Antiviral and Anti-Inflammatory Activities of Fluoxetine in a SARS-CoV-2 Infection Mouse Model.

The coronavirus disease 2019 (COVID-19) pandemic continues to cause significant morbidity and mortality worldwide. Since a large portion of the world's population is currently unvaccinated or incompletely vaccinated and has limited access to approved treatments against COVID-19, there is an urgent need to continue research on treatment options, especially those at low cost and which are immediately available to patients, particularly in low- and middle-income countries. Prior in vitro and observational studies have shown that fluoxetine, possibly through its inhibitory effect on the acid sphingomyelinase/ceramide system, could be a promising antiviral and anti-inflammatory treatment against COVID-19. In this report, we evaluated the potential antiviral and anti-inflammatory activities of fluoxetine in a K18-hACE2 mouse model of SARS-CoV-2 infection, and against variants of concern in vitro, i.e., SARS-CoV-2 ancestral strain, Alpha B.1.1.7, Gamma P1, Delta B1.617 and Omicron BA.5. Fluoxetine, administrated after SARS-CoV-2 infection, significantly reduced lung tissue viral titres and expression of several inflammatory markers (i.e., IL-6, TNFα, CCL2 and CXCL10). It also inhibited the replication of all variants of concern in vitro. A modulation of the ceramide system in the lung tissues, as reflected by the increase in the ratio HexCer 16:0/Cer 16:0 in fluoxetine-treated mice, may contribute to explain these effects. Our findings demonstrate the antiviral and anti-inflammatory properties of fluoxetine in a K18-hACE2 mouse model of SARS-CoV-2 infection, and its in vitro antiviral activity against variants of concern, establishing fluoxetine as a very promising candidate for the prevention and treatment of SARS-CoV-2 infection and disease pathogenesis.

Human NLRP1 is a sensor of pathogenic coronavirus 3CL proteases in lung epithelial cells.

Inflammation observed in SARS-CoV-2-infected patients suggests that inflammasomes, proinflammatory intracellular complexes, regulate various steps of infection. Lung epithelial cells express inflammasome-forming sensors and constitute the primary entry door of SARS-CoV-2. Here, we describe that the NLRP1 inflammasome detects SARS-CoV-2 infection in human lung epithelial cells. Specifically, human NLRP1 is cleaved at the Q333 site by multiple coronavirus 3CL proteases, which triggers inflammasome assembly and cell death and limits the production of infectious viral particles. Analysis of NLRP1-associated pathways unveils that 3CL proteases also inactivate the pyroptosis executioner Gasdermin D (GSDMD). Subsequently, caspase-3 and GSDME promote alternative cell pyroptosis. Finally, analysis of pyroptosis markers in plasma from COVID-19 patients with characterized severe pneumonia due to autoantibodies against, or inborn errors of, type I interferons (IFNs) highlights GSDME/caspase-3 as potential markers of disease severity. Overall, our findings identify NLRP1 as a sensor of SARS-CoV-2 infection in lung epithelia.

"What will we do if we get infected?": An interview-based study of the COVID-19 pandemic and its effects on the health and safety of sex workers in the United States.

Emerging evidence suggests that sex workers face unique and profound risks arising from the COVID-19 pandemic. To illuminate the pandemic's effects on sex worker health and safety and identify intervention opportunities, from May-August 2020 in-depth interviews were conducted with a purposive sample of 15 sex workers, four service providers and two individuals who were both. Sampled sex workers included eight people of color, eight cisgender women, five cisgender men, three non-binary people, and one transgender woman. Using Conservation of Resources Theory to define impacts on sex worker resources and resulting health and safety implications, a deductive thematic analysis was conducted. Seven resources were threatened due to the pandemic: work opportunity, sex work venues, social support, health services, money, food, and housing. The loss of these resources was exacerbated by stigma - notably sex work criminalization - and significantly undermined health and safety by increasing food and housing instability, increasing risks of violence, and diminishing safer sex negotiation. Six resources were activated in response: social support, digital skills, health knowledge, non-sex work employment, money, and resilience. While social support had numerous benefits, investing digital skills and non-sex work employment were generally of limited impact. The pandemic's negative health and safety effects were most profound at the intersections of race, gender, class, and migration status. These findings suggest sex workers need urgent and ongoing support, with investments in social support and sex work decriminalization likely to have the greatest effects on health and safety relative to and beyond the COVID-19 pandemic.

Willingness to Attend Sex Venues in the Context of the COVID-19 Pandemic in New York City: Results from an Online Survey with Sexual and Gender Minority Individuals.

Collective sex venues (places where people have sex in groups or in the presence of others, such as bathhouses or sex clubs) are locations where SARS-CoV-2 transmission is likely to occur. We conducted an online survey to examine the impact of the COVID-19 pandemic among 342 sexual and gender minority (SGM) individuals who had attended collective sex venues (CSV) in New York City (NYC) in the prior year. Almost 1 in 10 (9.9%) participants reported having received a positive test for SARS-CoV-2 infection or antibodies. Although a minority (27.5%) of participants reported being comfortable attending a CSV during the COVID-19 pandemic, multivariable ordinal logistic regression found that willingness was higher among participants who had taken the survey later in the pandemic (aOR = 2.90, CI95% 1.90 to 4.43), who attended CSV at higher frequencies (aOR = 1.94, CI95% 1.26 to 2.99), who used substances at CSV (aOR = 1.98, CI95% 1.22 to 3.23), and who had tested positive for SARS-CoV-2 infection or antibodies (aOR = 2.27, CI95% 1.17 to 4.39). In open survey answers, participants described reasons for or against attending CSV during the pandemic, as well as risk reduction strategies that would make them more comfortable attending (e.g., screening for test results, doing temperature checks, holding outdoor events, or restricting events to lower risk sexual practices). SGM individuals who attend CSV might be at increased risk for COVID-19. Public health officials should provide CSV organizers and attendees with guidelines on how to prevent or minimize transmission risk in the context of pandemics such as COVID-19.

Sex workers are returning to work and require enhanced support in the face of COVID-19: results from a longitudinal analysis of online sex work activity and a content analysis of safer sex work guidelines.

Sex workers confront unique challenges in the face of COVID-19. Data from an international sex work website popular with cisgender men and transgender men and women suggest that, after a period of physical distancing, many sex workers are returning to in-person work: from May to August 2020, active sex work profiles increased 9.4% (P < 0.001) and newly created profiles increased by 35.6% (P < 0.001). Analysis of sex work and COVID-19 guidelines published by five community-based organisations found that they focused on altering sexual practices, enhancing hygiene and pivoting to virtual work. To capitalise on these guidelines, funding and research for implementation and evaluation are needed to support COVID-19 risk reduction strategies for sex workers.

Investigating the effects of COVID-19 on global male sex work populations: a longitudinal study of digital data.

OBJECTIVES: Recommendations of 'social distancing' and home quarantines to combat the global COVID-19 pandemic have implications for sex and intimacy, including sex work. This study examined the effects of COVID-19 on male sex work globally and investigated how men who sold sex responded to and engaged with the virus in the context of work. METHODS: This study made use of an existing database of deidentified data extracted from the online profiles maintained by male sex workers on a large, international website. Website engagement metrics were calculated for the periods before (September to December 2019) and during COVID-19 (January to May 2020); Poisson regression analyses were used to assess changes over time before and after, while a content analysis was undertaken to identify modes of engagement with the virus. RESULTS: Data were collected from 78 399 profiles representing 19 388 individuals. In the 'before' period, the number of active profiles was stable (inter-rate ratio (IRR)=1.01, 95% CI 0.99 to 1.01, p=0.339) but during COVID-19 decreased by 26.3% (IRR=0.90, 95% CI 0.89 to 0.91, p<0.001). Newly created profiles also decreased during COVID-19 (59.4%; IRR=0.71, 95% CI 0.69 to 0.74, p<0.001) after a period of stability. In total, 211 unique profiles explicitly referenced COVID-19; 185 (85.8%) evoked risk reduction strategies, including discontinuation of in-person services (41.2%), pivoting to virtual services (38.9%), COVID-19 status disclosure (20.9%), enhanced sanitary and screening requirements (12.3%) and restricted travel (5.2%). Some profiles, however, seemed to downplay the seriousness of COVID-19 or resist protective measures (14.7%). CONCLUSIONS: These findings support the contention that COVID-19 has dramatically impacted the sex industry; globally, male sex workers may be facing considerable economic strain. Targeted education and outreach are needed to support male sex workers grappling with COVID-19, including around the most effective risk reduction strategies. Those involved with the sex industry must have access to state-sponsored COVID-19 financial and other aid programmes to support individual and public health.