Risk Factors for Hospitalization Among Patients with COVID-19 at a Community Ambulatory Clinic in Massachusetts During the Initial Pandemic Surge.

Among patients with COVID-19 evaluated in outpatient settings, factors associated with hospitalization remain poorly understood. Multivariable regressions were used to assess sociodemographic and clinical factors associated with increased odds of hospitalization among patients with confirmed COVID-19 between March 18, 2020 through April 25, 2020 at a community-based outpatient clinic in Massachusetts. Older age, BMI ≥ 25, self-reported dizziness/lightheadedness, temperature ≥ 99.5°F, tachycardia, and oxygen saturation < 95% were associated with increased odds of hospitalization after adjustment for age, sex, and BMI. There was also an association between speaking Spanish as primary language and increased odds of hospitalization (compared to English, adjusted OR = 2.99 [95% CI 1.39, 6.39]). Speaking Portuguese as primary language was not associated with increased odds of hospitalization (compared to English, adjusted OR = 1.83 [0.78, 4.28]). In addition to several clinical risk factors established among inpatients, our study found that primarily speaking Spanish, but not Portuguese, was a marker of hospitalization risk among a diverse outpatient cohort of patients with COVID-19.

Shigella flexneri regulation of ARF6 activation during bacterial entry via an IpgD-mediated positive feedback loop.

UNLABELLED: Entry into cells is critical for virulence of the human bacterial pathogens Shigella spp. Shigella spp. induce membrane ruffle formation and macropinocytic uptake, but the events instigating this process are incompletely understood. The host small GTPase ADP-ribosylation factor 6 (ARF6) functions in membrane trafficking at the plasma membrane and activates membrane ruffle formation. We demonstrate that ARF6 is required for efficient Shigella flexneri entry, is activated by S. flexneri dependent on the phosphatase activity of the type III secreted effector IpgD, and depends on cytohesin guanine nucleotide exchange factors (GEFs) for recruitment to entry sites. The cytohesin GEF ARF nucleotide binding site opener (ARNO) is recruited to these sites, also dependent on IpgD phosphatase activity. ARNO recruitment is independent of ARF6, indicating that, in addition to the described recruitment of ARNO by ARF6, ARNO is recruited upstream of ARF6. Our data provide evidence that ARF6, IpgD, phosphoinositide species, and ARNO constitute a previously undescribed positive feedback loop that amplifies ARF6 activation at bacterial entry sites, thereby promoting efficient S. flexneri uptake. IMPORTANCE: Shigella spp. cause diarrhea and dysentery by infection of epithelial cells in the human colon. Critical to disease is the ability of Shigella to enter into cells, yet the mechanisms involved in entry are incompletely understood. We demonstrate that the small GTPase ADP-ribosylation factor 6 (ARF6) is required for efficient cellular entry of Shigella flexneri and that activation of ARF6 depends on the phosphatase activity of the Shigella protein IpgD, which is introduced into cells via the bacterial type III secretion system. We further show that IpgD phosphatase activity is required for recruitment of the ARF6 guanine nucleotide exchange factor (GEF) ARF nucleotide binding site opener (ARNO) to bacterial entry sites and that ARNO lies upstream of ARF6 activation. These relationships define a positive feedback loop that contributes to activation of ARF6 at S. flexneri entry sites and leads to local amplification of signals that promote bacterial entry.