Clinical trial NCT04750330: Mitochondrial DNA and Nuclear SNPs to Predict Severity of COVID-19 Infection
Official title: Mitochondrial DNA and Nuclear SNPs to Predict Severity of COVID-19 Infection
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Covid19
Keywords: COVID-19
Severity
mtDNA
SARS-CoV-2 Infection
Radiomics
Lead sponsor: Maastricht University
Sponsor class: OTHER
Collaborators: name: Innovative Medicines Initiative
First posted: 2021-02-11
Enrollment: 394
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population consists of patients, diagnosed with COVID-19 in the period ranging from December 2019 until December 2022. The case cohort consists of patients, who were admitted to the hospital ICU. The control group consists of patients, who were not admitted to the hospital or admitted to the hospital but not to the ICU.

Brief summary: In December 2019, the first people got infected with COVID-19 in Wuhan, China. Within weeks, this highly infectious disease spread all over the world. Nearly one year later everyone is still trying to battle this disease and facing the consequences it causes. What became clear is that the disease and its severity differs largely between infected people. However, knowledge about who will experience severe COVID-19 and who does not is still unclear. Therefore, the aim of this study is to investigate the prognostic value of certain parameters (mtDNA and CT radiomics signature) for the severity of COVID-19.

Detailed description: In December 2019, the first cases of coronavirus disease 2019 (COVID-19) were diagnosed in Wuhan, China. Within a couple of weeks, the highly contagious disease spread across the world, requiring rapid and drastic measures, unparalleled in recent decades. Currently, there have been approximately 97.8 million cases, including 2.1 million deaths, reported to the WHO (website accessed January 25th, 2021, https://covid19.who.int). Data from published epidemiology and virologic studies show that the virus is mainly passed on by respiratory droplets, by direct contact with infected people, or by contact with contaminated objects and surfaces. The severity of the disease greatly differs between people. It ranges from non-symptomatic contamination or minor symptoms, such as a cold or sore throat, to life-threatening pneumonia and death. Especially, the elderly population and people with underlying comorbidities are vulnerable and experience more severe symptoms. In addition, studies have shown that males have a higher mortality risk.

COVID-19 is currently diagnosed using reverse-transcription polymerase chain reaction (RT-PCR). In the beginning of the pandemic the use of chest computed tomography (CT) was more common, since CT can capture imaging features from the lung associated with COVID-19 early in the course of the disease. However, performing a CT-can takes remarkably longer than current RT-PCR tests. While the epidemic continues, the consequences are slowly becoming more apparent. As the true population infection rate is unknown, the proportion of patients requiring hospital admission is difficult to estimate. In a meta-analysis including 1481 unique publications a pooled rate of ICU admission of 10.9% and the pooled rate of mortality was 4.3%. The negative effects of an ICU stay strongly depend on the length of the stay and include, but are not limited to, risk of lung emboly, severe muscle loss, dysphagia and psychological problems, often necessitating a long period of rehabilitation.

To minimize long-term health consequences early prognosis of the severity of the disease would be beneficial. The link between the severity of COVID-19 and mitochondrial DNA (mtDNA), Nuclear SNPs, imaging features and radiomics has not been studied yet. However, literature about mechanistic insights in the functioning of the immune system and its link to genetic variation, including mtDNA, are promising. In addition, studies focusing on imaging features and radiomics have yielded interesting findings.

Eligibility criteria: Inclusion Criteria:

* Confirmed COVID-19 disease
* Age at least 18 years
* Willing and able to provide a saliva sample
* Able to understand the patient study information
* Signed informed consent

Exclusion Criteria:

Exclusion criteria for hospitalized patients

* Severe illness other than COVID-19 at hospital admission Exclusion criteria for non-hospitalized patients
* Severe COVID-19 illness leading to death or requiring active treatment without hospital admission

Primary outcomes:
measure: COVID-19 Severity
timeFrame: When the patient is discharged from the hospital, up to 2 months
Secondary outcomes:
measure: Overall survival of the hospitalized population
timeFrame: When the patient is discharged from the hospital, up to 2 months
Other outcomes:
measure: Mitochondrial DNA for prediction of COVID-19 severity
timeFrame: Baseline up to 2 years after having had COVID-19
measure: Nuclear SNPs for prediction of COVID-19 severity
timeFrame: Baseline up to 2 years after having had COVID-19
measure: Radiomic features for COVID-19 severity prediction
timeFrame: Baseline
Locations:
city: Athens
country: Greece
facility: Regional Chest Diseases Hospital of Athens <Sotiria>
city: Firenze
country: Italy
facility: University of Florence
city: Setúbal
country: Portugal
facility: Centro Hospitalar de Setúbal
Study officials:
affiliation: Head of Department of Precision Medicine, Maastricht University
name: Philippe Lambin, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
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