SARS-CoV-2 vaccination, booster, and infection in pregnant population enhances passive immunity in neonates.

The effects of heterogeneous infection, vaccination and boosting histories prior to and during pregnancy have not been extensively studied and are likely important for protection of neonates. We measure levels of spike binding antibodies in 4600 patients and their neonates with different vaccination statuses, with and without history of SARS-CoV-2 infection. We investigate neutralizing antibody activity against different SARS-CoV-2 variant pseudotypes in a subset of 259 patients and determined correlation between IgG levels and variant neutralizing activity. We further study the ability of maternal antibody and neutralizing measurements to predict neutralizing antibody activity in the umbilical cord blood of neonates. In this work, we show SARS-CoV-2 vaccination and boosting, especially in the setting of previous infection, leads to significant increases in antibody levels and neutralizing activity even against the recent omicron BA.1 and BA.5 variants in both pregnant patients and their neonates.

Longitudinal antibody response kinetics following SARS-CoV-2 messenger RNA vaccination in pregnant and nonpregnant persons.

BACKGROUND: For some vaccine-preventable diseases, the immunologic response to vaccination is altered by a pregnant state. The effect of pregnancy on SARS-CoV-2 vaccine response remains unclear. OBJECTIVE: We sought to characterize the peak and longitudinal anti-S immunoglobulin G, immunoglobulin M, and immunoglobulin A responses to messenger RNA-based SARS-CoV-2 vaccination in pregnant persons and compare them with those in nonpregnant, reproductive-aged persons. STUDY DESIGN: We conducted 2 parallel prospective cohort studies among pregnant and nonpregnant persons who received SARS-CoV-2 messenger RNA vaccinations. Blood was collected at the time of first and second vaccine doses, 2 weeks post second dosage, and with serial longitudinal follow-up up to 41.7 weeks post vaccination initiation. Anti-S immunoglobulin M, immunoglobulin G, and immunoglobulin A were analyzed by enzyme-linked immunosorbent assay. We excluded those with previous evidence of SARS-CoV-2 infection by history or presence of antinucleocapsid antibodies. In addition, for this study, we did not include individuals who received a third or booster vaccine dosage during the study period. We also excluded pregnant persons who were not fully vaccinated (14 days post receipt of the second vaccine dosage) by time of delivery and nonpregnant persons who became pregnant through the course of the study. We studied the effect of gestational age at vaccination on the anti-S response using Spearman correlation. We compared the peak anti-S antibody responses between pregnant and nonpregnant persons using a Mann-Whitney U test. We visualized and studied the longitudinal anti-S antibody response using locally weighted scatterplot smoothing, Mann-Whitney U test, and mixed analysis of variance test. RESULTS: Data from 53 pregnant and 21 nonpregnant persons were included in this analysis. The median (interquartile range) age of the pregnant and nonpregnant participants was 35.0 (33.3-37.8) years and 36.0 (33.0-41.0) years, respectively. Six (11.3%) participants initiated vaccination in the first trimester, 23 (43.3%) in the second trimester, and 24 (45.3%) in the third trimester, with a median gestational age at delivery of 39.6 (39.0-40.0) weeks. The median (interquartile range) follow-up time from vaccine initiation to the last blood sample collected was 25.9 (11.9) weeks and 28.9 (12.9) weeks in the pregnant and nonpregnant cohort, respectively. Among pregnant persons, anti-S immunoglobulin G, immunoglobulin A, and immunoglobulin M responses were not associated with gestational age at vaccine initiation (all P>.05). The anti-S immunoglobulin G response at 2 weeks post second dosage was not statistically different between pregnant and nonpregnant persons (P>.05). However, the anti-S immunoglobulin M and immunoglobulin A responses at 2 weeks post second dosage were significantly higher in nonpregnant persons (P<.001 for both). The anti-S immunoglobulin G and immunoglobulin M levels 6 to 8 months after vaccine initiation fell to comparable proportions of the peak 2 weeks post second dosage antibody levels between pregnant and nonpregnant persons (immunoglobulin G P=.77; immunoglobulin M P=.51). In contrast, immunoglobulin A levels 6 to 8 months after vaccine initiation fell to statistically significantly higher proportions of peak 2 weeks post second dosage antibody levels in pregnant compared with nonpregnant persons (P=.002). Maternal anti-S immunoglobulin G levels were strongly correlated with umbilical cord anti-S immunoglobulin G levels (R=0.8, P<.001). CONCLUSION: The anti-S immunoglobulin A, immunoglobulin M, and immunoglobulin G response to SARS-CoV-2 vaccination in pregnancy is independent of gestational age of vaccine initiation. Maintenance of the immunoglobulin G response is comparable between pregnant and nonpregnant persons. The differential peak response of immunoglobulin M and immunoglobulin A and the differential decline of anti-S immunoglobulin A between pregnant and nonpregnant persons requires further investigation.

Placental pathology, neonatal birth weight, and Apgar score in acute and distant SARS-CoV-2 infection.

Background: Most research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy has been on acute infections with limited data on the effect of distant infection. Aim: We examined placental pathology and neonatal outcomes in distant SARS-CoV-2 infection earlier in pregnancy compared to acute infections late in pregnancy/at birth and to non-SARS-CoV-2 infected patients with other placental pathologies/clinical presentations. Methods: Placentas birthed to unvaccinated patients with SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) testing and serology testing results from time of delivery were included in this study. A total of 514 singleton placentas between April 18, 2020, and July 26, 2021, were included: 77 acute SARS-CoV-2 infection (RT-PCR positive and serology negative); 222 distant SARS-CoV-2 infection (RT-PCR negative but serology IgG-positive); and 215 non-SARS-Cov-2 infected (RT-PCR negative, serology negative, and history negative) with other placental pathologies: preeclampsia/hypertension, intrauterine growth restriction (IUGR), diabetes, chorioamnionitis, and meconium. Placental pathology findings, Apgar scores, and neonatal birth weights were compared. Results: Placentas from the acute group had significantly more villous agglutination (10.4%, P = 0.015) and eosinophilic T-cell vasculitis (5.2%, P = 0.004) compared to placentas from the distant group (2.7% and 0%) and non-SARS-CoV-2 placentas (1.9% and 0.9%). One acute case showed SARS-CoV-2 placentitis and resulted in preterm delivery at 25 weeks. Both the preeclampsia/hypertension and the IUGR groups showed significantly more maternal vascular malperfusion findings compared to the acute (6.5%, 6.5% and 1.3%) and distant (7.7%, 7.7%, and 3.2%) groups. Fetal vascular malperfusion findings such as thrombosis of fetal vessels (17.4% P = 0.042) and intramural fibrin deposition (21.7% P = 0.026) were significantly higher in the IUGR group compared to acute (7.8%; 2.6%) and distant (3.6%; 8.1%) infection. Many neonates born to patients infected with SARS-CoV-2 had birth weights outside of 95% confidence range of observed birth weights. There was no association of Apgar scores with infection status or placental pathology. Conclusion: Acute and distant SARS-CoV-2 infections present differing placental pathology. Relevance for Patients: SARS-CoV-2 infection during pregnancy has demonstrable effects on the placenta with potential significant impacts for maternal and fetal health. Prevention of maternal SARS-CoV-2 infection, primarily through vaccination, remains the best mitigation strategy to prevent sequelae of maternal SARS-CoV-2 infection.

Challenges in the Development of Biological Approaches for the Treatment of Degenerative Disc Disease.

There are numerous innovative and promising approaches aimed at slowing, reversing, or healing degenerative disc disease. However, multiple treatment-specific impediments slow progress toward realizing the benefits of these therapies. First, the exact pathophysiology underlying degenerative disc disease remains complicated and challenging to study. In addition, the study of the spine and intervertebral disc in animal models is difficult to translate to humans, hindering the utility of preclinical research. Biological treatments are subject to the complex biomechanical environment in which native discs degenerate. The regulatory approval environment for these therapeutics will likely involve a high degree of scrutiny. Finally, patient selection and assessment of outcomes are a particular challenge in this clinical setting.

Innovative Biological Treatment Methods for Degenerative Disc Disease.

Low back pain is the leading cause of work absences and years lived with disability, and it is often associated with degenerative disc disease. In recent years, biological treatment approaches such as the use of growth factors, cell injections, annulus fibrosus (AF) repair, nucleus pulposus replacement, and tissue-engineered discs have been explored as means for preventing or reversing degenerative disc disease. Both animal and clinical studies have shown promising results for cell-based therapy on the grounds of its regenerative potential. Clinical data also indicate that stem cell injection is safe when appropriately performed, albeit its long-term safety and efficacy are yet to be explored. Numerous challenges also remain to be overcome, such as isolating, differentiating, and preconditioning the disc cells, as well as managing the nutrient-deficient and oxygen-deficient micromilieu of the intervertebral disc (IVD). AF repair methods including devices used in clinical trials have shown success in decreasing reherniation rates and improving overall clinical outcomes. In addition, recent studies that combined AF repair and nucleus pulposus replacement have shown improved biomechanical stability in IVDs after the combined treatment. Tissue-engineered IVDs for total disc replacement are still being developed, and future studies are necessary to overcome the challenges in their delivery, efficacy, and safety.

Association of Gestational Age at Coronavirus Disease 2019 (COVID-19) Vaccination, History of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection, and a Vaccine Booster Dose With Maternal and Umbilical Cord Antibody Levels at Delivery.

OBJECTIVE: To describe maternal and umbilical cord blood anti-spike immunoglobulin (Ig)G levels at delivery with coronavirus disease 2019 (COVID-19) vaccination before and during pregnancy and to assess the association of prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and a vaccine booster dose with anti-spike maternal and umbilical cord IgG levels. METHODS: We conducted a retrospective cohort study of women with self-reported COVID-19 vaccination (Pfizer-BioNTech, Moderna, or Johnson & Johnson/Janssen), including a booster dose, during or before pregnancy, who delivered at 34 weeks of gestation or more. Maternal and umbilical cord blood samples at delivery were analyzed for semi-quantitative anti-spike IgG. We examined the association between timing of maternal vaccination and maternal and umbilical cord anti-spike levels using a rank sum test. The relationships between a prior history of SARS-CoV-2 infection and maternal and umbilical cord anti-spike IgG levels, and between a booster dose and maternal and umbilical cord anti-spike levels, were also evaluated using a rank sum test. RESULTS: We included data from 1,359 vaccinated pregnant women, including 20 women who received a booster dose, and 1,362 umbilical cord samples. Maternal anti-spike IgG levels were detectable at delivery regardless of timing of vaccination throughout pregnancy among fully vaccinated women; however, early third-trimester vaccination was associated with the highest anti-spike IgG levels in maternal and umbilical cord blood. Among women with a history of SARS-CoV-2 infection, maternal and cord blood antibody response achieved with vaccination in early pregnancy was comparable with third-trimester vaccination in pregnant women without a history of SARS-CoV-2 infection. A booster dose in the third trimester was associated with maternal anti-spike IgG levels greater than third-trimester vaccination in women with or without a history of SARS-CoV-2 infection. DISCUSSION: Vaccination against COVID-19 before and throughout pregnancy was associated with detectable maternal anti-spike IgG levels at delivery. A complete vaccination course, prior history of SARS-CoV-2 infection, and a third-trimester booster dose were associated with the highest maternal and umbilical cord antibody levels.

The World of Neurosurgery Reimagined Post COVID-19: Crisis ↔ Opportunities.

The COVID-19 pandemic has impacted neurosurgery in unforeseeable ways. Neurosurgical patient care, research, and education have undergone extraordinary modifications as medicine and mankind have adapted to overcome the challenges posed by this pandemic. Some changes will disappear as the situation slowly recovers to a prepandemic status quo. Others will remain: This pandemic has sparked some long-overdue systemic transformations across all levels of medicine, including in neurosurgery, that will be beneficial in the future. In this paper, we present some of the challenges faced across different levels of neurosurgical clinical care, research, and education, the changes that followed, and how some of these modifications have transformed into opportunities for improvement and growth in the future.