Mental health impact on healthcare workers due to the COVID-19 pandemic: a U.S. cross-sectional survey study.

BACKGROUND: The COVID-19 pandemic has impacted the mental health and well-being of health care workers (HCWs). This study examined mental health outcomes and COVID-related stress impacts among a diverse sample of ambulatory HCWs, including clinicians and support staff, as well as the associations between mental health outcomes and work impairments in this population. Detailing these results can help in designing interventions to alleviate this burden. METHODS: "The Health Care Worker Stress Survey" was administered to ambulatory care providers and support staff at three multispecialty care delivery organizations as part of an online, cross-sectional study conducted between June 8, 2020, and July 13, 2020. RESULTS: The greatest stress impact reported by HCWs was the uncertainty regarding when the COVID-19 outbreak would be under control, while the least reported concern was about self-dying from COVID-19. Differences in COVID-19 stress impacts were observed by age, gender, and occupational risk factors. Approximately 50% of participants reported more than a minimal level of anxiety, including 22.5% who indicated moderate to severe levels of anxiety. Higher levels of anxiety were observed with younger ages and female gender, while occupational roles with increased exposure risk did not report higher levels of anxiety. Roughly two-thirds of the sample reported less than good sleep quality and one-third to one-half of the sample reported other sleep related problems that differed by age and gender. Role limitations due to emotional health correlated with COVID-19 related stress, anxiety and sleep problems. CONCLUSIONS: Using established, validated measures, we quantified mental health outcomes within a diverse sample of ambulatory care HCWs during the pandemic. Younger and female HCWs reported greater anxiety burden; HCWs with higher occupational risk of COVID exposure did not report higher levels of anxiety. Notable proportions of HCWs reported sleep and work impairments. Due to the cross-sectional nature of the study, it is difficult to attribute these patterns to the pandemic. These results underscore the depth and extent of mental health outcomes in HCWs in ambulatory settings and raise important questions on new interventions to relieve that burden. Further research is needed to study specific interventions to support the mental health and wellbeing of HCWs.

Tributyltin stimulates synthesis of interferon gamma and tumor necrosis factor alpha in human lymphocytes.

Tributyltin (TBT) is found in human blood and other tissues and thus is of considerable concern as to its effects on human health. Previous studies have demonstrated that TBT has detrimental effects on immune function. Recently, we found that exposures to TBT caused increased secretion of two important proinflammatory cytokines, tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ). Elevation of either of these cytokines has the potential to cause chronic inflammation, which is an important factor in a number of diseases including cancer. The current study examined the mechanism of TBT-induced elevations of TNFα and IFNγ secretion and found that the p38 mitogen-activated protein kinase pathway was essential to the ability of TBT to stimulate secretion. Additionally, this study demonstrated that increased secretion of these cytokines was due to TBT-induced increases in their overall synthesis, rather than simply being due to an increase in the release of already formed proteins. The TBT-induced increases in synthesis were evident within 6 hours of exposure. The p38 mitogen-activated protein kinase pathway is also necessary for the TBT-induced increases in both TNFα and IFNγ synthesis. The role of increased transcription of TNFα and IFNγ mRNA in response to TBT exposures as a possible explanation for the increased synthesis of these cytokines was also examined. It was found that increased mRNA levels did not appear to explain fully the increases in either TNFα or IFNγ synthesis. Thus, TBT is able to increase secretion of two important proinflammatory cytokines by increasing their synthesis.

Tributyltin exposure alters cytokine levels in mouse serum.

Tributyltin (TBT), a toxic environmental contaminant, has been widely utilized for various industrial, agricultural and household purposes. Its usage has led to a global contamination and its bioaccumulation in aquatic organisms and terrestrial mammals. Previous studies suggest that TBT has debilitating effects on the overall immune function of animals, rendering them more vulnerable to diseases. TBT (at concentrations that have been detected in human blood) alters secretion of inflammatory cytokines from human lymphocytes ex vivo. Thus, it is important to determine if specified levels of TBT can alter levels of cytokines in an in vivo system. Mice were exposed to biologically relevant concentrations of TBT (200, 100 or 25 nM final concentrations). The quantitative determination of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL2, IL5, IL7, IL12ßp40, IL13, IL15, keratinocyte chemoattractant (KC), macrophage inflammatory protein 1ß (MIP), MIP2 and regulated on activation normal T-cell-expressed and secreted (RANTES) was performed in mouse sera by MAGPIX analysis and Western blot. Results indicated alterations (both decreases and increases) in several cytokines. The pro-inflammatory cytokines IFNγ, TNFα, IL-1ß, IL-2, IL5, IL12ßp40 and IL-15 were altered as were the chemokines MIP-1 and RANTES and the anti-inflammatory cytokine IL-13. Increases in IFNγ and TNFα were seen in the serum of mice exposed to TBT for less than 24 h. Levels of IL1ß, IL-12 ßp40, IL-5 and IL-15 were also modulated in mouse serum, depending on the specific experiment and exposure level. IL-2 was consistently decreased in mouse serum when animals were exposed to TBT. There were also TBT-induced increases in MIP-1ß, RANTES and IL-13. These results from human and murine samples clearly suggest that TBT exposures modulate the secretion inflammatory cytokines.

Secretion of interferon gamma from human immune cells is altered by exposure to tributyltin and dibutyltin.

Tributyltin (TBT) and dibutyltin (DBT) are widespread environmental contaminants found in food, beverages, and human blood samples. Both of these butyltins (BTs) interfere with the ability of human natural killer (NK) cells to lyse target cells and alter secretion of the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) from human immune cells in vitro. The capacity of BTs to interfere with secretion of other pro-inflammatory cytokines has not been examined. Interferon gamma (IFNγ) is a modulator of adaptive and innate immune responses, playing an important role in overall immune competence. This study shows that both TBT and DBT alter secretion of IFNγ from human immune cells. Peripheral blood cell preparations that were increasingly reconstituted were used to determine if exposures to either TBT or DBT affected IFNγ secretion and how the makeup of the cell preparation influenced that effect. IFNγ secretion was examined after 24 h, 48 h, and 6 day exposures to TBT (200 - 2.5 nM) and DBT (5 - 0.05 µM) in highly enriched human NK cells, a monocyte-depleted preparation of PBMCs, and monocyte-containing PBMCs. Both BTs altered IFNγ secretion from immune cells at most of the conditions tested (either increasing or decreasing secretion). However, there was significant variability among donors as to the concentrations and time points that showed changes as well as the baseline secretion of IFNγ. The majority of donors showed an increase in IFNγ secretion in response to at least one concentration of TBT or DBT at a minimum of one length of exposure.