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1.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327674

ABSTRACT

The onset of severe SARS-CoV-2 infection is characterized by the presence of afucosylated IgG1 responses against the viral spike (S) protein, which can trigger exacerbated inflammatory responses. Here, we studied IgG glycosylation after BNT162b2 SARS-CoV-2 mRNA vaccination to explore whether vaccine-induced S protein expression on host cells also generates afucosylated IgG1 responses. SARS-CoV-2 naive individuals initially showed a transient afucosylated anti-S IgG1 response after the first dose, albeit to a lower extent than severely ill COVID-19 patients. In contrast, previously infected, antigen-experienced individuals had low afucosylation levels, which slightly increased after immunization. Afucosylation levels after the first dose correlated with low fucosyltransferase 8 (FUT8) expression levels in a defined plasma cell subset. Remarkably, IgG afucosylation levels after primary vaccination correlated significantly with IgG levels after the second dose. Further studies are needed to assess efficacy, inflammatory potential, and protective capacity of afucosylated IgG responses. One sentence summary A transient afucosylated IgG response to the BNT162b2 mRNA vaccine was observed in naive but not in antigen-experienced individuals, which predicted antibody titers upon the second dose.

2.
Microbiol Spectr ; 9(2): e0073121, 2021 10 31.
Article in English | MEDLINE | ID: covidwho-1410324

ABSTRACT

COVID-19 patients produce circulating and mucosal antibodies. In adults, specific saliva antibodies have been detected. Nonetheless, seroprevalence is routinely investigated, while little attention has been paid to mucosal antibodies. We therefore assessed SARS-CoV-2-specific antibody prevalence in serum and saliva in children in the Netherlands. We assessed SARS-CoV-2 antibody prevalence in serum and saliva of 517 children attending medical services in the Netherlands (irrespective of COVID-19 exposure) from April to October 2020. The prevalence of SARS-CoV-2 spike (S), receptor binding domain (RBD), and nucleocapsid (N)-specific IgG and IgA were evaluated with an exploratory Luminex assay in serum and saliva and with the Wantai SARS-CoV-2 RBD total antibody enzyme-linked immunosorbent assay in serum. Using the Wantai assay, the RBD-specific antibody prevalence in serum was 3.3% (95% confidence interval [CI]. 1.9 to 5.3%). With the Luminex assay, we detected heterogeneity between antibodies for S, RBD, and N antigens, as IgG and IgA prevalence ranged between 3.6 and 4.6% in serum and between 0 and 4.4% in saliva. The Luminex assay also revealed differences between serum and saliva, with SARS-CoV-2-specific IgG present in saliva but not in serum for 1.5 to 2.7% of all children. Using multiple antigen assays, the IgG prevalence for at least two out of three antigens (S, RBD, or N) in serum or saliva can be calculated as 3.8% (95% CI, 2.3 to 5.6%). Our study displays the heterogeneity of the SARS-CoV-2 antibody response in children and emphasizes the additional value of saliva antibody detection and the combined use of different antigens. IMPORTANCE Comprehending humoral immunity to SARS-CoV-2, including in children, is crucial for future public health and vaccine strategies. Others have suggested that mucosal antibody measurement could be an important and more convenient tool to evaluate humoral immunity compared to circulating antibodies. Nonetheless, seroprevalence is routinely investigated, while little attention has been paid to mucosal antibodies. We show the heterogeneity of SARS-CoV-2 antibodies, in terms of both antigen specificity and differences between circulating and mucosal antibodies, emphasizing the additional value of saliva antibody detection next to detection of antibodies in serum.


Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing/methods , Coronavirus Nucleocapsid Proteins/immunology , SARS-CoV-2/immunology , Saliva/immunology , Spike Glycoprotein, Coronavirus/immunology , Adolescent , COVID-19/diagnosis , Child , Child, Preschool , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunity, Humoral/immunology , Immunoglobulin A/blood , Immunoglobulin G/blood , Male , Phosphoproteins/immunology , Prevalence , Sensitivity and Specificity , Seroepidemiologic Studies
3.
Arch Dis Child Fetal Neonatal Ed ; 107(2): 156-160, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1367410

ABSTRACT

OBJECTIVE: The aim of this study was to determine the experience with, and the feasibility of, point-of-view video recordings using eye-tracking glasses for training and reviewing neonatal interventions during the COVID-19 pandemic. DESIGN: Observational prospective single-centre study. SETTING: Neonatal intensive care unit at the Leiden University Medical Center. PARTICIPANTS: All local neonatal healthcare providers. INTERVENTION: There were two groups of participants: proceduralists, who wore eye-tracking glasses during procedures, and observers who later watched the procedures as part of a video-based reflection. MAIN OUTCOME MEASURES: The primary outcome was the feasibility of, and the proceduralists and observers' experience with, the point-of-view eye-tracking videos as an additional tool for bedside teaching and video-based reflection. RESULTS: We conducted 12 point-of-view recordings on 10 different patients (median gestational age of 30.9±3.5 weeks and weight of 1764 g) undergoing neonatal intubation (n=5), minimally invasive surfactant therapy (n=5) and umbilical line insertion (n=2). We conducted nine video-based observations with a total of 88 observers. The use of point-of-view recordings was perceived as feasible. Observers further reported the point-of-view recordings to be an educational benefit for them and a potentially instructional tool during COVID-19. CONCLUSION: We proved the practicability of eye-tracking glasses for point-of-view recordings of neonatal procedures and videos for observation, educational sessions and logistics considerations, especially with the COVID-19 pandemic distancing measures reducing bedside teaching opportunities.


Subject(s)
COVID-19/epidemiology , Eye-Tracking Technology , Intensive Care Units, Neonatal , Internship and Residency/methods , Video Recording , Gestational Age , Humans , Infant, Newborn , Infant, Premature , Intubation/methods , Pandemics , Prospective Studies , Pulmonary Surfactants/administration & dosage , SARS-CoV-2
4.
Science ; 371(6532)2021 02 26.
Article in English | MEDLINE | ID: covidwho-1066801

ABSTRACT

Immunoglobulin G (IgG) antibodies are crucial for protection against invading pathogens. A highly conserved N-linked glycan within the IgG-Fc tail, which is essential for IgG function, shows variable composition in humans. Afucosylated IgG variants are already used in anticancer therapeutic antibodies for their increased activity through Fc receptors (FcγRIIIa). Here, we report that afucosylated IgG (approximately 6% of total IgG in humans) are specifically formed against enveloped viruses but generally not against other antigens. This mediates stronger FcγRIIIa responses but also amplifies brewing cytokine storms and immune-mediated pathologies. Critically ill COVID-19 patients, but not those with mild symptoms, had high concentrations of afucosylated IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), amplifying proinflammatory cytokine release and acute phase responses. Thus, antibody glycosylation plays a critical role in immune responses to enveloped viruses, including COVID-19.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , Immunoglobulin G/immunology , SARS-CoV-2/immunology , Adult , Aged , Antibodies, Viral/blood , Antibodies, Viral/chemistry , COVID-19/physiopathology , Cells, Cultured , Critical Illness , Cytomegalovirus/immunology , Female , Fucose/analysis , Glycosylation , HIV/immunology , Hepatitis B Vaccines/immunology , Humans , Immunoglobulin Fc Fragments/chemistry , Immunoglobulin Fc Fragments/immunology , Immunoglobulin G/blood , Immunoglobulin G/chemistry , Inflammation , Interleukin-6/biosynthesis , Interleukin-6/immunology , Macrophages/immunology , Male , Middle Aged , Parvovirus B19, Human/immunology , Severity of Illness Index , Spike Glycoprotein, Coronavirus/immunology , Vaccines, Subunit/immunology , Young Adult
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