COVID-19 Clinical Trials and Expanded Access

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.

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 NanoCOAT study is a multi-center, prospective, non-randomized, feasibility,observational, non-significant risk study. The NanoCOAT study will enroll a minimum of 10and a maximum of 100 subjects in a potential for a multi-site in order to collect dataand analyze physiological and biometric trends due to Covid-19.

To evaluate if omalizumab is effective in decreasing mortality in severe hospitalizedCOVID-19 cases.

The purpose of the study is to describe disability following hospitalization in people ofworking-age surviving COVID-19.

The COVID-19 pandemic has been characterized by high morbidity and mortality, especiallyin certain subgroups of patients. To date, no treatment has been shown to be effective inpatients with early-onset disease and mild symptoms. Experimental studies havedemonstrated a potential anti-inflammatory role of Fluvoxamine, Fluoxetine, Budesonideand Spirulin Platensis in SARS-CoV-2 infections and observational studies have suggesteda reduced complications in patients with COVID-19 disease.

This study investigates the possible adverse effects and effectiveness of convalescentplasma for patients infected with SARS-CoV-2. Following provision of informed consent,patients will be randomized into three groups: High-titre convalescent plasma, low-titreconvalescent plasma or placebo. Primary outcomes of the study will cover safety andeither intubation or initiation of systemic corticosteroids. Safety information collectedwill include serious adverse events judged to be related to administration ofconvalescent plasma. Microbiological and other laboratory parameters will be followed up.

Sample Size: n=570Accrual Ceiling: n=627Study Population: Patients age 18 to 100 yearsThe study duration includes 51 months to recruit patients and 24 months of totalfollow-up time counted from the first day of COVID-19 symptoms or date of confirmedCOVID-19 diagnosis.Study Design: This is a prospective, observational cohort study to evaluate the short-and long-term end-organ complications of COVID-19 and to establish a COVID-19 biobank.Participant Cohorts: 1. Individuals who had previous asymptomatic or mild COVID-19 (mild=never required supplemental oxygen during the acute phase of the infection) 2. Individuals who had previous moderate or severe COVID-19 (moderate=required supplemental oxygen by nasal cannula during the acute phase of the infection; severe=required supplemental oxygen by either high-flow nasal cannula, non-invasive positive pressure ventilation or intubation) 3. Individuals who had COVID-19 but did not have signs or symptoms related to COVID-19 lasting beyond 4 weeks from the date of COVID-19 symptom-onset or diagnosis 4. Individuals who have not had COVID-19 (i.e. individuals who tested negative for COVID-19 and who never had symptoms consistent with COVID-19)

The COVID-19 can cause important sequels in the respiratory system by bilateral pneumoniaand frequently presents loss of strength, dyspnea, polyneuropathies and multi-organicaffectation. Long COVID-19 has been defined as the condition occurring in individualswith a history of probable or confirmed SARS-CoV-2 infection, with related symptomslasting at least 2 months and not explainable by an alternative diagnosis. The practiceof digital physiotherapy presents itself as a promising complementary treatment method tostandard physiotherapy, playing a key role in the recovery of function in subjects whohave passed the disease and who maintain some symptomatology over time. The aims of thisresearch are to explore the effect of a digital physiotherapy intervention on functionalrecovery in patients diagnosed with Long COVID-19 and to identify the level of adherenceto the treatment carried out. Physiotherapy interventions acquires a fundamental role inthe recovery of the functions and the quality of life. As secondary objectives, the aimis to identify the satisfaction and perception of patients with the intervention and thepresence of barriers to its implementation (throught a qualitative research), as well asto evaluate the cost-effectiveness from the perspective of the health system. Aquasi-experimental pre-post study assessed initially and at the end of the 4-weekintervention the functional capacity (1-min STS and SPPB) and the adherence (software).The hypothesis of this research is that the implementation of a TR program presentspositive results. If hypothesis is confirmed, that would be an opportunity to define newpolicies and interventions to address this disease and its consequences.

NAPKON-HAP is the deep phenotyping platform of the National Pandemic Cohort Network(NAPKON) in Germany. NAPKON is a data and biospecimen collection of patients withCOVID-19 and is part of the University Medicine Network (NUM) in Germany. The primaryobjective of the study is to provide a comprehensive collection of data and biosamplesfor researchers from national consortia and for participation in international researchcollaborations for studying COVID-19 and future pandemics.Data is collected from patients with COVID-19 three times per week during theirhospitalization and at follow-up visits after hospital discharge 3, 6, 12, 24, and 36months after symptom onset. Data include epidemiological and demographic parameters,medical history and potential risk factors, documentation of routine medical procedures,and clinical course, including different patterns of organ involvement, quality of care,morbidity, and quality of life. Moreover, extensive serial high-quality bio samplingconsisting of various sample types is performed to allow deep molecular, immunological,and virological phenotyping.Patients not requiring Intensive Care Unit (ICU)/ Intermediate Care (IMC) treatment willreceive 7 and patients requiring ICU/IMC treatment will receive 16 full-phenotypingvisits including sampling for biobanking. During hospitalisation the planned bloodsampling rate in total is 35 ml at each visit. The total amounts and/or sampling datesmay differ according to the ethics committee's regulations for different study centers.At follow-up visits, the clinical assessment includes an update of the medical historyand recent medical events from which additional clinical data is collected (i.e.outpatient CT-scans, echocardiography, external laboratory data). Clinical symptoms arerecorded and a physical examination will be performed. Vital signs are recorded androutine blood testing and biosampling is continued. Quality of life is measured withpatient-reported outcome questionnaires.Follow-up visits at months 3 and 12 are "deep phenotyping" visits with a comprehensiveand detailed set of examinations. In the following visits at months 24 and 36, onlyexaminations with pathologic results from the last deep phenotyping visit at month 12will be performed.A shorter follow-up visit to record quality of life, recent medical events and with areduced number of examinations focusing on cardiorespiratory performance will take placeat month 6.In case of relevant medical events, new medical information or changes in theparticipant´s health status, an unscheduled visit can take place anytime within theentire study period.Data collection during follow up includes standardized quality of life assessmentincluding PROMIS® (Patient-Reported Outcomes Measurement Information System). Thepulmonary characterization will include body plethysmography, diffusion capacity,respiratory muscles strength measurement, spiroergometry, capillary blood gas analysisand lung imaging studies (low-dose Computed Tomography (CT), Magnetic Resonance Imaging(MRI) of the lung). Cardiological phenotyping includes echocardiography,electrocardiogram (ECG), 24h-ECG, 24h-blood pressure monitoring, stress cardiac MRI andpulse wave analysis. Neurocognitive testing includes brain MRI, electroencephalogram(EEG), somatosensory testing, refractometry (Visit 3 and 12 months), physical activitytest, neurocognitive tests, somatosensory phenotyping, taste- and smell-test.Endocrinological phenotyping will incorporate Advanced Glycation Endproducts (AGE)reader, continuous glucose monitoring for 14 days, Air Displacement Plethysmography (ADP)or bioelectrical impedance analysis (BIA).