Compartmentalized SARS-CoV-2 replication in upper versus lower respiratory tract after intranasal inoculation or aerosol exposure (preprint)

Non-human primate models are essential for the development of vaccines and antivirals against infectious diseases. Rhesus macaques are a widely utilized infection model for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We compared cellular tropism and virus replication in rhesus macaques inoculated with SARS-CoV-2 via the intranasal route, or via exposure to aerosols. Intranasal inoculation results in replication in the upper respiratory tract and limited lower respiratory tract involvement, whereas exposure to aerosols results in infection throughout the respiratory tract. In comparison to multi-route inoculation, the intranasal and aerosol inoculation routes result in reduced SARS-CoV-2 replication in the respiratory tract.

COVID-19 and Emergency Rental Assistance: Impact on Rent Arrears, Debt, and the Well-Being of Renters in Philadelphia

The federal government allocated an unprecedented level of funding to develop emergency rental assistance programs to help vulnerable low-income renter households remain housed during the COVID-19 pandemic. Using panel data from two waves of applicant surveys joined with administrative data, this article analyzes the impact of Phase 1 of the City of Philadelphia's COVID-19 Emergency Rental Assistance Program and asks how emergency rental assistance affected households in their rent arrears, rent-related debt, and mental health. Analysis shows that receiving emergency rental assistance was associated with lower arrears, a lower probability of rent-related debt, and a lower probability of experiencing frequent debilitating anxiety. The findings suggest that the initial rent relief provided crucial support for households in terms of financial and mental well-being but also underscore that housing affordability challenges that predated the pandemic cannot be addressed by an emergency rental assistance program created in response to a pandemic.

COVID-19 and the Motorcycle Taxi Sector in Sub-Saharan African Cities: A Key Stakeholders' Perspective

This article assesses the impact of the COVID-19 outbreak on the urban motorcycle taxi (MCT) sector in Sub-Saharan Africa (SSA). MCToperators in SSA provide essential transport services and have shown ingenuity and an ability to adapt and innovate when responding to different challenges, including health challenges. However, policymakers and regulators often remain somewhat hostile toward the sector. The article discusses the measures and restrictions put in place to reduce the spread of COVID-19 and key stakeholders' perspectives on these and on the sector's level of compliance. Primary data were collected in six SSA countries during the last quarter of 2020. Between 10 and 15 qualitative interviews with key stakeholders relevant to the urban MCT sector were conducted in each country. These interviews were conducted with stakeholders based in the capital city and a secondary city, to ensure a geographically broader understanding of the measures, restrictions, and perspectives. The impact of COVID-19 measures on the MCT and motor-tricycle taxi sector was significant and overwhelmingly negative. Lockdowns, restrictions on the maximum number of passengers allowed to be carried at once, and more generally, a COVID-19-induced reduction in demand, resulted in a drop in income for operators, according to the key stakeholders. However, some key stakeholders indicated an increase in MCT activity and income because of the motorcycles' ability to bypass police and army controls. In most study countries measures were formulated in a non-consultative manner. This, we argue, is symptomatic of governments' unwillingness to seriously engage with the sector. © National Academy of Sciences: Transportation Research Board 2021.

Interim position statement on doxycycline post-exposure prophylaxis (Doxy-PEP) for the prevention of bacterial sexually transmissible infections in Australia and Aotearoa New Zealand - the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM).

Recent studies have provided evidence for the effectiveness of using doxycycline (Doxy-PEP) to prevent bacterial sexually transmissible infections (STI), namely chlamydia, gonorrhoea, and syphilis, among gay, bisexual, and other men who have sex with men who have experienced multiple STIs. However, there remain several unanswered questions around potential adverse outcomes from Doxy-PEP, including the possibility of inducing antimicrobial resistance in STIs and other organisms, and the possibility of disrupting the microbiome of people who choose to use Doxy-PEP. This interim position statement from the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine aims to outline the current evidence for Doxy-PEP, and to highlight potential adverse outcomes, to enable clinicians to conduct evidence-based conversations with patients in Australia and Aotearoa New Zealand who intend to use Doxy-PEP.

Comparative Aerosol and Surface Stability of SARS-CoV-2 Variants of Concern.

SARS-CoV-2 transmits principally by air; contact and fomite transmission may also occur. Variants of concern are more transmissible than ancestral SARS-CoV-2. We found indications of possible increased aerosol and surface stability for early variants of concern, but not for the Delta and Omicron variants. Stability changes are unlikely to explain increased transmissibility.

Domestic and international tourism, an impossible opposition. (Tourisme territoire et societe.)

With the near general closure of borders in 2020, many European states have encouraged their citizens to resort to domestic tourism, i.e., within their borders, to avoid the collapse of an entire section of their economy. Is this the sign of a permanent evolution of the tourism model toward a practice of proximity, as some authors suggest that the crisis linked to COVID-19 could finally put an end to international (over-)tourism, which has been decried for several years? This analysis is subject to debate. By examining the crises of the 20th century and the beginning of the 21st century, this article proposes to understand how the dynamics of international tourism and domestic tourism in Europe have been associated, with a particular focus on the French case. It is a cumulative process (and not an opposing one) that gradually took place during the 20th century in Europe. If international tourism has been systematically perceived as a tool for capturing the foreign currency necessary for post-crisis recovery since the First World War, gradually serving as a model (as with a strategy to move upmarket during the Great Depression), domestic tourism, due to its permanence, has often been used by the tourist actors in order to lay the foundations for international tourism, for example with the investment plans in the second half of the 20th century. In that respect, the study of the long term offers a necessary perspective to better perceive the stakes involved in the management of tourism during the crisis that arose from the COVID-19 pandemic.

Landlords' rental businesses before and after the COVID-19 pandemic: Evidence from a National Cross-Site Survey.

This paper uses a survey of over 2500 rental property owners in ten cities across the United States to determine the impact of the COVID-19 pandemic on landlords' rent collection and business behavior. Our findings show that yearly rent collection was down significantly in 2020 relative to 2019-both within and across rental markets-and that an increasing number of owners have a large share of their portfolio behind on rent. Small owners and owners of color faced the highest exposure to deep tenant arrears in 2020, challenges they were also more likely to face prior to pandemic. Our findings show that owner business practices changed dramatically in 2020, with a higher share of landlords granting tenants rent extensions or forgiving back rent during the pandemic relative to prior. However, many owners also disinvested in their rental properties through deferred maintenance, missed mortgage payments, and property sale listings. Landlords of color pursued disinvestment strategies during the pandemic at an elevated rate compared to white landlords. Owners of properties in neighborhoods with more non-white residents were both more likely to experience decreased rent collection and more likely to pursue evictions and rental late fees holding constant rental payment rates, implying the pandemic has disproportionately affected renters in communities of color. Overall, our findings highlight the strain the pandemic has placed on the housing stock, which has implications for the long-term viability and affordability of many of these units. More concerningly, our results show that households of color-which have been disproportionately affected by the pandemic in other domains-were more likely to face punitive measures from landlords in both 2019 and 2020, suggesting the pandemic has exacerbated existing racial inequality in housing markets.

Histopathology and SARS-CoV-2 Cellular Localization in Eye Tissues of COVID-19 Autopsies.

Ophthalmic manifestations and tissue tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported in association with coronavirus disease 2019 (COVID-19), but the pathology and cellular localization of SARS-CoV-2 are not well characterized. The objective of this study was to evaluate macroscopic and microscopic changes and investigate cellular localization of SARS-CoV-2 across ocular tissues at autopsy. Ocular tissues were obtained from 25 patients with COVID-19 at autopsy. SARS-CoV-2 nucleocapsid gene RNA was previously quantified by droplet digital PCR from one eye. Herein, contralateral eyes from 21 patients were fixed in formalin and subject to histopathologic examination. Sections of the droplet digital PCR-positive eyes from four other patients were evaluated by in situ hybridization to determine the cellular localization of SARS-CoV-2 spike gene RNA. Histopathologic abnormalities, including cytoid bodies, vascular changes, and retinal edema, with minimal or no inflammation in ocular tissues were observed in all 21 cases evaluated. In situ hybridization localized SARS-CoV-2 RNA to neuronal cells of the retinal inner and outer layers, ganglion cells, corneal epithelia, scleral fibroblasts, and oligodendrocytes of the optic nerve. In conclusion, a range of common histopathologic alterations were identified within ocular tissue, and SARS-CoV-2 RNA was localized to multiple cell types. Further studies will be required to determine whether the alterations observed were caused by SARS-CoV-2 infection, the host immune response, and/or preexisting comorbidities.

Impact of pre-existing type 2 diabetes with and without cardiovascular disease on patients with COVID-19.

AIM: To compare adverse outcomes among COVID-19 patients with pre-existing type 2 diabetes (T2D) only, T2D and cardiovascular disease (CVD), or neither. METHODS: This retrospective cohort study used administrative claims, laboratory and mortality data from the HealthCore Integrated Research Database. Patients with COVID-19 were identified from 3 January 2020 to 31 May 2021 and stratified by the presence of T2D and CVD. Outcomes included hospitalization, intensive care unit (ICU) admission, mortality and complications following COVID-19 infection. Propensity score matching and multivariable analyses were performed. RESULTS: A total of 321 232 COVID-19 patients were identified (21 651 T2D + CVD, 28 184 T2D only, and 271 397 neither) with a mean (SD) follow-up of 5.4 (3.0) months. After matching, 6 967 patients were identified for each group, and residual baseline differences remained. Adjusted analyses showed that COVID-19 patients with T2D + CVD were 59% more probable to be hospitalized, 74% more probable to be admitted to the ICU, and had a 26% higher mortality risk than those with neither. COVID-19 patients with T2D only were 28% and 32% more probable to be admitted to the hospital and ICU than those with neither, respectively. Among all T2D + CVD patients, acute respiratory distress syndrome (31%) and acute kidney disease (24%) were observed. CONCLUSION: Our study highlights the incrementally poorer outcomes associated with pre-existing T2D + CVD in COVID-19 patients compared with those without T2D/CVD and suggests consideration of a more optimal management approach in these patients.

SARS-CoV-2 infection and persistence in the human body and brain at autopsy.

Coronavirus disease 2019 (COVID-19) is known to cause multi-organ dysfunction1-3 during acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with some patients experiencing prolonged symptoms, termed post-acute sequelae of SARS-CoV-2 (refs. 4,5). However, the burden of infection outside the respiratory tract and time to viral clearance are not well characterized, particularly in the brain3,6-14. Here we carried out complete autopsies on 44 patients who died with COVID-19, with extensive sampling of the central nervous system in 11 of these patients, to map and quantify the distribution, replication and cell-type specificity of SARS-CoV-2 across the human body, including the brain, from acute infection to more than seven months following symptom onset. We show that SARS-CoV-2 is widely distributed, predominantly among patients who died with severe COVID-19, and that virus replication is present in multiple respiratory and non-respiratory tissues, including the brain, early in infection. Further, we detected persistent SARS-CoV-2 RNA in multiple anatomic sites, including throughout the brain, as late as 230 days following symptom onset in one case. Despite extensive distribution of SARS-CoV-2 RNA throughout the body, we observed little evidence of inflammation or direct viral cytopathology outside the respiratory tract. Our data indicate that in some patients SARS-CoV-2 can cause systemic infection and persist in the body for months.

SARS-CoV-2 Omicron BA.1 and BA.2 are attenuated in rhesus macaques as compared to Delta.

Since the emergence of SARS-CoV-2, five different variants of concern (VOCs) have been identified: Alpha, Beta, Gamma, Delta, and Omicron. Because of confounding factors in the human population, such as preexisting immunity, comparing severity of disease caused by different VOCs is challenging. Here, we investigate disease progression in the rhesus macaque model upon inoculation with the Delta, Omicron BA.1, and Omicron BA.2 VOCs. Disease severity in rhesus macaques inoculated with Omicron BA.1 or BA.2 was lower than those inoculated with Delta and resulted in significantly lower viral loads in nasal swabs, bronchial cytology brush samples, and lung tissue in rhesus macaques. Cytokines and chemokines were up-regulated in nasosorption samples of Delta animals compared to Omicron BA.1 and BA.2 animals. Overall, these data suggest that, in rhesus macaques, Omicron replicates to lower levels than the Delta VOC, resulting in reduced clinical disease.

Severe acute respiratory disease in American mink experimentally infected with SARS-CoV-2.

An animal model that fully recapitulates severe COVID-19 presentation in humans has been a top priority since the discovery of SARS-CoV-2 in 2019. Although multiple animal models are available for mild to moderate clinical disease, models that develop severe disease are still needed. Mink experimentally infected with SARS-CoV-2 developed severe acute respiratory disease, as evident by clinical respiratory disease, radiological, and histological changes. Virus was detected in nasal, oral, rectal, and fur swabs. Deep sequencing of SARS-CoV-2 from oral swabs and lung tissue samples showed repeated enrichment for a mutation in the gene encoding nonstructural protein 6 in open reading frame 1ab. Together, these data indicate that American mink develop clinical features characteristic of severe COVID-19 and, as such, are uniquely suited to test viral countermeasures.

Surgical Management of Pneumothorax and Pleural Space Disease.

Pleural space diseases constitute a wide range of benign and malignant conditions, including pneumothorax, pleural effusion and empyema, chylothorax, pleural-based tumors, and mesothelioma. The focus of this article is the surgical management of the 2 most common pleural disorders seen in modern thoracic surgery practice: spontaneous pneumothorax and empyema.

Measuring economic freedom during the Covid-19 pandemic

The Covid-19 pandemic in 2020 led to extensive new government regulations and lockdown policies that, according to some prominent definitions, severely reduced economic freedom. However, many of these new pandemic-related regulatory restrictions on economic freedom are largely missed by the Economic Freedom of the World Report (EFW). This paper first adjusts the Our World in Data Covid-19 Stringency Index into a measure of lockdown regulatory freedom and then merges it into the EFW index to better measure countries' 2020 cross-sectional relative economic freedom. We find significant differences in the relative ranking of economic freedom between countries once we adjust for lockdown regulatory restrictions.

Digital twin-enabled built environment sensing and monitoring through semantic enrichment of BIM with SensorML

Effective environmental condition monitoring provides constant surveillance of the built environment and reveals deteriorations that could impact the daily operation of facilities, especially amid COVID situations. However, the current Industry Foundation Classes (IFC) data schema for Building Information Modelling (BIM) provided limited support to represent full semantics related to environmental sensing and monitoring. How to semantically enrich the IFC schema with enhanced data description capability for informed decision-making in smart facilities management (FM) amid COVID situations remains an open question. This paper develops a semi-automatic extension and integration of IFC data schema with Sensor Model Language (SensorML) specification in order to support automated built environment sensing and monitoring. Referring to SensorML, an extended IFC model view definition for a comprehensive description of required sensor metadata and sensing entities is presented. An Internet of Things (IoT) sensor network is then established to realise continuous data collection from a variety of wireless sensing devices. The spatial-temporal data captured by the IoT sensor network are extracted by a regular expression-based data distillation algorithm and integrated with the digital twin, in which spatial interpolation algorithms further analyse, compute, and visualise the state of the environment. The proposed method is demonstrated via an experimental study which supports real-time environmental monitoring and delivers more actionable insights to facility managers to sustain the daily operation of buildings. This study contributes new methods and models to semantically enrich the digital twin from the data perspective for environmental condition monitoring during the pandemic time which fosters the development of holistic building facility management.