Fetal Demise and Failed Antibody Therapy During Zika Virus Infection of Pregnant Macaques

Zika virus (ZIKV) infection of pregnant women is associated with pathologic complications of fetal development. Here, we infect pregnant rhesus macaques (Macaca mulatta) with a minimally passaged ZIKV isolate from Rio de Janeiro, where a high rate of fetal development complications was observed. The infection of pregnant macaques with this virus results in maternal viremia, virus crossing into the amniotic fluid (AF), and in utero fetal deaths. We also treated three additional ZIKV-infected pregnant macaques with a cocktail of ZIKV-neutralizing human monoclonal antibodies (nmAbs) at peak viremia. While the nmAbs can be effective in clearing the virus from the maternal sera of treated monkeys, it is not sufficient to clear ZIKV from AF. Our report suggests that ZIKV from Brazil causes fetal demise in non-human primates (NHPs) without additional mutations or confounding co-factors. Treatment with a neutralizing anti-ZIKV nmAb cocktail is insufficient to fully stop vertical transmission

La loi de Stefan et l'électrodynamique non linéaire

On étudie certaines conséquences qu'entraînerait l'abandon de la linéarité des équations de l'éledtrodynamiqne (comme dans la théorie de Born). On étudie en particulier, dans des hypothèses très générales, ce que devient la loi de Stefan pour les très hautes températures et on classe les diverses possibilités qui s'offrent à la théorie. On examine enfin ce que devient dans une telle théorie la loi du déplacement de Wien

Role of Embryoscopy in Patients with Missed Abortion. A Preliminary Experience

Missed abortion occurs in 10-20% of pregnancies, the most frequent cause being genetic alterations such as aneuploidies, polyploidies, or monosomies. Embryoscopy is the direct visualization of the embryo by hysteroscopy. It allows to collect targeted biopsy of the embryo and trophoblast for genetic analysis minimizing the change of maternal contamination of the specimen To describe the hysteroscopic findings and the genetic results of the embryoscopies performed between January 2020 and 2021 at the Sanatorio Finochietto in Buenos Aires Argentina. We present a case series of 55 consecutive embryoscopies performed in patients diagnosed with missed abortion during the first trimester. Embryo and trophoblast biopsies under direct visualization were collected when possible. Ambulatory hysteroscopy unit. Patients diagnosed with missed abortion during the first trimester of pregnancy. Diagnostic embryoscopy with embryo and trophoblast biopsy. 55 embryoscopies were performed in patients between 28 and 45 years old with a diagnosis of missed abortion. The average gestational age was 7.2 weeks. Of these, 38 genetic biopsies were collected, 13 patients had a normal karyotype, 13 had chromosomal abnormalities (10 trisomies, 3 triploidies) and in 12 the specimen was inadequate for evaluation. Embryoscopy revealed 5 macroscopic malformations, 3 in patients with normal type, and two with alterations, which presented syndactyly and hydrocephalus, prominent umbilical herniation. Embryoscopy allows direct visualization of the morphological alterations of the embryos, obtain a direct biopsy for its genetic study, and evaluate the uterine cavity. This procedure could be very useful in couples with missed abortions, since it provides significant information for genetic counseling

Outcomes of women with laboratory evidence of Zika infection in pregnancy

Abstract Background Zika virus (ZIKV) infection in pregnancy is a global health concern. With onset of local transmission, obstetricians in Miami-Dade County, FL, United States, are now in the unique position of providing care to both pregnant women with locally-transmitted and travel-associated ZIKV infections. This study provides data regarding the testing and pregnancy outcomes of women with laboratory evidence of ZIKV infection in pregnancy. Methods A retrospective chart review was conducted using laboratory records of ZIKV testing (PCR and IgM) completed from January through December 2016 at multiple tertiary care centers located in Miami-Dade County. Testing was based on CDC guidelines at time of testing, leading to heterogeneity in tests performed. Data was extracted from charts of women with positive ZIKV PCR in serum and/or urine or positive ZIKV IgM with confirmatory, pending, or insufficient PRNT results. Routine obstetrics parameters and the presence of fetal or neonatal abnormalities were recorded. Results Of the 2327 pregnant women screened for ZIKV, 88 (3.8%) screened positive with PCR and/or IgM in serum or urine. Of those women with positive ZIKV testing, 53 (60%) had no documented ZIKV symptoms and 40 (45%) had no known travel history outside of Miami-Dade County during their pregnancy. Sixty-six women had antenatal ultrasounds, 14 (21%) of which ever had a head circumference or biparetial diameter measurement less than the third percentile, but none showed evidence of intracranial calcifications. Fifty-four women with positive testing have delivered: 46 at term and 8 preterm. Fifty-four infants have been born to women with positive ZIKV testing; 2 infants (1.98%) had documented congenital abnormalities. One infant was born with clinically-defined microcephaly (1.9%) and intracranial calcifications and the other had only intracranial calcifications. Ninety-four positive IgM tests were sent to the CDC for confirmatory plaque reduction neutralization testing (PRNT). 49 PRNT tests returned positive (ZIKV titer ≥10), while 28 returned negative (ZIKV titer < 10), representing a false-positive rate of 30.4%. Conclusion As this epidemic persists, data from this unique cohort of pregnant women with both local and travel-associated ZIKV exposure contributes to the growing knowledge base regarding implications of ZIKV in pregnancy. Disclosures All authors: No reported disclosures

Mechanism of Multi-Organ Injury in Experimental COVID-19 and Its Inhibition by a Small Molecule Peptide

Severe disease from SARS-CoV-2 infection often progresses to multi-organ failure and results in an increased mortality rate amongst these patients. However, underlying mechanisms of SARS- CoV-2-induced multi-organ failure and subsequent death are still largely unknown. Cytokine storm, increased levels of inflammatory mediators, endothelial dysfunction, coagulation abnormalities, and infiltration of inflammatory cells into the organs contribute to the pathogenesis of COVID-19. One potential consequence of immune/inflammatory events is the acute progression of generalized edema, which may lead to death. We, therefore, examined the involvement of water channels in the development of edema in multiple organs and their contribution to organ dysfunction in a Murine Hepatitis Virus-1 (MHV-1) mouse model of COVID-19. Using this model, we recently reported multi-organ pathological abnormalities and animal death similar to that reported in humans with SARS-CoV-2 infection. We now identified an alteration in protein levels of AQPs 1, 4, 5, and 8 and associated oxidative stress, along with various degrees of tissue edema in multiple organs, which correlate well with animal survival post-MHV-1 infection. Furthermore, our newly created drug (a 15 amino acid synthetic peptide, known as SPIKENET) that was designed to prevent the binding of spike glycoproteins with their receptor(s), angiotensin- converting enzyme 2 (ACE2), and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) (SARS-CoV-2 and MHV-1, respectively), ameliorated animal death and reversed altered levels of AQPs and oxidative stress post-MHV-1 infection. Collectively, our findings suggest the possible involvement of altered aquaporins and the subsequent edema, likely mediated by the virus-induced inflammatory and oxidative stress response, in the pathogenesis of COVID- 19 and the potential of SPIKENET as a therapeutic option