Multifactorial seroprofiling dissects the contribution of pre-existing human coronaviruses responses to SARS-CoV-2 immunity

Abela, Irene A.; Pasin, Chloé; Schwarzmüller, Magdalena; Epp, Selina; Sickmann, Michèle E; Schanz, Merle; Rusert, Peter; Weber, Jacqueline; Schmutz, Stefan; Audigé, Annette; Maliqi, Liridona; Hunziker, Annika; Hesselman, Maria C; Niklaus, Cyrille R; Gottschalk, Jochen; Schindler, Emèry; Wepf, Alexander; Karrer, Urs; Wolfensberger, Aline; Rampini, S; Sauteur, Patrick M. Meyer; Berger, Christoph; Huber, Michael; Böni, Jürg; Braun, Dominique L; Marconato, Maddalena; Manz, Markus G.; Frey, Beat M.; Günthard, Huldrych F.; Kouyos, Roger D.; Trkola, Alexandra

doi:10.1038/s41467-021-27040-x

Cited by 41 publications

(70 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Seroreactivity to SARS-CoV-2 was profiled in EDTA plasma (1:100 diluted) using the in-house-developed multiplex bead assay ABCORA 2 ( 87 ). The assay measures IgG, IgA, and IgM reactivity to 4 SARS-CoV-2 antigens, RBD, S1, S2, and N (12 SARS-CoV-2 parameters), in addition to IgG, IgA, and IgM reactivity to S1 of HCoV-HKU1.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Antibodies from convalescent plasma promote SARS-CoV-2 clearance in individuals with and without endogenous antibody response

Marconato¹,

Abela²,

Hauser³

et al. 2022

Journal of Clinical Investigation

Self Cite

View full text Add to dashboard Cite

BACKGROUND Neutralizing antibodies are considered a key correlate of protection by current SARS-CoV-2 vaccines. The manner in which human infections respond to therapeutic SARS-CoV-2 antibodies, including convalescent plasma therapy, remains to be fully elucidated. METHODS We conducted a proof-of-principle study of convalescent plasma therapy based on a phase I trial in 30 hospitalized COVID-19 patients with a median interval between onset of symptoms and first transfusion of 9 days (IQR, 7–11.8 days). Comprehensive longitudinal monitoring of the virological, serological, and disease status of recipients allowed deciphering of parameters on which plasma therapy efficacy depends. RESULTS In this trial, convalescent plasma therapy was safe as evidenced by the absence of transfusion-related adverse events and low mortality (3.3%). Treatment with highly neutralizing plasma was significantly associated with faster virus clearance, as demonstrated by Kaplan-Meier analysis ( P = 0.034) and confirmed in a parametric survival model including viral load and comorbidity (adjusted hazard ratio, 3.0; 95% CI, 1.1–8.1; P = 0.026). The onset of endogenous neutralization affected viral clearance, but even after adjustment for their pretransfusion endogenous neutralization status, recipients benefitted from plasma therapy with high neutralizing antibodies (hazard ratio, 3.5; 95% CI, 1.1–11; P = 0.034). CONCLUSION Our data demonstrate a clear impact of exogenous antibody therapy on the rapid clearance of viremia before and after onset of the endogenous neutralizing response, and point beyond antibody-based interventions to critical laboratory parameters for improved evaluation of current and future SARS-CoV-2 therapies. TRIAL REGISTRATION ClinicalTrials.gov NCT04869072. FUNDING This study was funded via an Innovation Pool project by the University Hospital Zurich; the Swiss Red Cross Glückskette Corona Funding; Pandemiefonds of the UZH Foundation; and the Clinical Research Priority Program “Comprehensive Genomic Pathogen Detection” of the University of Zurich.

show abstract

Section: Methodsmentioning

confidence: 99%

“…Raw median fluorescence intensity (MFI) values were corrected for background binding to empty beads and recorded as MFI-FOE (fold over empty beads; ref. 87 ). Using predefined thresholds for positivity for each of the 12 measured SARS-CoV-2 parameters ( 87 ), signal over cutoff (SOC) values (MFI-FOE/threshold) were derived.…”

Section: Methodsmentioning

confidence: 99%

Antibodies from convalescent plasma promote SARS-CoV-2 clearance in individuals with and without endogenous antibody response

Marconato¹,

Abela²,

Hauser³

et al. 2022

Journal of Clinical Investigation

Self Cite

View full text Add to dashboard Cite

show abstract

“…In fact, several groups have discovered response to conserved cross-reactive epitopes on S proteins from β-coronaviruses [20,29]. Studies have described antiviral effects of the S2-reactive response demonstrating the benefits of the recall response [30][31][32], while others have shown S2-reactive Abs modulated the SARS-CoV-2 sterilizing response [33,34]. The robust response to S2 subunit may have been due to the competition of pre-existing cross-reactive MBCs with naïve B cells, reminiscent of cross-reactive response to head vs. stalk in influenza infection against novel HA subtypes [35][36][37].…”

Section: Discussionmentioning

confidence: 99%

Formation and Expansion of Memory B Cells against Coronavirus in Acutely Infected COVID-19 Individuals

Embong

Nguyen-Contant²,

Wang

et al. 2022

Pathogens

View full text Add to dashboard Cite

Infection with the β-coronavirus SARS-CoV-2 typically generates strong virus-specific antibody production. Antibody responses against novel features of SARS-CoV-2 proteins require naïve B cell activation, but there is a growing appreciation that conserved regions are recognized by pre-existing memory B cells (MBCs) generated by endemic coronaviruses. The current study investigated the role of pre-existing cross-reactive coronavirus memory in the antibody response to the viral spike (S) and nucleocapsid (N) proteins following SARS-CoV-2 infection. The breadth of reactivity of circulating antibodies, plasmablasts, and MBCs was analyzed. Acutely infected subjects generated strong IgG responses to the S protein, including the novel receptor binding domain, the conserved S2 region, and to the N protein. The response included reactivity to the S of endemic β-coronaviruses and, interestingly, to the N of an endemic α-coronavirus. Both mild and severe infection expanded IgG MBC populations reactive to the S of SARS-CoV-2 and endemic β-coronaviruses. Avidity of S-reactive IgG antibodies and MBCs increased after infection. Overall, findings indicate that the response to the S and N of SARS-CoV-2 involves pre-existing MBC activation and adaptation to novel features of the proteins, along with the potential of imprinting to shape the response to SARS-CoV-2 infection.

show abstract

“…However, this is consistent with the fact that cities with fewer cases had the least reductions in cases when schools were closed. Pakistan has also seen much fewer cases, hospitalizations, and deaths from COVID-19 than in Europe or North America, perhaps relating to its sparser social networks leading to fewer contacts among individuals within the community [34], or perhaps higher levels of nonspecific immunity from prior infections with disparate viruses [35]. However, both of these possible explanations are speculative at the moment.…”

Section: Discussionmentioning

confidence: 99%

Impact of school closures and reopening on COVID-19 caseload in 6 cities of Pakistan: An Interrupted Time Series Analysis

Mueed¹,

Ahmad²,

Abdullah³

et al. 2022

Preprint

View full text Add to dashboard Cite

Schools were closed all over Pakistan on November 26, 2020 to reduce community transmission of COVID-19 and reopened between January 18 and February 1, 2021. However, these closures were associated with significant economic and social costs, prompting a review of effectiveness of school closures to reduce the spread of COVID-19 infections in a developing country like Pakistan. A single-group interrupted time series analysis (ITSA) was used to measure the impact of school closures, as well as reopening schools on daily new COVID-19 cases in 6 major cities across Pakistan: Lahore, Karachi, Islamabad, Quetta, Peshawar, and Muzaffarabad. We found that closing schools reduced COVID-19 incidence in the community by approximately a third of all cases nationwide. However, any benefits were contingent on continued closure of schools, as cases bounced back once schools reopened. School closures are associated with a clear and statistically significant reduction in COVID-19 cases by 0.07 to 0.63 cases per 100,000 population, while reopening schools is associated with a statistically significant increase. Lahore is an exception to the effect of school closures, but it too saw an increase in COVID-19 cases after schools reopened in early 2021. We show that closing schools was a viable policy option, especially before vaccines became available. However, its social and economic costs must also be considered.

show abstract

Multifactorial seroprofiling dissects the contribution of pre-existing human coronaviruses responses to SARS-CoV-2 immunity

Cited by 41 publications

References 54 publications

Antibodies from convalescent plasma promote SARS-CoV-2 clearance in individuals with and without endogenous antibody response

Antibodies from convalescent plasma promote SARS-CoV-2 clearance in individuals with and without endogenous antibody response

Formation and Expansion of Memory B Cells against Coronavirus in Acutely Infected COVID-19 Individuals

Impact of school closures and reopening on COVID-19 caseload in 6 cities of Pakistan: An Interrupted Time Series Analysis

Contact Info

Product

Resources

About