Antibodies in serum of convalescent patients following mild COVID‐19 do not always prevent virus‐receptor binding

Gattinger, Pia; Borochova, Kristina; Dorofeeva, Yulia; Henning, Rainer; Kiss, Renáta; Kratzer, Bernhard; Mühl, Bernhard; Perkmann, Thomas; Trapin, Doris; Trella, Martina; Ettel, Paul; Tulaeva, Inna; Pickl, Winfried F.; Valenta, Rudolf

doi:10.1111/all.14523

Cited by 43 publications

(75 citation statements)

References 9 publications

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“…We found that 63.5% of asymptomatic individuals only elicited low levels of neutralizing, and the rest did not produce neutralizing antibodies at all. In addition, 11.8% mild patients also did not produce neutralizing antibody, in line with other reports 18,33,34 . In particular, we demonstrated that neutralizing antibody in asymptomatic individuals decreased rapidly and disappeared in a short time, which indicate that the effectiveness of antibody‐mediated immunity could not be used to guarantee the accuracy of an “immunity passport” or “risk‐free certificate.” Our findings might suggest the risks of “shield immunity” and notably, that asymptomatic individuals might still need immunization with vaccines.…”

Section: Discussionsupporting

confidence: 89%

Antibody dynamics to SARS‐CoV‐2 in asymptomatic COVID‐19 infections

Lei

Hou

et al. 2020

Allergy

119

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Background The missing asymptomatic COVID‐19 infections have been overlooked because of the imperfect sensitivity of the nucleic acid testing (NAT). Globally understanding the humoral immunity in asymptomatic carriers will provide scientific knowledge for developing serological tests, improving early identification, and implementing more rational control strategies against the pandemic. Measure Utilizing both NAT and commercial kits for serum IgM and IgG antibodies, we extensively screened 11 766 epidemiologically suspected individuals on enrollment and 63 asymptomatic individuals were detected and recruited. Sixty‐three healthy individuals and 51 mild patients without any preexisting conditions were set as controls. Serum IgM and IgG profiles were further probed using a SARS‐CoV‐2 proteome microarray, and neutralizing antibody was detected by a pseudotyped virus neutralization assay system. The dynamics of antibodies were analyzed with exposure time or symptoms onset. Results A combination test of NAT and serological testing for IgM antibody discovered 55.5% of the total of 63 asymptomatic infections, which significantly raises the detection sensitivity when compared with the NAT alone (19%). Serum proteome microarray analysis demonstrated that asymptomatics mainly produced IgM and IgG antibodies against S1 and N proteins out of 20 proteins of SARS‐CoV‐2. Different from strong and persistent N‐specific antibodies, S1‐specific IgM responses, which evolved in asymptomatic individuals as early as the seventh day after exposure, peaked on days from 17 days to 25 days, and then disappeared in two months, might be used as an early diagnostic biomarker. 11.8% (6/51) mild patients and 38.1% (24/63) asymptomatic individuals did not produce neutralizing antibody. In particular, neutralizing antibody in asymptomatics gradually vanished in two months. Conclusion Our findings might have important implications for the definition of asymptomatic COVID‐19 infections, diagnosis, serological survey, public health, and immunization strategies.

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Section: Discussionsupporting

confidence: 89%

Antibody dynamics to SARS‐CoV‐2 in asymptomatic COVID‐19 infections

Lei

Hou

et al. 2020

Allergy

119

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“…The fact that more than 25% of the convalescent patients did not mount a relevant anti‐RBD antibody response fits to our earlier finding that up to 50% of convalescent patients do not mount antibodies which can inhibit the docking of the virus via RBD to its receptor, ACE2 9 . Also in this study, we found that ~50%‐60% of COVID‐19 convalescent patients have antibodies inhibiting the binding of RBD to ACE2 and hence may be considered to have neutralizing capacity, which confirmed the findings of our last study 9 (data not shown).…”

Section: Discussionsupporting

confidence: 86%

“…Shortly thereafter, it was shown that the disease was caused by a novel beta coronavirus (CoV) subsequently called SARS‐CoV‐2, 4 and the respiratory disease caused by this virus was named COVID‐19 5,6 . Similar to SARS‐CoV, SARS‐CoV‐2 binds with the receptor‐binding domain (RBD) of its spike (S) protein to and enters the target cells via the angiotensin converting enzyme 2 (ACE2) receptor; 7‐9 however, alternative receptors for cell entry such as CD147/EMMPRIN/Basigin 10 and CD299 (formerly CD209L) may exist 11,12 . SARS‐CoV‐2 is highly infectious and is easily spread by aerosols 13,14 …”

Section: Introductionmentioning

confidence: 99%

Immunological imprint of COVID‐19 on human peripheral blood leukocyte populations

Kratzer

Trapin

Ettel

et al. 2020

Allergy

Self Cite

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Background SARS‐CoV‐2 has triggered a pandemic that is now claiming many lives. Several studies have investigated cellular immune responses in COVID‐19‐infected patients during disease but little is known regarding a possible protracted impact of COVID‐19 on the adaptive and innate immune system in COVID‐19 convalescent patients. Methods We used multiparametric flow cytometry to analyze whole peripheral blood samples and determined SARS‐CoV‐2‐specific antibody levels against the S‐protein, its RBD‐subunit, and viral nucleocapsid in a cohort of COVID‐19 convalescent patients who had mild disease ~10 weeks after infection (n = 109) and healthy control subjects (n = 98). Furthermore, we correlated immunological changes with clinical and demographic parameters. Results Even ten weeks after disease COVID‐19 convalescent patients had fewer neutrophils, while their cytotoxic CD8+ T cells were activated, reflected as higher HLA‐DR and CD38 expression. Multiparametric regression analyses showed that in COVID‐19‐infected patients both CD3+CD4+ and CD3+CD8+ effector memory cells were higher, while CD25+Foxp3+ T regulatory cells were lower. In addition, both transitional B cell and plasmablast levels were significantly elevated in COVID‐19‐infected patients. Fever (duration, level) correlated with numbers of central memory CD4+ T cells and anti‐S and anti‐RBD, but not anti‐NC antibody levels. Moreover, a “young immunological age” as determined by numbers of CD3+CD45RA+CD62L+CD31+ recent thymic emigrants was associated with a loss of sense of taste and/or smell. Conclusion Acute SARS‐CoV‐2 infection leaves protracted beneficial (ie, activation of T cells) and potentially harmful (ie, reduction of neutrophils) imprints in the cellular immune system in addition to induction of specific antibody responses.

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“…Furthermore, it should be noted that another possibility that out assay does not test is neutralization antibodies that are not directed against RBD. Thus, our neutralization method similar to other approaches 28,29 add a great diagnostic value. Finally, our cytokine profiling analysis could not define a clear correlation between antibodies response in severe patients and proinflammatory cytokines as IL-1β, IL-6, IL-8 and TNF-α.…”

Section: Discussionmentioning

confidence: 77%

Rapid seroconversion and persistent functional IgG antibodies in severe COVID-19 patients correlates with an IL-12p70 and IL-33 signature

Munitz

Edry-Botzer

Itan

et al. 2021

Sci Rep

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Despite ongoing efforts to characterize the host response toward SARS-CoV-2, a major gap in our knowledge still exists regarding the magnitude and duration of the humoral response. Analysis of the antibody response in mild versus moderate/severe patients, using our new developed quantitative electrochemiluminescent assay for detecting IgM/IgA/IgG antibodies toward SARS-CoV-2 antigens, revealed a rapid onset of IgG/IgA antibodies, specifically in moderate/severe patients. IgM antibodies against the viral receptor binding domain, but not against nucleocapsid protein, were detected at early stages of the disease. Furthermore, we observed a marked reduction in IgM/IgA antibodies over-time. Adapting our assay for ACE2 binding-competition, demonstrated that the presence of potentially neutralizing antibodies is corelated with IgG/IgA. Finally, analysis of the cytokine profile in COVID-19 patients revealed unique correlation of an IL-12p70/IL33 and IgG seroconversion, which correlated with disease severity. In summary, our comprehensive analysis has major implications on the understanding and monitoring of SARS-CoV-2 infections.

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Antibodies in serum of convalescent patients following mild COVID‐19 do not always prevent virus‐receptor binding

Abstract: The blood proteomic signature of early-onset pediatric atopic dermatitis shows systemic inflammation and is distinct from adult long-standing disease.

Cited by 43 publications

References 9 publications

Antibody dynamics to SARS‐CoV‐2 in asymptomatic COVID‐19 infections

Antibody dynamics to SARS‐CoV‐2 in asymptomatic COVID‐19 infections

Immunological imprint of COVID‐19 on human peripheral blood leukocyte populations

Rapid seroconversion and persistent functional IgG antibodies in severe COVID-19 patients correlates with an IL-12p70 and IL-33 signature

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