SARS-CoV-2 exposure, symptoms and seroprevalence in health care workers

Rudberg, Ann‐Sofie; Havervall, Sebastian; Månberg, Anna; Falk, Alexander; Aguilera, Katherina; Ng, Henry; Gabrielsson, Lena; Salomonsson, Ann-Christin; Hanke, Leo; Murell, Benjamin; McInerney, Gerald M.; Olofsson, Jennie; Andersson, Eni; Hellström, Cecilia; Bayati, Shaghayegh; Bergström, Sofia; Pin, Elisa; Sjöberg, Ronald; Tegel, Hanna; Hedhammar, My; Phillipson, Mia; Nilsson, Peter; Hober, Sophia; Thålin, Charlotte

doi:10.1101/2020.06.22.20137646

Cited by 23 publications

(54 citation statements)

References 23 publications

(22 reference statements)

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“…• Fever appears to have a consistent relationship with seropositivity and antibody titres [29,89,91], although other symptoms such as ageusia have also been associated [87,89].…”

Section: Symptom Profilementioning

confidence: 94%

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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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“…• Fever appears to have a consistent relationship with seropositivity and antibody titres [29,89,91], although other symptoms such as ageusia have also been associated [87,89].…”

Section: Symptom Profilementioning

confidence: 94%

“…• Several studies report an association between COVID-19 symptoms and: seropositivity [87][88][89], higher titres of IgG [29,79,90] and anti-RBD and anti-S antibodies [91]. • Two studies reported that asymptomatic healthcare workers did develop antibodies [92,93].…”

Section: Symptom Profilementioning

confidence: 99%

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

et al. 2020

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“…Two study reported that asymptomatic healthcare workers did develop antibodies. 161,162 • Fever appears to have a consistent relationship with seropositivity and antibody titres, 29,158,160 although other symptoms such as ageusia have also been associated. 156,158…”

mentioning

confidence: 99%

“…Three studies report an association between COVID-19 symptoms and seropositivity, [156][157][158] and with higher titres of IgG, 29,159 IgA, 159 and anti-RBD and anti-S antibodies. 160…”

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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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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“…Staff working in dedicated COVID-19 wards showed substantially higher rates of seropositivity (1·65 [1·34–2·03]; p<0·001) than other frontline health-care workers working in hospitals, reflecting increased risk for this group, a pattern that has also been reported in neighbouring Sweden. 4 Although Iversen and colleagues used a point-of-care lateral flow immunoassay, which is generally considered less conclusive than enzyme-linked immunosorbent assays or similar laboratory-based methods, 5 the authors did a comprehensive pre-study test assessment and estimated a sensitivity of 82·5–90·6% and specificity of 99·2–99·5%. High specificity is essential to minimise high rates of false positives when used in low-prevalence populations, such as the one studied.…”

mentioning

confidence: 99%