The main overarching aim of this study is to build a research clinic, as part of theNoRCoRP platform covering Nottingham and Nottinghamshire to facilitate learning andresearch in the whole population of patients who have had COVID-19.

The study is a multicenter, adaptive, randomized, double-blinded and placebo-controlledPhase II/III clinical trial. It will be conducted at selected investigational sitesglobally. The study is comprised of 2 parts.

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.

This study is designed as a 2-part, 2-cohort, double-blind, randomized, placebocontrolled, multicenter Phase 1/2 study to evaluate the safety, tolerability and efficacyof RJX in patients with COVID-19.

At present, the offer of tests for the serological diagnosis of CoVID-19 (detection ofIgG, IgM or IgA antibodies against CoV-2 SARS) is plethoric and is based on the use of avery large number of rapid diagnostic unit tests, a few dedicated high throughputautomated systems or reagents on existing open systems. The offer will continue to expandin the coming months.In order to meet the objectives mentioned by the Prime Minister, and confirmed in the HASreport of April 16, 2020 and in the opinion n°6 of the COVID-19 scientific councilconcerning the potential use of these serological tests at the end of the COVID-19epidemic, the Virology laboratory wishes to validate the sensitivity and specificity ofthe tests it intends to use.

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

This is a randomized, single blind, study. Males and females meeting inclusion criteriawho have symptoms of mild COVID-19 and in whom a positive PCR result for SARS-CoV-2 isobtained may be enrolled to the study treatment within 72 hours of the positive PCRresult. Eligible patients are those considered to be at high risk for COVID-19 diseaseprogression. This includes patients ≥ 65 years of age or with any one or more of certainmedical conditions including: cancer, COPD, cardiovascular disease, immunocompromisedstate resulting from solid organ transplant, obesity, sickle cell disease, history ofsmoking, and diabetes.

There is an unmet need to evaluate the impact of sub-clinical/mild COVID19 disease in theoutpatient setting on prevalent and incident renal injury, as this data is currentlyunavailable. To capture the diversity of race/ethnic risk and COVID19 related municipalshelter-in-place guidance, the investigators will enroll COVID19-negative andCOVID19-positive samples balanced by race/ethnicity from 3 different states, California,Michigan, and Illinois. Study endpoints will be assayed from urine samples mailed to thestudy team at 2, 6, and 12 months after their date of PCR test, with no requirement forthese individuals to leave their homes to participate.

The ongoing Coronavirus Disease 2019 (COVID-19) pandemic has been intensified by nopopulation-based immunity to the severe acute respiratory disease coronavirus 2(SARS-CoV2) and initially lack of effective treatments or vaccines available to mitigatethe pandemic. Currently, two COVID-19 vaccines are available for vaccination in Europethrough conditional marketing authorisation granted by the European Medicines Agency andfurther vaccine will be licensed. These vaccines have shown good vaccine efficacy inphase 3 vaccine trials. We will recruit subjects who will be prioritised for vaccinationwith the primary aim of comparing the immune responses after COVID-19 vaccination andnatural SARS-CoV-2 infection. In Western Norway we have recruited cohorts of health careworkers and patients infected with SARS-CoV-2 and will extend to COVID-19 vaccinees.Demographic, clinical data and repeated blood samples will be collected to evaluate thecomplications and kinetics, duration and breadth of the immune responses comparingnatural infection to vaccination.

The objective of the COVID-19 Vaccines International Pregnancy Exposure Registry(C-VIPER) is to evaluate obstetric, neonatal, and infant outcomes among women vaccinatedduring pregnancy with a COVID-19 vaccine.Specifically, the C-VIPER will estimate the risk of obstetric outcomes (spontaneousabortion, antenatal bleeding, gestational diabetes, gestational hypertension,intrauterine growth restriction, postpartum hemorrhage, fetal distress, uterine rupture,placenta previa, chorioamnionitis, Caesarean delivery, COVID-19), neonatal outcomes(major congenital malformations, low birth weight, neonatal death, neonatalencephalopathy, neonatal infections, neonatal acute kidney injury, preterm birth,respiratory distress in the newborn, small for gestational age, stillbirth, COVID-19),and infant outcomes (developmental milestones [motor, cognitive, language,social-emotional, and mental health skills], height, weight, failure to thrive, medicalconditions during the first 12 months of life, COVID-19) among pregnant women exposed tosingle (homologous) or mixed (heterologous) COVID-19 vaccine brand series from 30 daysprior to the first day of the last menstrual period to end of pregnancy and theiroffspring relative to a matched reference group who received no COVID-19 vaccines duringpregnancy.