COVID-19 Clinical Trials and Expanded Access

To measure the frequency of persistent liver dysfunction (raised liver enzymes, serumalbumin, prothrombin time, etc) in recovered COVID -19 patients.To compare the hepatic manifestations in post COVID -19 patients with and without liverdisease

The primary aim of our study is to understand the effects of Covid-19 disease on vascularinflammation and coagulation cascade, and secondarily, to investigate its utility inpredicting disease prognosis by analyzing serum PAI-1 levels in patients with differentseverity. The study is planned as a prospective, cross-sectional study that will includepatients admitted to Covid-19 services between January 18, 2021, and August 30, 2021. Atotal of 80 volunteers will be enrolled in the trial whose age, gender, and BMI areplanned to be matched.The study will be conducted on four groups. Group 1 (n=20; withmild symptoms), Group 2 (n=20; with moderate symptoms), Group 3 (n=20; with severesymptoms) and Group 4 (n=20; Control group).All participants who accepted the study will have their sociodemographic data, medicalhistory, and vital signs (respiratory rate, saturation, temperature, and blood pressurevalues) recorded at the start of the study. The pulmonologist in the study will alsoclassify the patient group's chest X-ray and chest tomography findings and the thymusgland dimensions. After all four groups of patients have given their consent for thestudy, a sample of 5cc blood will be obtained once for the PAI-1 analysis.

EC CORONACOLCHI is a multicenter, double-blind and randomized clinical trial with twobranches. Patients who meet all the inclusion criteria and none of the exclusion criteriawill be randomized 1: 1 to be included in one of the following groups: - Experimental group: colchicine for 2 weeks orally at the doses described, added to the standard treatment of COVID-19. - Control group: placebo for 2 weeks orally added to standard COVID-19 treatment.

This randomized controlled trial will evaluate the implementation and(cost-)effectiveness of the culturally and contextually adapted Doing What Matters intimes of stress (DWM) and Problem Management Plus (PM+) stepped-care programs amongstasylum seekers, refugees, and/or migrants living in Italy. Outcomes include mentalhealth, resilience, wellbeing, health inequalities, and costs to health systems.

Preliminary data suggest that inactivated vaccine-induced neutralizing antibodies againstSARS-CoV-2 decrease at six months after vaccination. Observational, unpublished data alsoindicate that vaccine effectiveness against Covid-19 wanes over time. Thus, theinvestigators aimed to determine the reactogenicity, safety, and immunogenicity of ahomologous or heterologous booster of SARS-CoV-2 vaccines among people already immunizedwith an inactivated SARS-CoV-2 vaccine. The study focuses on the elderly population andhealthcare workers.

For caregivers in the Bronx, the pandemic has caused unprecedented psychologicaldistress; in addition to combating social determinants of health (SDOH), these familiesnow face greater financial insecurity and challenges related to their school-agedchildren. Furthermore, social distancing requirements and limited telehealth resourcesfor Bronx families have posed greater barriers to healthcare. Such parental distresscontributes to heightened risk of transgenerational cycles of psychological stress,trauma and maltreatment. The social and economic impacts of the COVID-19 pandemic havehad significant consequences for family well-being, putting parents at higher risk ofexperiencing distress and potentially impairing their ability to provide supportive careto their children. Although children may be less susceptible to the most damagingphysical consequences of COVID-19, there are growing concerns regarding the short-andlong-term impacts of pandemic-related stressors on children. The marked upheaval offamily life over an extended period may make children vulnerable to mental healthconsequences associated with the public health crisis and infection mitigation efforts.School and childcare closures, unstable financial circumstances, social isolation andlack of support have a disproportionate, cumulative impact on parents and may underminetheir capacities to provide support for their children. Importantly, a large body ofevidence suggests that parental stress during times of disasters inducespsychopathologies in family members including children. Further, high anxiety anddepressive symptoms in parents during the pandemic have been associated with higher childabuse potential, whereas greater parental support was associated with lower perceivedstress and child abuse potential. In addition to psychological impacts, stress associatedwith caregiving can interfere with parents' ability to maintain their own health. Thismultimodal study addresses key strategies to mitigate the psychological and health impactof COVID-19 in parents.

Safe and effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinesmay reduce the transmission of and achieve population immunity against the COVID-19pandemic, which accounted for more than 3.75million deaths worldwide. With World HealthOrganization's (WHO) effort on ensuring equitable access to COVID-19 vaccines,vaccination rate may increase in the near future.On the other hand, vaccination hesitancy has emerged as a major hindrance on the globalvaccination campaigns in certain areas due to safety concerns, social factors, and publichealth policies. For instance, a recent survey conducted in Hong Kong showed a lowvaccine acceptance rate of 37%. Long-term safety concerns and post-vaccination eventsrelayed by the social media maybe reasons for vaccination hesitancy. Among which,cerebrovascular accidents (CVA) after vaccination were one of the most frequentlyreported post-vaccination events. These reports ranged from ischemic strokes in elderlypatients with multiple cardiovascular co-morbidities, to hemorrhage strokes in otherwise"young-and-fit" adults. While many of these events were investigated by the COVID-19immunization expert committee, an important premise to address the apprehension of CVAafter vaccination is the provision of evidence-based information of the impact ofCOVID-19 vaccines on brain health.In this prospective, longitudinal, observational study, we aim to elucidate therelationship between COVID-19 vaccines and cerebrovascular health in healthy citizens ina population-based cohort.

T-cell exhaustion may limit long-term immunity in COVID-19 patients. T cells can losetheir ability to fight viruses and tumors when they have prolonged exposure to theseenemies. New data suggests people who experience mild COVID-19 symptoms show themolecular signs of exhausted memory T cells and therefore could have a reduced ability tofight reinfection. On contrary people who develop severe COVID-19 symptoms may be betterprotected from reinfection. A recent study reported that the 82.1% of COVID-19 casesdisplayed low circulating lymphocyte counts . It has been reported that, in the case ofchronic viruses, continuous PD-1 expression causes T-cell exhaustion, and impairs theability of killing the infectious cells . The adumbration of patients with COVID-19 ischaracterized by a diminished lymphocyte percentage, with a similar proportion of CD4+and CD8+ T-cells. The quantity of T-cells, mostly CD8+ T-cells, presenting highexpression rates of late activity marker CD25 and exhaustion marker PD-1 increases.Therefore, SARS-CoV-2 is able to make changes by modifying the acquired immune system,including B and T cells. According to experiments, PD-1's expression, as an importantfactor in the induction and maintenance of circumferential tolerance keeping thestability of T-cells, has been found to have a higher percentage in different cells ofCOVID-19 patients. In an experiment conducted by Diao et al., on the patients withSARS-CoV-2, it was observed that the expression of PD-1 on the surface of T-cells wasincreased significantly; it was also shown that during the SARS-CoV-2 -induced disease,additional expressions of PD-1 and Tim-3 on the T-cells were directly related to thedisease's severity; the factors that were also increased in other viral infections. Tcell exhaustion" phenomenon could be reversed relatively easily, for example when the Tcells are no longer exposed to the virus or tumor. But unfortunately, although exhaustedT cells recovered from chronic infection (REC-TEX) regain some function and features ofmemory T cells (TMEM), they retain epigenetic scars indicating the control of geneexpression is "locked in" to their exhaustion history. Once T cells become exhausted,they remain fundamentally 'wired' to be exhausted-thus it may be hard to get them tobecome effective virus- and cancer-fighters again," said John Wherry, PhD, chair of thedepartment of Systems Pharmacology and Translational Therapeutics and director of thePenn Institute of Immunology in the Perelman School of Medicine at the University ofPennsylvania. Furthermore, COVID-19 may infect T lymphocyte cells and induce apoptosisand apoptotic markers. Lymphocytopenia was also found in the Middle East respiratorysyndrome (MERS) cases. MERS-CoV can directly infect human primary T lymphocytes andinduce T-cell apoptosis through extrinsic and intrinsic apoptosis pathways, but it cannotreplicate in T lymphocytes. However, it is unclear whether SARS-CoV-2 can also infect Tcells, resulting in lymphocytopenia. A study showed that T cells express a very lowexpression level of hACE2 on its cell surface and T-cell lines were significantly moresensitive to SARS-CoV-2 infection when compared with SARS-CoV . In other words, theseresults tell us that T lymphocytes may be more permissive to SARS-CoV-2 infection.Therefore, it is plausible that the S protein of SARS-CoV-2 might mediate potentinfectivity, even on cells expressing low hACE2, which would, in turn, explain why thetransmission rate of SARS-CoV-2 is so high. Through recent advances in genomic editing, Tcells can now be successfully modified via CRISPR/Cas9 technology. For instance, engaging(post-)transcriptional mechanisms to enhance T cell cytokine production, the retargetingof T cell antigen specificity or rendering T cells refractive to inhibitory receptorsignaling can augment T cell effector function. Therefore, CRISPR/Cas9-mediated genomeediting might provide novel strategies for inducing long term immunity againstCOVID-19.Immunotherapies with autologous T cells have become a powerful treatment optionfor many diseases like viral infection or cancer. These include the adoptive isolationand transfer of naturally-occurring virus/tumor-specific T cells and the transfer of Tlymphocytes that have been genetically modified . According to the investigator,exhausted virus-reactive CD8+ memory T cells will be isolated from patients with mildinfection using a modified antigen-reactive T cell enrichment (ARTE) assay. exhaustedvirus-reactive CD8+ memory T cells will be collected and both Programmed cell deathprotein 1(PDCD1) gene and ACE2 gene will be knocked out by CRISPR Cas9 in the laboratory.The lymphocytes will be selected and expanded ex vivo and infused back into patients.

An outbreak of the novel coronavirus nCoV-19 (SARS-CoV-2), responsible for thecoronavirus disease-19 (COVID-19), was first detected in Hubei province, Wuhan, China, onDecember 31, 2019. It has rapidly spread globally with approximately 157,343,044confirmed cases and 3,278,510 deaths till 7th May, 2021 [1]. World Health Organization(WHO) declared COVID- 19 pandemic on 11th March 2020.The world is facing the second wave of Coronavirus Disease 2019 (COVID-19) pandemic whichis the most troublesome challenge to public health. The second wave is running and nobodyknows where we are in the course of this disease. It becomes a significant challenge forthe public health, science, and medical sectors [2].According to the World Health Organization, about 80% of infections are mild orasymptomatic, 15% result in moderate to severe symptoms (requiring oxygen) and about 5%are critical infections, which require ventilation.We are learning something new every day. Our understanding of the pandemic is growing andchanging daily. The world is focusing on the short term - flattening the curve, treatingthe sick and discovering a vaccine. But there is more to this pandemic than the shortterm.We know a lot about the transmission and clinical feature of COVID-19, but relativelylittle about what happens after someone recovers. Much is still unknown about howCOVID-19 will affect people over time. There's still much to be learned from those whohave recovered from COVID-19.

Randomized, open, multicenter, collaborative and adaptive non-inferiority trial toevaluate the immunogenicity and reactogenicity of the heterologous vaccination schedulesmade up of the combination of vaccines available in Argentina (Sputnik-V, AstraZeneca,Sinopharm and Moderna); and to compare the immunogenicity and reactogenicity ofheterologous and homologous vaccination schedules.