COVID-19 Clinical Trials and Expanded Access

During the current pandemic, in Italy the majority of asymptomatic or pauci-symptomaticCOVID-19 cases were not identified nor diagnosed and this fact caused a decrease in theeffectiveness of the various containment measures implemented. Therefore, in a futurescenario where a new viral swarm is expected, the early identification of all infectedcases becomes essential to plan and activate a containment strategy for the spread of thevirus, given the current absence of vaccines.The typical radiological finding of COVID-19 is an interstitial pneumonia, which can beresponsible, in a significant portion of patients, of an acute respiratory distresssyndrome (ARDS).Low-dose chest CT and simple blood tests could identify sub-solid pulmonary nodules(SSNs) indicative of COVID-19 infection in asymptomatic subjects.Objectives of this observational study are the early detection of COVID-19 markersindicative of prior exposure or persisting viral infection in asymptomatic subjects andthe assessment of the frequency and outcome of COVID-19-related SSNs in asymptomaticsubjects by time, domicile, and other individual risk factors.SMILE lung CT screening program cohort has been considered, based on 960 subjects at highlung cancer risk for tobacco smoking (≥20 pack/year) and age (50-75 years), together withinflammatory and respiratory profile. SMILE utilizes a top technology dual-source CTscanner (Somatom Force) with the lowest radiation dose ever applied to lung screening.All chest CT images from screening subjects will be re-evaluated by two additional CADprograms, specifically designed for the analysis of SSNs and quantification of the totalvolume of lung parenchyma showing an increased density. This re-evaluation will improvethe sensitivity and specificity of radiomic assessment.This study cohort, enriched by the already established longitudinal biobank of frozenplasma samples, represent an ideal opportunity to assess the frequency of SSNs inasymptomatic subjects, due to the effect of COVID-19, particularly among subjects livingin areas at high risk of viral exposure. It will also be possible to evaluate ifCOVID-19-related SSNs are associated with chronic co-morbidity, other individual riskfactors, inflammatory (CRP) / immunomodulatory (25(OH)D) blood profile, and/or can betraced by immune markers such as IgM/IgG and other cytokines.Clinical data will be integrated with an analysis of the IgG-IgM profile specific forcovid-19, on the plasma samples taken at the time of the CT scan, or subsequently, incollaboration with University of Milan, Luigi Devoto Work Clinic.The lasting collaboration with the Radiological Science Department of the University ofParma in lung screening also offers the opportunity to validate the results obtained inthis cohort on chest CT performed at the University Parma Hospital during the last twomonths in symptomatic subjects for suspected covid-19 pneumonia.In collaboration with University of Milano Bicocca, Machine Learning (ML) tools will beapplied to predict the clinical relevance, severity and ultimate outcome of SSNs, basedon radiomic CT features, epidemiologic risk, co-morbidity and inflammatory/immune bloodbiomarkers. ML analysis will generate a predictive algorithm for clinical outcome ofSSNs, and specifically the risk of COV-I9 infection and unfavorable disease prognosis.

This is a multicenter prospective study that aims to investigate the clinical impact ofSARS-CoV-2 infection in pregnant women, pregnancy outcomes and perinatal transmission.

Until now there is no vaccine or reliable treatment for the COVID-19 pandemic. Thefundamental mechanisms of non-invasive low-level laser in photobiomodulation (PBM) andphotodynamic therapy is to stimulate the mitochondrial respiratory chain where atransient release of non-cytotoxic levels of reactive oxygen species (ROS) will lead topositive modulation of the immune response. As previous studies mentioned that the mostimportant strategy for COVID-19 management is oxygenation and faster rehabilitation ofthe damaged tissue, antiviral effects, and, finally, reduction or controlling the cytokinestorm by reducing inflammatory agents. PBM may be used as adjuvant therapy or even analternative therapy in all these mechanisms without side effects and drug interactions.Objectives The objective of this clinical trial is to use the photobiomodulation therapy(PBMT), and photodynamic therapy as adjuvant therapy or even an alternative therapy forCovide-19.Patients and methods A randomized controlled study will be conducted on 60 patients ofpositive COVID 19. The patients will be divided into 3 equal groups. Group, I willreceive a low-level laser (diode laser 980nm) from laser watch for 30 minutes, 20 J for 3to 5 days, and laser acupuncture. Group 2 will be treated with photodynamic therapy byinjecting the methylene blue as a photosensitizer and irradiated with laser watch (diodelaser 670 nm). Group 3 will serve as a control. Evaluation methods will includelaboratory investigations and CT chest.

SARS-CoV2 is responsible for a pandemic that has been evolving for approximately 18months. The virus' capacity for dissemination and its virulence are responsible forsignificant morbidity and mortality. The initial lack of knowledge of the pathogen and ofthe pathophysiology underlying the potential severity of the disease, particularly in therespiratory tract, led to numerous therapeutic attempts in this emergency context,centered on the control of an obviously exaggerated inflammatory response. A large numberof studies remained of insufficient quality to lead to relevant and applicableconclusions. Secondly, the benefit of corticosteroid therapy has been demonstrated in twotrials. Although Dexamethasone remains the only corticosteroid to improve survival, theseresults have reinforced the hypothesis of the interest of treatments reducing theinflammatory response, particularly cytokine. The widespread use, in the absence ofscientific data, of interleukin-6 receptor inhibitors (Sarilumab and Tocilizumab) hasbeen structured around studies whose results remain uncertain to this day because of theheterogeneity of the population treated and the results observed. A possible survivalbenefit seems to emerge for resuscitation patients who have not yet required invasiveventilation, the other situations being probably associated with the absence of effect oreven the potential danger of this treatment. Tocilizumab is notably associated in theliterature with the risk of secondary infections and mucosal healing abnormalities,favoring bleeding complications and digestive perforations. The objective of this studyis to evaluate the risk of digestive complications (hemorrhage, perforation,diverticulitis) and infectious complications related to the use of Tocilizumab accordingto the severity of the patients.

Wider research context: Since the recognition of SARS-CoV-2 outbreak in 2019, there arenow over 126 million COVID-19 cases worldwide with more than 2.7 million deaths. Reportson neurological manifestations vary in prevalence rates (6-84%) and range from mild(headache, hyposmia, myalgia) to severe (encephalopathy, strokes, seizures). Little isknown about long-term neurological outcomes of COVID-19 patients. The investigatorspropose a structured protocol to capture persistent and delayed neurologicalmanifestations, neurocognitive deficits and quality of life (QoL) 3 and 12 months afterCOVID-19. Objectives: The investigators hypothesize that neurological manifestations andneuropsychological/cognitive deficits can be detected after COVID-19, substantiallyimpact on patients' QoL and can be correlated with structural neuroimaging findings. Mainobjectives are to assess firstly long-term prevalence rates and natural history ofneurological manifestations, secondly neuropsychological/cognitive deficits afterCOVID-19, thirdly the impact of COVID-19 on measures of mental health, QoL and functionaloutcome, fourthly to correlate neurological manifestations and distinct neurocognitivedeficits with structural MRI abnormalities, and Fifthly to compare these results to age-and sex matched controls hospitalized with pneumonia (Cpneum) and to healthy controls forMRI-data (Chealthy). Approach: The investigators aim to enrol at least 225 patients withCOVID-19, in addition to 50 Cpneum and 80 Chealthy. COVID-19 patients will include (groupOóne) outpatients presenting to the hospital, (group two) in-patients not requiring ICUadmission, and (group three) patients admitted to the ICU. The investigators will notinclude asymptomatic patients, patients not presenting to the hospital, and those who donot consent to participate. The standardized protocol includes a firstly a structuredneurological examination, secondly olfactory testing, thirdly assessment of QoL, mentalhealth and functional outcome at 3 and 12 months, and fourthly screening for cognitivedeficits (at 3 months) and a structured neuropsychological testing (at 12 months) inCOVID-19 patients and controls. In a subset of at least 120 COVID-19 patients and 50controls (Cpneum) high field MRI will be performed at 3 and 12 months. Innovation: Theinvestigators aim to quantify COVID-19 related and specific neurological manifestationsand their impact on the individual health condition. The novelty lies in the prospectivedesign, the longitudinal follow-up including and the inclusion of a control group whichallows us to explore the natural history of COVID-19 related neurological manifestations.Preliminary analysis of our ongoing 3-month follow-up suggests persistent neurologicalmanifestations and a significant impact of COVID-19 on mental health, cognition and QoL.The investigators believe that our study results likely influence the long-term care ofCOVID-19 patients and help to identify those, who need further neuro-rehabilitativesupport

This is a prospective cohort study of pregnant patients at an urban academic centerdiagnosed with perinatal COVID-19 infection, followed up to 6 weeks postpartum.

In this study, COVID-19 positive patients will be added to a bidirectional textingprogram to receive daily surveys about their symptoms with the infection. This data willfurther the understanding of COVID-19 symptom development throughout the infectionperiod, as well as how those symptoms vary at different points of the day. This studywill be a single cohort, observational study of COVID-19 patients.

The purpose of this study is to characterize microvascular reactivity on the forearmmuscle using non-invasive near-infrared spectroscopy in critically ill COVID-19 patients,and to correlate its alterations with 28-day mortality in ICU COVID-19 patients.

Electronic medical record review of de-identified patients who tested positive forCOVID-19 (using a PCR test) at Methodist Dallas Medical Center (MDMC) from June 2020until the date of IRB approval. Data will be collected on de-identified patients thattest positive for COVID-19 (using a PCR test) at MDMC from the date of IRB approval untilDecember 2022. Disclaimer: Any cost associated with the procedures stated herein will bebilled directly to you or to your insurance (as applicable)

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