The long term vaccine-induced anti-SARS-CoV-2 immune response is impaired in quantity and quality under TNFα blockade.

The humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in patients with chronic inflammatory disease (CID) declines more rapidly with tumor necrosis factor-α (TNF-α) inhibition. Furthermore, the efficacy of current vaccines against Omicron variants of concern (VOC) including BA.2 is limited. Alterations within immune cell populations, changes in IgG affinity, and the ability to neutralize a pre-VOC strain and the BA.2 virus were investigated in these at-risk patients. Serum levels of anti-SARS-CoV-2 IgG, IgG avidity, and neutralizing antibodies (NA) were determined in anti-TNF-α patients (n = 10) and controls (n = 24 healthy individuals; n = 12 patients under other disease-modifying antirheumatic drugs, oDMARD) before and after the second and third vaccination by ELISA, immunoblot and live virus neutralization assay. SARS-CoV-2-specific B- and T cell subsets were analysed by multicolor flow cytometry. Six months after the second vaccination, anti-SARS-CoV-2 IgG levels, IgG avidity and anti-pre-VOC NA titres were significantly reduced in anti-TNF-α recipients compared to controls (healthy individuals: avidity: p ≤ 0.0001; NA: p = 0.0347; oDMARDs: avidity: p = 0.0012; NA: p = 0.0293). The number of plasma cells was increased in anti-TNF-α patients (Healthy individuals: p = 0.0344; oDMARDs: p = 0.0254), while the absolute number of SARS-CoV-2-specific plasma cells 7 days after 2nd vaccination were comparable. Even after a third vaccination, these patients had lower anti-BA.2 NA titres compared to both other groups. We show a reduced SARS-CoV-2 neutralizing capacity in patients under TNF-α blockade. In this cohort, the plasma cell response appears to be less specific and shows stronger bystander activation. While these effects were observable after the first two vaccinations and with older VOC, the differences in responses to BA.2 were enhanced.

Antibody Response and Maternofetal Antibody Transfer in SARS-CoV-2-Positive Pregnant Women: A Multicenter Observational Study.

Introduction Awareness of SARS-CoV-2 infection in pregnant women and the potential risk for infection of their neonates is increasing. The aim of this study was to examine the immune status of affected women and evaluate the dynamics of placental antibody transfer. Materials and Methods The study included 176 women with SARS-CoV-2 infection during pregnancy who delivered between April 2020 and December 2021 at eight obstetric maternity sites. Demographic data, maternal and neonatal characteristics were summarized. Antibody testing for IgA and IgG in maternal blood sera and umbilical cord samples was evaluated and IgG transfer ratios were calculated. Values were related to the time of infection during pregnancy and birth. Results The percentage of IgG positive women increased from 29.0% (95% CI 23.8 - 37.8) at presentation with a positive PCR test result to 75.7% (95% CI 71.6 - 79.8), the percentage of IgG positive umbilical cord blood samples increased from 17.1% (95% CI 13.0 - 21.3) to 76.4% (95% CI 72.2 - 80.7) at more than six weeks after infection. Regression lines differed significantly between maternal and fetal IgG responses (p < 0.0001). Newborns react with a latency of about one week; umbilical cord blood antibody concentrations are highly correlated with maternal concentration levels (ρ = 0.8042; p < 0.0001). IgG transplacental transfer ratios were dependent on infection-to-birth interval. Two of the umbilical cord blood samples tested positive for IgA. Conclusions These findings confirm vertical SARS-CoV-2 transmission is rare; however, antibodies are transferred to the fetus soon after infection during pregnancy. Since transplacental antibody transfer might have a protective value for neonatal immunization this information may be helpful when counseling affected women.

Antibody Response and Maternofetal Antibody Transfer in SARS-CoV-2-Positive Pregnant Women: A Multicenter Observational Study Immunantwort und Antikörper-Transfer zwischen Mutter und Kind bei schwangeren Frauen mit SARS-CoV-2-Infektion: eine multizentrische Beobachtungsstudie

Introduction Awareness of SARS-CoV-2 infection in pregnant women and the potential risk for infection of their neonates is increasing. The aim of this study was to examine the immune status of affected women and evaluate the dynamics of placental antibody transfer. Materials and Methods The study included 176 women with SARS-CoV-2 infection during pregnancy who delivered between April 2020 and December 2021 at eight obstetric maternity sites. Demographic data, maternal and neonatal characteristics were summarized. Antibody testing for IgA and IgG in maternal blood sera and umbilical cord samples was evaluated and IgG transfer ratios were calculated. Values were related to the time of infection during pregnancy and birth. Results The percentage of IgG positive women increased from 29.0% (95% CI 23.8 – 37.8) at presentation with a positive PCR test result to 75.7% (95% CI 71.6 – 79.8), the percentage of IgG positive umbilical cord blood samples increased from 17.1% (95% CI 13.0 – 21.3) to 76.4% (95% CI 72.2 – 80.7) at more than six weeks after infection. Regression lines differed significantly between maternal and fetal IgG responses (p < 0.0001). Newborns react with a latency of about one week;umbilical cord blood antibody concentrations are highly correlated with maternal concentration levels (ρ = 0.8042;p < 0.0001). IgG transplacental transfer ratios were dependent on infection-to-birth interval. Two of the umbilical cord blood samples tested positive for IgA. Conclusions These findings confirm vertical SARS-CoV-2 transmission is rare;however, antibodies are transferred to the fetus soon after infection during pregnancy. Since transplacental antibody transfer might have a protective value for neonatal immunization this information may be helpful when counseling affected women.

[SARS-CoV-2 and Perinatal Aspects]. / Perinatale Aspekte der SARS-CoV-2 Infektion.

The novel coronavirus SARS-CoV-2 has developed into a pandemic, yet still has many unknowns. The modalities of transmission, different symptoms and manifestations as well as concomitant circumstances of the disease are insufficiently characterized. Especially patient groups in special situations like pregnant women and newborns have to be considered separately. The current knowledge about pregnancy, labor and the first days of life is characterized by particular uncertainty due to the scarce data available. However, there is currently no evidence of significant unfavorable maternal and perinatal outcome. Many pregnant women with SARS-CoV-2 infection remain asymptomatic. The possibility of vertical transmission to the child cannot be excluded with certainty. However, indications of vertical transmission were detected only in individual cases. Newborn infections are also rather rare, unspecific and usually mild, with respiratory symptoms dominating. In this article, the data available to date are examined in order to provide better information, advice and treatment for pregnant women and newborns with SARS-CoV-2 and to provide suggestions for future research.