Anti-TNF therapy impairs both short- and long-term IgG responses after repeated vaccination.

BACKGROUND: Recently, it has been questioned whether vaccination of patients with inflammatory (auto)immune diseases under anti-tumor necrosis factor (TNF) treatment leads to impaired vaccine-induced immune responses and protection against breakthrough infections. However, the effects of TNF blockade on short- and long-term immune responses after repeated vaccination remain unclear. Vaccination studies have shown that initial short-term IgG antibodies (Abs) carry highly galactosylated and sialylated Fc glycans, whilst long-term IgG Abs have low levels of galactosylation and sialylation and are most likely generated by long-lived plasma cells (PCs) derived primarily from the germinal center (GC) response. Thus, IgG Fc glycosylation patterns may be applicable to distinguish short- and long-term vaccine responses after repeated vaccination under the influence of anti-TNF treatment. METHODS: We used COVID-19 vaccination as a model to investigate vaccine-induced IgG subclass levels and Fc glycosylation patterns, B cell subsets, and effector functions of short- and long-term Ab responses after up to three vaccinations in patients on anti-TNF or other immunosuppressive treatments and in healthy individuals. Using TriNetX, a global healthcare database, we determined the risk of SARS-CoV-2 breakthrough infections in vaccinated patients treated with anti-TNF or other immunosuppressive drugs. RESULTS: Anti-TNF treatment reduced the long-term abundance of all anti-S IgG subclasses with low levels of galactosylation and sialylation. Re-activation of potential memory B cells initially generated highly galactosylated and sialylated IgG antibodies, which were progressively reduced after each booster dose in anti-TNF-treated patients, especially in the elderly. The reduced short- and long-term IgG (1) levels in anti-TNF-treated patients correlated with diminished functional activity and an increased risk for the development of COVID-19. CONCLUSIONS: The data suggest that anti-TNF treatment reduces both GC-dependent long-lived PCs and GC-dependent memory B cell-derived short-lived PCs, hence both the long- and short-term IgG subclass responses, respectively, after repeated vaccination. We propose that anti-TNF therapy, especially in the elderly, reduces the benefit of booster vaccination.

Prevalence and Obstetric Management Changes During the COVID-19 Pandemic in Peripartum SARS-CoV-2-Positive Women - an Analysis of the CRONOS Registry Data.

The analysis of CRONOS data for this article presents the infection prevalence among parturients and subsequent changes in obstetric management over time in Germany. 2,184 women with peripartum SARS-CoV-2 infection (<14d before birth) were included. Monthly period prevalence was calculated using the number of affected women on the CRONOS registry relative to total monthly births in each hospital from March 2020 to May 2022 and compared to RKI data. Trends related to changes in obstetric management were calculated based on severity of illness. By June 2021, the obstetric population shows a discretely higher infection prevalence compared to the general population, falling below the RKI reported prevalence by October 2021. The overall rate of iatrogenic deliveries remains unchanged over time (p-value for trend=0.779). During wave 1 to 4, deliveries due to SARS-CoV-2 infection rose among moderately to severely ill women (p-value for trend 0.0000) and was increased compared to moderately ill women (p=0.001). We showed that comprehensive screening provides timely information on infection prevalence. Recruitment fatigue caused by higher clinician workload due to increased admissions and more cases with severe illness probably caused reduced prevalence reporting. Changes in obstetric management were related to COVID-19 symptom severity. A comprehensive national perinatal registry is needed to examine other areas of perinatal care in Germany.

Breastfeeding Rates During the COVID-19 Pandemic in Germany: Data from the CRONOS Registry.

SARS-CoV-2 infection and COVID-19 disease are thought to have an impact on breastfeeding rate - besides other known peripartal issues. Data of the national CRONOS registry regarding breastfeeding behavior in 6,746 women was analyzed regarding the time window between maternal SARS-CoV-2 infection and time of delivery. In addition, other influencing factors like the predominant viral variant, maternal disease severity, and gestational age at delivery were taken into account. Our data suggest that within the variables analyzed, in the case of acute maternal infection (<14 days before birth), breastfeeding behavior improved with increasing gestational age at birth (p<0.0001), with less severe maternal illness (p<0.0001) and as the pandemic progressed with less virulent viral variants (p=0.01). When adjusting for COVID-19-associated and non-associated factors, rooming-in remains the most important factor positively influencing breastfeeding behavior. With regards to the benefits for mother and infants from breastfeeding, a separation of mother and child even in case of infectious settings should be avoided.

Peripartal management of dichorial twin pregnancy in a bicornuate bicollis uterus: a case report and review of the literature.

INTRODUCTION: The management of a pregnancy in a bicornuate uterus is particularly challenging. A bicornuate uterus is a rare occurrence and a twin pregnancy in a bicornuate uterus even more rare. These pregnancies call for intensive diagnostic investigation and interdisciplinary care. CASE PRESENTATION: We report on a 27-year-old European woman patient (gravida I, para 0) with a simultaneous pregnancy in each cavity of a bicornuate bicollis uterus after embryo transfer. The condition was confirmed by hysteroscopy and laparoscopy. Several unsuccessful in vitro fertilization (IVF) attempts had been performed earlier before embryo transfer in each cornus. After a physiological course of pregnancy with differential screening at 12 + 6 weeks and 22 + 0 weeks of gestation, the patient presented with therapy-resistant contractions at 27 + 2 weeks. This culminated in the uncomplicated spontaneous delivery of the leading fetus and delayed spontaneous delivery of the second fetus. DISCUSSION: Only 16 cases of twin pregnancy in a bicornuate unicollis uterus have been reported worldwide and only 6 in a bicornuate bicollis uterus. The principal risks in such pregnancies are preterm labor, intrauterine growth restriction, malpresentation and preeclampsia. These typical risk factors of a twin pregnancy are greatly potentiated in the above mentioned setting. CONCLUSION: A twin pregnancy in the presence of a uterine malformation is rare and difficult to manage. These rare cases must be collected and reported in order to work out algorithms of monitoring and therapy as well as issue appropriate recommendations for their management.