Concerns about COVID-19 among undocumented women in justice-involved families

PurposeThe COVID-19 pandemic has exacerbated chronic disparities in income, employment and health-care access. Yet, little is known about how various sources of economic and emotional strain (i.e. caregiving, justice system involvement and documentation status) intersect during the pandemic. The purpose of this study is to understand how undocumented women in justice-involved families experienced the pandemic.Design/methodology/approachSurveys of 221 mothers of justice-involved youth examined differences between documented and undocumented parents in COVID-19 testing, health and economic concerns related to the pandemic and generalized anxiety.FindingsThe results revealed undocumented women were less likely to receive COVID-19 testing than documented women, despite no difference between the two groups in suspicion that they may have contracted the virus. Also, undocumented women were more concerned than documented women about losing a job, not having enough food, not having enough non-food supplies, not having access to basic utilities or internet, losing their usual childcare services and losing a loved one to COVID-19.Originality/valueThe findings highlight the vulnerability of justice-involved families who have an undocumented member and implications for long-term solutions to address these disparities are discussed.

TMPRSS2 Impacts Cytokine Expression in Murine Dendritic Cells.

BACKGROUND: The transmembrane protease serine 2 (TMPRSS2) proteolytically activates the envelope proteins of several viruses for viral entry via membrane fusion and is therefore an interesting and promising target for the development of broad-spectrum antivirals. However, the use of a host protein as a target may lead to potential side effects, especially on the immune system. We examined the effect of a genetic deletion of TMPRSS2 on dendritic cells. METHODS: Bone marrow cells from wild-type (WT) and TMPRSS2-deficient mice (TMPRSS2-/-) were differentiated to plasmacytoid dendritic cells (pDCs) and classical DCs (cDCs) and activated with various toll-like receptor (TLR) agonists. We analyzed the released cytokines and the mRNA expression of chemokine receptors, TLR7, TLR9, IRF7 and TCF4 stimulation. RESULTS: In cDCs, the lack of TMPRSS2 led to an increase in IL12 and IFNγ in TLR7/8 agonist resiquimod or TLR 9 agonist ODN 1668-activated cells. Only IL-10 was reduced in TMPRSS2-/- cells in comparison to WT cells activated with ODN 1668. In resiquimod-activated pDCs, the lack of TMPRSS2 led to a decrease in IL-6, IL-10 and INFγ. ODN 1668 activation led to a reduction in IFNα. The effect on receptor expression in pDCs and cDCs was low. CONCLUSION: The effect of TMPRSS2 on pDCS and cDCs depends on the activated TLR, and TMPRSS2 seems to affect cytokine release differently in pDCs and cDCs. In cDCs, TMPRSS2 seems to suppress cytokine release, whereas in pDCS TMPRSS2 possibly mediates cytokine release.

Comparing the Effects of Rocaglates on Energy Metabolism and Immune Modulation on Cells of the Human Immune System.

A promising new approach to broad spectrum antiviral drugs is the inhibition of the eukaryotic translation initiation factor 4A (elF4A), a DEAD-box RNA helicase that effectively reduces the replication of several pathogenic virus types. Beside the antipathogenic effect, modulation of a host enzyme activity could also have an impact on the immune system. Therefore, we performed a comprehensive study on the influence of elF4A inhibition with natural and synthetic rocaglates on various immune cells. The effect of the rocaglates zotatifin, silvestrol and CR-31-B (-), as well as the nonactive enantiomer CR-31-B (+), on the expression of surface markers, release of cytokines, proliferation, inflammatory mediators and metabolic activity in primary human monocyte-derived macrophages (MdMs), monocyte-derived dendritic cells (MdDCs), T cells and B cells was assessed. The inhibition of elF4A reduced the inflammatory potential and energy metabolism of M1 MdMs, whereas in M2 MdMs, drug-specific and less target-specific effects were observed. Rocaglate treatment also reduced the inflammatory potential of activated MdDCs by altering cytokine release. In T cells, the inhibition of elF4A impaired their activation by reducing the proliferation rate, expression of CD25 and cytokine release. The inhibition of elF4A further reduced B-cell proliferation, plasma cell formation and the release of immune globulins. In conclusion, the inhibition of the elF4A RNA helicase with rocaglates suppressed the function of M1 MdMs, MdDCs, T cells and B cells. This suggests that rocaglates, while inhibiting viral replication, may also suppress bystander tissue injury by the host immune system. Thus, dosing of rocaglates would need to be adjusted to prevent excessive immune suppression without reducing their antiviral activity.

In Vitro Safety, Off-Target and Bioavailability Profile of the Antiviral Compound Silvestrol.

We characterized the in vitro safety and bioavailability profile of silvestrol, a compound effective against various viruses, such as corona- and Ebolaviruses, with an EC50 value of about 5 nM. The cytotoxic profile of silvestrol was assessed in various cancer cell lines, as well as the mutagenic and genotoxic potential with Ames and micronuclei tests, respectively. To identify off-target effects, we investigated whether silvestrol modulates G-protein coupled receptor (GPCR) signaling pathways. To predict the bioavailability of silvestrol, its stability, permeability and cellular uptake were determined. Silvestrol reduced viability in a cell-type-dependent manner, mediated no off-target effects via GPCRs, had no mutagenic potential and minor genotoxic effects at 50 nM. Silvestrol did not disturb cell barrier integrity, showed low membrane permeability, was stable in liver microsomes and exhibited good cellular uptake. Efficient cellular uptake and increased cytotoxicity were observed in cell lines with a low expression level of the transport protein P-glycoprotein, the known efflux transporter of silvestrol. In conclusion, silvestrol showed low permeability but good cellular uptake and high stability. Cell-type-dependent cytotoxicity seems to be caused by the accumulation of silvestrol in cells lacking the ability to expel silvestrol due to low P-glycoprotein levels.

Characterization of ACE Inhibitors and AT1R Antagonists with Regard to Their Effect on ACE2 Expression and Infection with SARS-CoV-2 Using a Caco-2 Cell Model.

Blood-pressure-lowering drugs are proposed to foster SARS-CoV-2 infection by pharmacological upregulation of angiotensin-converting enzyme 2 (ACE2), the binding partner of the virus spike (S) protein, located on the surface of the host cells. Conversely, it is postulated that angiotensin-renin system antagonists may prevent lung damage caused by SARS-CoV-2 infection, by reducing angiotensin II levels, which can induce permeability of lung endothelial barrier via its interaction with the AT1 receptor (AT1R). METHODS: We have investigated the influence of the ACE inhibitors (lisinopril, captopril) and the AT1 antagonists (telmisartan, olmesartan) on the level of ACE2 mRNA and protein expression as well as their influence on the cytopathic effect of SARS-CoV-2 and on the cell barrier integrity in a Caco-2 cell model. RESULTS: The drugs revealed no effect on ACE2 mRNA and protein expression. ACE inhibitors and AT1R antagonist olmesartan did not influence the infection rate of SARS-CoV-2 and were unable to prevent the SARS-CoV-2-induced cell barrier disturbance. A concentration of 25 µg/mL telmisartan significantly reduced the virus replication rate. CONCLUSION: ACE inhibitors and AT1R antagonist showed neither beneficial nor detrimental effects on SARS-CoV-2-infection and cell barrier integrity in vitro at pharmacologically relevant concentrations.