COVID-19 Clinical Trials and Expanded Access

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 Observational, unpublished data alsoindicate that vaccine effectiveness against Covid-19 wanes over time.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.

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.

This phase 2 trial studies the immune response to GEO-CM04S1 (previously designated asCOH04S1) compared to standard of care (SOC) mRNA SARS-COV-2 vaccine in patients withblood cancer who have received stem cell transplant or cellular therapy.GEO-CM04S1 belongs to a category called modified vaccinia Ankara (MVA) vaccines, createdfrom a new version of MVA, called synthetic MVA. GEO-CM04S1 works by inducing immunity(the ability to recognize and fight against an infection) to SARS-CoV-2. The immunesystem is stimulated to produce antibodies against SARS-CoV-2 that would block the virusfrom entering healthy cells. The immune system also grows new disease fighting T cellsthat can recognize and destroy infected cells. Giving GEO-CM04S1 after cellular therapymay work better in reducing the chances of contracting coronavirus disease 2019(COVID-19) or developing a severe form of COVID-19 disease in patients with blood cancercompared to SOC mRNA SARS-CoV-2 vaccine.

Stress is underpinned by a biological reaction of the organism allowing the production ofenergy to respond to a change in the environment (or stressor). Stress reaction isexpressed in behavioural, cognitive, emotional and physiological terms. This biologicalresponse is non-specific because it is the same regardless of the stressor. Its evolutionover time has been conceptualised by Hans Selye (1956) in the General Adaptation Syndrome(GAS) which comprises three successive phases. (i) The first phase, known as the alarmphase, corresponds to the activation of all biological mechanisms according to a trendregulation, allowing a rapid response to the stressor. (ii) The second phase ofresistance which adjusts the stress response to the intensity of the perceived aggressionaccording to a constant regulation. (iii) When the aggression disappears, a recoveryphase dominated by the return of the parasympathetic brake allows a return to homeostasis(eustress).The "primum movens" of all pathologies is therefore the inability of the individual toadapt his stress response in duration and/or intensity to the course of the phases of theGAS (distress). The perception of not being in control of the situation contributes tothe perceived stress and constitutes a well-established risk of distress. It is a riskfactor for the emergence of burnout. It induces a biological cost called allostatic cost.Allostasis is a concept that characterizes the process of restoring homeostasis in thepresence of a physiological challenge. The term "allostasis" means "achieving stabilitythrough change", and refers in part to the process of increasing sympathetic activity andcorticotropic axis to promote adaptation and restore homeostasis. Allostasis works wellwhen allostasis systems are initiated when needed and turned off when they are no longerrequired. Restoring homeostasis involves effective functioning of the parasympatheticsystem. However, when the allostasis systems remain active, such as during chronicstress, they can cause tissue burnout and accelerate pathophysiological processes.The perception of uncontrollability depends on the stress situation, the psychologicaland physiological characteristics of the subject and his or her technical skills inresponding to the stressors of the situation. In particular, subjects with a high levelof mindfulness are more accepting of uncontrollability and less likely to activate thestress response.The COVID-19 pandemic situation is a situation characterized by many uncertainties aboutthe individual, family and work environment and the risk of COVID infection. Healthcareworkers, like the military, are high-risk occupations that are particularly exposed tothese uncertainties in the course of their work and continue to work in an uncertainsituation. These professionals are described as a population at risk ofoccupational/operational burnout that the level of burnout operationalises. Thisancillary study in a population of civilian and military non-healthcare workers willcomplement the study conducted among military health care workers. It will make itpossible to isolate the specificity of each profession (civilian or military, healthcarepersonnel or not) with regard to the risk of burnout in the COVID context.The objective of this project is to evaluate the impact of the perception of non-controlin the operational burnout of experts in their field of practice and to study thepsychological and physiological mechanisms mediating the relationship between thesubject's characteristics, perceived non-control and burnout.

A total of 300 healthy volunteers between the ages of 18 and 80 with no previous historyof COVID-19 will be entered into the study and will receive IPV by injection on Day 1.Blood specimens collected pre-inoculation will be tested for cross-reactivity topoliovirus and SARS-CoV-2 by Western blot. An additional specimen will be collected onDay 28 post-inoculation and, likewise tested for cross-reactivity to poliovirus andSARS-CoV-2.The number of subjects with an immune response to SARS-CoV-2 antigens followinginoculation with IPV will be summarized.

This is a phase I, randomized, placebo-controlled, double-blind study, to evaluate safetyand immunogenicity of a recombinant SARS-CoV-2 vaccine (CHO cell) in Chinese healthypopulation aged 18 years and older. After randomization, the trial for each subject willlast for approximately 13 months. Screening period is 1 week prior to randomization (Day-7 to Day -1), and each dose of either SARS-CoV-2 vaccine (CHO Cell) or placebo will begiven intramuscularly (IM) on Day 0 and Day 14 for a two-dose regimen, or on Day 0, Day14, and Day 28 for a three-dose regimen. Subjects who are ≥18 years old and ≤ 59 yearsold will be enrolled in adult group, and healthy elderly population who are >59 years oldwill be enrolled in elderly group. After adult group completes the follow-up 7 days afterfirst vaccination, elderly group will be recruited.

A Phase I, double- blinded, randomized, placebo- controlled study to test the safety ofLomecel-B in Adults suffering from mild to severe acute respiratory distress syndrome(ARDS) due to COVID-19 resultant from 2019-nCoV coronavirus infection, or resultant frominfluenza virus infection.

This study will collect information on immune response and adverse events aftervaccination against coronavirus disease (COVID-19) in a vulnerable patient cohort.Understanding the ability or disability to mount a protective immune response aftervaccination will help to counsel patients during the pandemic and support decisions onwhom to vaccinate and to identify patients who require other measures to protect themfrom COVID-19.

Background: Coronavirus disease 2019 (COVID-19) has affected almost every country in theworld, especially in terms of health system capacity and economic burden. People fromsub-Saharan Africa (SSA) often face interaction between human immunodeficiency virus(HIV) infection and non-communicable diseases such as cardiovascular disease. Role of HIVinfection and anti-retroviral treatment (ART) in altered cardiovascular risk isquestionable and there is still need to further carry out research in this field.However, thus far it is unclear, what impact the COVID-19 co-infection in people livingwith HIV (PLHIV), with or without therapy will have. The ENDOCOVID project aims toinvestigate whether and how HIV-infection in COVID-19 patients modulates the time courseof the disease, alters cardiovascular risk, and changes vascular endothelial function andcoagulation parameters/ thrombosis risk.Methods: In this long-term study, cardiovascular research on PLHIV with or without ARTwith COVID-19 and HIV-negative with COVID-19 will be carried out via clinical andbiochemical measurements for cardiovascular risk factors and biomarkers of cardiovasculardisease (CVD). Vascular and endothelial function will be measured by brachial arteryflow-mediated dilatation (FMD), carotid intima-media thickness (IMT) assessments, andretinal blood vessel analyses, along with vascular endothelial biomarkers andcoagualation markers. The correlation between HIV-infection in COVID-19 PLHIV with orwithout ART and its role in enhancement of cardiovascular risk and endothelialdysfunction will be assessed. Potential changes in these endpoints by COVID-19 will befollowed for 4 weeks across the three groups (PLHIVwith or without ART and HIVnegatives).Impact of project: The ENDOCOVID project aims to evaluate in the long-term thecardiovascular risk and vascular endothelial function in PLHIV thus revealing animportant transitional cardiovascular phenotype in COVID-19.

A multicenter, randomized, double-blind, placebo-controlled trial for hospitalizedmoderate COVID-19 patients