The coronavirus disease 2019 (COVID-19) pandemic has claimed over 7 million lives worldwide, providing a stark reminder of the importance of pandemic preparedness. Due to the lack of approved antiviral drugs effective against coronaviruses at the start of the pandemic, the world largely relied on repurposed efforts. Here, we summarise results from randomised controlled trials to date, as well as selected in vitro data of directly acting antivirals, host-targeting antivirals, and immunomodulatory drugs. Overall, repurposing efforts evaluating directly acting antivirals targeting other viral families were largely unsuccessful, whereas several immunomodulatory drugs led to clinical improvement in hospitalised patients with severe disease. In addition, accelerated drug discovery efforts during the pandemic progressed to multiple novel directly acting antivirals with clinical efficacy, including small molecule inhibitors and monoclonal antibodies. We argue that large-scale investment is required to prepare for future pandemics; both to develop an arsenal of broad-spectrum antivirals beyond coronaviruses and build worldwide clinical trial networks that can be rapidly utilised.

An Update on SARS-CoV-2 Clinical Trial Results—What We Can Learn for the Next Pandemic

The purpose of this study is to fill a knowledge gap by analyzing the motivations of tenants to co-living spaces in Klang Valley, Malaysia as the motives of co-living spaces are related to how well that space supports their needs.,Tenants’ behaviors were examined using a convergent parallel mixed-method approach, which included a survey and an in-depth interview. A total of 175 respondents were interviewed using purposive sampling.,The results show that the preference for co-living attributes has changed during the pandemic. User ratings of preference for physical and leasing attributes of co-living spaces are significant in terms of co-living motivations. The findings also revealed that tenants prefer twin-sharing and master bedrooms when choosing a co-living space to stay in.,Identifying the factors that influence such motivations is critical for housing developers and co-living service providers to pay close attention to improving tenants’ living experiences.,There is interest in the co-living spaces that are available for rent. However, very little research is based on an understanding of how the tenants in Klang Valley, Malaysia perceive this type of living arrangement. A better understanding and prediction of tenants’ needs and preferences may lead to a better understanding of the attributes that influence their motivations for using co-living spaces.

Understanding tenants’ motivations for co-living arrangements: a case study of Klang Valley, Malaysia

Abstract There have been 774,075,242 cases of COVID-19 and 7,012,986 deaths worldwide as of January 2024. In the early stages of the pandemic, there was an urgent need to reduce the severity of the disease and prevent the need for hospitalization to avoid stress on healthcare systems worldwide. The repurposing of drugs to prevent clinical deterioration of COVID-19 patients was trialed in many studies using many different drugs. Fluvoxamine (an SSRI and sigma-1 receptor agonist) was initially identified to potentially provide beneficial effects in COVID-19-infected patients, preventing clinical deterioration and the need for hospitalization. Fourteen clinical studies have been carried out to date, with seven of those being randomized placebo-controlled studies. This systematic review and meta-analysis covers the literature from the outbreak of SARS-CoV-2 in late 2019 until January 2024. Search terms related to fluvoxamine, such as its trade names and chemical names, along with words related to COVID-19, such as SARS-CoV-2 and coronavirus, were used in literature databases including PubMed, Google Scholar, Scopus, and the ClinicalTrials.gov database from NIH, to identify the trials used in the subsequent analysis. Clinical deterioration and death data were extracted from these studies where available and used in the meta-analysis. A total of 7153 patients were studied across 14 studies (both open-label and double-blind placebo-controlled). 681 out of 3553 (19.17%) in the standard care group and 255 out of 3600 (7.08%) in the fluvoxamine-treated group experienced clinical deterioration. The estimated average log odds ratio was 1.087 (95% CI 0.200 to 1.973), which differed significantly from zero (z = 2.402, p = 0.016). The seven placebo-controlled studies resulted in a log odds ratio of 0.359 (95% CI 0.1111 to 0.5294), which differed significantly from zero (z = 3.103, p = 0.002). The results of this study identified fluvoxamine as effective in preventing clinical deterioration, and subgrouping analysis suggests that earlier treatment with a dose of 200 mg or above provides the best outcomes. We hope the outcomes of this study can help design future studies into respiratory viral infections and potentially improve clinical outcomes. 

pdf/a-systematic-review-and-meta-analysis-investigating-dose-and-4tofrrt4lr.pdf

A systematic review and meta-analysis, investigating dose and time of fluvoxamine treatment efficacy for COVID-19 clinical deterioration, death, and Long-COVID complications

Coronaviruses (CoVs) are enveloped positive-sense single-stranded RNA viruses with a genome that is 27–31 kbases in length. Critical genes include the spike (S), envelope (E), membrane (M), nucleocapsid (N) and nine accessory open reading frames encoding for non-structural proteins (NSPs) that have multiple roles in the replication cycle and immune evasion (1). There are seven known human CoVs that most likely appeared after zoonotic transfer, the most recent being SARS-CoV-2, responsible for the COVID-19 pandemic. Antivirals that have been approved by the FDA for use against COVID-19 such as Paxlovid can target and successfully inhibit the main protease (MPro) activity of multiple human CoVs; however, alternative proteomes encoded by CoV genomes have a closer genetic similarity to each other, suggesting that antivirals could be developed now that target future CoVs. New zoonotic introductions of CoVs to humans are inevitable and unpredictable. Therefore, new antivirals are required to control not only the next human CoV outbreak but also the four common human CoVs (229E, OC43, NL63, HKU1) that circulate frequently and to contain sporadic outbreaks of the severe human CoVs (SARS-CoV, MERS and SARS-CoV-2). The current study found that emerging antiviral drugs, such as Paxlovid, could target other CoVs, but only SARS-CoV-2 is known to be targeted in vivo. Other drugs which have the potential to target other human CoVs are still within clinical trials and are not yet available for public use. Monoclonal antibody (mAb) treatment and vaccines for SARS-CoV-2 can reduce mortality and hospitalisation rates; however, they target the Spike protein whose sequence mutates frequently and drifts. Spike is also not applicable for targeting other HCoVs as these are not well-conserved sequences among human CoVs. Thus, there is a need for readily available treatments globally that target all seven human CoVs and improve the preparedness for inevitable future outbreaks. Here, we discuss antiviral research, contributing to the control of common and severe CoV replication and transmission, including the current SARS-CoV-2 outbreak. The aim was to identify common features of CoVs for antivirals, biologics and vaccines that could reduce the scientific, political, economic and public health strain caused by CoV outbreaks now and in the future.

Antivirals for Broader Coverage against Human Coronaviruses

Favipiravir and hyperuricemia in patients with COVID-19-suggestions for future studies.

Co-living as an emerging market : an assessment of co-living's long-term resiliency

Social determinants of health (SDoH) surveys are data sets that provide useful health-related information about individuals and communities. This study aims to develop a user-friendly web application that allows clinicians to get a predictive insight into the social needs of their patients before their in-patient visits using SDoH survey data to provide an improved and personalized service. The study used a longitudinal survey that consisted of 108,563 patient responses to 12 questions. Questions were designed to have a binary outcome as the response and the patient's most recent responses for each of these questions were modeled independently by incorporating explanatory variables. Multiple classification and regression techniques were used, including logistic regression, Bayesian generalized linear model, extreme gradient boosting, gradient boosting, neural networks, and random forests. Based on the area under the curve values, gradient boosting models provided the highest precision values. Finally, the models were incorporated into an R Shiny application, enabling users to predict and compare the impact of SDoH on patients' lives. The tool is freely hosted online by the University of Kansas Medical Center's Department of Biostatistics and Data Science. The supporting materials for the application are publicly accessible on GitHub.

An R Shiny Application (SDOH) for Predictive Modeling Using Regional Social Determinants of Health Survey Responses.

Objective The gold standard for breast cancer screening and prevention is regular mammography; thus, understanding what impacts adherence to this standard is essential in limiting cancer-associated costs. We assessed the impact of various understudied sociodemographic factors of interest on adherence to the receipt of regular mammograms. Methods A total Nc = 14,553 mammography-related claims from Nw = 6,336 female Kansas aged between 45 and 54 were utilized from insurance claim databases furnished by multiple providers. Adherence to regular mammography was quantified continuously via a compliance ratio, used to capture the number of eligible years in which at least one mammogram was received, as well as categorically. The relationship between race, ethnicity, rurality, insurance (public/private), screening facility type, and distance to nearest screening facility with both continuous and categorically defined compliance were individually assessed via Kruskal–Wallis one-way ANOVAs, chi-squared tests, multiple linear regression models, and multiple logistic regression, as appropriate. Findings from these individual models were used to inform the construction of a basic, multifaceted prediction model. Results Model results demonstrated that all factors race and ethnicity had at least some bearing on compliance with screening guidelines among mid-life female Kansans. The strongest signal was observed in the rurality variable, which demonstrated a significant relationship with compliance regardless of how it was defined. Conclusion Understudied factors that are associated with regular mammography adherence, such as rurality and distance to nearest facility, may serve as important considerations when developing intervention strategies for ensuring that female patients stick to prescribed screening regimens.

https://journals.sagepub.com/doi/pdf/10.1177/10732748231187836

Rurality Impacts Mammography Screening Adherence Among Mid-life Women in the Kansas Region

Background Studying patients’ social needs is critical to the understanding of health conditions and disparities, and to inform strategies for improving health outcomes. Studies have shown that people of color, low-income families, and those with lower educational attainment experience greater hardships related to social needs. The COVID-19 pandemic represents an event that severely impacted people’s social needs. This pandemic was declared by the World Health Organization on March 11, 2020, and contributed to food and housing insecurity, while highlighting weaknesses in the health care system surrounding access to care. To combat these issues, legislators implemented unique policies and procedures to help alleviate worsening social needs throughout the pandemic, which had not previously been exerted to this degree. We believe that improvements related to COVID-19 legislature and policy have positively impacted people’s social needs in Kansas and Missouri, United States. In particular, Wyandotte County is of interest as it suffers greatly from issues related to social needs that many of these COVID-19–related policies aimed to improve. Objective The research objective of this study was to evaluate the change in social needs before and after the COVID-19 pandemic declaration based on responses to a survey from The University of Kansas Health System (TUKHS). We further aimed to compare the social needs of respondents from Wyandotte County from those of respondents in other counties in the Kansas City metropolitan area. Methods Social needs survey data from 2016 to 2022 were collected from a 12-question patient-administered survey distributed by TUKHS during a patient visit. This provided a longitudinal data set with 248,582 observations, which was narrowed down into a paired-response data set for 50,441 individuals who had provided at least one response before and after March 11, 2020. These data were then bucketed by county into Cass (Missouri), Clay (Missouri), Jackson (Missouri), Johnson (Kansas), Leavenworth (Kansas), Platte (Missouri), Wyandotte (Kansas), and Other counties, creating groupings with at least 1000 responses in each category. A pre-post composite score was calculated for each individual by adding their coded responses (yes=1, no=0) across the 12 questions. The Stuart-Maxwell marginal homogeneity test was used to compare the pre and post composite scores across all counties. Additionally, McNemar tests were performed to compare responses before and after March 11, 2020, for each of the 12 questions across all counties. Finally, McNemar tests were performed for questions 1, 7, 8, 9, and 10 for each of the bucketed counties. Significance was assessed at P<.05 for all tests. Results The Stuart-Maxwell test for marginal homogeneity was significant (P<.001), indicating that respondents were overall less likely to identify an unmet social need after the COVID-19 pandemic. McNemar tests for individual questions indicated that after the COVID-19 pandemic, respondents across all counties were less likely to identify unmet social needs related to food availability (odds ratio [OR]=0.4073, P<.001), home utilities (OR=0.4538, P<.001), housing (OR=0.7143, P<.001), safety among cohabitants (OR=0.6148, P<.001), safety in their residential location (OR=0.6172, P<.001), child care (OR=0.7410, P<0.01), health care access (OR=0.3895, P<.001), medication adherence (OR=0.5449, P<.001), health care adherence (OR=0.6378, P<.001), and health care literacy (0.8729, P=.02), and were also less likely to request help with these unmet needs (OR=0.7368, P<.001) compared with prepandemic responses. Responses from individual counties were consistent with the overall results for the most part. Notably, no individual county demonstrated a significant reduction in social needs relating to a lack of companionship. Conclusions Post-COVID-19 responses showed improvement across almost all social needs–related questions, indicating that the federal policy response possibly had a positive impact on social needs across the populations of Kansas and western Missouri. Some counties were impacted more than others and positive outcomes were not limited to urban counties. The availability of resources, safety net services, access to health care, and educational opportunities could play a role in this change. Future research should focus on improving survey response rates from rural counties to increase their sample size, and to evaluate other explanatory variables such as food pantry access, educational status, employment opportunities, and access to community resources. Government policies should be an area of focused research as they may affect the social needs and health of the individuals considered in this analysis.

The Effects of COVID-19 Pandemic Policy on Social Needs Across the State of Kansas and Western Missouri: Paired Survey Response Testing

BACKGROUND
Studying a patient's social needs is critical to the understanding of health conditions, disparities, and how we can improve health outcomes. Studies have shown that people of color, low-income families, and those with lower educational attainment experience greater hardships related to social needs. An event that severely impacted people's social needs was the COVID-19 pandemic. This pandemic was declared by the World Health Organization on 03/11/2020 and contributed to food and housing insecurity and highlighted weaknesses in the healthcare system surrounding access to care.


OBJECTIVE
The research objective of this paper is to determine if a significant difference in social needs survey responses from the University of Kansas Health System (TUKHS) exists before and after the COVID-19 pandemic declaration. Additionally, we want to see how Wyandotte county's social needs survey responses compare to other counties in the Kansas City metro area.


METHODS
Social needs survey data from 2016 to 2022 was taken from a 12-question patient-administered survey distributed by(TUKHS) during a patient visit. This provided a longitudinal data set with 248,582 observations which was then subset down to a paired response dataset for 50,441 individuals who had at least one response before 03/11/2020 and at least one response thereafter. This data was then bucketed by county into Cass MO, Clay MO, Jackson MO, Johnson KS, Leavenworth KS, Platte MO, Wyandotte KS, and Other; this was done to create groupings with at least 1,000 responses in each category. A pre and post composite score was calculated for each individual by adding their responses coded (Yes=1 and No=0) across the 12 questions. A Stuart-Maxwell Marginal Homogeneity Test was then run to compare the pre and post period composite scores across all the counties. Additionally, Mcnemar's tests were ran to compare pre and post 03/11/2020 responses for each of the 12 questions across all the counties. Finally, Mcnemar's tests for questions 1,7,8,9, and 10 were ran for each of the bucketed counties.


RESULTS
McNemar tests for individual questions indicated that respondents across all counties were less likely after the COVID-19 pandemic to identify unmet social needs related to food availability (OR=0.4073,P<.001), home utilities (OR=0.4538,P<.001), Housing (OR=0.7143,P<.001), Safety among cohabitants (OR=0.6148,P<.001), Safety in their residential location (OR=0.6172,P<.001), Childcare (OR=0.7410,P<0.01), Healthcare access (OR=0.3895,P<.001), Medication adherence (OR=0.5449,P<.001), Healthcare adherence (OR=0.6378,P<.001), Healthcare literacy (0.8729,P=0.02), and were less likely to request help with these unmet needs (OR=0.7368,P<.001). Responses from individual counties were consistent with overall results for the most part. Notably, no individual counties saw a significant reduction in social needs relating to a lack of companionship.


CONCLUSIONS
Post-COVID-19 responses showed improvement across almost all questions, a possible indication that federal policy response positively impacted social needs across the populations of Kansas and Western Missouri. Some counties were impacted more than others and positive outcomes were not limited to urban counties.


CLINICALTRIAL

The Effects of COVID Pandemic Policy on Social Needs across the state of Kansas and Western Missouri: Paired Survey Response Testing.

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