primary immunodeficiency nosologies in the analysed group of patients (n=48).

Download (99KB)
Indexing metadata
3. Fig. 2. SARS-CoV-2 frequency in patients before and after tixagevimab/cylgavimab.

Download (81KB)
Indexing metadata

Copyright (c) 2023 Consilium Medicum

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
 
 


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies