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1.
J Am Soc Nephrol ; 33(3): 565-582, 2022 03.
Article in English | MEDLINE | ID: covidwho-1883777

ABSTRACT

BACKGROUND: Endothelial cell injury is a common nidus of renal injury in patients and consistent with the high prevalence of AKI reported during the coronavirus disease 2019 pandemic. This cell type expresses integrin α5 (ITGA5), which is essential to the Tie2 signaling pathway. The microRNA miR-218-5p is upregulated in endothelial progenitor cells (EPCs) after hypoxia, but microRNA regulation of Tie2 in the EPC lineage is unclear. METHODS: We isolated human kidney-derived EPCs (hkEPCs) and surveyed microRNA target transcripts. A preclinical model of ischemic kidney injury was used to evaluate the effect of hkEPCs on capillary repair. We used a genetic knockout model to evaluate the effect of deleting endogenous expression of miR-218 specifically in angioblasts. RESULTS: After ischemic in vitro preconditioning, miR-218-5p was elevated in hkEPCs. We found miR-218-5p bound to ITGA5 mRNA transcript and decreased ITGA5 protein expression. Phosphorylation of 42/44 MAPK decreased by 73.6% in hkEPCs treated with miR-218-5p. Cells supplemented with miR-218-5p downregulated ITGA5 synthesis and decreased 42/44 MAPK phosphorylation. In a CD309-Cre/miR-218-2-LoxP mammalian model (a conditional knockout mouse model designed to delete pre-miR-218-2 exclusively in CD309+ cells), homozygotes at e18.5 contained avascular glomeruli, whereas heterozygote adults showed susceptibility to kidney injury. Isolated EPCs from the mouse kidney contained high amounts of ITGA5 and showed decreased migratory capacity in three-dimensional cell culture. CONCLUSIONS: These results demonstrate the critical regulatory role of miR-218-5p in kidney EPC migration, a finding that may inform efforts to treat microvascular kidney injury via therapeutic cell delivery.


Subject(s)
Acute Kidney Injury/etiology , Acute Kidney Injury/metabolism , Endothelial Progenitor Cells/metabolism , Endothelial Progenitor Cells/pathology , Integrin alpha5/metabolism , MicroRNAs/physiology , Acute Kidney Injury/pathology , Animals , Disease Models, Animal , Humans , Mice , Mice, Inbred C57BL , Mice, Knockout , Receptor, TIE-2/physiology , Signal Transduction/physiology
2.
PLoS Biol ; 20(5): e3001609, 2022 05.
Article in English | MEDLINE | ID: covidwho-1822243

ABSTRACT

Despite the rapid creation of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines, the precise correlates of immunity against severe Coronavirus Disease 2019 (COVID-19) are still unknown. Neutralizing antibodies represent a robust surrogate of protection in early Phase III studies, but vaccines provide protection prior to the evolution of neutralization, vaccines provide protection against variants that evade neutralization, and vaccines continue to provide protection against disease severity in the setting of waning neutralizing titers. Thus, in this study, using an Ad26.CoV2.S dose-down approach in nonhuman primates (NHPs), the role of neutralization, Fc effector function, and T-cell immunity were collectively probed against infection as well as against viral control. While dosing-down minimally impacted neutralizing and binding antibody titers, Fc receptor binding and functional antibody levels were induced in a highly dose-dependent manner. Neutralizing antibody and Fc receptor binding titers, but minimally T cells, were linked to the prevention of transmission. Conversely, Fc receptor binding/function and T cells were linked to antiviral control, with a minimal role for neutralization. These data point to dichotomous roles of neutralization and T-cell function in protection against transmission and disease severity and a continuous role for Fc effector function as a correlate of immunity key to halting and controlling SARS-CoV-2 and emerging variants.


Subject(s)
COVID-19 , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Primates , Receptors, Fc , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
3.
Sci Adv ; 8(11): eabl6015, 2022 Mar 18.
Article in English | MEDLINE | ID: covidwho-1745843

ABSTRACT

Authorized vaccines against SARS-CoV-2 remain less available in low- and middle-income countries due to insufficient supply, high costs, and storage requirements. Global immunity could still benefit from new vaccines using widely available, safe adjuvants, such as alum and protein subunits, suited to low-cost production in existing manufacturing facilities. Here, a clinical-stage vaccine candidate comprising a SARS-CoV-2 receptor binding domain-hepatitis B surface antigen virus-like particle elicited protective immunity in cynomolgus macaques. Titers of neutralizing antibodies (>104) induced by this candidate were above the range of protection for other licensed vaccines in nonhuman primates. Including CpG 1018 did not significantly improve the immunological responses. Vaccinated animals challenged with SARS-CoV-2 showed reduced median viral loads in bronchoalveolar lavage (~3.4 log10) and nasal mucosa (~2.9 log10) versus sham controls. These data support the potential benefit of this design for a low-cost modular vaccine platform for SARS-CoV-2 and other variants of concern or betacoronaviruses.

5.
Pediatric Hematology Oncology Journal ; 2022.
Article in English | ScienceDirect | ID: covidwho-1740098

ABSTRACT

Introduction The clinical outcomes of COVID-19 infection in children with cancer have been variable worldwide. Therefore, we aimed to collect data from all regions in India through a national collaborative study and identify factors that cause mortality directly related to COVID-19 infection. Methods Data was collected prospectively on children across India on cancer therapy and diagnosed with COVID-19 infections from 47 centers from April 2020 to October 2021. Information was recorded on the demographics, the number of children that required intervention, and the outcome of the infection. In addition, we analyzed the impact of the delta variant in 2021. Results A total of 659 children were studied, of whom 64% were male and 36% were female. The data from the eastern region was sparse, and this was a collection bias. COVID-19 infection was predominantly seen in children less than five years. The delta variant had a higher impact in the southern region, and this was statistically significant. Of the 659 children, 30 children died (4.5%), however only 7 of the deaths were directly attributed to COVID-19 infection (1%). Conclusion The study reports the largest nationally representative cohort of children with cancer and COVID-19 to date in India. We identified demographic and clinical factors associated with increased all-cause mortality in patients with cancer. Complete characterization of the cohort has provided further insights into the effects of COVID-19 on cancer outcomes. The low mortality allows us to recommend that specific cancer treatments be continued without delays in therapy.

6.
Ann Epidemiol ; 68: 16-23, 2022 04.
Article in English | MEDLINE | ID: covidwho-1700089

ABSTRACT

PURPOSE: Seasonal influenza vaccination is an important public health strategy to reduce preventable illness, hospitalization, and death. Because of overlapping risk factors for severe illness from seasonal influenza and COVID-19, uptake of the seasonal influenza vaccination has heightened importance during the COVID-19 pandemic. We analyzed receipt of seasonal influenza vaccination among COVID-19 priority groups and further examined socio-demographic and behavioral factors associated with receiving the seasonal influenza vaccine among US adults. METHODS: Using the 2018 National Health Interview Survey, we classified 24,772 adults into four COVID-19 priority groups: healthcare workers, medically vulnerable, non-healthcare essential workers, and the general population. We performed multiple logistic regression to compare the relative odds of receiving the influenza vaccine by COVID-19 priority group, socio-demographics, and health-related factors. RESULTS: Healthcare workers, medically vulnerable adults, essential workers, and the general population comprised 8.9%, 58.4%, 6.6%, and 26.1 % of the US population, respectively. Compared with healthcare workers, the adjusted odds ratio (aOR) of receiving influenza vaccine were significantly lower in medically vulnerable adults (aOR=0.43, 95% CI=0.37, 0.48), essential workers (aOR=0.28, 95% CI=0.23, 0.34), and the general population (aOR=0.32, 95% CI=0.28, 0.37). Being young, male, Black, and having no health insurance were associated with lower relative odds of receiving the flu vaccine. CONCLUSIONS: Patterns of influenza vaccine cause concern for under-coverage of populations at high risk for both seasonal influenza and COVID-19. Achieving optimal protection against vaccine-preventable respiratory illness in US adults will require emphasis on those employed outside of the healthcare sector, younger age groups, and adults with lower socioeconomic resources.


Subject(s)
COVID-19 , Influenza Vaccines , Influenza, Human , Adult , COVID-19/epidemiology , COVID-19/prevention & control , Humans , Influenza Vaccines/therapeutic use , Influenza, Human/epidemiology , Influenza, Human/prevention & control , Male , Pandemics/prevention & control , Seasons , Vaccination
7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-322507

ABSTRACT

COVID-19 infections have well described systemic manifestations, especially respiratory problems. There are currently no specific treatments or vaccines against the current strain. With higher case numbers, a range of neurological symptoms are becoming apparent. The mechanisms responsible for these are not well defined, other than those related to hypoxia and microthrombi. We speculate that sustained systemic immune activation seen with SARS-CoV-2 may also cause secondary autoimmune activation in the CNS. Patients with chronic neurological diseases may be at higher risk because of chronic secondary respiratory disease and potentially poor nutritional status. Here, we review the impact of COVID-19 on people with chronic neurological diseases and potential mechanisms. We believe special attention to protecting people with neurodegenerative disease is warranted. We are concerned about a possible delayed pandemic in the form of an increased burden of neurodegenerative disease after acceleration of pathology by systemic COVID-19 infections.

8.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315487

ABSTRACT

Pneumomediastinum is a rare complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that has increased in incidence with the novel coronavirus disease 2019 pandemic. Although traditionally managed with conservative measures, we present the indications and methods for the first operative management of tension pneumomediastinum with concomitant SARS-CoV-2 infection.

9.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-306449

ABSTRACT

Background: The world witnessed a highly contagious and deadly disease, COVID-19, towards the end of 2019. India is one of the worst affected countries. We aimed to assess anxiety and depression levels among adult tobacco users and people who recently quit tobacco during COVID − 19 lockdown in India. Methods The study was conducted across two Indian cities, Delhi and Chennai (July-August, 2020) among adult tobacco users (n = 801). Telephonic interviews were conducted using validated mental health tools (Patient Health Questionnaire-PHQ-9 and Generalized Anxiety Disorder-GAD-7) to assess the anxiety and depression levels of the participants. Descriptive analysis and multiple logistic regression were used to study the prevalence and correlates of depression and anxiety. Results We found that 20.6% of tobacco users had depression symptoms (3.9% moderate to severe);20.7% had anxiety symptoms (3.8% moderate to severe). Risk factors associated with depression and anxiety included food, housing, and financial insecurity. Conclusion During COVID-19 lockdown, mental health of tobacco users (primarily women) was associated with food, housing and financial insecurity. The Indian Government rightly initiated several health, social and economic measures to shield the most vulnerable from COVID-19, including a ban on the sale of tobacco products. It is also necessary to prioritize easy access to tobacco cessation and mental health services to such vulnerable populations during pandemic situations.

10.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-326431

ABSTRACT

Older adults are at greater risk of experiencing negative physical and psychological impacts of the novel coronavirus 2019 (COVID-19) pandemic. Our ongoing study is assessing COVID-19 information exposure in adults aged 55 and above compared to other age groups living in Massachusetts and Georgia. This work investigates the potential association between information exposure and wellbeing as well as adherence to COVID-19 protective measures. Our initial results show that older adults received information related to COVID-19 less frequently than the middle-aged group, yet they feel more content and less stressed than the other age groups. Further analysis to identify other potential confounding variables is addressed.

11.
J Clin Med ; 11(3)2022 Feb 07.
Article in English | MEDLINE | ID: covidwho-1674681

ABSTRACT

Viscoelastic hemostatic assay (VHAs) are whole blood point-of-care tests that have become an essential method for assaying hemostatic competence in liver transplantation, cardiac surgery, and most recently, trauma surgery involving hemorrhagic shock. It has taken more than three-quarters of a century of research and clinical application for this technology to become mainstream in these three clinical areas. Within the last decade, the cup and pin legacy devices, such as thromboelastography (TEG® 5000) and rotational thromboelastometry (ROTEM® delta), have been supplanted not only by cartridge systems (TEG® 6S and ROTEM® sigma), but also by more portable point-of-care bedside testing iterations of these legacy devices (e.g., Sonoclot®, Quantra®, and ClotPro®). Here, the legacy and new generation VHAs are compared on the basis of their unique hemostatic parameters that define contributions of coagulation factors, fibrinogen/fibrin, platelets, and clot lysis as related to the lifespan of a clot. In conclusion, we offer a brief discussion on the meteoric adoption of VHAs across the medical and surgical specialties to address COVID-19-associated coagulopathy.

12.
NPJ Vaccines ; 7(1): 2, 2022 Jan 10.
Article in English | MEDLINE | ID: covidwho-1616986

ABSTRACT

SARS-CoV-2 Spike-specific binding and neutralizing antibodies, elicited either by natural infection or vaccination, have emerged as potential correlates of protection. An important question, however, is whether vaccine-elicited antibodies in humans provide direct, functional protection from SARS-CoV-2 infection and disease. In this study, we explored directly the protective efficacy of human antibodies elicited by Ad26.COV2.S vaccination by adoptive transfer studies. IgG from plasma of Ad26.COV2.S vaccinated individuals was purified and transferred into naïve golden Syrian hamster recipients, followed by intra-nasal challenge of the hamsters with SARS-CoV-2. IgG purified from Ad26.COV2.S-vaccinated individuals provided dose-dependent protection in the recipient hamsters from weight loss following challenge. In contrast, IgG purified from placebo recipients provided no protection in this adoptive transfer model. Attenuation of weight loss correlated with binding and neutralizing antibody titers of the passively transferred IgG. This study suggests that Ad26.COV2.S-elicited antibodies in humans are mechanistically involved in protection against SARS-CoV-2.

13.
Sci Transl Med ; 13(618): eabj2641, 2021 Nov 03.
Article in English | MEDLINE | ID: covidwho-1546435

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that result in increased transmissibility and partial evasion of neutralizing antibodies have recently emerged. Whether natural immunity induced by the original SARS-CoV-2 WA1/2020 strain protects against rechallenge with these SARS-CoV-2 variants remains a critical unresolved question. In this study, we show that natural immunity induced by the WA1/2020 strain leads to partial but incomplete protection against the SARS-CoV-2 variants B.1.1.7 (alpha) and B.1.351 (beta) in rhesus macaques. We challenged rhesus macaques with B.1.1.7 and B.1.351 and showed that infection with these variants resulted in high viral replication in the upper and lower respiratory tract. We then infected rhesus macaques with the WA1/2020 strain and rechallenged them on day 35 with the WA1/2020, B.1.1.7, or B.1.351 variants. Natural immunity to WA1/2020 led to robust protection against rechallenge with WA1/2020 but only partial protection against rechallenge with B.1.351. An intermediate degree of protection was observed in rhesus macaques against rechallenge with B.1.1.7. These data demonstrate partial but incomplete protective efficacy of natural immunity induced by WA1/2020 against SARS-CoV-2 variants of concern. Our findings have important implications for both vaccination and public health strategies in the context of emerging SARS-CoV-2 variants of concern.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antibodies, Neutralizing , Antibodies, Viral , Humans , Macaca mulatta , Reinfection
14.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-293187

ABSTRACT

As the outbreak of COVID-19 has become a severe worldwide pandemic, every country fights against the spread of this deadly disease with incredible efforts. There are numerous researches along with every conceivable dimension for COVID-19. Among these researches, different demographic and contextual factors of populations and communities also play an essential role in providing more information for decision-makers. This paper mainly utilizes existing data on county contextual factors at the United States county-level to develop a model that can capture the dynamic trajectory of COVID-19 (i.e., cases) and its impacts across the United States. Moreover, our methods applied to contextual data achieves better results compared with existing measures of vulnerability.

15.
Nature ; 601(7893): 410-414, 2022 01.
Article in English | MEDLINE | ID: covidwho-1521758

ABSTRACT

The CVnCoV (CureVac) mRNA vaccine for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was recently evaluated in a phase 2b/3 efficacy trial in humans1. CV2CoV is a second-generation mRNA vaccine containing non-modified nucleosides but with optimized non-coding regions and enhanced antigen expression. Here we report the results of a head-to-head comparison of the immunogenicity and protective efficacy of CVnCoV and CV2CoV in non-human primates. We immunized 18 cynomolgus macaques with two doses of 12 µg lipid nanoparticle-formulated CVnCoV or CV2CoV or with sham (n = 6 per group). Compared with CVnCoV, CV2CoV induced substantially higher titres of binding and neutralizing antibodies, memory B cell responses and T cell responses as well as more potent neutralizing antibody responses against SARS-CoV-2 variants, including the Delta variant. Moreover, CV2CoV was found to be comparably immunogenic to the BNT162b2 (Pfizer) vaccine in macaques. Although CVnCoV provided partial protection against SARS-CoV-2 challenge, CV2CoV afforded more robust protection with markedly lower viral loads in the upper and lower respiratory tracts. Binding and neutralizing antibody titres were correlated with protective efficacy. These data demonstrate that optimization of non-coding regions can greatly improve the immunogenicity and protective efficacy of a non-modified mRNA SARS-CoV-2 vaccine in non-human primates.


Subject(s)
COVID-19 Vaccines/genetics , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunogenicity, Vaccine , Nucleosides/chemistry , Vaccines, Synthetic/genetics , Vaccines, Synthetic/immunology , /immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/standards , Female , Macaca fascicularis/immunology , Male , Nucleosides/genetics , Respiratory System/immunology , Respiratory System/virology , SARS-CoV-2/immunology , T-Lymphocytes/immunology , Vaccines, Synthetic/standards , Viral Load , /standards
16.
South Asian J Cancer ; 10(1): 32-35, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1392961

ABSTRACT

Background Coronavirus disease 2019 (COVID-19) pandemic had an overwhelming impact on health care worldwide. Cancer patients represent a subgroup that is vulnerable and is under high risk. It is, therefore, necessary to analyze factors that predict outcomes in these patients so that they can be triaged accordingly to mitigate the effects of COVID-19 on cancer management. To date, the impact of COVID-19 on cancer patients remain largely unknown. Methods Data of 291 cancer patients undergoing active treatment from March 23 to August 15, 2020 were retrospectively reviewed; the incidence, demographic and clinical characteristics, treatment, and outcomes of cancer patients infected by COVID-19 were included in the analysis. Discussion During the index period (March 23-August 15, 2020), 4,494 confirmed cases of COVID-19 were admitted at our institute. In the department of medical oncology out of 578 patients presented to outpatient department, 291 patients were admitted for active treatment. Considering the cancer patients, infection rate was 7.9% (23/291) and mortality 13% (3/23). Median age was 40 years and the majority of patients were male (60%). The most common cancer type was acute lymphoblastic leukemia presented at various stages of treatment. Twenty patients (86.9%) were discharged after full clinical recovery and negative real-time polymerase chain reaction on a nasopharyngeal swab. Anticancer treatment was modified according to the type of cancer under intensive surveillance. Conclusion Although mortality rate in COVID-19 cancer patients is elevated, our results support the feasibility and safety of continuing anticancer treatment during pandemic by endorsing consistent preventive measures, but however should be modified based on the type and prognosis of cancer.

17.
Clin Case Rep ; 9(8): e04656, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1359778

ABSTRACT

Tension pneumomediastinum is a rare complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that has increased in incidence with the novel coronavirus disease 2019 pandemic. Although traditionally managed with conservative measures, we present the indications and methods for the first operative management of tension pneumomediastinum with concomitant SARS-CoV-2 infection.

18.
BMJ Open ; 11(7): e048086, 2021 07 22.
Article in English | MEDLINE | ID: covidwho-1322822

ABSTRACT

BACKGROUND: The COVID-19 pandemic adversely affected the socially vulnerable and minority communities in the USA initially, but the temporal trends during the year-long pandemic remain unknown. OBJECTIVE: We examined the temporal association of county-level Social Vulnerability Index (SVI), a percentile-based measure of social vulnerability to disasters, its subcomponents and race/ethnic composition with COVID-19 incidence and mortality in the USA in the year starting in March 2020. METHODS: Counties (n=3091) with ≥50 COVID-19 cases by 6 March 2021 were included in the study. Associations between SVI (and its subcomponents) and county-level racial composition with incidence and death per capita were assessed by fitting a negative-binomial mixed-effects model. This model was also used to examine potential time-varying associations between weekly number of cases/deaths and SVI or racial composition. Data were adjusted for percentage of population aged ≥65 years, state-level testing rate, comorbidities using the average Hierarchical Condition Category score, and environmental factors including average fine particulate matter of diameter ≥2.5 µm, temperature and precipitation. RESULTS: Higher SVI, indicative of greater social vulnerability, was independently associated with higher COVID-19 incidence (adjusted incidence rate ratio per 10 percentile increase: 1.02, 95% CI 1.02 to 1.03, p<0.001) and death per capita (1.04, 95% CI 1.04 to 1.05, p<0.001). SVI became an independent predictor of incidence starting from March 2020, but this association became weak or insignificant by the winter, a period that coincided with a sharp increase in infection rates and mortality, and when counties with higher proportion of white residents were disproportionately represented ('third wave'). By spring of 2021, SVI was again a predictor of COVID-19 outcomes. Counties with greater proportion of black residents also observed similar temporal trends in COVID-19-related adverse outcomes. Counties with greater proportion of Hispanic residents had worse outcomes throughout the duration of the analysis. CONCLUSION: Except for the winter 'third wave', when majority of the white communities had the highest incidence of cases, counties with greater social vulnerability and proportionately higher minority populations experienced worse COVID-19 outcomes.


Subject(s)
COVID-19 , Health Status Disparities , Humans , Incidence , Pandemics , SARS-CoV-2 , United States/epidemiology
20.
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