Are we underestimating seroprevalence of SARS-CoV-2?

Burgess, Stephen; Ponsford, Mark

doi:10.1136/bmj.m3364

Cited by 68 publications

(67 citation statements)

References 25 publications

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“…The difference in performance between these two assays may be due to differences in the immunogenicity of the N-protein compared to the S-protein RBD [4][5][6] . Notably, patients with asymptomatic or mild disease had a weaker serological response compared to those with moderate disease, confirming previous reports 4, [7][8][9] . Thus, an RBD antigen-based assay may be more sensitive for assessing seroconversion in immunosuppressed patients, particularly for those that have mild disease, or those on multiple immunosuppressive agents.…”

Section: J O U R N a L P R E -P R O O Fsupporting

confidence: 90%

Serologic Screening for Coronavirus Disease 2019 in Patients With Glomerular Disease

Turner‐Stokes¹,

Jiang²,

Johnson³

et al. 2021

Kidney International Reports

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Section: J O U R N a L P R E -P R O O Fsupporting

confidence: 90%

Serologic Screening for Coronavirus Disease 2019 in Patients With Glomerular Disease

Turner‐Stokes¹,

Jiang²,

Johnson³

et al. 2021

Kidney International Reports

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“…Second, there is likely a healthy volunteer bias in serosurvey studies. Third, and most importantly, there is a lack of sensitivity of serology (29)(30)(31)(32)(33)(34). Many reports now document there is often a rapid loss of antibody in COVID-19 patients that were less severely ill (29)(30)(31)(32)(33)(34)(35)(36).…”

Section: Important New Information Emerging the Infection Fatality Ramentioning

confidence: 99%

“…Third, and most importantly, there is a lack of sensitivity of serology (29)(30)(31)(32)(33)(34). Many reports now document there is often a rapid loss of antibody in COVID-19 patients that were less severely ill (29)(30)(31)(32)(33)(34)(35)(36). Moreover, at least 10% of COVID-19 patients never seroconvert, and many more may only develop a mucosal IgA response (37,38), or only a T-cell response (which may be the case in up to 50% of mild infections) (39,40).…”

Section: Important New Information Emerging the Infection Fatality Ramentioning

confidence: 99%

COVID-19: Rethinking the Lockdown Groupthink

Joffe

2021

Front. Public Health

101

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The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused the Coronavirus Disease 2019 (COVID-19) worldwide pandemic in 2020. In response, most countries in the world implemented lockdowns, restricting their population's movements, work, education, gatherings, and general activities in attempt to “flatten the curve” of COVID-19 cases. The public health goal of lockdowns was to save the population from COVID-19 cases and deaths, and to prevent overwhelming health care systems with COVID-19 patients. In this narrative review I explain why I changed my mind about supporting lockdowns. The initial modeling predictions induced fear and crowd-effects (i.e., groupthink). Over time, important information emerged relevant to the modeling, including the lower infection fatality rate (median 0.23%), clarification of high-risk groups (specifically, those 70 years of age and older), lower herd immunity thresholds (likely 20–40% population immunity), and the difficult exit strategies. In addition, information emerged on significant collateral damage due to the response to the pandemic, adversely affecting many millions of people with poverty, food insecurity, loneliness, unemployment, school closures, and interrupted healthcare. Raw numbers of COVID-19 cases and deaths were difficult to interpret, and may be tempered by information placing the number of COVID-19 deaths in proper context and perspective relative to background rates. Considering this information, a cost-benefit analysis of the response to COVID-19 finds that lockdowns are far more harmful to public health (at least 5–10 times so in terms of wellbeing years) than COVID-19 can be. Controversies and objections about the main points made are considered and addressed. Progress in the response to COVID-19 depends on considering the trade-offs discussed here that determine the wellbeing of populations. I close with some suggestions for moving forward, including focused protection of those truly at high risk, opening of schools, and building back better with a economy.

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“…It also permits further flexibility in evolution of testing e.g. SARS-CoV-2 IgA from serum / plasma or saliva 22 or the detection of antibodies to the nucleocapsid, RBD and spike proteins in a single assay. 17 Furthermore, assay performance will be improved when certified reference The volume of blood applied to the filter paper collection device, and the location of the sub-punch (peripheral vs central) can have a significant impact on the result obtained for certain metabolites.…”

Section: Dbs Specimen Stability Studiesmentioning

confidence: 99%

Development of a high-throughput SARS-CoV-2 antibody testing pathway using dried blood spot specimens

et al. 2020

Self Cite

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Background: Serologic assays for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) have roles in seroepidemiology, convalescent plasma-testing, antibody durability and vaccine studies. Currently, SARS-CoV-2 serology is performed using serum/plasma collected by venepuncture. Dried bloodspot (DBS) testing offers significant advantages; as it is minimally invasive, avoids venepuncture with specimens being mailed to the laboratory. Methods: A pathway utilising a newborn screening laboratory infrastructure was developed using an Enzyme-Linked Immunosorbent assay (ELISA) to detect IgG antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein in DBS specimens. Paired plasma and DBS specimens from SARS-CoV-2 antibody positive and negative subjects and PCR positive subjects were tested. DBS specimen stability, effect of blood volume and punch location were also evaluated. Results: DBS from antibody-negative (n=85) and positive (n=35) subjects and PCR positive subjects (n=11) had a mean (SD; range) optical density (OD) of 0.14 (0.046; 0.03-0.27), 0.98 (0.41; 0.31-1.64) and 1.12 (0.37; 0.49-1.54), respectively. An action value OD >0.28 correctly assigned all cases. The weighted Deming regression for comparison of the DBS and the plasma assay yielded: y=0.004041+1.005x, r=0.991, Sy/x 0.171, n=82. Extraction efficiency of antibodies from DBS was >99%. DBS were stable for at least 28 days at ambient room temperature and humidity. Conclusions: SARS-CoV-2 IgG RBD antibodies can be reliably detected in DBS. DBS serological testing offers lower costs than either point of care or serum/plasma assays that require patient travel, phlebotomy and hospital/clinic resources; the development of a DBS assay may be particularly important for resource poor settings.

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Are we underestimating seroprevalence of SARS-CoV-2?

Abstract: Current antibody tests fail to identify people who had mild infections

Cited by 68 publications

References 25 publications

Serologic Screening for Coronavirus Disease 2019 in Patients With Glomerular Disease

Serologic Screening for Coronavirus Disease 2019 in Patients With Glomerular Disease

COVID-19: Rethinking the Lockdown Groupthink

Development of a high-throughput SARS-CoV-2 antibody testing pathway using dried blood spot specimens

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