Persistent SARS-CoV-2 infection in patients with secondary antibody deficiency: successful clearance following combination casirivimab and imdevimab (REGN-COV2) monoclonal antibody therapy

Autor: Adam Evans, Hayley Wardle, Ewan Hunter, Christopher J A Duncan, Yusri Taha, Shirelle Burton-Fanning, Matthew Bashton, Darren Smith, Helen Marr, Wendy Osborne, Matthias Schmid
Rok vydání: 2021
Předmět:
Male
Case Report
Infectious and parasitic diseases
RC109-216
0302 clinical medicine
Medicine
Secondary antibody deficiency
030212 general & internal medicine
Passive immunisation
Lymphoma
Follicular
Monoclonal antibody therapy
0303 health sciences
C100
Antibodies
Monoclonal
General Medicine
C500
Middle Aged
QR1-502
3. Good health
Drug Combinations
Infectious Diseases
Treatment Outcome
Female
Persistent Infection
B cell depleting therapy
Microbiology (medical)
Omicron
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
RM1-950
Primary and secondary immunodeficiency
Antibodies
Monoclonal
Humanized
Microbiology
03 medical and health sciences
Humans
In patient
Antibody deficiency
COVID-19 Serotherapy
030304 developmental biology
Aged
Chronic COVID-19
business.industry
SARS-CoV-2
Immunization
Passive
COVID-19
Antibodies
Neutralizing
COVID-19 Drug Treatment
B900
Immunology
Therapeutics. Pharmacology
business
Ronapreve (REGN-COV2)
Zdroj: Annals of Clinical Microbiology and Antimicrobials
Annals of Clinical Microbiology and Antimicrobials, Vol 20, Iss 1, Pp 1-9 (2021)
ISSN: 1476-0711
Popis: Background There is growing evidence that antibody responses play a role in the resolution of SARS-CoV-2 infection. Patients with primary or secondary antibody deficiency are at increased risk of persistent infection. This challenging clinical scenario is associated with adverse patient outcome and potentially creates an ecological niche for the evolution of novel SARS-CoV-2 variants with immune evasion capacity. Case reports and/or series have implied a therapeutic role for convalescent plasma (CP) to secure virological clearance, although concerns have been raised about the effectiveness of CP and its potential to drive viral evolution, and it has largely been withdrawn from clinical use in the UK. Case presentation We report two cases in which persistent SARS-CoV-2 infection was cleared following administration of the monoclonal antibody combination casirivimab and imdevimab (REGN-COV2, Ronapreve). A 55-year-old male with follicular lymphoma, treated with B cell depleting therapy, developed SARS-CoV-2 infection in September 2020 which then persisted for over 200 days. He was hospitalised on four occasions with COVID-19 and suffered debilitating fatigue and malaise throughout. There was no clinical response to antiviral therapy with remdesivir or CP, and SARS-CoV-2 was consistently detected in nasopharyngeal swabs. Intrahost evolution of several spike variants of uncertain significance was identified by viral sequence analysis. Delivery of REGN-COV2, in combination with remdesivir, was associated with clinical improvement and viral clearance within 6 days, which was sustained for over 150 days despite immunotherapy for relapsed follicular lymphoma. The second case, a 68-year-old female with chronic lymphocytic leukaemia on ibrutinib, also developed persistent SARS-CoV-2 infection. Despite a lack of response to remdesivir, infection promptly cleared following REGN-COV2 in combination with remdesivir, accompanied by resolution of inflammation and full clinical recovery that has been maintained for over 290 days. Conclusions These cases highlight the potential benefit of REGN-COV2 as therapy for persistent SARS-CoV-2 infection in antibody deficient individuals, including after failure of CP treatment. Formal clinical studies are warranted to assess the effectiveness of REGN-COV2 in antibody-deficient patients, especially in light of the emergence of variants of concern, such as Omicron, that appear to evade REGN-COV2 neutralisation.
Databáze: OpenAIRE
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