Identifying environmental factors that influence immune response to SARS-CoV-2: Systematic evidence map protocol.

BACKGROUND: Widespread environmental contamination can directly interact with human immune system functions. Environmental effects on the immune system may influence human susceptibility to respiratory infections as well as the severity of infectious diseases, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Furthermore, the efficacy of vaccines to respiratory diseases may be impacted by environmental exposures through immune perturbations. Given the quick pace of research about COVID-19 and associated risk factors, it is critical to identify and curate the streams of evidence quickly and effectively. OBJECTIVE: We developed this systematic evidence map protocol to identify and organize existing human and animal literature on high-priority environmental chemical classes (Per- and polyfluoroalkyl substances, pesticides, phthalates, quaternary ammonium compounds, and air pollutants) and their potential to influence three key outcomes: (1) susceptibility to respiratory infection, including SARS-CoV-2 (2) severity of the resultant disease progression, and (3) impact on vaccine efficacy. The result of this project will be an online, interactive database which will show what evidence is currently available between involuntary exposures to select environmental chemicals and immune health effects, data gaps that require further research, and data rich areas that may support further analysis. SEARCH AND STUDY ELIGIBILITY: We will search PubMed for epidemiological or toxicological literature on select toxicants from each of the chemical classes and each of the three outcomes listed above. STUDY APPRAISAL AND SYNTHESIS OF METHODS: For each study, two independent reviewers will conduct title and abstract screening as well as full text review for data extraction of study characteristics. Study quality will not be evaluated in this evidence mapping. The main findings from the systematic evidence map will be visualized using a publicly available and interactive database hosted on Tableau Public.

Establishment of Intestinal Organoid from Rousettus leschenaultii and the Susceptibility to Bat-Associated Viruses, SARS-CoV-2 and Pteropine Orthoreovirus.

Various pathogens, such as Ebola virus, Marburg virus, Nipah virus, Hendra virus, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and SARS-CoV-2, are threatening human health worldwide. The natural hosts of these pathogens are thought to be bats. The rousette bat, a megabat, is thought to be a natural reservoir of filoviruses, including Ebola and Marburg viruses. Additionally, the rousette bat showed a transient infection in the experimental inoculation of SARS-CoV-2. In the current study, we established and characterized intestinal organoids from Leschenault's rousette, Rousettus leschenaultii. The established organoids successfully recapitulated the characteristics of intestinal epithelial structure and morphology, and the appropriate supplements necessary for long-term stable culture were identified. The organoid showed susceptibility to Pteropine orthoreovirus (PRV) but not to SARS-CoV-2 in experimental inoculation. This is the first report of the establishment of an expandable organoid culture system of the rousette bat intestinal organoid and its sensitivity to bat-associated viruses, PRV and SARS-CoV-2. This organoid is a useful tool for the elucidation of tolerance mechanisms of the emerging rousette bat-associated viruses such as Ebola and Marburg virus.

ACE2 models of frequently contacted animals provide clues of their SARS-CoV-2 S protein affinity and viral susceptibility.

The outbreak of atypical pneumonia (coronavirus disease 2019 [COVID-19]) has been a global pandemic and has caused severe losses to the global economy. The virus responsible for COVID-9, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has a spike glycoprotein (S protein) that binds angiotensin-converting enzyme 2 (ACE2) present on host cell membranes to gain entry. Based on the full-length human ACE2 cryo-EM structure, we generated homology models of full-length ACE2 proteins from various species (gorilla, monkey, pig, bovine, sheep, cat, dog, mouse, and rat). Although these ACE2 molecules were found to share similar overall structures, their S-ACE2 interface residues differed. These differences likely result in variations in the ACE2 binding affinities to the SARS-CoV-2 S protein. The highest affinities are predicted for human, gorilla, and monkey, while mouse and rat ACE2 are predicted to have the lowest affinities. Cat ACE2 is predicted to have a lower S protein affinity than dog ACE2. Although affinity is not the only factor that affects viral susceptibility, it is one of the most important factors. Thus, we believe that care should be taken with these animals to prevent the spread of SARS-CoV-2 among animal and human populations.

Analysis of the susceptibility to COVID-19 in pregnancy and recommendations on potential drug screening.

To analyze the susceptibility of SARS-CoV-2 in pregnancy and the drugs that can be used to treat pregnancy with COVID-19, so as to provide evidence for drug selection in clinic. By reviewing the existing literature, this paper analyzes the susceptibility of pregnant women to virus, especially to SARS-CoV-2, from the aspects of anatomical, reproductive endocrine and immune changes during pregnancy and screens effective and fetal-safe treatments from the existing drugs. The anatomical structure of the respiratory system is changed during pregnancy, and the virus transmitted by droplets and aerosols is more easily inhaled by pregnant women and is difficult to remove. Furthermore, the prognosis is worse after infection when compared with non-pregnancy women. And changes in reproductive hormones and immune systems during pregnancy collectively make them more susceptible to certain infections. More importantly, angiotensin-converting enzyme (ACE)-2, the SARS-CoV-2 receptor, has been proven highly increased during pregnancy, which may contribute to the susceptibility to SARS-CoV-2. When it comes to treatment, specific drugs for COVID-19 have not been found at present, and taking old drugs for new use in treating COVID-19 has become an emergency method for the pandemic. Particularly, drugs that show superior maternal and fetal safety are worthy of consideration for pregnant women with COVID-19, such as chloroquine, metformin, statins, lobinavir/ritonavir, glycyrrhizic acid, and nanoparticle-mediated drug delivery (NMDD), etc. Pregnant women are susceptible to COVID-19, and special attention should be paid to the selection of drugs that are both effective for maternal diseases and friendly to the fetus. However, there are still many deficiencies in the study of drug safety during pregnancy, and broad-spectrum, effective and fetal-safe drugs for pregnant women need to be developed so as to cope with more infectious diseases in the future.