COVID-19 Clinical Trials and Expanded Access

A pilot study to investigate the effects of the prone positioning (PP) on hospitalpatients diagnosed with COVID-19 pneumonia.Investigators that early self-proning may prevent intubation and improve mortality inpatients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2).Up to 100 participants with a primary diagnosis of confirmed COVID-19 pneumonia will beenrolled to the study.All participants will be screened and those that meet inclusion and exclusion criteriawill be enrolled to one of two groups: one with prone positioning (on the belly) and theother with standard supine positioning (on the back). The patient and nursing staff willmonitor times spent in various positions.Outcome measures include incidence of intubation, max oxygen requirements, length ofhospital stay, ventilator-free days, worsening of oxygenation saturation, and mortality.

In this study we cross-reference several nationwide high-quality Swedish registers inorder to study risk factors for severe Covid-19 outcomes.

Thymalfasin (thymosin alpha 1 or Ta1), the active pharmaceutical ingredient in ZADAXIN®injection, is a 28-amino acid synthetic peptide, identical to natural Ta1 produced by thethymus gland. Ta1 is a biological response modifier which activates various cells of theimmune system, and is therefore expected to have clinical benefits in disorders whereimmune responses are impaired or ineffective, including acute and chronic viral andbacterial infections, cancers, and vaccine non-responsiveness. Patients with end-stagerenal disease (ESRD) on hemodialysis, in addition to their intrinsic kidney disease andfrequent burden of comorbidities, also have increased risk of exposure to communicablediseases as they are treated several times each week at hemodialysis centers with severalother patients and clinic staff in attendance. The majority of patients are over 60 yearsof age and many are receiving immunosuppressive medications. Accordingly, ESRD patientsare particularly susceptible to COVID-19 infection. Ta1 has been shown to be safelyadministered to hemodialysis patients. It is our hypothesis that a course of Ta1administered to individuals with ESRD will reduce the rate and severity of infection withCOVID-19.

This is an observational study. The aim is to describe the natural history and clinicalevolution over time of hospitalized patients affected by Severe Acute RespiratorySyndrome-Coronavirus-2 (SARS-COV-2) infection, including the genetic pathology of thedisease and improve therapeutic procedures.

The aim of this preliminary study is to describe the potential decline in forcedexpiratory volume in 1 second (FEV1) or forced vital capacity (FVC) as measured by homespirometry in high-risk subjects infected with COVID-19. We hypothesize that themagnitude of such a decline in FEV1 and/or FVC may be associated with clinicaldeterioration and hospitalization. The study will ultimately inform a larger subsequentRCT that will evaluate the efficacy of home spirometry in the early detection (prerespiratory symptoms) of respiratory complications and therefore prompt early medicalattention which is a key for improving outcome.

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.