SARS CoV-2 detected in neonatal stool remote from maternal COVID-19 during pregnancy.

BACKGROUND: In utero transmission of SARS coronavirus 2 (SARS-CoV-2) has not been fully investigated. We investigated whether newborns of mothers with COVID-19 during pregnancy might harbor SARS-CoV-2 in the gastrointestinal tract. METHODS: This cohort study investigated stool from 14 newborns born at 25-41 weeks admitted at delivery to our urban academic hospital whose mothers had COVID-19 during pregnancy. Eleven mothers had COVID-19 resolved more than 10 weeks before delivery. Newborn stool was evaluated for SARS-CoV-2 RNA, Spike protein, and induction of inflammatory cytokines interleukin-6 (IL-6) and interferon-γ (IFN-γ) in macrophages. RESULTS: Despite negative SARS CoV-2 nasal PCRs from all newborns, viral RNAs and Spike protein were detected in the stool of 11 out of 14 newborns as early as the first day of life and increased over time in 6. Stool homogenates from all 14 newborns elicited elevated inflammatory IL-6 and IFN-γ from macrophages. Most newborns were clinically well except for one death from gestational autoimmune liver disease and another who developed necrotizing enterocolitis. CONCLUSIONS: These findings suggest in utero transmission of SARS-CoV-2 and possible persistent intestinal viral reservoirs in the newborns. Further investigation is required to understand the mechanisms and their clinical implications. IMPACT: SARS-CoV-2 RNAs or Spike protein was detected in the stool of 11 out of 14 preterm newborns born to mothers with resolved COVID-19 weeks prior to delivery despite negative newborn nasal PCR swabs. These novel findings suggest risk of in utero SARS-CoV-2 transmission to the fetal intestine during gestation. The presence of SARS-CoV-2 RNAs and Spike protein in the intestines of newborns may potentially impact the development of the gut microbiome and the immune system; the long-term health impact on the preterm infants should be further investigated.

Bioactive Compositions of Cinnamon (Cinnamomum verum J. Presl) Extracts and Their Capacities in Suppressing SARS-CoV-2 Spike Protein Binding to ACE2, Inhibiting ACE2, and Scavenging Free Radicals.

Cinnamon (Cinnamomum verum J. Presl) bark and its extracts are popular ingredients added to food and supplement products. It has various health effects, including potentially reducing the risk of coronavirus disease-2019 (COVID-19). In our study, the bioactives in cinnamon water and ethanol extracts were chemically identified, and their potential in suppressing SARS-CoV-2 spike protein-angiotensin-converting enzyme 2 (ACE2) binding, reducing ACE2 availability, and scavenging free radicals was investigated. Twenty-seven and twenty-three compounds were tentatively identified in cinnamon water and ethanol extracts, respectively. Seven compounds, including saccharumoside C, two emodin-glucuronide isomers, two physcion-glucuronide isomers, and two type-A proanthocyanidin hexamers, were first reported in cinnamon. Cinnamon water and ethanol extracts suppressed the binding of SARS-CoV-2 spike protein to ACE2 and inhibited ACE2 activity in a dose-dependent manner. Cinnamon ethanol extract had total phenolic content of 36.67 mg gallic acid equivalents (GAE)/g and free radical scavenging activities against HO• and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS•+) of 1688.85 and 882.88 µmol Trolox equivalents (TE)/g, which were significantly higher than those of the water extract at 24.12 mg GAE/g and 583.12 and 210.36 µmol TE/g. The free radical scavenging activity against 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•) of cinnamon ethanol extract was lower than that of the water extract. The present study provides new evidence that cinnamon reduces the risk of SARS-CoV-2 infection and COVID-19 development.

Chemical Compositions of Clove (Syzygium aromaticum (L.) Merr. & L.) Extracts and Their Potentials in Suppressing SARS-CoV-2 Spike Protein-ACE2 Binding, Inhibiting ACE2, and Scavenging Free Radicals.

COVID-19 is initiated by binding the SARS-CoV-2 spike protein to angiotensin-converting enzyme 2 (ACE2) on host cells. Food factors capable of suppressing the binding between the SARS-CoV-2 spike protein and ACE2 or reducing the ACE2 availability through ACE2 inhibitions may potentially reduce the risk of SARS-CoV-2 infection and COVID-19. In this study, the chemical compositions of clove water and ethanol extracts were investigated, along with their potentials in suppressing SARS-CoV-2 spike protein-ACE2 binding, reducing ACE2 availability, and scavenging free radicals. Thirty-four compounds were tentatively identified in the clove water and ethanol extracts, with six reported in clove for the first time. Clove water and ethanol extracts dose-dependently suppressed SARS-CoV-2 spike protein binding to ACE2 and inhibited ACE2 activity. The water extract had stronger inhibitory effects than the ethanol extract on a dry weight basis. The clove water extract also had more potent free radical scavenging activities against DPPH• and ABTS•+ (536.9 and 3525.06 µmol TE/g, respectively) than the ethanol extract (58.44 and 2298.01 µmol TE/g, respectively). In contrast, the ethanol extract had greater total phenolic content (TPC) and relative HO• scavenging capacity (HOSC) values (180.03 mg GAE/g and 2181.08 µmol TE/g, respectively) than the water extract (120.12 mg GAE/g and 1483.02 µmol TE/g, respectively). The present study demonstrated the potential of clove in reducing the risk of SARS-CoV-2 infection and COVID-19 development.

Gut microbiota-derived metabolites confer protection against SARS-CoV-2 infection.

The gut microbiome is intricately coupled with immune regulation and metabolism, but its role in Coronavirus Disease 2019 (COVID-19) is not fully understood. Severe and fatal COVID-19 is characterized by poor anti-viral immunity and hypercoagulation, particularly in males. Here, we define multiple pathways by which the gut microbiome protects mammalian hosts from SARS-CoV-2 intranasal infection, both locally and systemically, via production of short-chain fatty acids (SCFAs). SCFAs reduced viral burdens in the airways and intestines by downregulating the SARS-CoV-2 entry receptor, angiotensin-converting enzyme 2 (ACE2), and enhancing adaptive immunity via GPR41 and 43 in male animals. We further identify a novel role for the gut microbiome in regulating systemic coagulation response by limiting megakaryocyte proliferation and platelet turnover via the Sh2b3-Mpl axis. Taken together, our findings have unraveled novel functions of SCFAs and fiber-fermenting gut bacteria to dampen viral entry and hypercoagulation and promote adaptive antiviral immunity.