, et al. (2020) Enhanced contact investigations for nine early travel-related cases of SARS-CoV-2 in the United States. PLoS ONE 15(9): e0238342.

BACKGROUND: Akt signalling regulates glycolysis and drives the Warburg effect in cancer, thus decreased glucose utilisation is a pharmacodynamic marker of Akt inhibition. However, cancer cells can utilise alternative nutrients to glucose for energy such as lactate, which is often elevated in tumours together with increased acidity. We therefore hypothesised that lactic acidosis may confer resistance to Akt inhibition. METHODS: The effect of the pan-Akt inhibitor uprosertib (GSK2141795), on HCT116 and LS174T colon cancer cells was evaluated in the presence and absence of lactic acid in vitro. Expression of downstream Akt signalling proteins was determined using a phosphokinase array and immunoblotting. Metabolism was assessed using 1 H nuclear magnetic resonance spectroscopy, stable isotope labelling and gas chromatography-mass spectrometry. RESULTS: Lactic acid-induced resistance to uprosertib was characterised by increased cell survival and reduced apoptosis. Uprosertib treatment reduced Akt signalling and glucose uptake irrespective of lactic acid supplementation. However, incorporation of lactate carbon and enhanced respiration was maintained in the presence of uprosertib and lactic acid. Inhibiting lactate transport or oxidative phosphorylation was sufficient to potentiate apoptosis in the presence of uprosertib. CONCLUSIONS: Lactic acidosis confers resistance to uprosertib, which can be reversed by inhibiting lactate transport or oxidative metabolism.

Background Coronavirus disease 2019 (COVID-19), the respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China and has since become pandemic. As part of initial response activities in the United States, enhanced contact investigations were conducted to enable early identification and isolation of additional cases and to learn more about risk factors for transmission. Methods Close contacts of nine early travel-related cases in the United States were identified. Close contacts meeting criteria for active monitoring were followed, and selected individuals were targeted for collection of additional exposure details and respiratory samples. Respiratory samples were tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction (RT-PCR) at the Centers for Disease Control and Prevention. Results There were 404 close contacts who underwent active monitoring in the response jurisdictions; 338 had at least basic exposure data, of whom 159 had at least 1 set of respiratory samples collected and tested. Across all known close contacts under monitoring, two additional cases were identified; both secondary cases were in spouses of travel-associated case patients. The secondary attack rate among household members, all of whom had at least 1 respiratory sample tested, was 13% (95% CI: 4 - 38%). Conclusions The enhanced contact tracing investigations undertaken around nine early travel-related cases of COVID-19 in the United States identified two cases of secondary transmission, both spouses. Rapid detection and isolation of the travel-associated case patients, enabled by public awareness of COVID-19 among travelers from China, may have mitigated transmission risk among close contacts of these cases.

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Background: It is well established that pregnant persons with SARS-CoV-2 are at an increased risk for preterm birth, however, less is known about perinatal outcomes for neonates with intrauterine exposure to SARS-CoV-2. Methods: Characteristics of 50 SARS-CoV-2 positive neonates born to SARS-CoV-2 pregnant persons positive between May 22, 2020, and February 22, 2021, in Los Angeles County, CA, were assessed. Pattern of neonate SARS-CoV-2 test results and time to positive test was analyzed. Objective clinical severity criteria were applied to assess neonatal disease severity. Results: Median gestational age was 39 weeks with 8 (16%) neonates born preterm. Most (74%) were asymptomatic, while 13 (26%) were symptomatic from any cause. Four (8%) symptomatic neonates met criteria for severe disease, of which 2 (4%) were likely secondary to COVID-19. The other 2 with severe disease had more likely alternate diagnoses, and 1 of these neonates subsequently died at 7 months of life. Among 12 (24%) that were positive within 24 hours after birth, one was persistently positive and represented likely intrauterine transmission. Sixteen (32%) were admitted to the neonatal intensive care unit. Conclusion: In this case series of 50 SARS-CoV-2 positive mother-neonate pairs, we found that most neonates were asymptomatic regardless of when they tested positive during the 14 days after birth, that there was relatively low risk of COVID-19 associated severe disease, and that intrauterine transmission can occur in rare cases. Although short-term outcomes are mostly promising, more research is needed to study long-term consequences of SARS-CoV-2 infection in neonates born to positive pregnant persons.

Maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the second and third trimesters of pregnancy may impact fetal development via vertical transmission, complications of coronavirus disease 2019 (COVID-19), or placental injury. However, potential associations between prenatal SARS-CoV-2 infection and fetal loss are not well understood. This case series of thirteen second and third trimester fetal losses reported by local public health departments to California's state public health surveillance included maternal clinical and demographic characteristics as well as placental pathology, fetal autopsy reports, and coroner report. There was no evidence that maternal COVID-19 disease severity, placental injury, or SARS-CoV-2 vertical transmission contributed to pregnancy loss. However, this case series is a limited sample; more research is needed to identify factors of prenatal SARS-CoV-2 that may contribute to fetal death in the second and third trimesters.

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