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BackgroundCOVID-19 has been a major public health threat for the past two years, with disproportionate effects on the elderly, immunocompromised, and pregnant women. While much has been done in delineating immune dysfunctions and pathogenesis in the former two groups, less is known about the diseases progression in expectant women and children born to them. To address this knowledge gap, we profiled the immune responses in maternal and child sera as well as breast milk in terms of antibody and cytokine expression and performed histopathological studies on placentae obtained from mothers convalescent from antenatal COVID-19. Methods and findingsA total of 17 mother-child dyads (8 cases of antenatal COVID-19 and 9 healthy unrelated controls; 34 individuals in total) were recruited to the Gestational Immunity For Transfer (GIFT) study. Maternal and infant sera, and breast milk samples were collected over the first year of life. All samples were analyzed for IgG and IgA against whole SARS-CoV-2 spike protein, the spike receptor-binding domain (RBD), and previously reported immunodominant epitopes, with conventional ELISA approaches. Cytokine levels were quantified in maternal sera using multiplex microbead-based Luminex arrays. The placentae were examined microscopically. We found high levels of virus-specific IgG in convalescent mothers and similarly elevated titers in newborn children. Virus-specific IgG in infant circulation waned within 3-6 months of life. Virus-specific IgA levels were variable among convalescent individuals sera and breast milk. Convalescent mothers also showed a blood cytokine signature indicative of a persistent pro-inflammatory state. Four placentae presented signs of acute inflammation marked by neutrophil infiltration even though >50 days had elapsed between virus clearance and delivery. Administration of a single dose of BNT162b2 mRNA vaccine to mothers convalescent from antenatal COVID-19 increased virus-specific IgG and IgA titers in breast milk. ConclusionsAntenatal SARS-CoV-2 infection led to high plasma titres of virus-specific antibodies in infants postnatally. However, this was not reflected in milk; milk-borne antibody levels varied widely. Additionally, placentae from COVID-19 positive mothers exhibited signs of acute inflammation with neutrophilic involvement, particularly in the subchorionic region. Virus neutralisation by plasma was not uniformly achieved, and the presence of antibodies targeting known immunodominant epitopes did not assure neutralisation. Antibody transfer ratios and the decay of transplacentally transferred virus-specific antibodies in neonatal circulation resembled that for other pathogens. Convalescent mothers showed signs of chronic inflammation marked by persistently elevated IL17RA levels in their blood. A single dose of the Pfizer BNT162b2 mRNA vaccine provided significant boosts to milk-borne virus-specific antibodies, highlighting the importance of receiving the vaccine even after natural infection with the added benefit of enhanced passive immunity. The study is registered at clinicaltrials.gov under the identifier NCT04802278.
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The scale and duration of neutralizing antibody responses targeting SARS-CoV-2 viral variants represents a critically important serological parameter that predicts protective immunity for COVID-19. In this study, we present longitudinal data illustrating the impact of age, sex and comorbidities on the kinetics and strength of vaccine-induced neutralizing antibody responses for key variants in an Asian volunteer cohort. We demonstrate a reduction in neutralizing antibody titres across all groups six months post-vaccination and show a marked reduction in the serological binding and neutralizing response targeting Omicron compared to other viral variants. We also highlight the increase in cross-protective neutralizing antibody responses against Omicron induced by a third dose (booster) of vaccine. These data illustrate how key virological factors such as immune escape mutation combined with host factors such as age and sex of the vaccinated individuals influence the strength and duration of cross-protective serological immunity for COVID-19.
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The rapid rise of coronavirus disease 2019 patients who suffer from vascular events after their initial recovery is expected to lead to a worldwide shift in disease burden. We aim to investigate the impact of COVID-19 on the pathophysiological state of blood vessels in convalescent patients. Here, convalescent COVID-19 patients with or without preexisting conditions (i.e. hypertension, diabetes, hyperlipidemia) were compared to non-COVID-19 patients with matched cardiovascular risk factors or healthy participants. Convalescent patients had elevated circulating endothelial cells (CECs), and those with underlying cardiovascular risk had more pronounced endothelial activation hallmarks (ICAM1, P-selectin or CX3CL1) expressed by CECs. Multiplex microbead-based immunoassays revealed some levels of cytokine production sustained from acute infection to recovery phase. Several proinflammatory and activated T lymphocyte-associated cytokines correlated positively with CEC measures, implicating cytokine-driven endothelial dysfunction. Finally, the activation markers detected on CECs mapped to the counter receptors (i.e. ITGAL, SELPLG, and CX3CR1) found primarily on CD8+ T cells and natural killer cells, suggesting that activated endothelial cells could be targeted by cytotoxic effector cells. Clinical trials in preventive therapy for post-COVID-19 vascular complications may be needed. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=69 SRC="FIGDIR/small/20232835v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@d34a61org.highwire.dtl.DTLVardef@1b82feeorg.highwire.dtl.DTLVardef@152ea88org.highwire.dtl.DTLVardef@a3b382_HPS_FORMAT_FIGEXP M_FIG C_FIG
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The emergence of a SARS-CoV-2 variant with a point mutation in the spike (S) protein, D614G, has taken precedence over the original Wuhan isolate by May 2020. With an increased infection and transmission rate, it is imperative to determine whether antibodies induced against the D614 isolate may cross-neutralize against the G614 variant. In this report, profiling of the anti-SARS-CoV-2 humoral immunity reveals similar neutralization profiles against both S protein variants, albeit waning neutralizing antibody capacity at the later phase of infection. These findings provide further insights towards the validity of current immune-based interventions. IMPORTANCERandom mutations in the viral genome is a naturally occurring event that may lead to enhanced viral fitness and immunological resistance, while heavily impacting the validity of licensed therapeutics. A single point mutation from aspartic acid (D) to glycine (G) at position 614 of the SARS-CoV-2 spike (S) protein, termed D614G, has garnered global attention due to the observed increase in transmissibility and infection rate. Given that a majority of the developing antibody-mediated therapies and serological assays are based on the S antigen of the original Wuhan reference sequence, it is crucial to determine if humoral immunity acquired from the original SARS-CoV-2 isolate is able to induce cross-detection and cross-protection against the novel prevailing D614G variant.
