Dynamics of IgG seroconversion and pathophysiology of COVID-19 infections

Staines, Henry M.; Kirwan, Daniela E.; Clark, David J.; Adams, Emily; Augustin, Yolanda; Byrne, Rachel L; Cocozza, Michael; Cubas-Atienza, Ana I; Cuevas, Luís E.; Cusinato, Martina; Davies, Benedict M O; Davis, Mark M.; Davis, Paul J.; Duvoix, Annelyse; Eckersley, Nicholas M; Forton, Daniel; Fraser, Alice; Garrod, Gala; Hadcocks, Linda; Hu, Qinxue; Johnson, Michael; Kay, Grant A; Klekotko, Kesja; Lewis, Zawditu; Mensah-Kane, Josephine; Menzies, Stefanie K.; Monahan, Irene; Moore, Catherine; Nebe-von-Caron, Gerhard; Owen, Sophie I; Sainter, Chris; Sall, Amadou Alpha; Schouten, James; Williams, Chris; Wilkins, John A.; Woolston, Kevin; Fitchett, Joseph R; Krishna, Sanjeev; Planche, Tim

doi:10.1101/2020.06.07.20124636

Cited by 44 publications

(56 citation statements)

References 17 publications

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“…Older adults • Five studies found no association between antibody response and age, for both antibody positivity 147 or IgM/IgG titre. 21,58,148,167 • One study found that 'older' patients were more likely to seroconvert, 153 and concentration of IgG was related to age. 34…”

Section: Agementioning

confidence: 99%

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Antibody response to SARS-CoV-2 infection in humans: a systematic review

Post

Eddy

Huntley

et al. 2020

Preprint

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Introduction Progress in characterising the humoral immune response to Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) has been rapid but areas of uncertainty persist. This review comprehensively evaluated evidence describing the antibody response to SARS-CoV-2 published from 01/01/2020-26/06/2020. Methods Systematic review. Keyword-structured searches were carried out in MEDLINE, Embase and COVID-19 Primer. Articles were independently screened on title, abstract and full text by two researchers, with arbitration of disagreements. Data were double-extracted into a pre-designed template, and studies critically appraised using a modified version of the MetaQAT tool, with resolution of disagreements by consensus. Findings were narratively synthesised. Results 150 papers were included. Most studies (75%) were observational in design, and included papers were generally of moderate quality based on hospitalised patients. Few considered mild or asymptomatic infection. Antibody dynamics were well described in the acute phase, and up to around 3 months from disease onset, although inconsistencies remain concerning clinical correlates. Development of neutralising antibodies following SARS-CoV-2 infection is typical, although titres may be low. Specific and potent neutralising antibodies have been isolated from convalescent plasma. Cross reactivity but limited cross neutralisation occurs with other HCoVs. Evidence for protective immunity in vivo is limited to small, short-term animal studies, which show promising initial results in the immediate recovery phase. Interpretation Published literature on immune responses to SARS-CoV-2 is of variable quality with considerable heterogeneity with regard to methods, study participants, outcomes measured and assays used. Antibody dynamics have been evaluated thoroughly in the acute phase but longer follow up and a comprehensive assessment of the role of demographic characteristics and disease severity is needed. The role of protective neutralising antibodies is emerging, with implications for therapeutics and vaccines. Large, cross-national cohort studies using appropriate statistical analysis and standardised serological assays and clinical classifications should be prioritised.

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Section: Agementioning

confidence: 99%

“…Three studies report an association between co-morbidities and seroconversion or antibody positivity, 64,153 with one finding immunocompromised individuals developed a lower response. 154…”

mentioning

confidence: 99%

Antibody response to SARS-CoV-2 infection in humans: a systematic review

Post

Eddy

Huntley

et al. 2020

Preprint

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“…CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint The copyright holder for this this version posted September 27, 2020. ; https://doi.org/10.1101/2020.09.25.20183459 doi: medRxiv preprint close to the cut-off, when the reference venous blood was positive and capillary blood was indeterminate (Adams et al, 2020;Staines et al, 2020).…”

Section: Participant Characteristicsmentioning

confidence: 99%

“…The copyright holder for this this version posted September 27, 2020. ; https://doi.org/10.1101/2020.09.25.20183459 doi: medRxiv preprint sensitivity (21% to 92%), that was significantly inferior to ELISAs performed on venous blood (Flower et al, 2020). Studies have shown high sensitivity of ELISAs for the detection of SARS-CoV-2 antibodies in venous blood (Adams et al, 2020;Lisboa Bastos et al, 2020;Staines et al, 2020). Capillary blood is a well-established specimen in ELISA diagnostics but it is yet to be evaluated in SARS-CoV-2 infection.…”

Section: Introductionmentioning

confidence: 99%

Self-sampling of capillary blood for serological testing of SARS-CoV-2 by COVID-19 IgG ELISA

Brown

Byrne

Fraser

et al. 2020

Preprint

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Serological testing is emerging as a powerful tool to progress our understanding of COVID-19 exposure, transmission and immune response. Large-scale testing is limited by the need for in-person blood collection by staff trained in venepuncture. Capillary blood self-sampling and postage to laboratories for analysis could provide a reliable alternative. Two-hundred and nine matched venous and capillary blood samples were obtained from thirty nine participants and analysed using a COVID-19 IgG ELISA to detect antibodies against SARS-CoV-2. Thirty seven out of thirty eight participants were able to self-collect an adequate sample of capillary blood (≥50 μl). Using plasma from venous blood collected in lithium heparin as the reference standard, matched capillary blood samples, collected in lithium heparin-treated tubes and on filter paper as dried blood spots, achieved a Cohen′s kappa coefficient of >0.88 (near-perfect agreement). Storage of capillary blood at room temperature for up to 7 days post sampling did not affect concordance. Our results indicate that capillary blood self-sampling is a reliable and feasible alternative to venepuncture for serological assessment in COVID-19.

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“…(6,7) Similarly, with SARS-CoV-2, immune responses associated with the natural course of SARS-CoV-2 viral infection suggest that anti-Spike IgG antibody responses are usually weak (except for the fortunately less frequent severe cases) and their durability lasts for up to 3 months, in most cases, or decline by up to 70% within this time period. (8) In addition, 2-9% of individuals do not seroconvert even 2 months after infection with SARS-CoV-2, (9) suggesting that individuals reached immunity using another arm of the adaptive immune system, T cells. Indeed, it could be concluded that virtually all subjects with a history of SARS-CoV-2 infection mount T cell responses against the virus, including seronegatives and subjects with severe disease.…”

Section: Introductionmentioning

confidence: 99%

Peptide vaccine candidate mimics the heterogeneity of natural SARS-CoV-2 immunity in convalescent humans and induces broad T cell responses in mice models

Somogyi¹,

Csiszovszki²,

Molnár³

et al. 2020

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We developed a global peptide vaccine against SARS-CoV-2 that addresses the dual challenges of heterogeneity in the immune responses of different individuals and potential heterogeneity of the infecting virus. PolyPEPI-SCoV-2 is a polypeptide vaccine containing nine 30-mer peptides derived from all four major structural proteins of the SARS-CoV-2. Vaccine peptides were selected based on their frequency as HLA class I and class II personal epitopes (PEPIs) restricted to multiple autologous HLA alleles of individuals in an in silico cohort of 433 subjects of different ethnicities. PolyPEPI-SCoV-2 vaccine administered with Montanide ISA 51VG adjuvant generated robust, Th1-biased CD8+ and CD4+ T cell responses against all four structural proteins of the virus, as well as binding antibodies upon subcutaneous injection into BALB/c and CD34+ transgenic mice. In addition, PolyPEPI-SCoV-2-specific, polyfunctional CD8+ and CD4+ T cells were detected ex vivo in each of the 17 asymptomatic/mild COVID-19 convalescents' blood investigated, 1-5 months after symptom onset. The PolyPEPI-SCoV-2-specific T cell repertoire used for recovery from COVID-19 was extremely diverse: donors had an average of seven different peptide-specific T cells, against the SARS-CoV-2 proteins, 87% of donors had multiple targets against at least three SARS-CoV-2 proteins and 53% against all four. In addition, PEPIs determined based on the complete HLA class I genotype of the convalescent donors were validated, with 84% accuracy, to predict PEPI-specific CD8+ T cell responses measured for the individuals. Extrapolation of the above findings to a US bone marrow donor cohort of 16,000 HLA-genotyped individuals with 16 different ethnicities (n=1,000 each ethnic group) suggest that PolyPEPI-SCoV-2 vaccination in a general population will likely elicit broad, multi-antigenic CD8+ and CD4+ T cell responses in 98% of individuals, independent of ethnicity, including Black, Asian, and Minority Ethnic (BAME) cohorts.

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Dynamics of IgG seroconversion and pathophysiology of COVID-19 infections

Cited by 44 publications

References 17 publications

Antibody response to SARS-CoV-2 infection in humans: a systematic review

Antibody response to SARS-CoV-2 infection in humans: a systematic review

Self-sampling of capillary blood for serological testing of SARS-CoV-2 by COVID-19 IgG ELISA

Peptide vaccine candidate mimics the heterogeneity of natural SARS-CoV-2 immunity in convalescent humans and induces broad T cell responses in mice models

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