Orthogonal SARS-CoV-2 Serological Assays Enable Surveillance of Low-Prevalence Communities and Reveal Durable Humoral Immunity

Ripperger, Tyler J.; Uhrlaub, Jennifer L.; Watanabe, Makiko; Wong, Rachel; Castaneda, Yvonne; Pizzato, Hannah A.; Thompson, Martha E.; Bradshaw, Christine M.; Weinkauf, Craig; Bime, Christian; Erickson, Heidi L.; Knox, Kenneth S.; Bixby, Billie; Parthasarathy, Sairam; Chaudhary, Sachin; Natt, Bhupinder; Cristan, Elaine; Aini, Tammer El; Rischard, Franz; Campion, Janet; Chopra, Madhav; Insel, Michael; Sam, Afshin; Knepler, James; Capaldi, Andrew P.; Spier, Catherine M.; Dake, Michael D.; Edwards, Taylor; Kaplan, Matt; Scott, Serena Jain; Hypes, Cameron; Mosier, Jarrod; Harris, David T.; LaFleur, Bonnie; Sprissler, Ryan; Nikolich‐Žugich, Janko; Bhattacharya, Deepta

doi:10.1016/j.immuni.2020.10.004

Cited by 326 publications

(385 citation statements)

References 69 publications

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“…Overall, the detection of SARS-CoV-2 Abs with commercial tests was higher despite important heterogeneity between the assays evaluated herein. In a previous study [3], about 40% of asymptomatic subjects became negative for IgG to the N protein within 3 to 6 months, which is consistent with that presented herein for the Architect assay. This suggests that assays detecting only antibodies against the N protein must not be used in long-term seroprevalence surveys.…”

supporting

confidence: 91%

Six-month antibody response to SARS-CoV-2 in healthcare workers assessed by virus neutralisation and commercial assays

Bal

Trabaud

Fassier

et al. 2020

Preprint

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We conducted a prospective study in healthcare workers (n=296) of the University Hospital of Lyon, France. Serum samples (n=296) collected six months after disease onset were tested using three commercial assays: the Wantai Ab assay detecting total antibodies against the receptor binding domain (RBD) of the S protein, the bioMerieux Vidas assay detecting IgG to the RBD and the Abbott Architect assay detecting IgG to the N protein. The neutralising antibody (NAb) titre was also determined for all samples with a virus neutralisation assay (VNA) using live virus. The positivity rate was 100% with the Wantai assay, 84.8% with the bioMerieux assay and 55.4% with the Abbott assay. Only 51% of HCWs were positive for the presence of NAb. Less than 10 % of HCWs had a NAb titre greater than 80. At a neutralising titre of 80, the area under the curves [IC 95%] was 0.71 [0.62-0.81], 0.75 [0.65-0.85] and 0.95 [0.92-0.97] for Wantai, Abbott and Vidas respectively. The data presented herein suggest that commercial assays detecting antibodies against the N protein must not be used in long-term seroprevalence surveys while the Wantai assay could be useful for this purpose. VNA should remain the gold standard to assess the protective antibody response, but some commercial assays could be used as first-line screening of long-term presence of NAb.

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supporting

confidence: 91%

Six-month antibody response to SARS-CoV-2 in healthcare workers assessed by virus neutralisation and commercial assays

Bal

Trabaud

Fassier

et al. 2020

Preprint

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“…Further evidence is required to evaluate comprehensively the apparent waning of the nAb response over time: in the studies included here although nAb may be detectable, higher quality studies suggest that titres are generally low, and the response is short lived. Although this is supported by recently published data (beyond the date cut off for inclusion in this study) from a UK cohort of healthcare professionals with follow up to three months [163], durable neutralising antibody response up to seven months have now been described [164]. Ongoing vaccine research has highlighted a need for evidence of longer-term protection due to nAbs, and the titres at which these effects are achieved-neither of which were fully addressed by studies included in this review.…”

Section: Summary Of Findingssupporting

confidence: 73%

“…It is not possible to draw robust conclusions on the associations of antibody response with age, sex, ethnicity or comorbidities, and although disease severity positively correlated with higher IgG antibody titres in a number of studies, distinguishing causation from correlation is not possible. More recent evidence shows that while responses may be of lower magnitude in milder cases, they are still elicited and may be protective-although evidence on response patterns in milder illness remains in short supply [164,169].…”

Section: Summary Of Findingsmentioning

confidence: 99%

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

et al. 2020

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Background Progress in characterising the humoral immune response to Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) has been rapid but areas of uncertainty persist. Assessment of the full range of evidence generated to date to understand the characteristics of the antibody response, its dynamics over time, its determinants and the immunity it confers will have a range of clinical and policy implications for this novel pathogen. 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 Public Health Ontario Meta-tool for Quality Appraisal of Public Health Evidence (MetaQAT) tool, with resolution of disagreements by consensus. Findings were narratively synthesised. Results 150 papers were included. Most studies (113 or 75%) were observational in design, were based wholly or primarily on data from hospitalised patients (108, 72%) and had important methodological limitations. Few considered mild or asymptomatic infection. Antibody dynamics were well described in the acute phase, up to around three months from disease onset, but the picture regarding correlates of the antibody response was inconsistent. IgM was consistently detected before IgG in included studies, peaking at weeks two to five and declining over a further three to five weeks post-symptom onset depending on the patient group; IgG peaked around weeks three to seven post-symptom onset then plateaued, generally persisting for at least eight weeks. Neutralising antibodies were detectable within seven to 15 days following disease onset, with levels increasing until days 14–22 before levelling and then decreasing, but titres were lower in those with asymptomatic or clinically mild disease. Specific and potent neutralising antibodies have been isolated from convalescent plasma. Cross-reactivity but limited cross-neutralisation with other human coronaviridae was reported. Evidence for protective immunity in vivo was limited to small, short-term animal studies, showing promising initial results in the immediate recovery phase. Conclusions Literature on antibody responses to SARS-CoV-2 is of variable quality with considerable heterogeneity of methods, study participants, outcomes measured and assays used. Although acute phase antibody dynamics are well described, longer-term patterns are much less well evidenced. Comprehensive assessment of the role of demographic characteristics and disease severity on antibody responses is needed. Initial findings of low neutralising antibody titres and possible waning of titres over time may have implications for sero-surveillance and disease control policy, although further evidence is needed. The detection of potent neutralising antibodies in convalescent plasma is important in the context of development of therapeutics and vaccines. Due to limitations with the existing evidence base, large, cross-national cohort studies using appropriate statistical analysis and standardised serological assays and clinical classifications should be prioritised.

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“…In contrast, data from some studies have indicated that neutralizing antibody titers remain stable ranging from 75 days to 6 months PSO in COVID-19 convalescent individuals with a broad spectrum of disease severity (130,134,141,142). In particular, a large cohort study by Wajnberg et al analyzed humoral responses in 30,032 antibody-positive individuals in New York City, and demonstrated relatively stable anti-S IgG antibody titers over five months, with these titers correlating with virus neutralization (130).…”

Section: Duration Of Sars-cov-2 Neutralizing Antibodiesmentioning

confidence: 98%

Humoral Responses and Serological Assays in SARS-CoV-2 Infections

et al. 2020

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In December 2019, the novel betacoronavirus Severe Acute Respiratory Disease Coronavirus 2 (SARS-CoV-2) was first detected in Wuhan, China. SARS-CoV-2 has since become a pandemic virus resulting in hundreds of thousands of deaths and deep socioeconomic implications worldwide. In recent months, efforts have been directed towards detecting, tracking, and better understanding human humoral responses to SARS-CoV-2 infection. It has become critical to develop robust and reliable serological assays to characterize the abundance, neutralization efficiency, and duration of antibodies in virus-exposed individuals. Here we review the latest knowledge on humoral immune responses to SARS-CoV-2 infection, along with the benefits and limitations of currently available commercial and laboratory-based serological assays. We also highlight important serological considerations, such as antibody expression levels, stability and neutralization dynamics, as well as cross-reactivity and possible immunological back-boosting by seasonal coronaviruses. The ability to accurately detect, measure and characterize the various antibodies specific to SARS-CoV-2 is necessary for vaccine development, manage risk and exposure for healthcare and at-risk workers, and for monitoring reinfections with genetic variants and new strains of the virus. Having a thorough understanding of the benefits and cautions of standardized serological testing at a community level remains critically important in the design and implementation of future vaccination campaigns, epidemiological models of immunity, and public health measures that rely heavily on up-to-date knowledge of transmission dynamics.

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Orthogonal SARS-CoV-2 Serological Assays Enable Surveillance of Low-Prevalence Communities and Reveal Durable Humoral Immunity

Cited by 326 publications

References 69 publications

Six-month antibody response to SARS-CoV-2 in healthcare workers assessed by virus neutralisation and commercial assays

Six-month antibody response to SARS-CoV-2 in healthcare workers assessed by virus neutralisation and commercial assays

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

Humoral Responses and Serological Assays in SARS-CoV-2 Infections

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