Impact of pregnancy on polyfunctional IgG and memory B cell responses to Tdap immunization.

BACKGROUND: Maternal pertussis immunization using Tdap vaccine is recommended in many countries to protect newborns from severe post-natal infection. Immunological changes during pregnancy may influence the response to vaccines. The quality of IgG and memory B cell responses to Tdap immunization in pregnant women has not yet been described. METHODS: The impact of pregnancy on the response to Tdap vaccination was assessed by comparing humoral immune responses in 42 pregnant and 39 non-pregnant women. The levels of serum pertussis antigens and tetanus toxoid-specific IgG, IgG subclasses, IgG Fc-mediated effector functions, as well as memory B cell frequencies were assessed before and at several time points after vaccination. RESULTS: Tdap immunization induced similar levels of pertussis and tetanus-specific IgG and IgG subclasses in pregnant and non-pregnant women. Pregnant women produced IgG promoting complement deposition, and neutrophils and macrophages phagocytosis at levels comparable to non-pregnant women. They were also able to expand pertussis and tetanus-specific memory B cells at similar frequencies as non-pregnant women, suggesting equivalent "boostability". Higher levels of vaccine-specific IgG, IgG subclasses, and IgG Fc-mediated effector functions were detected in cord blood as compared to maternal blood, indicating efficient transport across the placenta. CONCLUSIONS: This study demonstrates that pregnancy does not affect the quality of effector IgG and memory B cell responses to Tdap immunization and that polyfunctional IgG are efficiently transferred across the placenta. REGISTRY'S URL AND THE TRIAL'S REGISTRATION NUMBER: ClinicalTrials.Gov (NCT03519373).

Safety and immunogenicity of a reduced dose of the BNT162b2 mRNA COVID-19 vaccine (REDU-VAC): A single blind, randomized, non-inferiority trial

Fractional dosing of COVID-19 vaccines could accelerate vaccination rates in low-income countries. Dose-finding studies of the mRNA vaccine BNT162b2 (Pfizer-BioNTech) suggest that a fractional dose induces comparable antibody responses to the full dose in people <55 years. Here, we report the safety and immunogenicity of a fractional dose regimen of the BNT162b2 vaccine. REDU-VAC is a participant-blinded, randomised, phase 4, non-inferiority study. Adults 18–55 years old, either previously infected or infection naïve, were randomly assigned to receive 20μg/20μg (fractional dose) or 30μg/30μg (full dose) of BNT162b2. The primary endpoint was the geometric mean ratio (GMR) of SARS-CoV-2 anti-RBD IgG titres at 28 days post second dose between the reduced and full dose regimens. The reduced dose was considered non-inferior to the full dose if the lower limit of the two-sided 95% CI of the GMR was >0.67. Primary analysis was done on the per-protocol population, including infection naïve participants only. 145 participants were enrolled and randomized, were mostly female (69.5%), of European origin (95%), with a mean age of 40.4 years (SD 7.9). At 28 days post second dose, the geometric mean titre (GMT) of anti-RBD IgG of the reduced dose regimen (1,705 BAU/mL) was not non-inferior to the full dose regimen (2,387 BAU/mL), with a GMR of 0.714 (two-sided 95% CI 0.540–0.944). No serious adverse events occurred. While non-inferiority of the reduced dose regimen was not demonstrated, the anti-RBD IgG titre was only moderately lower than that of the full dose regimen and, importantly, still markedly higher than the reported antibody response to the licensed adenoviral vector vaccines. These data suggest that reduced doses of the BNT162b2 mRNA vaccine may offer additional benefit as compared to the vaccines currently in use in most low and middle-income countries, warranting larger immunogenicity and effectiveness trials. Trial Registration: The trial is registered at ClinicalTrials.gov (NCT04852861).

Third dose of COVID-19 mRNA vaccine closes the gap in immune response between naïve nursing home residents and healthy adults.

BACKGROUND: Nursing home residents, a frail and old population group, respond poorly to primary mRNA COVID-19 vaccination. A third dose has been shown to boost protection against severe disease and death in this immunosenescent population, but limited data is available on the immune responses it induces. METHODS: In this observational cohort study, peak humoral and cellular immune responses were compared 28 days after the second and third doses of the BNT162b2 mRNA COVID-19 vaccine in residents and staff members of two Belgian nursing homes. Only individuals without evidence of previous SARS-CoV-2 infection at third dose administration were included in the study. In addition, an extended cohort of residents and staff members was tested for immune responses to a third vaccine dose and was monitored for vaccine breakthrough infections in the following six months. The trial is registered on ClinicalTrials.gov (NCT04527614). FINDINGS: All included residents (n = 85) and staff members (n = 88) were SARS-CoV-2 infection naïve at third dose administration. Historical blood samples from 28 days post second dose were available from 42 residents and 42 staff members. Magnitude and quality of humoral and cellular immune responses were strongly boosted in residents post third compared to post second dose. Increases were less pronounced in staff members than in residents. At 28 days post third dose, differences between residents and staff had become mostly insignificant. Humoral, but not cellular, responses induced by a third dose were predictive of subsequent incidence of vaccine breakthrough infection in the six months following vaccination. INTERPRETATION: These data show that a third dose of mRNA COVID-19 vaccine largely closes the gap in humoral and cellular immune response observed after primary vaccination between NH residents and staff members but suggest that further boosting might be needed to achieve optimal protection against variants of concern in this vulnerable population group.

Antibody response in children with multisystem inflammatory syndrome related to COVID-19 (MIS-C) compared to children with uncomplicated COVID-19.

Objectives: To comprehensively analyze the quality of the antibody response between children with Multisystem inflammatory syndrome (MIS-C) and age-matched controls at one month after SARS-CoV-2 exposure, and infected in the same time-period. Methods: Serum from 20 MIS-C children at admission, and 14 control children were analyzed. Antigen specific antibody isotypes and subclasses directed against various antigens of SARS-CoV-2 as well as against human common coronavirus (HCoVs) and commensal or pathogenic microorganisms were assessed by a bead-based multiplexed serological assay and by ELISA. The functionality of these antibodies was also assessed using a plaque reduction neutralization test, a RBD-specific avidity assay, a complement deposition assay and an antibody-dependent neutrophil phagocytosis (ADNP) assay. Results: Children with MIS-C developed a stronger IgA antibody response in comparison to children with uncomplicated COVID-19, while IgG and IgM responses are largely similar in both groups. We found a typical class-switched antibody profile with high level of IgG and IgA titers and a measurable low IgM due to relatively recent SARS-CoV-2 infection (one month). SARS-CoV-2-specific IgG antibodies of MIS-C children had higher functional properties (higher neutralization activity, avidity and complement binding) as compared to children with uncomplicated COVID-19. There was no difference in the response to common endemic coronaviruses between both groups. However, MIS-C children had a moderate increase against mucosal commensal and pathogenic strains, reflecting a potential association between a disruption of the mucosal barrier with the disease. Conclusion: Even if it is still unclear why some children develop a MIS-C, we show here that MIS-C children produce higher titers of IgA antibodies, and IgG antibodies with higher functionality, which could reflect the local gastro-intestinal mucosal inflammation potentially induced by a sustained SARS-CoV-2 gut infection leading to continuous release of SARS-CoV-2 antigens.

Humoral and cellular immune correlates of protection against COVID-19 in kidney transplant recipients.

As solid organ transplant recipients are at high risk of severe COVID-19 and respond poorly to primary SARS-CoV-2 mRNA vaccination, they have been prioritized for booster vaccination. However, an immunological correlate of protection has not been identified in this vulnerable population. We conducted a prospective monocentric cohort study of 65 kidney transplant recipients who received 3 doses of BNT162b2 mRNA vaccine. Associations among breakthrough infection (BTI), vaccine responses, and patient characteristics were explored in 54 patients. Symptomatic COVID-19 was diagnosed in 32% of kidney transplant recipients during a period of 6 months after booster vaccination. During this period, SARS-CoV-2 delta and omicron were the dominant variants in the general population. Univariate Analyses identified the avidity of SARS-CoV-2 receptor binding domain binding IgG, neutralizing antibodies, and SARS-CoV-2 S2-specific interferon gamma responses as correlates of protection against BTI. No demographic or clinical parameter correlated with the risk of BTI. In multivariate analysis, the risk of BTI was best predicted by neutralizing antibody and S2-specific interferon gamma responses. In conclusion, T cell responses may help compensate for the suboptimal antibody response to booster vaccination in kidney transplant recipients. Further studies are needed to confirm these findings.

Objective Olfactory Findings in Hospitalized Severe COVID-19 Patients.

OBJECTIVE: We investigate the prevalence of the self-reported and objective sudden loss of smell (SLS) in patients with severe coronavirus disease 2019 (COVID-19). METHODS: Severe COVID-19 patients with self-reported SLS were recruited at hospitalization discharge. Epidemiological and clinical data were collected. The Sino-nasal Outcome Test-22 (SNOT-22) was used to evaluate rhinological complaints. Subjective olfactory and gustatory functions were assessed with the National Health and Nutrition Examination Survey (NHNES). Objective SLS was evaluated using psychophysical tests. Potential associations between olfactory evaluation and the clinical outcomes (duration of hospitalization; admission biology; one month serology (IgG), and chest computed tomography findings) were studied. RESULTS: Forty-seven patients completed the study (25 females). Subjectively, eighteen (38.3%) individuals self-reported subjective partial or total SLS. Among them, only three and four were anosmic and hyposmic, respectively (38.9%). Considering the objective evaluation in the entire cohort, the prevalence of SLS was 21.3%. Elderly patients and those with diabetes had lower objective olfactory evaluation results than young and non-diabetic individuals. CONCLUSIONS: The prevalence of SLS in severe COVID-19 patients appears to be lower than previously estimated in mild-to-moderate COVID-19 forms. Future comparative studies are needed to explore the predictive value of SLS for COVID-19 severity.

Safety and immunogenicity of a reduced dose of the BNT162b2 mRNA COVID-19 vaccine (REDU-VAC): A single blind, randomized, non-inferiority trial.

Fractional dosing of COVID-19 vaccines could accelerate vaccination rates in low-income countries. Dose-finding studies of the mRNA vaccine BNT162b2 (Pfizer-BioNTech) suggest that a fractional dose induces comparable antibody responses to the full dose in people <55 years. Here, we report the safety and immunogenicity of a fractional dose regimen of the BNT162b2 vaccine. REDU-VAC is a participant-blinded, randomised, phase 4, non-inferiority study. Adults 18-55 years old, either previously infected or infection naïve, were randomly assigned to receive 20µg/20µg (fractional dose) or 30µg/30µg (full dose) of BNT162b2. The primary endpoint was the geometric mean ratio (GMR) of SARS-CoV-2 anti-RBD IgG titres at 28 days post second dose between the reduced and full dose regimens. The reduced dose was considered non-inferior to the full dose if the lower limit of the two-sided 95% CI of the GMR was >0.67. Primary analysis was done on the per-protocol population, including infection naïve participants only. 145 participants were enrolled and randomized, were mostly female (69.5%), of European origin (95%), with a mean age of 40.4 years (SD 7.9). At 28 days post second dose, the geometric mean titre (GMT) of anti-RBD IgG of the reduced dose regimen (1,705 BAU/mL) was not non-inferior to the full dose regimen (2,387 BAU/mL), with a GMR of 0.714 (two-sided 95% CI 0.540-0.944). No serious adverse events occurred. While non-inferiority of the reduced dose regimen was not demonstrated, the anti-RBD IgG titre was only moderately lower than that of the full dose regimen and, importantly, still markedly higher than the reported antibody response to the licensed adenoviral vector vaccines. These data suggest that reduced doses of the BNT162b2 mRNA vaccine may offer additional benefit as compared to the vaccines currently in use in most low and middle-income countries, warranting larger immunogenicity and effectiveness trials. Trial Registration: The trial is registered at ClinicalTrials.gov (NCT04852861).

Younger Children Develop Higher Effector Antibody Responses to SARS-CoV-2 Infection.

Background: The basis of the less severe clinical presentation of coronavirus disease 2019 (COVID-19) in children as compared with adults remains incompletely understood. Studies have suggested that a more potent boosting of immunity to endemic common cold coronaviruses (HCoVs) may protect children. Methods: To test this hypothesis, we conducted a detailed analysis of antibodies induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children aged 2 months to 14 years. Results: Younger children had higher titers of antibodies to SARS-CoV-2 receptor binding domain (RBD), S1 but not S2 domain, and total spike (S) protein, higher avidity RBD immunoglobulin G, and higher titers of neutralizing and complement-activating antibodies as compared with older children. In contrast, older children had higher titers of antibodies to HCoVs, which correlated with antibodies to the SARS-CoV-2 S2 domain but not with neutralizing or complement-activating antibodies. Conclusions: These results reveal a unique capacity of young children to develop effector antibody responses to SARS-CoV-2 infection independently of their immunity to HCoVs.

Chemerin plasma levels are increased in COVID-19 patients and are an independent risk factor of mortality.

Background: Chemerin is an extracellular protein with chemotactic activities and its expression is increased in various diseases such as metabolic syndrome and inflammatory conditions. Its role in lung pathology has not yet been extensively studied but both known pro- and anti-inflammatory properties have been observed. The aim of our study was to evaluate the involvement of the chemerin/ChemR23 system in the physiopathology of COVID-19 with a particular focus on its prognostic value. Methods: Blood samples from confirmed COVID-19 patients were collected at day 1, 5 and 14 from admission to Erasme Hospital (Brussels - Belgium). Chemerin concentrations and inflammatory biomarkers were analyzed in the plasma. Blood cells subtypes and their expression of ChemR23 were determined by flow cytometry. The expression of chemerin and ChemR23 was evaluated on lung tissue from autopsied COVID-19 patients by immunohistochemistry (IHC). Results: 21 healthy controls (HC) and 88 COVID-19 patients, including 40 in intensive care unit (ICU) were included. Plasma chemerin concentration were significantly higher in ICU patients than in HC at all time-points analyzed (p<0.0001). Moreover, they were higher in deceased patients compared to survivors (p<0.05). Logistic univariate regression and multivariate analysis demonstrated that chemerin level at day 14 of admission was an independent risk factor for death. Accordingly, chemerin levels correlated with inflammatory biomarkers such as C-reactive protein and tumor necrosis factor α. Finally, IHC analysis revealed a strong expression of ChemR23 on smooth muscle cells and chemerin on myofibroblasts in advanced acute respiratory distress syndrome (ARDS). Discussion: Increased plasma chemerin levels are a marker of severity and may predict death of COVID-19 patients. However, multicentric studies are needed, before chemerin can be considered as a biomarker of severity and death used in daily clinical practice. Further studies are also necessary to identify the precise mechanisms of the chemerin/ChemR23 system in ARDS secondary to viral pneumonia.

Poor Antibody Response to BioNTech/Pfizer Coronavirus Disease 2019 Vaccination in Severe Acute Respiratory Syndrome Coronavirus 2-Naive Residents of Nursing Homes.

BACKGROUND: Residents of nursing homes (NHs) are at high risk of coronavirus disease 2019 (COVID-19)-related disease and death and may respond poorly to vaccination because of old age and frequent comorbid conditions. METHODS: Seventy-eight residents and 106 staff members, naive to infection or previously infected with severe acute respiratory syndrome coronavirus (SARS-CoV-2), were recruited in NHs in Belgium before immunization with 2 doses of 30 µg BNT162b2 messenger RNA (mRNA) vaccine at days 0 and 21. Binding antibodies (Abs) to SARS-CoV-2 receptor-binding domain (RBD), spike domains S1 and S2, RBD Ab avidity, and neutralizing Abs against SARS-CoV-2 wild type and B.1.351 were assessed at days 0, 21, 28, and 49. RESULTS: SARS-CoV-2-naive residents had lower Ab responses to BNT162b2 mRNA vaccination than naive staff. These poor responses involved lower levels of immunoglobulin (Ig) G to all spike domains, lower avidity of RBD IgG, and lower levels of Abs neutralizing the vaccine strain. No naive residents had detectable neutralizing Abs to the B.1.351 variant. In contrast, SARS-CoV-2-infected residents had high responses to mRNA vaccination, with Ab levels comparable to those in infected staff. Cluster analysis revealed that poor vaccine responders included not only naive residents but also naive staff, emphasizing the heterogeneity of responses to mRNA vaccination in the general population. CONCLUSIONS: The poor Ab responses to mRNA vaccination observed in infection-naive NH residents and in some naive staff members suggest suboptimal protection against breakthrough infection, especially with variants of concern. These data support the administration of a third dose of mRNA vaccine to further improve protection of NH residents against COVID-19.

Functional reprogramming of monocytes in patients with acute and convalescent severe COVID-19.

Severe COVID-19 disease is associated with dysregulation of the myeloid compartment during acute infection. Survivors frequently experience long-lasting sequelae, but little is known about the eventual persistence of this immune alteration. Herein, we evaluated TLR-induced cytokine responses in a cohort of mild to critical patients during acute or convalescent phases (n = 97). In the acute phase, we observed impaired cytokine production by monocytes in the patients with the most severe COVID-19. This capacity was globally restored in convalescent patients. However, we observed increased responsiveness to TLR1/2 ligation in patients who recovered from severe disease, indicating that these cells display distinct functional properties at the different stages of the disease. In patients with acute severe COVID-19, we identified a specific transcriptomic and epigenomic state in monocytes that can account for their functional refractoriness. The molecular profile of monocytes from recovering patients was distinct and characterized by increased chromatin accessibility at activating protein 1 (AP1) and MAF loci. These results demonstrate that severe COVID-19 infection has a profound impact on the differentiation status and function of circulating monocytes, during both the acute and the convalescent phases, in a completely distinct manner. This could have important implications for our understanding of short- and long-term COVID-19-related morbidity.

Insights From Early Clinical Trials Assessing Response to mRNA SARS-CoV-2 Vaccination in Immunocompromised Patients.

It is critical to protect immunocompromised patients against COVID-19 with effective SARS-CoV-2 vaccination as they have an increased risk of developing severe disease. This is challenging, however, since effective mRNA vaccination requires the successful cooperation of several components of the innate and adaptive immune systems, both of which can be severely affected/deficient in immunocompromised people. In this article, we first review current knowledge on the immunobiology of SARS-COV-2 mRNA vaccination in animal models and in healthy humans. Next, we summarize data from early trials of SARS-COV-2 mRNA vaccination in patients with secondary or primary immunodeficiency. These early clinical trials identified common predictors of lower response to the vaccine such as anti-CD19, anti-CD20 or anti-CD38 therapies, low (naive) CD4+ T-cell counts, genetic or therapeutic Bruton tyrosine kinase deficiency, treatment with antimetabolites, CTLA4 agonists or JAK inhibitors, and vaccination with BNT162b2 versus mRNA1273 vaccine. Finally, we review the first data on third dose mRNA vaccine administration in immunocompromised patients and discuss recent strategies of temporarily holding/pausing immunosuppressive medication during vaccination.

Boosting of cross-reactive antibodies to endemic coronaviruses by SARS-CoV-2 infection but not vaccination with stabilized spike.

Preexisting antibodies to endemic coronaviruses (CoV) that cross-react with SARS-CoV-2 have the potential to influence the antibody response to COVID-19 vaccination and infection for better or worse. In this observational study of mucosal and systemic humoral immunity in acutely infected, convalescent, and vaccinated subjects, we tested for cross-reactivity against endemic CoV spike (S) protein at subdomain resolution. Elevated responses, particularly to the ß-CoV OC43, were observed in all natural infection cohorts tested and were correlated with the response to SARS-CoV-2. The kinetics of this response and isotypes involved suggest that infection boosts preexisting antibody lineages raised against prior endemic CoV exposure that cross-react. While further research is needed to discern whether this recalled response is desirable or detrimental, the boosted antibodies principally targeted the better-conserved S2 subdomain of the viral spike and were not associated with neutralization activity. In contrast, vaccination with a stabilized spike mRNA vaccine did not robustly boost cross-reactive antibodies, suggesting differing antigenicity and immunogenicity. In sum, this study provides evidence that antibodies targeting endemic CoV are robustly boosted in response to SARS-CoV-2 infection but not to vaccination with stabilized S, and that depending on conformation or other factors, the S2 subdomain of the spike protein triggers a rapidly recalled, IgG-dominated response that lacks neutralization activity.

Three doses of BNT162b2 vaccine confer neutralising antibody capacity against the SARS-CoV-2 Omicron variant.

We report the levels of neutralising antibodies against Wuhan, Delta and Omicron variants in unimmunized infected (group 1), immunised and boosted (group 2) and infected immunised and boosted (group 3) adult individuals. Our observations support the rapid administration of a booster vaccine dose to prevent infection and disease caused by Omicron.

The prior infection with SARS-CoV-2 study (PICOV) in nursing home residents and staff - study protocol description and presentation of preliminary findings on symptoms.

BACKGROUND: The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented itself as one of the most important health concerns of the 2020's, and hit the geriatric population the hardest. The presence of co-morbidities and immune ageing in the elderly lead to an increased susceptibility to COVID-19, as is the case for other influenza-like illnesses (ILI) or acute respiratory tract infections (ARI). However, little is known, about the impact of a previous or current infection on the other in terms of susceptibility, immune response, and clinical course. The aim of the "Prior Infection with SARS-COV-2" (PICOV) study is to compare the time to occurrence of an ILI or ARI between participants with a confirmed past SARS-CoV-2 infection (previously infected) and those without a confirmed past infection (naïve) in residents and staff members of nursing homes. This paper describes the study design and population characteristics at baseline. METHODS: In 26 Belgian nursing homes, all eligible residents and staff members were invited to participate, resulting in 1,226 participants. They were classified as naïve or previously infected based on the presence of detectable SARS-CoV-2 antibodies and/or a positive RT-qPCR result before participation in the study. Symptoms from a prior SARS-CoV-2 infection between March and August 2020 were compared between previously infected residents and staff members. RESULTS: Infection naïve nursing home residents reported fewer symptoms than previously infected residents: on average 1.9 and 3.1 symptoms, respectively (p = 0.016). The same effect was observed for infection naïve staff members and previously infected staff members (3.1 and 6.1 symptoms, respectively; p <0.0001). Moreover, the antibody development after a SARS-CoV-2 infection differs between residents and staff members, as previously infected residents tend to have a higher rate of asymptomatic cases compared to previously infected staff members (20.5% compared to 12.4%; p <0.0001). CONCLUSIONS: We can postulate that COVID-19 disease development and symptomatology are different between a geriatric and younger population. Therefore, the occurrence and severity of a future ILI and/or ARI might vary from resident to staff.

Predictors of neutralizing antibody response to BNT162b2 vaccination in allogeneic hematopoietic stem cell transplant recipients.

BACKGROUND: Factors affecting response to SARS-CoV-2 mRNA vaccine in allogeneic hematopoietic stem cell transplantation (allo-HCT) recipients remain to be elucidated. METHODS: Forty allo-HCT recipients were included in a study of immunization with BNT162b2 mRNA vaccine at days 0 and 21. Binding antibodies (Ab) to SARS-CoV-2 receptor binding domain (RBD) were assessed at days 0, 21, 28, and 49 while neutralizing Ab against SARS-CoV-2 wild type (NT50) were assessed at days 0 and 49. Results observed in allo-HCT patients were compared to those obtained in 40 healthy adults naive of SARS-CoV-2 infection. Flow cytometry analysis of peripheral blood cells was performed before vaccination to identify potential predictors of Ab responses. RESULTS: Three patients had detectable anti-RBD Ab before vaccination. Among the 37 SARS-CoV-2 naive patients, 20 (54%) and 32 (86%) patients had detectable anti-RBD Ab 21 days and 49 days postvaccination. Comparing anti-RBD Ab levels in allo-HCT recipients and healthy adults, we observed significantly lower anti-RBD Ab levels in allo-HCT recipients at days 21, 28 and 49. Further, 49% of allo-HCT patients versus 88% of healthy adults had detectable NT50 Ab at day 49 while allo-HCT recipients had significantly lower NT50 Ab titers than healthy adults (P = 0.0004). Ongoing moderate/severe chronic GVHD (P < 0.01) as well as rituximab administration in the year prior to vaccination (P < 0.05) correlated with low anti-RBD and NT50 Ab titers at 49 days after the first vaccination in multivariate analyses. Compared to healthy adults, allo-HCT patients without chronic GVHD or rituximab therapy had comparable anti-RBD Ab levels and NT50 Ab titers at day 49. Flow cytometry analyses before vaccination indicated that Ab responses in allo-HCT patients were strongly correlated with the number of memory B cells and of naive CD4+ T cells (r > 0.5, P < 0.01) and more weakly with the number of follicular helper T cells (r = 0.4, P = 0.01). CONCLUSIONS: Chronic GVHD and rituximab administration in allo-HCT recipients are associated with reduced Ab responses to BNT162b2 vaccination. Immunological markers could help identify allo-HCT patients at risk of poor Ab response to mRNA vaccination. TRIAL REGISTRATION: The study was registered at clinicaltrialsregister.eu on 11 March 2021 (EudractCT # 2021-000673-83).

Robust innate responses to SARS-CoV-2 in children resolve faster than in adults without compromising adaptive immunity.

SARS-CoV-2 infection in children is less severe than it is in adults. We perform a longitudinal analysis of the early innate responses in children and adults with mild infection within household clusters. Children display fewer symptoms than adults do, despite similar initial viral load, and mount a robust anti-viral immune signature typical of the SARS-CoV-2 infection and characterized by early interferon gene responses; increases in cytokines, such as CXCL10 and GM-CSF; and changes in blood cell numbers. When compared with adults, the antiviral response resolves faster (within a week of symptoms), monocytes and dendritic cells are more transiently activated, and genes associated with B cell activation appear earlier in children. Nonetheless, these differences do not have major effects on the quality of SARS-CoV-2-specific antibody responses. Our findings reveal that better early control of inflammation as observed in children may be key for rapidly controlling infection and limiting the disease course.

Pediatric COVID-19: Immunopathogenesis, Transmission and Prevention.

Children are unique in the context of the COVID-19 pandemic. Overall, SARS-CoV-2 has a lower medical impact in children as compared to adults. A higher proportion of children than adults remain asymptomatic following SARS-CoV-2 infection and severe disease and death are also less common. This relative resistance contrasts with the high susceptibility of children to other respiratory tract infections. The mechanisms involved remain incompletely understood but could include the rapid development of a robust innate immune response. On the other hand, children develop a unique and severe complication, named multisystem inflammatory syndrome in children, several weeks after the onset of symptoms. Although children play an important role in the transmission of many pathogens, their contribution to the transmission of SARS-CoV-2 appears lower than that of adults. These unique aspects of COVID-19 in children must be considered in the benefit-risk analysis of vaccination. Several COVID-19 vaccines have been authorized for emergency use in adolescents and clinical studies are ongoing in children. As the vaccination of adolescents is rolled out in several countries, we shall learn about the impact of this strategy on the health of children and on transmission within communities.