SARS-CoV-2 Infections and Serologic Responses from a Sample of U.S. Navy Service Members — USS Theodore Roosevelt, April 2020

Payne, Daniel C.; Smith-Jeffcoat, Sarah E.; Nowak, Gosia; Chukwuma, Uzo; Geibe, Jesse R.; Hawkins, Robert J.; Johnson, Jeffrey A.; Thornburg, Natalie J.; Schiffer, Jarad; Weiner, Zachary J.; Bankamp, Bettina; Bowen, Michael D.; MacNeil, Adam; Patel, Monita R.; Deussing, Eric C.; Gillingham, Bruce L.; Tiller, Rebekah; Galloway, Rene; Rogers, Shannon; Whitaker, Brett; Kondas, Ashley V.; Smith, P. B.; Lee, Christopher; Graziano, James

doi:10.15585/mmwr.mm6923e4

Cited by 188 publications

(188 citation statements)

References 8 publications

Supporting

Mentioning

170

Contrasting

Unclassified

Order By: Relevance

“…While seemingly counterintuitive, it is consistent with previous literature and may be a result of higher antigen burdens or hyperactive immune responses among other reasons (30)(31)(32)(33)(34). A study of service members in the US Navy with predominantly mild symptoms revealed that ~40% of those with a positive ELISA by the CDC assay had no neutralizing titers at a cutoff of 1:40 (35). Similarly, a recent study demonstrated neutralizing titers at <1:50 in 33% of recovered patients and below 1:1000 in 79% of Tang 13 patients (23).…”

Section: Discussionsupporting

confidence: 86%

Association between SARS-CoV-2 neutralizing antibodies and commercial serological assays

Tang

Case

Franks

et al. 2020

Preprint

View full text Add to dashboard Cite

AbstractIntroductionCommercially available SARS-CoV-2 serological assays based on different viral antigens have been approved for the qualitative determination of anti-SARS-CoV-2 antibodies. However, there is limited published data associating the results from commercial assays with neutralizing antibodies.Methods67 specimens from 48 patients with PCR-confirmed COVID-19 and a positive result by the Roche Elecsys SARS-CoV-2, Abbott SARS-CoV-2 IgG, or EUROIMMUN SARS-CoV-2 IgG assays and 5 control specimens were analyzed for the presence of neutralizing antibodies to SARS-CoV-2. Correlation, concordance, positive percent agreement (PPA), and negative percent agreement (NPA) were calculated at several cutoffs. Results were compared in patients categorized by clinical outcomes.ResultsThe correlation between SARS-CoV-2 neutralizing titer (EC50) and the Roche, Abbott, and EUROIMMUN assays was 0.29, 0.47, and 0.46 respectively. At an EC50 of 1:32, the concordance kappa with Roche was 0.49 (95% CI; 0.23-0.75), with Abbott was 0.52 (0.28-0.77), and with EUROIMMUN was 0.61 (0.4-0.82). At the same neutralizing titer, the PPA and NPA for the Roche was 100% (94-100) & 56% (30-80); Abbott was 96% (88-99) & 69% (44-86); and EUROIMMUN was 91% (80-96) & 81% (57-93) for distinguishing neutralizing antibodies. Patients who died, were intubated, or had a cardiac injury from COVID-19 infection had significantly higher neutralizing titers relative to those with mild symptoms.ConclusionCOVID-19 patients generate an antibody response to multiple viral proteins such that the calibrator ratios on the Roche, Abbott, and EUROIMMUN assays are all associated with SARS-CoV-2 neutralization. Nevertheless, commercial serological assays have poor NPA for SARS-CoV-2 neutralization, making them imperfect proxies for neutralization.

show abstract

Section: Discussionsupporting

confidence: 86%

Association between SARS-CoV-2 neutralizing antibodies and commercial serological assays

Tang

Case

Franks

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Neutralizing activity against SARS-CoV-2 WT or D614G S glycoprotein, as measured by the neutralization half-maximum inhibitory dilution (ID 50 ), was detected in 71% of patients 6 weeks after the onset of symptoms. While we acknowledge that the sensitivity of any given neutralization assay could affect calculations of the percentage of donors with neutralization activity, we note that the percentage of convalescent plasma with undetectable neutralization titers reported here is similar to what was reported in recent studies (11,20,21). SARS-CoV-2 neutralization was specific since no neutralization was observed against pseudoparticles expressing VSV-G (Fig.…”

supporting

confidence: 87%

Decline of Humoral Responses against SARS-CoV-2 Spike in Convalescent Individuals

Beaudoin-Bussières

Laumaea

Anand

et al. 2020

mBio

180

106

View full text Add to dashboard Cite

In the absence of effective vaccines and with limited therapeutic options, convalescent plasma is being collected across the globe for potential transfusion to coronavirus disease 2019 (COVID-19) patients. The therapy has been deemed safe, and several clinical trials assessing its efficacy are ongoing. While it remains to be formally proven, the presence of neutralizing antibodies is thought to play a positive role in the efficacy of this treatment. Indeed, neutralizing titers of ≥1:160 have been recommended in some convalescent plasma trials for inclusion. Here, we performed repeated analyses at 1-month intervals on 31 convalescent individuals to evaluate how the humoral responses against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein, including neutralization, evolve over time. We observed that the levels of receptor-binding-domain (RBD)-specific IgG and IgA slightly decreased between 6 and 10 weeks after the onset of symptoms but that RBD-specific IgM levels decreased much more abruptly. Similarly, we observed a significant decrease in the capacity of convalescent plasma to neutralize pseudoparticles bearing wild-type SARS-CoV-2 S or its D614G variant. If neutralization activity proves to be an important factor in the clinical efficacy of convalescent plasma transfer, our results suggest that plasma from convalescent donors should be recovered rapidly after resolution of symptoms. IMPORTANCE While waiting for an efficient vaccine to protect against SARS-CoV-2 infection, alternative approaches to treat or prevent acute COVID-19 are urgently needed. Transfusion of convalescent plasma to treat COVID-19 patients is currently being explored; neutralizing activity in convalescent plasma is thought to play a central role in the efficacy of this treatment. Here, we observed that plasma neutralization activity decreased a few weeks after the onset of the symptoms. If neutralizing activity is required for the efficacy of convalescent plasma transfer, our results suggest that convalescent plasma should be recovered rapidly after the donor recovers from active infection.

show abstract

“…However, their clinical value inherently depends on available knowledge of SARS-CoV-2 immunology, which remains limited at present. Several key immunological issues, including the rate of neutralizing antibody production among infected individuals, (4,5) the length of antibody persistence, (6) the relationship between disease severity and antibody titer, (7) and the antibody titer required for protective immunity, (6,8) are in early stages of critical evaluation. While further inquiry is needed, the urgency of pandemic response efforts has led many clinical laboratories to provide serological testing to their healthcare systems and communities despite an incomplete understanding of the underlying immunology.…”

Section: Introductionmentioning

confidence: 99%

Comparison of the Clinical Performances of the Abbott Alinity IgG, Abbott Architect IgM, and Roche Elecsys Total SARS-CoV-2 Antibody Assays

Harley

Gunsolus

2020

J Clin Microbiol

View full text Add to dashboard Cite

Critical evaluation of SARS-CoV-2 serologic assays is needed to guide clinical decision-making and ensure these assays provide optimal benefit to patients and the public. Here, three commercially available assays with widespread distribution capabilities are compared. A total of 667 specimens, 103 from patients with confirmed SARS-CoV-2 infections and 564 collected prior to the emergence of SARS-CoV-2, were analyzed in parallel using the Roche Elecsys SARS-CoV-2 Total Antibody and Abbott Alinity SARS-CoV-2 IgG assays; a subset of 55 samples from patients with confirmed SARS-CoV-2 infections was additionally evaluated using the Abbott Architect SARS-CoV-2 IgM assay. Qualitative percent agreement between the Abbott IgG and Roche total antibody assays was 98.7% (658/667), with Cohen's kappa 0.919 (95% CI 0.867-0.972). Qualitative percent agreement with the Abbott IgM assay was 92.7% (51/55, Abbott IgG) and 85.5% (47/55, Roche total antibody). Diagnostic specificities determined using pre-COVID-19 samples for the Abbott IgG and Roche total antibody assays were 99.65% (95% CI 98.72-99.90%) and 100.00% (95% CI 99.32-100.00%), respectively, spanning claims made by each manufacturer. Diagnostic sensitivities increased for all three assays with increasing time since the onset of symptoms. Among 51 patients with confirmed SARS-CoV-2 infections, 23 (45.1%), 24 (47.1%), and 22 (43.1%) were reactive by the Abbott IgG, Roche total antibody, and Abbott IgM assays, respectively, with sampling times 0-56 days post-positive PCR (median/mean 2/6.2 days). Combining IgG and IgM screening identified 4/55 additional samples with detectable antibodies that would not have been observed using the assays independently. Notably, one immunocompromised patient with confirmed SARS-CoV-2 infection showed no detectable antibodies using any of the three assays 43 days after onset of symptoms.

show abstract

SARS-CoV-2 Infections and Serologic Responses from a Sample of U.S. Navy Service Members — USS Theodore Roosevelt, April 2020

Cited by 188 publications

References 8 publications

Association between SARS-CoV-2 neutralizing antibodies and commercial serological assays

Association between SARS-CoV-2 neutralizing antibodies and commercial serological assays

Decline of Humoral Responses against SARS-CoV-2 Spike in Convalescent Individuals

Comparison of the Clinical Performances of the Abbott Alinity IgG, Abbott Architect IgM, and Roche Elecsys Total SARS-CoV-2 Antibody Assays

Contact Info

Product

Resources

About