Routes of Infections, Inflammation, Immunity, Immunity Response and Inflammatory Injury: Elucidation of a Biological Fight

Infections, inflammation, immunity, and inflammatory injury are different segments of biological events and link up altogether. Route of infection has no similarity with the cellular signaling pathway of inflammation, even though when inflammation is induced by infection. The organism responds toward infection that is initiated by the pathogen via inflammation, which is a natural way of defense initiated by innate immunity as a safeguard

SARS-CoV-2 virus transfers to skin through contact with contaminated solids

Transfer of SARS-CoV-2 from solids to fingers is one step in infection via contaminated solids, and the possibility of infection from this route has driven calls for increased frequency of handwashing during the COVID-19 pandemic. To analyze this route of infection, we measured the percentage of SARS-CoV-2 that was transferred from a solid to an artificial finger. A droplet of SARS-CoV-2 suspension (1 µL) was placed on a solid, and then artificial skin was briefly pressed against the solid with a light force (3 N). Transfer from a variety of solids was detected, and transfer from the non-porous solids, glass, stainless steel, and Teflon, was substantial when the droplet was still wet. The viral titer for the finger was 13–16% or 0.8–0.9 log less than for the input droplet. Transfer still occurred after the droplet evaporated, but was smaller, 3–9%. We found a lower level of transfer from porous solids but did not find a significant effect of solid wettability for non-porous solids.

Clinical characteristics of pregnant women with COVID-19 in Japan: a nationwide questionnaire survey

Background Few reports have presented an overall view of pregnant women with coronavirus disease 2019 (COVID-19) across an entire country and throughout the entire gestation period. Furthermore, no such reports are available for Japan. We examined the clinical characteristics and outcomes of pregnant women with COVID‑19 on a national scale in Japan. Methods A nationwide questionnaire-based survey for all 2,185 maternity services in Japan was conducted between July and August 2020. Information regarding maternal characteristics and epidemiological, clinical, treatment, and perinatal outcomes of pregnant women diagnosed with COVID-19 between 16 January and 30 June 2020 were collected. Main outcome measures were incidence of pregnant women with COVID-19 and infant infection, positive rate of the universal screening test for asymptomatic pregnant women, identification of infection route and rates of maternal death, and severe cases. Results Responses from 1,418 institutions were assessed (65% of all delivery institutions in Japan). Seventy-two pregnant women were reported to have been diagnosed with COVID-19. The positive rate of the universal screening test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among asymptomatic pregnant women was 0.03% (2/7428). The most common route of infection was familial (57%). Fifty-eight pregnant women with COVID-19 were symptomatic, of whom five (8.6%) had a severe infection and one died (a tourist). Severe respiratory symptoms, oxygen administration, and pneumonia were frequently reported in the third trimester and postpartum period compared with in early pregnancy (22.2% vs 2.5% [P = 0.03], 38.9% vs 7.5% [P = 0.01], and 50.0% vs 7.5% [P < 0.001], respectively). All pregnant women with COVID-19 underwent caesarean sections, regardless of symptoms. There were no SARS-CoV-2 transmissions to newborns. Conclusions In Japan, the number of cases of COVID-19 infection in pregnant women is very low. Compared with early pregnancy, late pregnancy may be a risk factor for exacerbation of symptoms and familial transmission is the most common route of infection. The importance of infection prevention should be emphasised, especially in women in late pregnancy, their families, and any cohabitants.

Utility of endoscopic transpapillary pancreatic cyst drainage for intraductal papillary mucinous neoplasm infection

A 61-year-old woman with intraductal papillary mucinous neoplasm (IPMN) infection, who was treated with antibiotics, developed IPMN reinfection with febrile epigastric pain and was febrile. CT showed that the diameter of the IPMN had grown and hardened, with thickening of the cyst wall. Endoscopic retrograde pancreatography was then performed and a nasopancreatic cyst drainage tube was placed into the cyst. Symptoms and inflammatory findings improved considerably 17 days after endoscopic drainage. Few reports and evidence have been found regarding IPMN infections, and the frequency of onset, route of infection and optimal drainage method remain unknown. This study indicated that endoscopic transpapillary pancreatic cyst drainage was effective and is highly recommended for IPMN infection.

#13: Respiratory and Intestinal Epithelial Cells Exhibit Differential Susceptibility and Innate Immune Responses to Contemporary EV-D68 Isolates

Background Enterovirus D68 (EV-D68) has been implicated in outbreaks of severe respiratory illness and associated with acute flaccid myelitis (AFM), a disease which causes paralysis in previously healthy patients, mostly children. AFM peaked in even numbered years, at least 2014–2018. While 2020 was expected to be a peak AFM year, few cases were seen, likely due to non-specific social distancing measures due to SARS-CoV-2. EV-D68 is primarily described as a respiratory pathogen, in contrast to ‘classic’ enteroviruses that are spread via the fecal-oral route. However, similar to other enteroviruses, EV-D68 has been detected in wastewater, suggesting it might also have an enteric route of transmission. Methods We used a panel of EV-D68 isolates, including a historic isolate from 2009 and multiple contemporary isolates from AFM peak years to define dynamics of viral replication and host response to infection. We performed comparative studies in primary human bronchial epithelial cells grown at an air-liquid interface and in primary human stem-cell derived intestinal enteroids. These human primary cell-based models more accurately reflect the cells targeted by EV-D68 in vivo. We defined growth characteristics, temperature sensitivity, infection polarity, and acid sensitivity in these parallel models. We used unbiased Luminex-based multianalyte profiling and bulk RNA-sequencing to define the innate immune response in each model. Results Conclusions Our findings suggest that a subset of contemporary isolates of EV-D68 have the potential to target both the human airway and gastrointestinal tracts as a potential route of infection, identifying a previously unrecognized potential route of infection as well as defining, for the first time, the innate immune response to infection in multiple relevant primary epithelial models. These findings are highly significant and are the first to characterize the viral replication and host innate immune response to a diverse panel of historic and contemporary EV-D68 isolates in both the respiratory and intestinal tracts.

SARS-CoV-2 virus transfers to skin through contact with contaminated solids

Transfer of SARS-CoV-2 from solids to fingers is one step in infection via contaminated solids, and the possibility of infection from this route has driven calls for increased frequency of handwashing during the COVID-19 pandemic. To analyze this route of infection, we measured the percentage of SARS-CoV-2 that was transferred from a solid to an artificial finger. A droplet of SARS-CoV-2 suspension (1 µL) was placed on a solid, and then artificial skin was briefly pressed against the solid with a light force (3 N). Transfer from a variety of solids was detected, and transfer from the non-porous solids, glass, stainless steel, and Teflon, was substantial (13-16 %) when the droplet was still wet. Transfer still occurred after the droplet evaporated, but it was smaller. We found a lower level of transfer from porous solids but did not find a significant effect of solid wettability for non-porous solids.

COVID-19 and the small intestine

The SARS-CoV-2 virus enters the body through the angiotensin-converting enzyme 2 (ACE-2), which is the entry point of the virus into the cell. The most dense fabric of ACE-2 is the lungs. The small intestine also contains large amounts of ACE-2 in the enterocyte membrane and is often involved in this process. Intestinal symptoms can appear at different stages of the disease. The review describes the mechanisms of interaction of SARS-CoV-2 with enterocytes, the fecal-oral route of infection, diagnosis and treatment of COVID-19 with intestinal symptoms.

Aerosolized Exposure to H5N1 Influenza Virus Causes Less Severe Disease Than Infection via Combined Intrabronchial, Oral, and Nasal Inoculation in Cynomolgus Macaques

Infection with highly pathogenic avian H5N1 influenza virus in humans often leads to severe respiratory disease with high mortality. Experimental infection in non-human primates can provide additional insight into disease pathogenesis. However, such a model should recapitulate the disease symptoms observed in humans, such as pneumonia and inflammatory cytokine response. While previous studies in macaques have demonstrated the occurrence of typical lesions in the lungs early after infection and a high level of immune activation, progression to severe disease and lethality were rarely observed. Here, we evaluated a routinely used combined route of infection via intra-bronchial, oral, and intra-nasal virus inoculation with aerosolized H5N1 exposure, with or without the regular collection of bronchoalveolar lavages early after infection. Both combined route and aerosol exposure resulted in similar levels of virus replication in nose and throat and similar levels of immune activation, cytokine, and chemokine release in the blood. However, while animals exposed to H5N1 by combined-route inoculation developed severe disease with high lethality, aerosolized exposure resulted in less lesions, as measured by consecutive computed tomography and less fever and lethal disease. In conclusion, not virus levels or immune activation, but route of infection determines fatal outcome for highly pathogenic avian H5N1 influenza infection.

Viral route of infection determines the effect of Drosophila melanogaster gut bacteria on host resistance and tolerance to disease

The microbial community interacting with a host can modulate the outcome of pathogenic infections. For instance, Wolbachia, one of the most prevalent invertebrate endosymbionts, strongly increases resistance of Drosophila melanogaster and other insect hosts, to many RNA viruses. D. melanogaster is also in continuous association with gut bacteria, whose role in antiviral immunity is poorly characterized. Here we asked how gut-colonizing bacteria impact viral titres and host survival, and how these interact with route of infection or Wolbachia presence. We compared germ-free flies and flies associated with two gut bacteria species recently isolated from wild flies (Acetobacter thailandicus and Lactobacillus brevis). We found that Wolbachia-conferred protection to both DCV or FHV is not affected by the presence or absence of these gut bacteria. Flies carrying A. thailandicus have lower DCV loads than germ-free flies, upon systemic infection, but reduced survival, indicating that these bacteria increase resistance to virus and decrease disease tolerance. Association with L. brevis, alone or in combination with A. thailandicus, did not lead to changes in survival to systemic infection. In contrast to the effect on systemic infection, we did not observe an impact of these bacteria on survival or viral loads after oral infection. Overall, the impact of gut-associated bacteria in resistance and tolerance to viruses was mild, when compared with Wolbachia. These results indicate that the effect of gut-associated bacteria to different viral infections, and different routes of infection, is complex and understanding it requires a detailed characterization of several parameters of infection.

Gut Microbiome Profiles and Associated Metabolic Pathways in HIV-Infected Treatment-Naïve Patients

The normal composition of the intestinal microbiota is a key factor for maintaining healthy homeostasis, and accordingly, dysbiosis is well known to be present in HIV-1 patients. This article investigates the gut microbiota profile of antiretroviral therapy-naive HIV-1 patients and healthy donors living in Latin America in a cohort of 13 HIV positive patients (six elite controllers, EC, and seven non-controllers, NC) and nine healthy donors (HD). Microbiota compositions in stool samples were determined by sequencing the V3-V4 region of the bacterial 16S rRNA, and functional prediction was inferred using PICRUSt. Several taxa were enriched in EC compared to NC or HD groups, including Acidaminococcus, Clostridium methylpentosum, Barnesiella, Eubacterium coprostanoligenes, and Lachnospiraceae UCG-004. In addition, our data indicate that the route of infection is an important factor associated with changes in gut microbiome composition, and we extend these results by identifying several metabolic pathways associated with each route of infection. Importantly, we observed several bacterial taxa that might be associated with different viral subtypes, such as Succinivibrio, which were more abundant in patients infected by HIV subtype B, and Streptococcus enrichment in patients infected by subtype C. In conclusion, our data brings a significant contribution to the understanding of dysbiosis-associated changes in HIV infection and describes, for the first time, differences in microbiota composition according to HIV subtypes. These results warrant further confirmation in a larger cohort of patients.