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

Abstract 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have been raised about the effectiveness of CP and its potential to drive viral evolution, and it has largely been withdrawn from clinical use in the UK.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.

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Persistent SARS-CoV-2 Infection in Patients With Secondary Antibody Deficiency: Successful Clearance Following Combination Casirivimab and Imdevimab (REGN-COV2) Monoclonal Antibody Therapy

10.21203/rs.3.rs-991639/v1 ◽

2021 ◽

Author(s):

Yusri Taha ◽

Hayley Wardle ◽

Adam B. Evans ◽

Ewan R. Hunter ◽

Helen Marr ◽

...

Keyword(s):

Monoclonal Antibody ◽

Follicular Lymphoma ◽

Case Reports ◽

Viral Evolution ◽

Antibody Therapy ◽

Antibody Deficiency ◽

Passive Immunisation ◽

Secondary Antibody ◽

Increased Risk ◽

The Uk

Abstract 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 passive immunisation with 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.

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535. Comparison of Outcomes in Patients Positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection After Monoclonal Antibody Therapy (MAT) with Bamlamivimab or Casirivimab-Imdevimab

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.734 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S369-S369

Author(s):

Courtney Nichols ◽

Mark Lustberg ◽

Mohammad Mahdee Sobhanie ◽

Joy Lehman ◽

Erica E Reed ◽

...

Keyword(s):

Monoclonal Antibody ◽

Research Study ◽

Hospital Admissions ◽

Antibody Therapy ◽

Scientific Research ◽

Panel Member ◽

Monoclonal Antibody Therapy ◽

Study Investigator ◽

Increased Risk ◽

Significant Difference

Abstract Background Limited options currently exist for treatment of patients diagnosed with symptomatic coronavirus 2019 (COVID-19). Monoclonal antibody therapy (MAT) has been investigated as a therapeutic option for symptomatic COVID-19 patients in the outpatient setting at high-risk for progression to severe disease based on emergency use authorization (EUA) criteria. No published studies have compared outcomes for patients treated with different MAT for COVID-19. Methods This was a single-center, retrospective cohort study at The Ohio State University Wexner Medical Center to compare COVID-19-related emergency room (ER) visits, admissions, and mortality at 30 days after MAT infusion for adult patients with symptomatic SARS-CoV-2 between November 16, 2020 and February 2, 2021 who received bamlanivimab versus those who received casirivimab-imdevimab. Statistical analysis used logistic regression analysis to determine the odds ratio (OR) to evaluate the relationship between patient characteristics, MAT, and outcomes. Results The cohort included 943 patients with SARS-CoV-2 who received MAT, including 658 patients who received bamlanivimab and 285 who received casirivimab-imdevimab. Outcome results between patients who received bamlanivimab and casirivimab-imdevimab showed no statistically significant difference seen in the number of COVID-19 related ER visits (3.2% vs 3.5%, p = 0.80), hospital admissions (4.6% vs 2.8%, p = 0.21), or mortality (0.5% vs 0.7%, p = 0.63). Multivariate analysis showed no statistically significant difference in outcomes between the groups when accounting for potential confounders. As reflected in the Table, chronic lymphocytic leukemia (CLL), gender, and asthma were associated with increased COVID-19 related ER visit within 30 days of infusion and age, chronic obstructive pulmonary disease, CLL, and lupus were associated with increased risk for COVID-19 related admission within 30 days of infusion. Age and obesity with body mass index greater than 35 mg/kg2 were associated with increased risk for COVID-19 related mortality at 30 days. Conclusion COVID-19 related outcomes were similar when comparing patients with COVID-19 treated with bamlanivimab versus those treated with casirivimab-imdevimab. Disclosures Mohammad Mahdee Sobhanie, M.D., Regeneron (Scientific Research Study Investigator)Regeneron (Scientific Research Study Investigator, Was a sub-investigator for Regeneron 2066 and 2069) Carlos Malvestutto, M.D., Lilly (Scientific Research Study Investigator)Regeneron Inc. (Scientific Research Study Investigator)ViiV Healthcare (Advisor or Review Panel member)

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Prescribing Immunoglobulin Replacement Therapy for Patients with Non-classical and Secondary Antibody Deficiency: an Analysis of the Practice of Clinical Immunologists in the UK and Republic of Ireland

Journal of Clinical Immunology ◽

10.1007/s10875-017-0469-4 ◽

2018 ◽

Vol 38 (2) ◽

pp. 204-213 ◽

Cited By ~ 9

Author(s):

John David M. Edgar ◽

◽

Alex G. Richter ◽

Aarnoud P. Huissoon ◽

Dinakantha S. Kumararatne ◽

...

Keyword(s):

Replacement Therapy ◽

Antibody Deficiency ◽

Secondary Antibody ◽

Republic Of Ireland ◽

Immunoglobulin Replacement Therapy ◽

Immunoglobulin Replacement ◽

The Uk

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A web-like network of type vi collagen in human skin is revealed by immuno-electron microscopy

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100103978 ◽

1988 ◽

Vol 46 ◽

pp. 382-383

Author(s):

Douglas R. Keene ◽

Robert W. Glanville ◽

Eva Engvall

Keyword(s):

Electron Microscopy ◽

Monoclonal Antibody ◽

Human Skin ◽

Basement Membranes ◽

Primary Antibody ◽

Fat Cells ◽

Secondary Antibody ◽

Type Vi Collagen ◽

Dermal Matrix ◽

Immuno Electron Microscopy

A mouse monoclonal antibody (5C6) prepared against human type VI collagen (1) has been used in this study to immunolocalize type VI collagen in human skin. The enbloc method used involves exposing whole tissue pieces to primary antibody and 5 nm gold conjugated secondary antibody before fixation, and has been described in detail elsewhere (2).Biopsies were taken from individuals ranging in age from neonate to 65 years old. By immuno-electron microscopy, type VI collagen is found to be distributed as a fine branching network closely associated with (but not attached to) banded collagen fibrils containing types I and III collagen (Fig. 1). It appears to enwrap fibers, to weave between individual fibrils within a fiber, and to span the distance separating fibers, creating a “web-like network” which entraps fibers within deep papillary and reticular dermal layers (Fig. 2). Relative to that in the dermal matrix, the concentration of type VI collagen is higher around endothelial basement membranes limiting the outer boundaries of nerves, capillaries, and fat cells (Fig. 3).

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Bowel ischaemia after endovascular aneurysm repair

VASA ◽

10.1024/0301-1526/a000698 ◽

2018 ◽

Vol 47 (4) ◽

pp. 273-277

Author(s):

Christopher Lowe ◽

Oussama El Bakbachi ◽

Damian Kelleher ◽

Imran Asghar ◽

Francesco Torella ◽

...

Keyword(s):

Case Reports ◽

Endovascular Aneurysm Repair ◽

Artery Occlusion ◽

Bibliographic Databases ◽

Bowel Ischaemia ◽

Prophylactic Measures ◽

Increased Risk ◽

Prisma Statement ◽

Meta Analyses ◽

Aneurysm Repair

Abstract. The aim of this review was to investigate presentation, aetiology, management, and outcomes of bowel ischaemia following EVAR. We present a case report and searched electronic bibliographic databases to identify published reports of bowel ischaemia following elective infra-renal EVAR not involving hypogastric artery coverage or iliac branch devices. We conducted our review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement standards. In total, five cohort studies and three case reports were included. These studies detailed some 6,184 infra-renal elective EVARs, without procedure-related occlusion of the hypogastric arteries, performed between 1996 and 2014. Bowel ischaemia in this setting is uncommon with an incidence ranging from 0.5 to 2.8 % and includes a spectrum of severity from mucosal to transmural ischaemia. Due to varying reporting standards, an overall proportion of patients requiring bowel resection could not be ascertained. In the larger series, mortality ranged from 35 to 80 %. Atheroembolization, hypotension, and inferior mesenteric artery occlusion were reported as potential causative factors. Elderly patients and those undergoing prolonged procedures appear at higher risk. Bowel ischaemia is a rare but potentially devastating complication following elective infra-renal EVAR and can occur in the setting of patent mesenteric vessels and hypogastric arteries. Mortality ranges from 35 to 80 %. Further research is required to identify risk factors and establish prophylactic measures in patients that have an increased risk of developing bowel ischaemia after standard infra-renal EVAR.

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