Background Data regarding the association of antibody levels elicited after immunization with the BNT162b2 mRNA Covid-19 vaccine with epidemiological and clinical parameters are limited. Methods We prospectively measured the total (TAbs-RBD) and the neutralizing antibodies (NAbs-RBD) against the receptor binding domain (RBD) of SARS-CoV-2 spike protein in a cohort of 268 Healthcare workers before immunization, 20 days after the 1 st dose and 30 days after the 2 nd dose of the BNT162b2 vaccine. A statistical analysis for possible association of antibodies’ levels with epidemiological and clinical parameters was performed. Results The mean age (±SD) of the participants was 45.45 years (± 11.93) (range: 24-70 years) and 211 (79.9%) were females. Statistically significant differences were detected regarding both TAbs-RBD and NAbs-RBD between the first and second doses of the vaccine (P<0.001). The median (IQR) percentage (%) of NAbs-RBD after the 1 st dose was 51.07% (31.60%) and after the 2 nd dose 95.31% (3.70%) (P<0.001).The correlation between the TAbs-RBD and NAbs-RBD was after the 1 st dose, Spearman’s, rho: 0.861 ( P <0.001) and after the 2 nd dose rho: 0.989 ( P <0.001). Twenty days after the 1 st dose, 56/264 (21.2%) of the participants did not have detectable NAbs-RBD, while one month after the 2 nd dose all of them had detectable NAbs-RBD. After the 2 nd vaccine dose, a statistically significant negative association of TAbs-RBD was detected for age (P<0.001), smoking ( P =0.011), and immunosuppressive medications (P<0.001), while a positive association was detected for BMI (P=0.004) and systemic adverse events after immunization (P=0.001). Conclusion A significant correlation of TAbs-RBD and NAbs-RBD was detected after both vaccine doses. Older age, smoking, and immunosuppressive medications negatively affected the final antibody level after SARS-CoV-2 immunization. Our findings emphasize the significance of the 2 nd vaccine dose especially in the older age groups.

The SARS-CoV-2 virus is rapidly evolving via mutagenesis, lengthening the pandemic, and threatening the public health. Until August 2021, 12 variants of SARS-CoV-2 named as variants of concern (VOC; Alpha to Delta) or variants of interest (VOI; Epsilon to Mu), with significant impact on transmissibility, morbidity, possible reinfection and mortality, have been identified. The VOC Delta (B.1.617.2) of Indian origin is now the dominant and the most contagious variant worldwide as it provokes a strong binding to the human ACE2 receptor, increases transmissibility and manifests considerable immune escape strategies after natural infection or vaccination. Although the development and administration of SARS-CoV-2 vaccines, based on different technologies (mRNA, adenovirus carrier, recombinant protein, etc.), are very promising for the control of the pandemic, their effectiveness and neutralizing activity against VOCs varies significantly. In this review, we describe the most significant circulating variants of SARS-CoV-2, and the known effectiveness of currently available vaccines against them.

Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1 , OAS2 , or RNASEL in five unrelated children with MIS-C. The cytosolic dsRNA-sensing OAS1 and OAS2 generate 2′-5′-linked oligoadenylates (2-5A) that activate the ssRNA-degrading RNase L. Monocytic cell lines and primary myeloid cells with OAS1 , OAS2 , or RNASEL deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or SARS-CoV-2 stimulation. Exogenous 2-5A suppresses cytokine production in OAS1- but not RNase L-deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by MAVS deficiency. Recessive OAS–RNase L deficiencies in these patients unleash the production of SARS-CoV-2–triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C.

Host immune responses to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), especially in children, are still under investigation. Children with coronavirus disease 2019 (COVID‐19) constitute a significant study group of immune responses as they rarely present with severe clinical manifestations, require hospitalization, or develop complications such as multisystem inflammatory syndrome in children (MIS‐C) associated with SARS‐CoV‐2 infection. The deciphering of children’s immune responses during COVID‐19 infection will provide information about the protective mechanisms, while new potential targets for future therapies are likely to be revealed. Despite the limited immunological studies in children with COVID‐19, this review compares data between adults and children in terms of innate and adaptive immunity to SARS‐CoV‐2, discusses the possible reasons why children are mostly asymptomatic, and highlights unanswered or unclear immunological issues. Current evidence suggests that the activity of innate immunity seems to be crucial to the early phases of SARS‐CoV‐2 infection and adaptive memory immunity is vital to prevent reinfection.

The availability of antigen tests for SARS-CoV-2 represents a major step for the mass surveillance of the incidence of infection, especially regarding COVID-19 asymptomatic and/or early-stage patients. Recently, we reported the development of a Bioelectric Recognition Assay-based biosensor able to detect the SARS-CoV-2 S1 spike protein expressed on the surface of the virus in just three minutes, with high sensitivity and selectivity. The working principle was established by measuring the change of the electric potential of membrane-engineered mammalian cells bearing the human chimeric spike S1 antibody after attachment of the respective viral protein. In the present study, we applied the novel biosensor to patient-derived nasopharyngeal samples in a clinical set-up, with absolutely no sample pretreatment. More importantly, membrane-engineered cells were pre-immobilized in a proprietary biomatrix, thus enabling their long-term preservation prior to use as well as significantly increasing their ease-of-handle as test consumables. The plug-and-apply novel biosensor was able to detect the virus in positive samples with a 92.8% success rate compared to RT-PCR. No false negative results were recorded. These findings demonstrate the potential applicability of the biosensor for the early, routine mass screening of SARS-CoV-2 on a scale not yet realized.

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Limited prospective serosurveillance data in children regarding severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection have been reported. We prospectively investigated SARS‐CoV‐2 seropositivity in children during a 16‐month period of the coronavirus disease 2019 (COVID‐19) pandemic, including the four waves of the pandemic, before SARS‐CoV‐2 adolescents' vaccination. Serum samples from children admitted to the major tertiary Greek pediatric hospital for any cause, except for COVID‐19 infection, were randomly collected from 05/2020 to 08/2021. The study period was divided into four 4‐month periods representing relevant epidemic waves. Total SARS‐CoV‐2 antibodies for nucleocapsid protein were determined using the Elecsys® Anti‐SARS‐CoV‐2 reagent. A total of 3099 children (0–16 years) were included in the study. A total of 344 (11.1%) seropositive children were detected (males: 205 [59.5%]; median age [interquartile range [IQR]]: 3 years [0.6–10]). Seropositivity rates (%) increased during the four 4‐month periods: 1.4%, 8.6%, 17.2%, and 17.6%, respectively. A correlation of seropositivity rates in children with new diagnosed SARS‐CoV‐2 cases in the community was detected. No significant differences were detected between males and females. Seropositivity was significantly higher in hospitalized than in nonhospitalized children and in non‐Greek compared to Greek children (p < 0.001). The lowest seropositivity rate before school opening (9/2021) was detected in the age groups 6–12 years (14.4%) and 12–16 years (16.1%). However, compared with the other age groups, the lowest median antibody titers were observed in children 0–1 year (median [IQR]: 13.9 cut‐off index: [4.5–53.9] [p < 0.001]). Although the seropositivity of children was related to the community epidemic waves, the exposure was limited. Low seropositivity rates in school‐age children support the need for SARS‐CoV‐2 immunization.