COVID-19 Clinical Trials and Expanded Access

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.

The purpose of the study is to evaluate the presence of early vascular aging 6 months and12 months after COVID-19 infection.

The primary objective is to assess the ability of COVID-19 IgG and IgM assays to detectan immune response in COVID-19 patients in the Henry Ford Health System (HFHS), bothduring hospitalization and over the following 12 months.

COVID-19 has become a global problem. There is an urgent need to improve the diagnosisand screening of patients and healthcare workers for COVID-19 in the UK. Mask basedsampling is a method of detecting SARS-COV-2 (the virus responsible for COVID-19) in thebreath of suspected COVID-19 patients or healthcare workers in the mask that they wouldwear in hospital. The investigators have previously demonstrated the utility of thismethod in other respiratory infections, such as tuberculosis.This project aims to investigate the utility of mask-based sampling is a tool for thediagnosis and quantification of COVID-19 in breath and the implications in a healthcaresetting using three cohorts of participants. Initially we will compare the amount ofCOVID-19 detected by mask sampling compared with standard nasopharyngeal swab, which isthe current gold standard test, in patients who present to hospital with COVID-19symptoms.We will address the length of time COVID-19 is breathed out by people affected by thevirus and the how infectious the virus is over time in a cohort of symptomatic healthcareworkers who are isolating at home. This will allow us to understand how long someonestays infectious for and may have the potential to inform public health measures, forinstance when healthcare workers can return to work or duration of isolation. Finally wewill investigate asymptomatic carriage of COVID-19 by different healthcare workers indifferent areas of the hospital during a screening study. This will allow us tounderstand the extent of infection amongst healthcare workers and allow us to addresshospital acquired transmission.

Lower Respiratory Tract infections are a common cause of admission to the intensive careunit. Children routinely receive antibiotics until the tests confirm whether theinfection is bacterial or viral. The exclusion of bacterial infection may take 48 hoursor longer for culture tests on biological samples to be completed. In many cases, theresults may be inconclusive or negative if the patient has already received antibioticsprior to the sample being taken.A rapid assay to detect the most likely cause of infection could improve the speed withwhich antibiotic therapy is rationalised or curtailed.This study aims to assess whether a new genetic testing kit which can identify thepresence of bacteria and viruses within hours rather than days is a feasible tool inimproving antibiotic prescribing and rationalisation of therapy in critically illchildren with suspected lower respiratory tract infection.

COVID-19 (Coronavirus disease 2019) is a new infectious disease caused by a virus namedas SARS-CoV2 (Severe Acute Respiratory Syndrome Coronavirus-2). Although it can have adevastating effect on many organs, the respiratory tract is particularly affected. In thecourse of the disease, a wide clinical spectrum is observed, from flu-like illness tolung failure. Some of the patients who survived the disease continue to have problemssuch as shortness of breath, fatigue, decrease in walking distance, decrease inparticipation in daily life activities. These problems suggest that the effects onrespiratory and cardiac functions continue even after the disease ends. This study wasdesigned to demonstrate the effects and extent of COVID-19 on cardiopulmonary capacity.

Richmond Research Institute (RRI) is applying existing and new COVID-19 PCR and antibodytests to help develop methodologies which provide fast and accurate results. Infectionwith coronavirus (SARS-CoV-2) is currently a worldwide pandemic and reliable testing forCOVID-19 is crucial to understand who is infected and therefore a risk to others byspreading the infection. RRI are currently carrying out the following tests:A. Using a membrane-based immunoassay to detect IgG and IgM antibodies to SARS-CoV-2 inwhole blood, serum or plasma specimens helps to assess whether an individual haspreviously had the virus and is potentially immuneB. Polymerase Chain Reaction (PCR) testing using an established method to check foractive SARS-CoV-2 infections.C. Quantification of anti-SARS-CoV-2 IgG and IgM antibodies in whole blood samples.The above tests are being used by RRI to follow infections (PCR) and immunity (IgG) intheir workforce, as well as their families (including children) and visitors to theirsite.Collecting this data allows the gathering of epidemiological data on SARS-CoV-2 includingincidence, prevalence, information on asymptomatic carriers and efficacy of vaccination.Furthermore, identifying individuals that are infected with SARS-CoV-2 has greatpotential to improve health outcomes by allowing infected individuals to seek the correctmedical treatment as well as self-isolate and reduce transmission.

Emergent experimental and anecdotal evidence has indicated that critically ill COVID-19patients demonstrate two patient sub-types (called phenotypes). In one group the diseaseprogresses slowly and patients have a low potential of developing mild respiratoryfailure, but in the other group, an exaggerated immune response(hyper-inflammation/cytokine storm) may be linked to the onset of precipitous respiratoryfailure, termed acute respiratory distress syndrome. This syndrome is responsible for alarge portion of COVID-19 associated mortality. Thus, determining links betweenhyper-inflammation and acute respiratory distress syndrome in COVID-19 patients is ofimmediate importance. Blood samples will undergo a number of analyses to help us tounderstand as much as possible about COVID-19. We will also study any differences inphysiologic and cytokine levels before and after patients are treated withimmunomodulatory therapies as part of clinical care in COVID-19 patients.