Quantifying antibody kinetics and RNA shedding during early-phase SARS-CoV-2 infection

Borremans, Benny; Gamble, Amandine; Prager, KC; Sarah, K; Abby, M McClain; Cox, Caitlin; Savage, Van; Lloyd‐Smith, James O.

doi:10.1101/2020.05.15.20103275

Cited by 22 publications

(33 citation statements)

References 60 publications

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“…A number of studies reported seroconversion for total antibody (combined IgG, IgM and/or IgA), [15][16][17][18][19][20][21] however the focus of findings presented is for specific antibody isotypes. For IgG, mean or median time to seroconversion ranged from 12 -15 days post symptom onset, 7,9,15,[22][23][24][25][26] with wide variation in first to last detection of IgG from 4 -73 days post symptom onset although reporting methods varied by study. 15,[27][28][29][30][31][32][33] For IgM, mean or median time to seroconversion ranged from 4-14 days post symptom onset, 7,9,15,[22][23][24]26,31,34 again with variations in reporting methods, study quality, and sample size giving rise to uncertainty around findings.…”

Section: Time To Seroconversionmentioning

confidence: 99%

“…Across the included studies, the majority of subjects developed detectable neutralising antibodies in response to SARS-CoV-2 infection in both human 7,18,22,29, and animal 41,[89][90][91][92] participants.…”

Section: Neutralising Antibody Kineticsmentioning

confidence: 99%

“…were found in all individuals tested, suggesting specific neutralising antibodies are produced following infection despite low overall plasma neutralising ability. 87 Neutralising antibodies were generally detectable between 7 -15 days following disease onset, 7,18,75,84,85,88,93,94 increasing over days 14 -22 before plateauing 22,68,69,88,93,94 and declining over a period of six weeks. 69,85,88,95 Evidence from one medium-quality pre-print study suggests neutralising antibody titres reduced significantly among 27 convalescent patients around six weeks following disease onset to a mean neutralisation half maximum inhibitory dilution (ID50) of 596.…”

Section: Neutralising Antibody Kineticsmentioning

confidence: 99%

“…• Most studies report no relationship between time to seroconversion for IgG or IgM and disease severity. 22,35,53,56 • A number of studies report earlier antibody response to more severe disease 134,135 , including specifically for IgG; 7 a shorter time to peak antibody titre, 19,26,[136][137][138] including specifically for IgA; 30 and that IgG persists for longer in severe disease compared to milder cases. 139,140 • Three studies report an earlier antibody response to milder disease, 19,43 including specifically IgM 141 and IgA, 140 shorter time to peak for IgG, 140 and IgG persists for longer compared to severe cases.…”

Section: Onward Research Questionsmentioning

confidence: 99%

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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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Section: Time To Seroconversionmentioning

confidence: 99%

Section: Neutralising Antibody Kineticsmentioning

confidence: 99%

Section: Neutralising Antibody Kineticsmentioning

confidence: 99%

Section: Onward Research Questionsmentioning

confidence: 99%

See 2 more Smart Citations

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

Post

Eddy

Huntley

et al. 2020

Preprint

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“…Since December 2019, Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has spread at an unprecedented speed and scale, resulting in 500,000 deaths, 11,500,000 diagnosed cases (as of 10/7/2020) 1 and likely many more undiagnosed cases with mild or no symptoms (10 fold) 2 . Nucleic acid (PCR) tests are widely used for clinical diagnosis and provide good estimates on the duration of viral shedding [3][4][5] . However, it remains uncertain how many people develop protective antibodies after recovery and for how long [6][7][8] .…”

Section: Introductionmentioning

confidence: 99%

Evaluating SARS-CoV-2 spike and nucleocapsid proteins as targets for IgG antibody detection in severe and mild COVID-19 cases using a Luminex bead-based assay

Mariën

Míchiels

Heyndríckx

et al. 2020

Preprint

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Large-scale serosurveillance of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) will only be possible if serological tests are sufficiently reliable, rapid and inexpensive. Current assays are either labour-intensive and require specialised facilities (e.g. virus neutralization assays), or expensive with suboptimal specificity (e.g. commercial ELISAs). Bead-based assays offer a cost-effective alternative and allow for multiplexing to test for antibodies of other pathogens. Here, we compare the performance of four antigens for the detection of SARS-CoV-2 specific IgG antibodies in a panel of sera that includes both severe (n=40) and mild (n=52) cases, using a neutralization and a Luminex bead-based assay. While we show that neutralising antibody levels are significantly lower in mild than in severe cases, we demonstrate that a combination of recombinant nucleocapsid protein (NP), receptor-binding domain (RBD) and the whole spike protein (S1S2) results in a highly sensitive (96%) and specific (99%) bead-based assay that can detect IgG antibodies in both groups. Although S1-specific IgG levels correlate most strongly with neutralizing antibody levels, they fall below the detection threshold in 10% of the cases in our Luminex assay. In conclusion, our data supports the use of RBD, NP and S1S2 for the development of SARS-CoV-2 serological bead-based assays. Finally, we argue that low antibody levels in mild/asymptomatic cases might complicate the epidemiological assessment of large-scale surveillance studies.

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Infectious diseases epidemiology, quantitative methodology, and clinical research in the midst of the COVID-19 pandemic: Perspective from a European country

Molenberghs

Buyse

Abrams

et al. 2020

Contemporary Clinical Trials

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Starting from historic reflections, the current SARS-CoV-2 induced COVID-19 pandemic is examined from various perspectives, in terms of what it implies for the implementation of non-pharmaceutical interventions, the modeling and monitoring of the epidemic, the development of early-warning systems, the study of mortality, prevalence estimation, diagnostic and serological testing, vaccine development, and ultimately clinical trials. Emphasis is placed on how the pandemic had led to unprecedented speed in methodological and clinical development, the pitfalls thereof, but also the opportunities that it engenders for national and international collaboration, and how it has simplified and sped up procedures. We also study the impact of the pandemic on clinical trials in other indications. We note that it has placed biostatistics, epidemiology, virology, infectiology, and vaccinology, and related fields in the spotlight in an unprecedented way, implying great opportunities, but also the need to communicate effectively, often amidst controversy.

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Quantifying antibody kinetics and RNA shedding during early-phase SARS-CoV-2 infection

Cited by 22 publications

References 60 publications

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

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

Evaluating SARS-CoV-2 spike and nucleocapsid proteins as targets for IgG antibody detection in severe and mild COVID-19 cases using a Luminex bead-based assay

Infectious diseases epidemiology, quantitative methodology, and clinical research in the midst of the COVID-19 pandemic: Perspective from a European country

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