Distinct early IgA profile may determine severity of COVID-19 symptoms: an immunological case series

Dahlke, Christine; Heidepriem, Jasmin; Kobbe, Robin; Santer, René; Koch, Till; Fathi, Anahita; Ly, My L.; Schmiedel, Stefan; Seeberger, Peter H.; Addo, Marylyn M.; Loeffler, Felix F.

doi:10.1101/2020.04.14.20059733

Cited by 42 publications

(57 citation statements)

References 17 publications

(15 reference statements)

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“…IgA response against SARS-CoV-2 has been reported to be rapid and persistent [ 18 , 19 ] and possibly associated with mucosal immune response in the gut and lungs. Notably, IgA production has been associated with disease severity, suggesting that IgA production might occur locally at the mucosal sites, possibly correlating with the viral load, the duration of the viral exposure and the virus entry route [ 13 , 26 ]. Consistently, a recent communication [ 14 ] confirmed that the highest levels of IgG and IgA antibodies against the Spike S1 domain, encompassing the N-terminal half of the protein with the RBD, were associated with severe disease [ 13 , 14 ].…”

Section: Discussionmentioning

confidence: 99%

Persistence of Anti-SARS-CoV-2 Antibodies in Non-Hospitalized COVID-19 Convalescent Health Care Workers

Bruni

Cecatiello

Díaz‐Basabe

et al. 2020

JCM

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Although antibody response to SARS-CoV-2 can be detected early during the infection, several outstanding questions remain to be addressed regarding the magnitude and persistence of antibody titer against different viral proteins and their correlation with the strength of the immune response. An ELISA assay has been developed by expressing and purifying the recombinant SARS-CoV-2 Spike Receptor Binding Domain (RBD), Soluble Ectodomain (Spike), and full length Nucleocapsid protein (N). Sera from healthcare workers affected by non-severe COVID-19 were longitudinally collected over four weeks, and compared to sera from patients hospitalized in Intensive Care Units (ICU) and SARS-CoV-2-negative subjects for the presence of IgM, IgG and IgA antibodies as well as soluble pro-inflammatory mediators in the sera. Non-hospitalized subjects showed lower antibody titers and blood pro-inflammatory cytokine profiles as compared to patients in Intensive Care Units (ICU), irrespective of the antibodies tested. Noteworthy, in non-severe COVID-19 infections, antibody titers against RBD and Spike, but not against the N protein, as well as pro-inflammatory cytokines decreased within a month after viral clearance. Thus, rapid decline in antibody titers and in pro-inflammatory cytokines may be a common feature of non-severe SARS-CoV-2 infection, suggesting that antibody-mediated protection against re-infection with SARS-CoV-2 is of short duration. These results suggest caution in using serological testing to estimate the prevalence of SARS-CoV-2 infection in the general population.

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Section: Discussionmentioning

confidence: 99%

Persistence of Anti-SARS-CoV-2 Antibodies in Non-Hospitalized COVID-19 Convalescent Health Care Workers

Bruni

Cecatiello

Díaz‐Basabe

et al. 2020

JCM

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“…However, these predicted epitopes were largely limited to those with sequence homology between SARS-CoV-1 and SARS-CoV-2, given the paucity of available SARS-CoV-2 assay data. Several studies have identified linear B cell epitopes on the SARS-CoV-2 surface glycoprotein from sera of viral exposed patients using peptide arrays [56][57][58] as well as phage immunoprecipitation sequencing (PhIP-Seq) 59 . These studies are an important source of information but their results may include many epitopes from degraded proteins and thus would not be able to promote viral neutralization in vivo due to a lack of surface exposure .…”

Section: Discussionmentioning

confidence: 99%

“…In addition to identifying SARS-CoV-2 T cell epitopes, we sought to identify a set of linear B cell epitopes on the Spike protein which would serve as good targets for stimulating neutralizing antibody responses ( Figure 1 ). Epitope candidates were derived from four published preprint mapping/array studies [56][57][58][59] and one as-of-yet unpublished PEPperCHIP ® peptide array study (for study details see Methods: Antibody epitope curation ). Starting with an initial candidate pool of 58 linear epitopes with data to support in vivo generation in humans ( Figure 4A, Table S4 ), we applied a set of filtering criteria to narrow our target space ( Figure 4B ):…”

Section: B Cell Epitope Predictionmentioning

confidence: 99%

“…Linear B cell epitopes on the SARS-CoV-2 surface glycoprotein were curated from four published studies [56][57][58][59] . Three of these studies screened polyclonal sera of convalescent COVID-19 patients using either peptide arrays 56,58 or phage immuno-precipation sequencing (PhIP-Seq) 59 . One study characterized the epitopes of monoclonal neutralizing antibodies 57 .…”

Section: Antibody Epitope Curationmentioning

confidence: 99%

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Landscape and Selection of Vaccine Epitopes in SARS-CoV-2

Smith

Entwistle

Willis

et al. 2020

Preprint

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There is an urgent need for a vaccine with efficacy against SARS-CoV-2. We hypothesize that peptide vaccines containing epitope regions optimized for concurrent B cell, CD4 + T cell, and CD8 + T cell stimulation would drive both humoral and cellular immunity with high specificity, potentially avoiding undesired effects such as antibody-dependent enhancement (ADE). Additionally, such vaccines can be rapidly manufactured in a distributed manner. In this study, we combine computational prediction of T cell epitopes, recently published B cell epitope mapping studies, and epitope accessibility to select candidate peptide vaccines for SARS-CoV-2. We begin with an exploration of the space of possible T cell epitopes in SARS-CoV-2 with interrogation of predicted HLA-I and HLA-II ligands, overlap between predicted ligands, protein source, as well as concurrent human/murine coverage. Beyond MHC affinity, T cell vaccine candidates were further refined by predicted immunogenicity, viral source protein abundance, sequence conservation, coverage of high frequency HLA alleles and co-localization of CD4 + and CD8 + T cell epitopes. B cell epitope regions were chosen from linear epitope mapping studies of convalescent patient serum, followed by filtering to select regions with surface accessibility, high sequence conservation, spatial localization near functional domains of the spike glycoprotein, and avoidance of glycosylation sites. From 58 initial candidates, three B cell epitope regions were identified. By combining these B cell and T cell analyses, as well as a manufacturability heuristic, we propose a set of SARS-CoV-2 vaccine peptides for use in subsequent murine studies and clinical trials. Figure 2: Landscape of SARS-CoV-2 MHC ligands. (A&B) Selection criteria for (A) HLA-I and (B) shows predicted (x-axis) versus IEDB (y-axis) binding affinity, with horizontal line representing 500nM IEDB binding affinity and vertical line representing corresponding predicted binding affinity for 90% specificity in binding prediction. Histogram (top) shows all predicted SARS-CoV-2 HLA ligand candidates. (C) Landscape of predicted HLA ligands, showing nested HLA ligands comprising HLA-I and -II ligands with complete overlap (top), and LOESS fitted curve (span = 0.1) for HLA-I/II ligands by location along the . Red track represents SARS epitopes identified in literature review with sequence identity in SARS-CoV-2. Predicted HLA ligands with conserved sequences to this literature set are represented in the lollipop plot with a red stick. (D) Summary of total number of predicted HLA-I/II ligands and nested HLA ligands. (E) Summary of nested HLA ligand coverage by protein, with raw counts (left) or counts normalized by protein length (right). (F) Summary of murine/human MHC ligand overlap. (G) Distribution of population frequencies among predicted HLA-I, -II, and nested HLA ligands.

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“…In fact, the levels of SARS-CoV-2 antibodies vary widely in patients after recovery, and although infrequently, IgG antibodies could be undetectable in some patients: how these patients recovered without the help of antibodies and whether they were at risk of reinfection of SARS-CoV-2 should be further explored [8]. Soon after disease onset in a mild case, Dahllke observed an increased frequency of plasmablasts concomitantly with a strong SARS-CoV-2-specific IgA response, while a case with more severe progression showed a delayed, but eventually a very strong and broad SARS-CoV-2-specific IgA response [9].…”

Section: Indirect Testmentioning

confidence: 99%

Nasopharyngeal and Oropharyngeal Swabs, And/Or Serology for SARS COVID-19: What Are We Looking For?

Sanduzzi

Zamparelli

2020

IJERPH

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Governments and clinicians that were fully involved in the dramatic SARS-CoV-2 outbreak during the last few weeks in Italy (and more or less all over the world) are fiercely debating the use of methods for screening this viral infection. Thus, all countries are employing a lot of resources in order to test more and more subjects. For this purpose, there are different strategies, based on either direct or indirect tests. Among the first category, the main assays used for SARS-CoV-2 are based on a real-time reverse transcriptase polymerase chain reaction (RT-PCR). Such tests can be performed on nasopharyngeal and oropharyngeal swabs for the categories of those with symptoms and those potentially exposed. In order to integrate the molecular assays in the diagnosis of SARS-CoV-2, a wide range of serology immunoassays (IAs) have also been developed. If we want to identify "immune" people in order to let them to come back to work, serology is the best (and probably the only) approach.On March the 16, 2020, Tedros Adhanom Ghebreyesus, WHO General Director, concluding his speech about SARS-Cov-2 to the United Nations Assembly pronounced the famous sentence: "test, test, test".Governments and clinicians that where fully involved in the dramatic SARS-CoV-2 outbreak during the last few weeks in Italy, (and more or less all over the world) are fiercely debating the use of methods for screening this viral infection. Thus, all countries are employing a lot of resources in order to test more and more subjects. For this purpose, there are different possible strategies, based on either direct or indirect tests: Direct TestsThe main assays used for SARS-CoV-2 are based on a real-time reverse transcriptase polymerase chain reaction (RT-PCR) that needs a few hours to give an answer. Most molecular tests have been approved by the United States Food and Drug Administration (FDA) under emergency use authorization (EUA) and are Conformité Européenne (CE) marked [1,2].Such tests can be performed on nasopharyngeal and oropharyngeal swabs in symptomatic people (fever, dry cough, asthenia). Another strategy is to test all health care workers and individuals in the potentially exposed category (policemen, military); nasopharyngeal and oropharyngeal swabs could also be used for those in close contact with SARS-CoV-2-positive people or for people who live in close and crowded settings (e.g., nursing homes). Theoretically, nasopharyngeal and oropharyngeal swabs Int.

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Distinct early IgA profile may determine severity of COVID-19 symptoms: an immunological case series

Cited by 42 publications

References 17 publications

Persistence of Anti-SARS-CoV-2 Antibodies in Non-Hospitalized COVID-19 Convalescent Health Care Workers

Persistence of Anti-SARS-CoV-2 Antibodies in Non-Hospitalized COVID-19 Convalescent Health Care Workers

Landscape and Selection of Vaccine Epitopes in SARS-CoV-2

Nasopharyngeal and Oropharyngeal Swabs, And/Or Serology for SARS COVID-19: What Are We Looking For?

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