Dynamics of Neutralizing Antibody Titers in the Months After Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Crawford, Katharine H.D.; Dingens, Adam S.; Eguia, Rachel; Wolf, Caitlin R; Wilcox, Naomi; Logue, Jennifer K.; Shuey, Kiel; Casto, Amanda M.; Fiala, Brooke; Wrenn, Samuel; Pettie, Deleah; King, Neil P.; Greninger, Alexander L.; Chu, Helen Y.; Bloom, Jesse D

doi:10.1093/infdis/jiaa618

Cited by 229 publications

(241 citation statements)

References 41 publications

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“…The magnitude of the following decline in neutralizing antibody titres reported here is similar to that observed in several newly reported pre-prints 12,13,20,31,[34][35][36][37][38][39] . In these studies, similar to our observations, those who generated a high neutralizing antibody titre still had high neutralizing antibody titres regardless of the initial decline 12,13,31,35,39 and, for those with lower disease severity, two studies reported 7/34 (ref. 12 ) and 5/80 (ref.…”

Section: Discussionsupporting

confidence: 90%

“…In these studies, similar to our observations, those who generated a high neutralizing antibody titre still had high neutralizing antibody titres regardless of the initial decline 12,13,31,35,39 and, for those with lower disease severity, two studies reported 7/34 (ref. 12 ) and 5/80 (ref. 31 ) individuals with a decline to undetectable neutralizing antibodies (ID 50 < 20 or ID 50 < 50, respectively) at the last timepoint studied.…”

Section: Discussionsupporting

confidence: 90%

“…S glycoprotein is the target for neutralizing antibodies, and a number of highly potent monoclonal antibodies have been isolated that predominantly target the RBD [8][9][10][11] . A wide range of SARS-CoV-2-neutralizing antibody titres has been reported after infection and these vary depending on the length of time from infection and the severity of disease [3][4][5]12,13 . Further knowledge on the magnitude, timing and longevity of neutralizing antibody responses after SARS-CoV-2 infection is vital for understanding the role neutralizing antibodies might play in disease clearance and protection from reinfection and/or disease.…”

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confidence: 99%

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Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans

et al. 2020

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Antibody responses to SARS-CoV-2 can be detected in most infected individuals 10-15 d after the onset of COVID-19 symptoms. However, due to the recent emergence of SARS-CoV-2 in the human population, it is not known how long antibody responses will be maintained or whether they will provide protection from reinfection. Using sequential serum samples collected up to 94 d post onset of symptoms (POS) from 65 individuals with real-time quantitative PCR-confirmed SARS-CoV-2 infection, we show seroconversion (immunoglobulin (Ig)M, IgA, IgG) in >95% of cases and neutralizing antibody responses when sampled beyond 8 d POS. We show that the kinetics of the neutralizing antibody response is typical of an acute viral infection, with declining neutralizing antibody titres observed after an initial peak, and that the magnitude of this peak is dependent on disease severity. Although some individuals with high peak infective dose (ID 50 > 10,000) maintained neutralizing antibody titres >1,000 at >60 d POS, some with lower peak ID 50 had neutralizing antibody titres approaching baseline within the follow-up period. A similar decline in neutralizing antibody titres was observed in a cohort of 31 seropositive healthcare workers. The present study has important implications when considering widespread serological testing and antibody protection against reinfection with SARS-CoV-2, and may suggest that vaccine boosters are required to provide long-lasting protection.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 90%

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confidence: 99%

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Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans

et al. 2020

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“…positive patients had statistically significant higher antibody levels against most antigens compared to not ventilated COVID-19 positive patients. This confirms similar findings that individuals with more severe disease have higher antibody levels (9,10,11,12,13,14). Further studies need to be done to understand the relationship between increased antibody production and ventilation.…”

Section: Correlation Of Igg Antibody Levels and Il-10supporting

confidence: 87%

IgG Antibodies against SARS-CoV-2 Correlate with Days from Symptom Onset, Viral Load and IL-10

Young

Kornmeier²,

Carpenter

et al. 2020

Preprint

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The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a pandemic of the respiratory disease coronavirus disease 2019 (COVID-19). Antibody testing is essential to identify persons exposed to the virus and potentially in predicting disease immunity. 183 COVID-19 patients (68 of whom required mechanical ventilation) and 41 controls were tested for plasma IgG, IgA and IgM against the SARS-CoV-2 S1, S2, receptor binding domain (RBD) and N proteins using the MILLIPLEX® SARS-CoV-2 Antigen Panel. Plasma cytokines were concurrently measured using the MILLIPLEX® MAP Human Cytokine/Chemokine/Growth Factor Panel A. As expected the 183 COVID-19 positive patients had high levels of IgG, IgA and IgM anti-SARS-CoV-2 antibodies against each of the viral proteins. Sensitivity of anti-S1 IgG increased from 60% to 93% one week after symptom onset. S1-IgG and S1-IgA had specificities of 98% compared to the 41 COVID-19 negative patients. The 68 ventilated COVID-19 positive patients had higher antibody levels than the 115 COVID-19 positive patients who were not ventilated. IgG antibody levels against S1 protein had the strongest positive correlation to days from symptom onset. There were no statistically significant differences in IgG, IgA and IgM antibodies against S1 based on age. We found that patients with the highest levels of anti-SARS-CoV-2 antibodies had the lowest viral load in the nasopharynx. Finally there was a correlation of high plasma IL-10 with low anti-SARS-CoV-2 antibodies. Anti-SARS-CoV-2 antibody levels, as measured by a novel antigen panel, increased within days after symptom onset, achieving > 90% sensitivity and specificity within one week, and were highest in patients who required mechanical ventilation. Antibody levels were inversely associated with viral load but did not differ as a function of age. The correlation of high IL-10 with low antibody response suggests a potentially suppressive role of this cytokine in the humoral immune response in COVID-19.

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“…Neutralizing antibodies to SARS-CoV-2 develop in most individuals after infection but decay with time 7,8,[27][28][29][30][31] . These antibodies are effective in prevention and therapy in animal models and are likely to play a role in protection from re-infection in humans 32 .…”

Section: Extended Data Fig 8b-k and Supplementarymentioning

confidence: 99%

Evolution of Antibody Immunity to SARS-CoV-2

Gaebler

Wang

Lorenzi

et al. 2020

Preprint

178

221

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SARS-CoV-2 has infected 47 million individuals and is responsible for over 1.2 million deaths to date. Infection is associated with development of variable levels of antibodies with neutralizing activity that can protect against infection in animal models. Antibody levels decrease with time, but the nature and quality of the memory B cells that would be called upon to produce antibodies upon re-infection has not been examined. Here we report on the humoral memory response in a cohort of 87 individuals assessed at 1.3 and 6.2 months after infection. We find that IgM, and IgG anti-SARS-CoV-2 spike protein receptor binding domain (RBD) antibody titers decrease significantly with IgA being less affected. Concurrently, neutralizing activity in plasma decreases by five-fold in pseudotype virus assays. In contrast, the number of RBD-specific memory B cells is unchanged. Memory B cells display clonal turnover after 6.2 months, and the antibodies they express have greater somatic hypermutation, increased potency and resistance to RBD mutations, indicative of continued evolution of the humoral response. Analysis of intestinal biopsies obtained from asymptomatic individuals 3 months after COVID-19 onset, using immunofluorescence, electron tomography or polymerase chain reaction, revealed persistence of SARS-CoV-2 in the small bowel of 7 out of 14 volunteers. We conclude that the memory B cell response to SARS-CoV-2 evolves between 1.3 and 6.2 months after infection in a manner that is consistent with antigen persistence.

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Dynamics of Neutralizing Antibody Titers in the Months After Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Cited by 229 publications

References 41 publications

Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans

Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans

IgG Antibodies against SARS-CoV-2 Correlate with Days from Symptom Onset, Viral Load and IL-10

Evolution of Antibody Immunity to SARS-CoV-2

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