Passive and active immunity in infants born to mothers with SARS-CoV-2 infection during pregnancy: Prospective cohort study

OBJECTIVETo investigate maternal immunoglobulins (IgM, IgG) response to SARS-CoV-2 infection during pregnancy and IgG transplacental transfer, to characterize neonatal antibody response to SARS-CoV-2 infection, and to longitudinally follow actively- and passively-acquired SARS-CoV-2 antibodies in infants. DESIGNA prospective observational study. SETTINGA public healthcare system in Santa Clara County (CA, USA). PARTICIPANTSWomen with SARS-CoV-2 infection during pregnancy and their infants were enrolled between April 15, 2020 and March 31, 2021. OUTCOMESSARS-CoV-2 serology analyses in the cord and maternal blood at delivery and longitudinally in infant blood between birth and 28 weeks of life. RESULTSOf 145 mothers who tested positive for SARS-CoV-2 during pregnancy, 86 had symptomatic infections: 78 with mild-moderate symptoms, and eight with severe-critical symptoms. Of the 147 newborns, two infants showed seroconversion at two weeks of age with high levels of IgM and IgG, including one premature infant with confirmed intrapartum infection. The seropositivity rates of the mothers at delivery was 65% (95% CI 0.56-0.73) and the cord blood was 58% (95% CI 0.49-0.66). IgG levels significantly correlated between the maternal and cord blood (Rs= 0.93, p< 0.0001). IgG transplacental transfer ratio was significantly higher when the first maternal positive PCR was 60-180 days before delivery compared to <60 days (1.2 vs. 0.6, p=<0.0001). Infant IgG negative conversion rate over follow-up periods of 1-4, 5-12, and 13-28 weeks were 8% (4/48), 12% (3/25), and 38% (5/13), respectively. The IgG seropositivity in the infants was positively related to IgG levels in the cord blood and persisted up to six months of age. CONCLUSIONSMaternal SARS-CoV-2 IgG is efficiently transferred across the placenta when infections occur more than two months before delivery. Maternally-derived passive immunity may protect infants up to six months of life. Neonates mount a strong antibody response to perinatal SARS-CoV-2 infection.

Clinical Trends Among U.S. Adults Hospitalized with COVID-19, March-December 2020

BackgroundThe COVID-19 pandemic has caused substantial morbidity and mortality. ObjectivesTo describe monthly demographic and clinical trends among adults hospitalized with COVID-19. DesignPooled cross-sectional. Setting99 counties within 14 states participating in the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET). PatientsU.S. adults (aged [≥]18 years) hospitalized with laboratory-confirmed COVID-19 during March 1-December 31, 2020. MeasurementsMonthly trends in weighted percentages of interventions and outcomes including length of stay (LOS), intensive care unit admissions (ICU), invasive mechanical ventilation (IMV), vasopressor use and in-hospital death (death). Monthly hospitalization, ICU and death rates per 100,000 population. ResultsAmong 116,743 hospitalized adults, median age was 62 years. Among 18,508 sampled adults, median LOS decreased from 6.4 (March) to 4.6 days (December). Remdesivir and systemic corticosteroid use increased from 1.7% and 18.9% (March) to 53.8% and 74.2% (December), respectively. Frequency of ICU decreased from 37.8% (March) to 20.5% (December). IMV (27.8% to 8.7%), vasopressors (22.7% to 8.8%) and deaths (13.9% to 8.7%) decreased from March to October; however, percentages of these interventions and outcomes remained stable or increased in November and December. Percentage of deaths significantly decreased over time for non-Hispanic White patients (p-value <0.01) but not non-Hispanic Black or Hispanic patients. Rates of hospitalization (105.3 per 100,000), ICU (20.2) and death (11.7) were highest during December. LimitationsCOVID-NET covers approximately 10% of the U.S. population; findings may not be generalizable to the entire country. ConclusionsAfter initial improvement during April-October 2020, trends in interventions and outcomes worsened during November-December, corresponding with the 3rd peak of the U.S. pandemic. These data provide a longitudinal assessment of trends in COVID-19-associated outcomes prior to widespread COVID-19 vaccine implementation.

3-Methylcrotonyl-coenzyme A carboxylase is a component of the mitochondrial leucine catabolic pathway in plants

3-Methylcrotonyl-coenzyme A carboxylase (MCCase) is a mitochondrial biotin-containing enzyme whose metabolic function is not well understood in plants. In soybean (Glycine max) seedlings the organ-specific and developmentally induced changes in MCCase expression are regulated by mechanisms that control the accumulation of MCCase mRNA and the activity of the enzyme. During soybean cotyledon development, when seed-storage proteins are degraded, leucine (Leu) accumulation peaks transiently at 8 d after planting. The coincidence between peak MCCase expression and the decline in Leu content provides correlative evidence that MCCase is involved in the mitochondrial catabolism of Leu. Direct evidence for this conclusion was obtained from radiotracer metabolic studies using extracts from isolated mitochondria. These experiments traced the metabolic fate of [U-14C]Leu and NaH14CO3, the latter of which was incorporated into methylglutaconyl-coenzyme A (CoA) via MCCase. These studies directly demonstrate that plant mitochondria can catabolize Leu via the following scheme: Leu --> alpha-ketoisocaproate --> isovaleryl-CoA --> 3-methylcrotonyl-CoA --> 3-methylglutaconyl-CoA --> 3-hydroxy-3-methylglutaryl-CoA --> acetoacetate + acetyl-CoA. These findings demonstrate for the first time, to our knowledge, that the enzymes responsible for Leu catabolism are present in plant mitochondria. We conclude that a primary metabolic role of MCCase in plants is the catabolism of Leu.

Regulatory Oversight of Genetically Engineered Microorganisms: Has Regulation Inhibited Innovation?

/ Using detailed interviews with company representatives and researchers in the field, this paper examines the factors that might account for the slow pace of development of genetically engineered microorganisms (GEMs) intended for environmental release. We specifically analyzed the role of the regulatory system in shaping innovation. We identified at least two cases where industry decided to discontinue the development of a genetically engineered microbial product because of concerns over regulatory oversight. However, most often industry decisions to continue or halt development of GEMs were based on an evaluation of the particular product's efficacy and potential for profitability. Thus the inability of GEMs to perform up to expectations in the field, rather than the regulatory constraints, appears to be the factor responsible for the slow pace of development. KEY WORDS: Genetically engineered microorganisms; Biotechnology; Regulation of biotechnology; Innovation; Environmental release