Compassionate use of REGN-COV2 in the treatment of COVID-19 in a patient with impaired humoral immunity

Abstract

Background The role of antibodies in coronavirus disease 2019 (COVID-19) in patients with X-linked agammaglobulinaemia (XLA) has yet to be characterised and clinical courses observed in this cohort of patients have been heterogeneous. Whilst some exhibit spontaneous recovery, others have experienced a more protracted disease length. Previous reports have described successful use of convalescent plasma, however there is a paucity of information around the use of the REGN-COV2 antibody cocktail in these patients. Case Report A patient with XLA was admitted to hospital with COVID-19 and remained persistently symptomatic with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) swab positivity despite treatment with Remdesivir and dexamethasone. Attempts at modulating the immune response with anakinra were unsuccessful. Consent for compassionate use of REGN-COV2 was obtained with administration taking place on day 87 of his illness. This was followed by a period of convalescence and SARS-CoV-2 nasopharyngeal swab negativity. As a consequence of prolonged immunosuppression, the patient developed pneumocystis pneumonia. Conclusion This case highlights the role of antibodies in clearing SARS-CoV-2 in a hypogammaglobulinaemic host and demonstrates the consequences of prolonged immunosuppression and delayed treatment. We propose that this may be of particular significance given the capacity of SARS-CoV-2 to develop advantageous mutations in a chronically infected host.

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

“…Interestingly, in our cases there was limited evidence of a clinical or virological response to remdesivir in vivo. Similar findings have been observed elsewhere [ 23 , 28 ], in situations where in vitro sensitivity of the SARS-CoV-2 isolate has been demonstrated [ 28 ], although in other reports a response to remdesivir was seen, albeit followed by viral recrudescence [ 14 , 19 , 36 , 39 , 40 ]. It remains an open question whether remdesivir is needed as an adjunct to REGN-COV2 or other mAb therapies in the management of chronic COVID-19 in immunocomromised patients.…”

“…Interestingly, this patient had evidence of vRNA in bronchoalveolar lavage which was absent from the upper respiratory tract. Nguyen and colleagues reported effectiveness of REGN-COV2 in combination with remdesivir in a patient with X-linked agammaglobulinaemia (XLA) and persistent COVID-19 [ 23 ]. Conversely, Choi and colleagues reported use of REGN-COV2 in a rituximab-treated patient who was critically ill with COVID-19 and aspergillus coinfection and died 11 days after administration [ 36 ].…”

“…Thus while immunomodulation with agents such as dexamethasone and/or tocilizumab is a logical strategy in immunocompetent patients, supported by clear evidence from randomised controlled trials [ 42 , 43 ], there may also be a clinical need for antiviral therapies and/or interventions designed to enhance antiviral responses in immunocompromised patients. This is relevant since patients with pre-existing immunocompromise are at increased risk of infectious complications of agents such as corticosteroids or anticytokine therapies [ 23 ].…”

Corticosteroids: A boon or bane for COVID-19 patients?

“…On November 21, 2020, USFDA gave REGN-CoV-2 emergency approval for the treatment of mild or moderate COVID-19 symptoms in patients aged 12 and above (weighing at least 40 kg) and are at higher risk for developing severe COVID-19. This approval is based on the findings of a clinical trial that indicated a reduction in COVID-19-related hospitalization or emergency department visits in those at high risk of illness progression within 28 days of starting treatment [44] , [45] , [46] .…”

Persistent SARS-CoV-2 Infection in a Patient with Nephrotic Syndrome under Rituximab Therapy: Successful Treatment with a Combination of Remdesivir and Monoclonal Antibodies

“…The coronavirus disease 2019 (COVID-19) pandemic continues to affect the global population. There have been several reports of immunocompromised patients developing persistent and prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16).…”