Outcomes Following SARS-CoV-2 Infection in Patients With Primary and Secondary Immunodeficiency in The United Kingdom

Shields, Adrian M; Anantharachagan, Ariharan; Arumugakani, Gururaj; Baker, Kenneth F.; Bahal, Sameer; Baxendale, Helen; Bermingham, William; Bhole, Malini; Boules, Evon; Bright, Philip; Chopra, Charu; Cliffe, Lucy; Cleave, Betsy; Dempster, John; Devlin, Lisa; Dhalla, Fatima; Diwakar, Lavanya; Drewe, Elizabeth; Duncan, Christopher; Dziadzio, Magdalena; Elcombe, Suzanne; Elkhalifa, Shuayb; Gennery, Andrew R.; Ghanta, Harichandrana; Goddard, Sarah; Grigoriadou, Sofia; Hackett, Scott; Hayman, Grant; Herriot, Richard; Herwadkar, Archana; Huissoon, Aarnoud; Jain, Rashmi; Jolles, Stephen; Johnston, Sarah; Khan, Sujoy; Laffan, James; Lane, Peter J. L.; Leeman, Lucy; Lowe, David M.; Mahabir, Shanti; Lochlainn, Dylan J. Mac; McDermott, Elizabeth; Misbah, Siraj; Moghaddas, Fiona; Morsi, Hadeil; Murng, Sai; Noorani, Sadia; O’Brien, Rachael; Patel, Smita Y.; Price, Arthur; Rahman, Tasneem; Senevirantne, S.; Shrimpton, Anna; Stroud, Catherine; Thomas, Moira; Townsend, Katie; Vaitla, Prashantha M.; Verma, Nisha; Williams, Anthony P.; Burns, Siobhan O.; Savic, Sinisa; Richter, Alex

doi:10.21203/rs.3.rs-920110/v1

Cited by 3 publications

(3 citation statements)

References 12 publications

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“…Yet, we and others have documented survival and SARS-CoV-2 viral clearance in the absence of either B cells or detectable humoral immunity ( 5 , 25 ), suggesting SARS-CoV-2 neutralising antibodies are but one aspect of protective immunity against the virus. Longitudinal vaccine efficacy studies in individuals with immunodeficiency are necessary to develop a comprehensive understanding of the relationship between measurable in vitro immunological parameters and protection against severe disease, and allow further stratification of the ongoing risk posed by COVID-19 ( 26 , 27 ).…”

Section: Discussionmentioning

confidence: 99%

Increased Seroprevalence and Improved Antibody Responses Following Third Primary SARS-CoV-2 Immunisation: An Update From the COV-AD Study

et al. 2022

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BackgroundPatients with primary and secondary antibody deficiency are vulnerable to COVID-19 and demonstrate diminished responses following two-dose SARS-CoV-2 vaccine schedules. Third primary vaccinations have been deployed to enhance their humoral and cellular immunity.ObjectivesTo determine the immunogenicity of the third primary SARS-CoV-2 immunisation in a heterogeneous cohort of patients with antibody deficiency.MethodsParticipants enrolled in the COV-AD study were sampled before and after their third vaccine dose. Serological and cellular responses were determined using ELISA, live-virus neutralisation and ELISPOT assays.ResultsFollowing a two-dose schedule, 100% of healthy controls mounted a serological response to SARS-CoV-2 vaccination, however, 38.6% of individuals with antibody deficiency remained seronegative. A third primary SARS-CoV-2 vaccine significantly increased anti-spike glycoprotein antibody seroprevalence from 61.4% to 76.0%, the magnitude of the antibody response, its neutralising capacity and induced seroconversion in individuals who were seronegative after two vaccine doses. Vaccine-induced serological responses were broadly cross-reactive against the SARS-CoV-2 B.1.1.529 variant of concern, however, seroprevalence and antibody levels remained significantly lower than healthy controls. No differences in serological responses were observed between individuals who received AstraZeneca ChAdOx1 nCoV-19 and Pfizer BioNTech 162b2 during their initial two-dose vaccine schedule. SARS-CoV-2 infection-naive participants who had received a heterologous vaccine as a third dose were significantly more likely to have a detectable T cell response following their third vaccine dose (61.5% vs 11.1%).ConclusionThese data support the widespread use of third primary immunisations to enhance humoral immunity against SARS-CoV-2 in individuals with antibody deficiency.

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Section: Discussionmentioning

confidence: 99%

Increased Seroprevalence and Improved Antibody Responses Following Third Primary SARS-CoV-2 Immunisation: An Update From the COV-AD Study

et al. 2022

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show abstract

“…Yet, we and others have documented survival and SARS-CoV-2 viral clearance in the absence of either B cells or detectable humoral immunity (5,25), suggesting SARS-CoV-2 neutralising antibodies are but one aspect of protective immunity against the virus. Longitudinal vaccine efficacy studies in individuals with immunodeficiency are necessary to develop a comprehensive understanding of the relationship between measurable in vitro immunological parameters and protection against severe disease, and allow further stratification of the ongoing risk posed by COVID-19 (26,27).…”

Section: Discussionmentioning

confidence: 99%

Increased seroprevalence and improved antibody responses following third primary SARS-CoV-2 immunisation: an update from the COV-AD study

Shields

Faustini²,

Hill³

et al. 2022

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BackgroundPatients with primary and secondary antibody deficiency are vulnerable to COVID-19 and demonstrate diminished responses following two-dose SARS-CoV-2 vaccine schedules. Third primary vaccinations have been deployed to enhance their humoral and cellular immunity. ObjectivesTo determine the immunogenicity of the third primary SARS-CoV-2 immunisation in a heterogeneous cohort of patients with antibody deficiency. MethodsParticipants enrolled in the COV-AD study were sampled before and after their third vaccine dose. Serological and cellular responses were determined using ELISA, live-virus neutralisation and ELISPOT assays. ResultsA third primary SARS-CoV-2 vaccine significantly increased anti-spike glycoprotein antibody seroprevalence from 61.4% to 76.0%, the magnitude of the antibody response, its neutralising capacity and induced seroconversion in individuals who were seronegative after two vaccine doses. Vaccine-induced serological responses were broadly cross-reactive against the SARS-CoV-2 B.1.1.529 variant of concern, however, overall seroprevalence and antibody levels remained significantly lower than healthy controls. No differences in serological responses were observed between individuals who received the AstraZeneca ChAdOx1 nCoV-19 and Pfizer BioNTech 162b2 during their initial two-dose vaccine schedule. SARS-CoV-2 infection naive participants who had received a heterologous vaccine as a third dose were significantly more likely to have a detectable T cell responses following their third vaccine dose (61.5% vs 11.1%). ConclusionThese data support the widespread use of third primary immunisations to enhance humoral immunity against SARS-CoV-2 in individuals with antibody deficiency.

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“…Individuals with medical conditions that compromise their ability to mount immune responses, such as primary and secondary immunodeficiencies, are at increased risk for severe illness and death following SARS-CoV-2 infection ( 13, 14 ). Patients with primary and secondary immunodeficiencies also have an impaired SARS-CoV-2-specific antibody response following a primary vaccination series ( 15 – 24 ).…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 booster vaccination rescues attenuated IgG1 memory B cell response in primary antibody deficiency patients

Lin

Doss

Davis-Adams

et al. 2022

Preprint

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SARS-CoV-2 vaccines have proven effective in eliciting an immune response capable of providing protective immunity in healthy individuals. However, whether SARS-CoV-2 vaccination induces a long-lived immune response in immunocompromised individuals is poorly understood. Primary antibody deficiency (PAD) syndromes are among the most common immunodeficiency disorders in adults and are characterized by an impaired ability to mount robust antibody responses following infection or vaccination. Here, we present data from a prospective study in which we analyzed the B and T cell response in PAD patients following SARS-COV-2 vaccination. Unexpectedly, individuals with PAD syndromes mounted a SARS-CoV-2 specific B and CD4+ T cell response that was comparable in magnitude to healthy individuals. Many individuals with PAD syndromes displayed reduced IgG1+ and CD11c+ memory B cell responses following the primary vaccination series. However, the IgG1 class-switching defect was largely rescued following mRNA booster vaccination. Boosting also elicited an increase in the SARS-CoV-2-specific B and T cell response and the development of Omicron-specific memory B cells in COVID-19-naive PAD patients. Together, these data indicate that SARS-CoV-2 vaccines elicit memory B and T cells in PAD patients that may contribute to long-term protective immunity.

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Outcomes Following SARS-CoV-2 Infection in Patients With Primary and Secondary Immunodeficiency in The United Kingdom

Cited by 3 publications

References 12 publications

Increased Seroprevalence and Improved Antibody Responses Following Third Primary SARS-CoV-2 Immunisation: An Update From the COV-AD Study

Increased Seroprevalence and Improved Antibody Responses Following Third Primary SARS-CoV-2 Immunisation: An Update From the COV-AD Study

Increased seroprevalence and improved antibody responses following third primary SARS-CoV-2 immunisation: an update from the COV-AD study

SARS-CoV-2 booster vaccination rescues attenuated IgG1 memory B cell response in primary antibody deficiency patients

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