Congenital Infection Influence on Early Brain Development Through the Gut-Brain Axis.

The mechanisms by which various pathogens cause congenital infections have been studied extensively, aiding in the understanding of the detrimental effects these infections can have on fetal/neonatal neurological development. Recent studies have focused on the gut-brain axis as pivotal in neurodevelopment, with congenital infections causing substantial disruptions. There remains controversy surrounding the purported sterility of the placenta as well as concerns regarding the effects of exposure to antibiotics used during pregnancy on neonatal microbiome development and how early exposure to microbes or antibiotics can shape the gut-brain axis. Long-term neurodevelopmental consequences, such as autism spectrum disorder, attention deficit hyperactivity disorder, and cerebral palsy, may be attributable, in part, to early life infection and changes in the immature gut microbiome. The goal of this review is thus to critically evaluate the current evidence related to early life infection affecting neurodevelopment through the gut-brain axis.

Temporal Trend of COVID-19 Clinical Severity and the Ethnic/Racial Disparity: A Report from the Maryland Study Group.

OBJECTIVES: This study aimed to evaluate the temporal trend of novel coronavirus disease 2019 (COVID-19) symptoms and severity of clinical outcomes among pregnant women over a calendar year in the State of Maryland and compare clinical outcomes between different ethnic and racial groups. STUDY DESIGN: We conducted a retrospective, multicenter observational study of the temporal trend of COVID-19 clinical presentation during pregnancy in the State of Maryland. We reviewed consecutive charts of adult pregnant females, aged 18 to 55 years, with laboratory-confirmed severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection between March 1, 2020, and February 28, 2021, and managed within the University of Maryland Medical System and Johns Hopkins Medicine. We excluded cases with insufficient data for assessing the COVID-19 diagnosis, pregnancy status, or clinical outcomes. We evaluated the evolution of COVID-19 symptoms at the time of presentation. Also, we compared COVID-19 infection rate, hospitalization rate, oxygen use, and intensive care unit (ICU) admission rates between different ethnic and racial groups. RESULTS: We included 595 pregnant women with laboratory-confirmed COVID-19 over the study period. The prevalence of respiratory and systemic symptoms decreased over time with incidence rate ratios (IRRs) of 0.91 per month (95% confidence interval [CI]: 0.88-0.95) and 0.87 per month (95% CI: 0.83-0.95), respectively. The prevalence of hospitalization, O2 requirement, and ICU admission decreased over time with IRRs of 0.86 per month (95% CI: 0.82-0.91), 0.91 per month (95% CI: 0.84-0.98), and 0.70 per month (95% CI: 0.57-0.85), respectively. The Hispanic and Black populations had a higher COVID-19 infection rate and hospitalization rate than the non-Hispanic White population (p = 0.004, p < 0.001, and p < 0.001, respectively). CONCLUSION: Understanding the concepts of viral evolution could potentially help the fight against pandemics like COVID-19. Moreover, this might improve the knowledge of how pandemics affect disadvantaged populations and help close the gap in health care inequities. KEY POINTS: · A trade-off between virulence and transmissibility is determined by the natural selection of viruses.. · Understanding the concepts of viral evolution can help the fight against pandemics like COVID-19.. · Evolution of SARS-CoV-2 over time resulted in decreased virulence and increased infectivity..

Analysis of Clinical Outcomes of Pregnant Patients Treated With Nirmatrelvir and Ritonavir for Acute SARS-CoV-2 Infection.

Importance: Pregnant people are at increased risk of poor outcomes due to infection with SARS-CoV-2, and there are limited therapeutic options available. Objective: To evaluate the clinical outcomes associated with nirmatrelvir and ritonavir used to treat SARS-CoV-2 infection in pregnant patients. Design, Setting, and Participants: This case series included pregnant patients who were diagnosed with SARS-CoV-2 infection, received nirmatrelvir and ritonavir, and delivered their offspring within the Johns Hopkins Health System between December 22, 2021, and August 20, 2022. Exposures: Treatment with nirmatrelvir and ritonavir for SARS-CoV-2 infection during pregnancy. Main Outcomes and Measures: Clinical characteristics and outcomes were ascertained through manual record review. Results: Forty-seven pregnant patients (median [range] age, 34 [22-43] years) were included in the study, and the median (range) gestational age of their offspring was 28.4 (4.3-39.6) weeks. Medication was initiated at a median (range) of 1 (0-5) day after symptom onset, and only 2 patients [4.3%] did not complete the course of therapy because of adverse effects. Thirty patients (63.8%) treated with nirmatrelvir and ritonavir had a comorbidity in addition to pregnancy that could be a risk factor for developing severe COVID-19. Twenty-five patients [53.2%] delivered after treatment with nirmatrelvir and ritonavir. Twelve of these patients [48.0%] underwent cesarean delivery, 9 [75.0%] of which were scheduled. Two of 47 patients [4.3%] were hospitalized for conditions related to preexisting comorbidities. Conclusions and Relevance: In this case series, pregnant patients who were treated with nirmatrelvir and ritonavir tolerated treatment well, although there was an unexpectedly high rate of cesarean deliveries. The lack of an increase in serious adverse effects affecting pregnant patients or offspring suggests that clinicians can use this drug combination to treat pregnant patients with SARS-CoV-2 infection.

Dexamethasone for Severe COVID-19: How Does It Work at Cellular and Molecular Levels?

The coronavirus disease 2019 (COVID-19) caused by infection of the severe respiratory syndrome coronavirus-2 (SARS-CoV-2) significantly impacted human society. Recently, the synthetic pure glucocorticoid dexamethasone was identified as an effective compound for treatment of severe COVID-19. However, glucocorticoids are generally harmful for infectious diseases, such as bacterial sepsis and severe influenza pneumonia, which can develop respiratory failure and systemic inflammation similar to COVID-19. This apparent inconsistency suggests the presence of pathologic mechanism(s) unique to COVID-19 that renders this steroid effective. We review plausible mechanisms and advance the hypothesis that SARS-CoV-2 infection is accompanied by infected cell-specific glucocorticoid insensitivity as reported for some other viruses. This alteration in local glucocorticoid actions interferes with undesired glucocorticoid to facilitate viral replication but does not affect desired anti-inflammatory properties in non-infected organs/tissues. We postulate that the virus coincidentally causes glucocorticoid insensitivity in the process of modulating host cell activities for promoting its replication in infected cells. We explore this tenet focusing on SARS-CoV-2-encoding proteins and potential molecular mechanisms supporting this hypothetical glucocorticoid insensitivity unique to COVID-19 but not characteristic of other life-threatening viral diseases, probably due to a difference in specific virally-encoded molecules and host cell activities modulated by them.

The Israeli study of Pfizer BNT162b2 vaccine in pregnancy: considering maternal and neonatal benefits.

Pregnant patients with COVID-19 are more likely to require intensive care and die compared with noninfected pregnant women. While the consequences of COVID-19 disease in pregnancy prompted many health care organizations to support vaccination in pregnancy, vaccine effects for mother and infant remained unclear. In this issue of the JCI, Beharier and Mayo et al. explored maternal and neonatal responses to the Pfizer BNT162b2 SARS-CoV-2 mRNA vaccine. The authors examined blood samples from women and cord blood of neonates following childbirth. Samples were stratified into three groups: vaccine recipients, unvaccinated participants with past positive SARS-CoV-2 test, and unvaccinated participants without prior infection. Vaccinated mothers and mothers with previous infection generated and transferred protective IgG antibodies across the placenta. This study provides evidence to support the safety and efficacy of COVID-19 vaccination in pregnancy with protection to the neonate against infection, outlining clear vaccine benefits for both maternal and child health.

Pregnancy alters interleukin-1 beta expression and antiviral antibody responses during severe acute respiratory syndrome coronavirus 2 infection.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2, the disease-causing pathogen of the coronavirus disease 2019 pandemic, has resulted in morbidity and mortality worldwide. Pregnant women are more susceptible to severe coronavirus disease 2019 and are at higher risk of preterm birth than uninfected pregnant women. Despite this evidence, the immunologic effects of severe acute respiratory syndrome coronavirus 2 infection during pregnancy remain understudied. OBJECTIVE: This study aimed to assess the impact of severe acute respiratory syndrome coronavirus 2 infection during pregnancy on inflammatory and humoral responses in maternal and fetal samples and compare antibody responses to severe acute respiratory syndrome coronavirus 2 among pregnant and nonpregnant women. STUDY DESIGN: Immune responses to severe acute respiratory syndrome coronavirus 2 were analyzed using samples from pregnant (n=33) and nonpregnant (n=17) women who tested either positive (pregnant, 22; nonpregnant, 17) or negative for severe acute respiratory syndrome coronavirus 2 (pregnant, 11) at Johns Hopkins Hospital. We measured proinflammatory and placental cytokine messenger RNAs, neonatal Fc receptor expression, and tetanus antibody transfer in maternal and cord blood samples. In addition, we evaluated antispike immunoglobulin G, antispike receptor-binding domain immunoglobulin G, and neutralizing antibody responses to severe acute respiratory syndrome coronavirus 2 in serum or plasma collected from nonpregnant women, pregnant women, and cord blood. RESULTS: Pregnant women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection expressed more interleukin-1 beta, but not interleukin 6, in blood samples collected within 14 days vs >14 days after performing severe acute respiratory syndrome coronavirus 2 test. Pregnant women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection also had reduced antispike receptor-binding domain immunoglobulin G titers and were less likely to have detectable neutralizing antibody than nonpregnant women. Although severe acute respiratory syndrome coronavirus 2 infection did not disrupt neonatal Fc receptor expression in the placenta, maternal transfer of severe acute respiratory syndrome coronavirus 2 neutralizing antibody was inhibited by infection during pregnancy. CONCLUSION: Severe acute respiratory syndrome coronavirus 2 infection during pregnancy was characterized by placental inflammation and reduced antiviral antibody responses, which may impact the efficacy of coronavirus disease 2019 treatment in pregnancy. In addition, the long-term implications of placental inflammation for neonatal health require greater consideration.

Role of Inflammation in Virus Pathogenesis during Pregnancy.

Viral infections during pregnancy lead to a spectrum of maternal and fetal outcomes, ranging from asymptomatic disease to more critical conditions presenting with severe maternal morbidity, stillbirth, preterm birth, intrauterine growth restriction, and fetal congenital anomalies, either apparent at birth or later in life. In this article, we review the pathogenesis of several viral infections that are particularly relevant in the context of pregnancy and intrauterine inflammation. Understanding the diverse mechanisms employed by viral pathogens as well as the repertoire of immune responses induced in the mother may help to establish novel therapeutic options to attenuate changes in the maternal-fetal interface and prevent adverse pregnancy outcomes.

COVID-19 in pregnancy: Placental and neonatal involvement.

Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused over 12 million infections and more than 550 000 deaths.1 Morbidity and mortality appear partly due to host inflammatory response.2 Despite rapid, global research, the effect of SARS-CoV-2 on the developing fetus remains unclear. Case reports indicate that vertical transmission is uncommon; however, there is evidence that placental and fetal infection can occur.3-7 Placentas from infected patients show inflammatory, thrombotic, and vascular changes that have been found in other inflammatory conditions.8,9 This suggests that the inflammatory nature of SARS-CoV-2 infection during pregnancy could cause adverse obstetric and neonatal events. Exposure to intrauterine inflammation and placental changes could also potentially result in long-term, multisystemic defects in exposed infants. This review will summarize the known literature on the placenta in SARS-CoV-2 infection, evidence of vertical transmission, and possible outcomes of prenatal exposure to the virus.