COVID-19 Clinical Trials and Expanded Access

The VIGIL study was set up at the beginning of the pandemic, in the spring of 2020, at atime when diagnostic testing for SARS-CoV-2 had to be performed according to specificclinical criteria (even if no clinical picture suggestive of COVID had been clearlyidentified). The management of sick young children (with respiratory tract infection thatcould be attributed to COVID) by pediatricians (infectious diseases specialists,emergency physicians, general practitioners, and outpatients) was facilitated by analgorithm whose objective was to help define the indications for SARS-CoV-2 PCR andsubsequently for antigenic testing. The current technique of deep nasopharyngeal swabbing(for PCR or antigenic testing) is delicate and difficult in children, and is therefore aserious handicap for community-based screening, especially since infectious episodes arefrequent in children. Since then, nasal self-tests that can be easily used in childrenhave been commercialized and have facilitated screening.Because of the similarity between the clinical signs of respiratory tract infections inchildren, it is often impossible to distinguish between different viral respiratoryinfections and epidemics may overlap in time. However, the identification of the pathogenis the key to improve management of these infectious diseases. The VIGIL study istherefore continuing, still facilitated by the existence of an active pediatric networkexisting for 20 years. ACTIV AFPA and GPIP have created networks of hospital andambulatory pediatricians who actively participate in various observatorieshttps://www.jpeds.com/article/S0022-3476(17)31606-2/fulltext To date, these observatorieshave resulted in the publication of more than 80 articles in international journals(https://www.activ-france.com/fr/publications).

The aim of the study is to clinically use bovine Lf as a safe antiviral adjuvant fortreatment and to assess the potential in reducing mortality and morbidity rates inCOVID-19 patients. The study was approved by the ethical committee of the Egyptian Centerfor Research and Regenerative Medicine in 11-5-2020.

This study aims to evaluate the impact of the COVID-19 pandemic and its measures onlifestyle in Dutch children between 4 - 18 years.

Antioxidants, and particularly polyphenols, have shown protection in respiratorypathologies, which is related to the decrease in the severity of the clinical picture andsuppression of inflammation. This suppression of inflammation may be related to theinhibition of NF-kB polyphenols, where its activation is related to the stimulation of150 stimuli including cytokines (IL-1β, IL-6, THF-α, GM-CSF, MCP-1), TLRs, among others.There may be other additional mechanisms that can help control virus-induced respiratorypathologies, among which are the regulation of reactive oxygen species (ROS) associatedwith tissue destruction caused by the virus and a selective antiviral action can bereported. direct.The standardized P2Et extract obtained from C. spinosa, by the Immunobiology Group of thePontificia Universidad Javeriana, is highly antioxidant, decreases lipid peroxidation andtissue damage and induces complete autophagy in stressed or tumor cells. The induction ofa full autophagic flow could inhibit the replication of beta-coronaviruses likeSARS-CoV-2. Furthermore, P2Et can decrease the factors involved in tissue damage byreducing IL-6 and decrease ILC2 cells of the lung in animals with lung metastases(unpublished data).These antecedents suggest that the supplementation of patients with COVID-19 with theextract P2Et, could improve their general condition and decrease the inflammatorymediators and the viral load.

In light of the rapidly emerging pandemic of SARS-CoV-2 infections, the global populationand health care systems are facing unprecedented challenges through the combination oftransmission and the potential for severe disease. Acute respiratory distress syndrome(ARDS) has been found with unusual clinical features dominated by substantial alveolarfluid load. It is unknown whether this is primarily caused by endothelial dysfunctionleading to capillary leakage or direct virus induced damage. This knowledge gap issignificant because the initial balance between fluid management and circulatory supportappear to be decisive. On progression of the disease, bacterial superinfectionfacilitated by inflammation and virus related damage, has been identified as the mainfactor for patient outcome, but the role of the host versus the environment microbiomeremains unclear.The overarching aim of the present research proposal is to improve therapeutic strategiesin critically ill patients with ARDS due to SARS-CoV-2 infection by advancing thepathophysiological understanding of this novel disease. This research thus focuses oninflammation, microcirculatory dysfunction and superinfection, aiming to elucidate riskfactors (RF) for the development of severe ARDS in SARS-CoV-2 infected patients andcontribute to the rationale for therapeutic strategies. The hypotheses are that (I) theprimary damage to the lung in SARS-CoV-2 ARDS is mediated through an exaggeratedpro-inflammatory response causing primary endothelial dysfunction, and subsequentlyacting two-fold on the degradation of the lung parenchyma - through the primary cytokineresponse, and through recruitment of the inflammatory-monocyte-lymphocyte-neutrophilaxis. The pronounced inflammation and primary damage to the lung disrupts the pulmonarymicrobiome, leading secondarily to pulmonary superinfections. (II) Pulmonary bacterialsuperinfections are a significant cause of morbidity and mortality in COVID-19 patients.Pathogen colonization main Risk Factor for lower respiratory tract infections. Toestablish colonization, pathogens have to interact with the local microbiota (a.k.a.microbiome) and certain microbiome profiles will be more resistant to pathogen invasion.Finally, (III) Handheld devices used in clinical routine are a potential reservoir andcarrier of both, SARS-CoV-2, as well as bacteria causing nosocomial pneumonia.

The Covid-19 viral pandemic has caused significant global losses and disruption to allaspects of society. One of the major difficulties in controlling the spread of thiscoronavirus has been the delayed and mild (or lack of) presentation of symptoms ininfected individuals, and the insufficient Covid-19 testing capacity in the UK. Thiswarrants the development of alternative diagnostic tools that reliably assess Covid-19infection in the early stages of infection, while also being low- cost, low-burden, andeasily administered to a wide proportion of the population.This study aims to validate machine learning models as a diagnostic tool that predictsinfection with SARS-CoV-2 based on app-reported symptoms and phenotypic data, against the'gold-standard' swab PCR-test. This study will take place within the Covid Symptom Studyapp, the free symptom tracking mobile application launched in March 2020.

COVID-19 is a rapidly evolving pandemic with approximately 5% of all patients whichrequire intensive care unit admission. In critically ill patients infected with COVID-19,approximately 15% had severe shock requiring medications to increase blood pressure. Itappears that blood vessel tone is altered and microcirculation is not well regulated inpatients with COVID-19. The underlying pathophysiology and contributing factors areunknown. The association with subsequent organ dysfunction and outcome is also unclear.Therefore, the investigators aim to investigate serial changes of relevant biomarkers inthis population to improve the understanding of this disease, to investigate theassociation with clinically important outcomes and to find out how best to treatpatients. The data will serve to develop strategies for individualised management of thishigh-risk group.

This study aims to find out whether the use of angiotensin II, which is a drug to raiseblood pressure has been approved by European Medical Agency in August 2019, as an add-onmedication to increase blood pressure in patients with COVID-19, acute severe lunginjury, inflammation and severe shock, compared with standard medication. In addition,the investigators will collect the data of Anakinra, another drug which is frequentlyused in this condition to reduce inflammation.The investigators will collect clinical data and outcomes from critical care patients.The investigators will analyse for whom these drugs are most beneficial and explorewhether there are any patients who don't benefit or have side effects.

This research aims to investigate the role of daily measurement of urinary cell cyclearrest markers and other serum and urinary biomarkers to predict the development of acutekidney injury in critically ill patients with COVID-19 and acute respiratory disease.

COVID-19 is a global major public health emergency that disproportionately affectspatients with risk factors such as advanced age, heart and lung disease, diabetes,hypertension, as well as compromised immunity. Despite the recent worldwide emergence ofthis disease and its rapid progression to a pandemic, very little is known about therisks facing solid organ recipients. The study aims to elucidate the prevalence ofsymptomatic, subclinical, and asymptomatic infection in the transplanted population byassessing their immunological response to SARS-CoV-2 infection. This will be studiedseroepidemiologically in the whole cohort and retrospectively in transplanted patientsadmitted to hospital for COVID-19.Primary objective: to elucidate the cumulative prevalence of SARS-CoV-2 infection in thetransplanted population related to symptoms and hospitalizations; to assess the magnitudeof immunological response and seroconversion kinetics for COVID-19. Secondary objectives:To examine the influence of medical parameters on COVID-19 infection and immune responsesuch as: age, comorbidities current and recent pharmacological treatment, organtransplanted, and blood type, HLA genotype.Study design:Part 1: Longitudinal cohort study for seroepidemiology and disease burden. Part 2:Retrospective case-series for seroconversion kinetics and clinical course assessment.Study population:All solid organ transplanted patients in Sweden