Project description:Coronavirus disease 2019 (COVID-19) accounts for over 180,000 deaths in the USA. Although COVID-19 affects all racial ethnicities, non-Hispanic Blacks have the highest mortality rates. Evidence continues to emerge, linking the disproportion of contagion and mortality from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a result of adverse social determinants of health. Yet, genetic predisposition may also play a credible role in disease transmission. SARS-CoV-2 enters cells by interaction between SARS-CoV-2 spike protein and the receptor molecule angiotensin converting enzyme 2 (ACE2) expressed on the surface of the target cells, such that polymorphisms and the expression level of ACE2 influence infectivity and consequent pathogenesis of SARS-CoV-2. Genetic polymorphisms in other multiple genes, such as acetylcholinesterase (AChE) and interleukin-6, are also closely associated with underlying diseases, such as hypertension and type 2 diabetes mellitus, which substantially raise SARS-CoV-2 mortality. However, it is unknown how these genetic polymorphisms contribute to the disparate mortality rates, with or without underlying diseases. Of particular interest is the potential that genetic polymorphisms in these genes may be influencing the disparity of COVID-19 mortality rates in Black communities. Here, we review the evidence that biological predisposition for high-risk comorbid conditions may be relevant to our ability to fully understand and therefore address health disparities of COVID-19 deaths in Blacks.
Project description:The “novel” coronavirus disease 2019 (abbreviated “COVID-19”) is the third coronavirus outbreak emerging during the past two decades. This infectious disease, sustained by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has been recently declared a global pandemic by the World Health Organization. Despite the concerning epidemiological burden, many people, including some policymakers, are underestimating this pandemic and are remaining enigmatically inactive against a human pathology which, for a combination of reasons, can be reasonably defined as a perfect storm (i.e., the “wrong virus” at the “wrong time”). These many paradigmatic aspects include SARS-CoV-2 structure and peculiar biology of infection, high risk of inter-human transmission, long incubation time combined with early and sustained viral load, existence of asymptomatic or mildly-symptomatic carriers, viral shedding for days after symptom relief, unfavorable progression towards respiratory distress and death in up to 5–10% of patients thus causing dramatic healthcare challenges, as well as environmental contamination. Last but not least, the combination of the current case fatality rate with the extraordinary number of people that could be potentially infected by SARS-CoV-2 would permit to estimate that the worldwide deaths for COVID-19 may even approximate those recorded during World War II if appropriate restrictive measures for preventing human-to-human transmission are not readily undertaken. Everybody should be inexcusably aware that this is not a drill, and that the consequences of inadequate action will be tragedy.
Project description:The aim of the present study was to understand if the course of the disease of patients suffering from dust mite allergy could have been negatively affected by the COVID-19 restrictions, which have been certainly important to fight the pandemic, but forced patients to stay at home for a long time.
Project description:The Covid-19 pandemic upended the country, with enormous economic and social shifts. Given the increased contact from families living in virtual confinement coupled with massive economic disarray, the Covid-19 pandemic may have created the ideal conditions to witness a rise in children's experience of abuse and neglect. Yet such a rise will be difficult to calculate given the drop in official mechanisms to track its incidence. The current investigation utilized two studies conducted early in the pandemic to evaluate maltreatment risk. In the first cross-sectional study, parents (n = 405) reported increased physical and verbal conflict and neglect which were associated with their perceived stress and loneliness. In the second study, parents (n = 106) enrolled in a longitudinal study reported increased parent-child conflict, which was associated with concurrent child abuse risk, with several links to employment loss, food insecurity, and loneliness; findings also demonstrated increases in abuse risk and psychological aggression relative to pre-pandemic levels. Findings are discussed in the context of a reactive welfare system rather than a pro-active public-health oriented approach to child maltreatment, connecting with families through multiple avenues. Innovative approaches will be needed to reach children faced with maltreatment to gauge its scope and impact in the pandemic's aftermath.
Project description:The COVID-19 pandemic caused a change in our society and put health systems in crisis worldwide. Different risk factors and comorbidities have been found that increase the risk of mortality when acquiring this infection. The use of alternative devices to the cigarette like the electronic cigarettes, the vapers have been studied widely and generators of great controversy since it has been discovered that they also produce different pulmonary affections. When developing the SARS-CoV2 infection, different theories have been generated about the greater predisposition to a worse prognosis of people who use electronic cigarettes; however, the information on this continues in discovery. A group of experts made up of oncologists, infectologists, pulmonologists, and epidemiologists met to review the literature and then generate theories about the impact of electronic cigarettes on SARS-CoV2 infection.
Project description:BackgroundThe COVID-19 pandemic has led to system-wide disruption of health services globally. We assessed the effect of the pandemic on the disruption of institutional delivery care in Nepal.MethodsWe conducted a prospective cohort study among 52 356 women in nine hospitals to assess the disruption of institutional delivery care during the pandemic (comparing March to August in 2019 with the same months in 2020). We also conducted a nested follow up cohort study with 2022 women during the pandemic to assess their provision and experience of respectful care. We used linear regression models to assess the association between provision and experience of care with volume of hospital births and women's residence in a COVID-19 hotspot area.ResultsThe mean institutional births during the pandemic across the nine hospitals was 24 563, an average decrease of 11.6% (P < 0.0001) in comparison to the same time-period in 2019. The institutional birth in high-medium volume hospitals declined on average by 20.8% (P < 0.0001) during the pandemic, whereas in low-volume hospital institutional birth increased on average by 7.9% (P = 0.001). Maternity services halted for a mean of 4.3 days during the pandemic and there was a redeployment staff to COVID-19 dedicated care. Respectful provision of care was better in hospitals with low-volume birth (β = 0.446, P < 0.0001) in comparison to high-medium-volume hospitals. There was a positive association between women's residence in a COVID-19 hotspot area and respectful experience of care (β = 0.076, P = 0.001).ConclusionsThe COVID-19 pandemic has had differential effects on maternity services with changes varying by the volume of births per hospital with smaller volume facilities doing better. More research is needed to investigate the effects of the pandemic on where women give birth and their provision and experience of respectful maternity care to inform a "building-back-better" approach in post-pandemic period.
Project description:Severe COVID-19 may progress into acute respiratory distress syndrome (ARDS) with high mortality risk. Its exact pathological mechanism, therapeutic obstacles and the clinical sequelae are critical and unresolved issues. Here, we reported a representative COVID-19 induced ARDS case experienced initially stable, then suddenly deteriorating up to final respiratory failure courses, until his death despite of lung transplantation. His lung pathology showed necrosis of parenchymal tissues, extensive immune cell infiltration and lung fibrosis. Single-cell RNA sequencing revealed various immune cell populations were largely expanded in his lung, and manifested inflammatory/activated functions. We also showed that cell-crosstalk between lung macrophages and fibroblasts promoted pulmonary fibrosis through IL-1B and TGF-Β signaling pathways. Although SARS-CoV-2 RNA remained undetectable in his respiratory tract specimens including BALF at the later stage of his disease, the presence of SARS-CoV-2 was definitely confirmed in his lung tissues. Thus, this case indicates the pathological mechanism of severe COVID-19 includes pulmonary SARS-CoV-2 persistence, deranged inflammation and the extensive lung fibrosis which set the barriers for effective treatments and indicate potential health complications for severe COVID-19 patients.
Project description:Acute cardiac injuries occur in 20%–25% of hospitalized COVID‐19 patients. Herein, we demonstrate that human cardiac organoids (hCOs) are a viable platform to model the cardiac injuries caused by COVID‐19 hyperinflammation. As IL‐1β is an upstream cytokine and a core COVID‐19 signature cytokine, it was used to stimulate hCOs to induce the release of a milieu of proinflammatory cytokines that mirror the profile of COVID‐19 cytokine storm. The IL‐1β treated hCOs recapitulated transcriptomic, structural, and functional signatures of COVID‐19 hearts. The comparison of IL‐1β treated hCOs with cardiac tissue from COVID‐19 autopsies illustrated the critical roles of hyper‐inflammation in COVID‐19 cardiac insults and indicated the cardioprotective effects of endothelium. The IL‐1β treated hCOs thus provide a defined and robust model to assess the efficacy and potential side effects of immunomodulatory drugs, as well as the reversibility of COVID‐19 cardiac in- juries at baseline and simulated exercise conditions.
Project description:AimsThe storm-like nature of the health crises caused by COVID-19 has led to unconventional clinical trial practices such as the relaxation of exclusion criteria. The question remains: how can we conduct diverse trials without exposing subgroups of populations to potentially harmful drug exposure levels? The aim of this study was to build a knowledge base of the effect of intrinsic/extrinsic factors on the disposition of several repurposed COVID-19 drugs.MethodsPhysiologically based pharmacokinetic (PBPK) models were used to study the change in the pharmacokinetics (PK) of drugs repurposed for COVID-19 in geriatric patients, different race groups, organ impairment and drug-drug interactions (DDIs) risks. These models were also used to predict epithelial lining fluid (ELF) exposure, which is relevant for COVID-19 patients under elevated cytokine levels.ResultsThe simulated PK profiles suggest no dose adjustments are required based on age and race for COVID-19 drugs, but dose adjustments may be warranted for COVID-19 patients also exhibiting hepatic/renal impairment. PBPK model simulations suggest ELF exposure to attain a target concentration was adequate for most drugs, except for hydroxychloroquine, azithromycin, atazanavir and lopinavir/ritonavir.ConclusionWe demonstrate that systematically collated data on absorption, distribution, metabolism and excretion, human PK parameters, DDIs and organ impairment can be used to verify simulated plasma and lung tissue exposure for drugs repurposed for COVID-19, justifying broader patient recruitment criteria. In addition, the PBPK model developed was used to study the effect of age and ethnicity on the PK of repurposed drugs, and to assess the correlation between lung exposure and relevant potency values from in vitro studies for SARS-CoV-2.