Antinucleocapsid Antibodies After SARS-CoV-2 Infection in the Blinded Phase of the Randomized, Placebo-Controlled mRNA-1273 COVID-19 Vaccine Efficacy Clinical Trial

Follmann, Dean; Janes, Holly; Buhule, Olive D.; Zhou, Honghong; Girard, Bethany; Marks, Kristen; Kotloff, Karen L.; Desjardins, Michaël; Corey, Lawrence; Neuzil, Kathleen M.; Miller, Jacqueline M.; Sahly, Hana M. El; Baden, Lindsey R.

doi:10.7326/m22-1300

Cited by 88 publications

(82 citation statements)

References 35 publications

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“…Fourth, the observed seroprevalence in these 10 primary sampling units might differ from that in the primary sampling units that were not yet visited. Finally, seroprevalence might further underestimate the cumulative number of vaccinations and infections: some persons with infection or vaccination might remain seronegative ( 9 ), and infection after vaccination might result in lower anti-N titers ( 10 ).…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Serology and Self-Reported Infection Among Adults — National Health and Nutrition Examination Survey, United States, August 2021–May 2022

Akinbami¹,

Kruszon-Moran²,

Wang³

et al. 2022

MMWR Morb. Mortal. Wkly. Rep.

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CDC COVID-19 surveillance systems monitor SARS-CoV-2 antibody prevalence to collect information about asymptomatic, undiagnosed, and unreported disease using national convenience samples of blood donor data from commercial laboratories (1,2). However, nonrandom sampling of data from these systems could affect prevalence estimates (1-3). The National Health and Nutrition Examination Survey (NHANES) collects SARS-CoV-2 serology data among a sample of the general U.S. civilian population (4). In addition, NHANES collects self-reported COVID-19 vaccination and disease history, and its statistical sampling design is not based on health care access or blood donation. Therefore, NHANES data can be used to better quantify asymptomatic SARS-CoV-2 infection prevalence and seropositivity attained through infection without vaccination. Preliminary NHANES 2021-2022 results indicated that 41.6% of adults aged ≥18 years had serology indicative of past infection and that 43.7% of these adults, including 57.1% of non-Hispanic Black or African American (Black) adults, reported never having had COVID-19, possibly representing asymptomatic infection. In addition, 25.5% of adults whose serology indicated past infection reported never having received COVID-19 vaccination. Prevalences of seropositivity in the absence of vaccination were higher among younger adults and Black adults, reflecting the lower observed vaccination rates among these groups (5). These findings raise health equity concerns given the disparities observed in SARS-CoV-2 infection and COVID-19 vaccination. Results from NHANES 2021-2022 can guide ongoing efforts to achieve vaccine equity in COVID-19 primary vaccination series and booster dose coverage.*The 2-year sample design of NHANES 2021-2022, includes 30 primary sampling units (usually a county) that are visited sequentially. In each 12-month data collection period, a nationally representative sample of 15 primary sampling units are visited. Preliminary data for adults aged ≥18 years from the first 10 primary sampling units (visited during periods of SARS-CoV-2 Delta [August-November 2021] and Omicron [December 2021-May 2022] variant predominance) (6) were analyzed as a convenience sample because data for all 15 primary * https://www.cdc.gov/coronavirus/2019-ncov/vaccines/stay-up-to-date.html (Accessed September 12, 2022).

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Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Serology and Self-Reported Infection Among Adults — National Health and Nutrition Examination Survey, United States, August 2021–May 2022

Akinbami¹,

Kruszon-Moran²,

Wang³

et al. 2022

MMWR Morb. Mortal. Wkly. Rep.

View full text Add to dashboard Cite

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“…The sensitivity of the conventional approach (63.3%) was higher than that reported in previous studies for vaccinated individuals (26.0%-40.4%). [15,16] Besides differences among assays, this discrepancy may be explained by the fact that the Omicron variant (for which vaccine efficacy is lower) was dominant during our study, whereas earlier variants (for which vaccine efficacy is higher) were dominant in previous studies. [19–22] As a result, individuals included in our study may have been exposed to higher viral loads than those included in previous studies, thereby increasing the likelihood of anti-N seroconversion.…”

Section: Discussionmentioning

confidence: 70%

“…The reduced rate of anti-N seroconversion among vaccinated individuals might be explained by reduced exposure to the N antigen following infection, [16] which may lead to anti-N levels that do not pass the seropositivity threshold of conventional anti-N assays. We postulated that this limitation could be addressed by comparing the anti-N levels of samples collected at different time points, thus enabling the detection of meaningful signal increases in response to recently acquired infections.…”

Section: Introductionmentioning

confidence: 99%

“…In a study of 4000 fully vaccinated health care workers, 23 experienced a breakthrough infection, but only six (26%) were seropositive for anti-N. [15] More recently, a study of COVE (i.e., mRNA-1273 vs. placebo to prevent COVID- 19) participants with a confirmed history of SARS-CoV-2 breakthrough infection found that only 40.4% of vaccine recipients were seropositive for anti-N, as compared with 93.4% among placebo recipients. [16] Although preliminary, this evidence is worrisome as it may invalidate conventional anti-N assays as a marker of SARS-CoV-2 infections, leaving few alternatives to assess the progression of the pandemic.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Development and use of a method based on the anti-N reactivity of longitudinal samples to better estimate SARS-CoV-2 seroprevalence in a vaccinated population

Bazin

Rochette

Perreault

et al. 2022

Preprint

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Background: Serosurveys have been key to public health decision-making since the beginning of the SARS-CoV-2 pandemic. However, emerging evidence suggests that vaccination decreases the sensitivity of anti-nucleocapsid (N) serologies, making them less reliable to assess recently-acquired infections. We therefore developed and tested a new approach based on the ratio of the anti-N absorbance of longitudinal samples to overcome this limitation. Methods: Previously vaccinated repeat plasma donors infected between 12/15/2021 and 03/20/2022 were included if they made at least one donation pre-infection (reference sample) and one donation post-infection (test sample). All samples were tested using an in-house anti-N ELISA, the sensitivity of which had been determined prior to the vaccination era. Instead of using the previously determined signal cut-off (conventional approach), seropositivity was determined based on the ratio between the anti-N absorbance of the test and reference samples. The approach was tested in a real-world setting during three cross-sectional serosurveys carried out among plasma donors in Québec (Canada) from 01/17/2022 to 03/18/2022. Results: Using a cut-off ratio of 1.5, this approach had a sensitivity of 95.2% among the 248 previously vaccinated and infected donors compared with 63.3% for the conventional approach. When tested in a real-world setting, the ratio-based approach yielded an adjusted seroprevalence of 27.4% (95% confidence interval [CI]=23.8%-30.9%) at the latest time point considered, compared to 15.1% (95% CI=12.2%-18.0%) for the conventional approach. Conclusions: This article describes a new and highly-sensitive approach that captures a significantly greater proportion of vaccinated individuals with a recent history of SARS-CoV-2 infection.

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Awareness of SARS-CoV-2 Omicron Variant Infection Among Adults With Recent COVID-19 Seropositivity

et al. 2022

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ImportanceSome individuals who were infected by the SARS-CoV-2 Omicron variant may have been completely unaware of their infectious status while the virus was actively transmissible.ObjectiveTo examine awareness of infectious status among individuals during the recent Omicron variant surge in a diverse and populous urban region of Los Angeles County.Design, Setting, and ParticipantsThis cohort study analyzed the records of adult employees and patients of an academic medical center who were enrolled in a longitudinal COVID-19 serological study in Los Angeles County, California. These participants had 2 or more serial anti-nucleocapsid IgG (IgG-N) antibody measurements at least 1 month apart, with the first occurring after the end of a regional Delta variant surge (September 15, 2021) and a subsequent one occurring after the start of a regional Omicron variant surge (December 15, 2021). Adults with evidence of new SARS-CoV-2 infection occurring during the Omicron variant surge period through May 4, 2022, were included in the present study sample.ExposuresRecent Omicron variant infection as evidenced by SARS-CoV-2 seroconversion.Main Outcomes and MeasuresAwareness of recent SARS-CoV-2 infection was ascertained from review of self-reported health updates, medical records, and COVID-19 testing data.ResultsOf the 210 participants (median [range] age, 51 (23-84) years; 136 women [65%]) with serological evidence of recent Omicron variant infection, 44% (92) demonstrated awareness of any recent Omicron variant infection and 56% (118) reported being unaware of their infectious status. Among those who were unaware, 10% (12 of 118) reported having had any symptoms, which they attributed to a common cold or other non–SARS-CoV-2 infection. In multivariable analyses that accounted for demographic and clinical characteristics, participants who were health care employees of the medical center were more likely than nonemployees to be aware of their recent Omicron variant infection (adjusted odds ratio, 2.46; 95% CI, 1.30-4.65).Conclusions and RelevanceResults of this study suggest that more than half of adults with recent Omicron variant infection were unaware of their infectious status and that awareness was higher among health care employees than nonemployees, yet still low overall. Unawareness may be a highly prevalent factor associated with rapid person-to-person transmission within communities.

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Antinucleocapsid Antibodies After SARS-CoV-2 Infection in the Blinded Phase of the Randomized, Placebo-Controlled mRNA-1273 COVID-19 Vaccine Efficacy Clinical Trial

Cited by 88 publications

References 35 publications

SARS-CoV-2 Serology and Self-Reported Infection Among Adults — National Health and Nutrition Examination Survey, United States, August 2021–May 2022

SARS-CoV-2 Serology and Self-Reported Infection Among Adults — National Health and Nutrition Examination Survey, United States, August 2021–May 2022

Development and use of a method based on the anti-N reactivity of longitudinal samples to better estimate SARS-CoV-2 seroprevalence in a vaccinated population

Awareness of SARS-CoV-2 Omicron Variant Infection Among Adults With Recent COVID-19 Seropositivity

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