Covid19mtDNA-COVIDNCT04750330
Mitochondrial DNA and Nuclear SNPs to Predict Severity of COVID-19 Infection
An observational study of Covid19, run by Maastricht University at 3 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Covid19
- How many people
- 394 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 1 Apr 2021to 12 Jun 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
About this study
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.
Read the 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.
- Conditions
- Covid19
- Keywords
- COVID-19, Severity, mtDNA, SARS-CoV-2 Infection, Radiomics
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Severe COVID-19 | Patients, diagnosed with COVID-19, who were admitted to the Intensive Care Unit (ICU) during hospitalisation | |
| Non-severe COVID-19 | Patients, diagnosed with COVID-19, who were admitted to the hospital but NOT to the Intensive Care Unit (ICU) during hospitalisation | |
| Minor COVID-19 | Patients, diagnosed with COVID-19, who were NOT admitted to the hospital and could recover at home |
What is being measured
The primary outcome is the main question the study is designed to answer.
COVID-19 Severity
Severity of COVID-19 classified as 'Severe', 'Non-severe' and 'Minor'
Measured: When the patient is discharged from the hospital, up to 2 months
Secondary outcomes (1)
Overall survival of the hospitalized population
Overall survival of the hospitalized population
Measured: When the patient is discharged from the hospital, up to 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2021
- Study start1 Apr 2021
- Primary completion12 Jun 2023
- Study completion12 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (41)Papers the sponsor has linked to this study.
- Other trials for Covid19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 394 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University
- Sponsor type
- University, hospital or other
- Collaborators
- Innovative Medicines Initiative
- Responsible party
- Sponsor
- Investigators
- Philippe Lambin, Prof. Dr., Principal investigator, Head of Department of Precision Medicine, Maastricht University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04750330
- Sponsor's protocol ID
- COVIDmtDNA1.0
- Acronym
- mtDNA-COVID
- Status last verified
- Jun 2023
- First submitted
- 26 Jan 2021
- Last updated
- 15 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Siordia JA Jr. Epidemiology and clinical features of COVID-19: A review of current literature. J Clin Virol. 2020 Jun;127:104357. doi: 10.1016/j.jcv.2020.104357. Epub 2020 Apr 10.
PubMed 32305884Bhopal SS, Bhopal R. Sex differential in COVID-19 mortality varies markedly by age. Lancet. 2020 Aug 22;396(10250):532-533. doi: 10.1016/S0140-6736(20)31748-7. Epub 2020 Aug 13. No abstract available.
PubMed 32798449Sheehy LM. Considerations for Postacute Rehabilitation for Survivors of COVID-19. JMIR Public Health Surveill. 2020 May 8;6(2):e19462. doi: 10.2196/19462.
PubMed 32369030Hosey MM, Needham DM. Survivorship after COVID-19 ICU stay. Nat Rev Dis Primers. 2020 Jul 15;6(1):60. doi: 10.1038/s41572-020-0201-1.
PubMed 32669623Li X, Zhou TC, Wu CH, Tao LL, Bi R, Chen LJ, Deng DY, Liu C, Otecko NO, Tang Y, Lai X, Zhang L, Wei J. Correlations between mitochondrial DNA haplogroup D5 and chronic hepatitis B virus infection in Yunnan, China. Sci Rep. 2018 Jan 17;8(1):869. doi: 10.1038/s41598-018-19184-6.
PubMed 29343698Zhang AM, Hu QX, Liu FL, Bi R, Yang BQ, Zhang W, Guo H, Logan I, Zheng YT, Yao YG. Mitochondrial DNA Haplogroup A Decreases the Risk of Drug Addiction but Conversely Increases the Risk of HIV-1 Infection in Chinese Addicts. Mol Neurobiol. 2016 Aug;53(6):3873-3881. doi: 10.1007/s12035-015-9323-y. Epub 2015 Jul 11.
PubMed 26162319Lai JH, Luo SF, Ho LJ. Operation of mitochondrial machinery in viral infection-induced immune responses. Biochem Pharmacol. 2018 Oct;156:348-356. doi: 10.1016/j.bcp.2018.08.044. Epub 2018 Aug 31.
PubMed 30172712Wu IC, Lin CC, Liu CS, Hsu CC, Chen CY, Hsiung CA. Interrelations Between Mitochondrial DNA Copy Number and Inflammation in Older Adults. J Gerontol A Biol Sci Med Sci. 2017 Jul 1;72(7):937-944. doi: 10.1093/gerona/glx033.
PubMed 28329339Malik AN, Parsade CK, Ajaz S, Crosby-Nwaobi R, Gnudi L, Czajka A, Sivaprasad S. Altered circulating mitochondrial DNA and increased inflammation in patients with diabetic retinopathy. Diabetes Res Clin Pract. 2015 Dec;110(3):257-65. doi: 10.1016/j.diabres.2015.10.006. Epub 2015 Oct 22.
PubMed 26625720Clohisey S, Baillie JK. Host susceptibility to severe influenza A virus infection. Crit Care. 2019 Sep 5;23(1):303. doi: 10.1186/s13054-019-2566-7.
PubMed 31488196Li B, Clohisey SM, Chia BS, Wang B, Cui A, Eisenhaure T, Schweitzer LD, Hoover P, Parkinson NJ, Nachshon A, Smith N, Regan T, Farr D, Gutmann MU, Bukhari SI, Law A, Sangesland M, Gat-Viks I, Digard P, Vasudevan S, Lingwood D, Dockrell DH, Doench JG, Baillie JK, Hacohen N. Genome-wide CRISPR screen identifies host dependency factors for influenza A virus infection. Nat Commun. 2020 Jan 9;11(1):164. doi: 10.1038/s41467-019-13965-x.
PubMed 31919360Chocron ES, Munkacsy E, Pickering AM. Cause or casualty: The role of mitochondrial DNA in aging and age-associated disease. Biochim Biophys Acta Mol Basis Dis. 2019 Feb 1;1865(2):285-297. doi: 10.1016/j.bbadis.2018.09.035. Epub 2018 Nov 9.
PubMed 30419337Carter-Timofte ME, Jorgensen SE, Freytag MR, Thomsen MM, Brinck Andersen NS, Al-Mousawi A, Hait AS, Mogensen TH. Deciphering the Role of Host Genetics in Susceptibility to Severe COVID-19. Front Immunol. 2020 Jun 30;11:1606. doi: 10.3389/fimmu.2020.01606. eCollection 2020.
PubMed 32695122Ovsyannikova IG, Haralambieva IH, Crooke SN, Poland GA, Kennedy RB. The role of host genetics in the immune response to SARS-CoV-2 and COVID-19 susceptibility and severity. Immunol Rev. 2020 Jul;296(1):205-219. doi: 10.1111/imr.12897. Epub 2020 Jul 13.
PubMed 32658335Benetti E, Tita R, Spiga O, Ciolfi A, Birolo G, Bruselles A, Doddato G, Giliberti A, Marconi C, Musacchia F, Pippucci T, Torella A, Trezza A, Valentino F, Baldassarri M, Brusco A, Asselta R, Bruttini M, Furini S, Seri M, Nigro V, Matullo G, Tartaglia M, Mari F; GEN-COVID Multicenter Study; Renieri A, Pinto AM. ACE2 gene variants may underlie interindividual variability and susceptibility to COVID-19 in the Italian population. Eur J Hum Genet. 2020 Nov;28(11):1602-1614. doi: 10.1038/s41431-020-0691-z. Epub 2020 Jul 17.
PubMed 32681121
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mitochondrial DNA and Nuclear SNPs to Predict Severity of COVID-19 Infection
- ClinicalTrials.gov ID
- NCT04750330
- Acronym / sponsor ID
- mtDNA-COVID / COVIDmtDNA1.0
- Conditions
- Covid19
- Keywords
- COVID-19, Severity, mtDNA, SARS-CoV-2 Infection, Radiomics
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 394 participants (actual)
- Lead sponsor
- Maastricht UniversityUniversity, hospital or other
- Collaborators
- Innovative Medicines Initiative
- Study start
- 1 Apr 2021 (actual)
- Primary completion
- 12 Jun 2023 (actual)
- Study completion
- 12 Jun 2023 (actual)
- First posted
- 11 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Severe COVID-19 | – | –Patients, diagnosed with COVID-19, who were admitted to the Intensive Care Unit (ICU) during hospitalisation |
| Non-severe COVID-19 | – | –Patients, diagnosed with COVID-19, who were admitted to the hospital but NOT to the Intensive Care Unit (ICU) during hospitalisation |
| Minor COVID-19 | – | –Patients, diagnosed with COVID-19, who were NOT admitted to the hospital and could recover at home |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (2 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
COVID-19 Severity
Time frame: When the patient is discharged from the hospital, up to 2 months
Severity of COVID-19 classified as 'Severe', 'Non-severe' and 'Minor'
1 secondary outcome
Overall survival of the hospitalized population
Time frame: When the patient is discharged from the hospital, up to 2 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2023.
- Background: PubMed 32305884Siordia JA Jr. Epidemiology and clinical features of COVID-19: A review of current literature. J Clin Virol. 2020 Jun;127:104357. doi: 10.1016/j.jcv.2020.104357. Epub 2020 Apr 10.
- Background: PubMed 32798449Bhopal SS, Bhopal R. Sex differential in COVID-19 mortality varies markedly by age. Lancet. 2020 Aug 22;396(10250):532-533. doi: 10.1016/S0140-6736(20)31748-7. Epub 2020 Aug 13. No abstract available.
- Background: PubMed 32369030Sheehy LM. Considerations for Postacute Rehabilitation for Survivors of COVID-19. JMIR Public Health Surveill. 2020 May 8;6(2):e19462. doi: 10.2196/19462.
- Background: PubMed 32669623Hosey MM, Needham DM. Survivorship after COVID-19 ICU stay. Nat Rev Dis Primers. 2020 Jul 15;6(1):60. doi: 10.1038/s41572-020-0201-1.
- Background: PubMed 29343698Li X, Zhou TC, Wu CH, Tao LL, Bi R, Chen LJ, Deng DY, Liu C, Otecko NO, Tang Y, Lai X, Zhang L, Wei J. Correlations between mitochondrial DNA haplogroup D5 and chronic hepatitis B virus infection in Yunnan, China. Sci Rep. 2018 Jan 17;8(1):869. doi: 10.1038/s41598-018-19184-6.
- Background: PubMed 26162319Zhang AM, Hu QX, Liu FL, Bi R, Yang BQ, Zhang W, Guo H, Logan I, Zheng YT, Yao YG. Mitochondrial DNA Haplogroup A Decreases the Risk of Drug Addiction but Conversely Increases the Risk of HIV-1 Infection in Chinese Addicts. Mol Neurobiol. 2016 Aug;53(6):3873-3881. doi: 10.1007/s12035-015-9323-y. Epub 2015 Jul 11.
- Background: PubMed 30172712Lai JH, Luo SF, Ho LJ. Operation of mitochondrial machinery in viral infection-induced immune responses. Biochem Pharmacol. 2018 Oct;156:348-356. doi: 10.1016/j.bcp.2018.08.044. Epub 2018 Aug 31.
- Background: PubMed 28329339Wu IC, Lin CC, Liu CS, Hsu CC, Chen CY, Hsiung CA. Interrelations Between Mitochondrial DNA Copy Number and Inflammation in Older Adults. J Gerontol A Biol Sci Med Sci. 2017 Jul 1;72(7):937-944. doi: 10.1093/gerona/glx033.
- Background: PubMed 26625720Malik AN, Parsade CK, Ajaz S, Crosby-Nwaobi R, Gnudi L, Czajka A, Sivaprasad S. Altered circulating mitochondrial DNA and increased inflammation in patients with diabetic retinopathy. Diabetes Res Clin Pract. 2015 Dec;110(3):257-65. doi: 10.1016/j.diabres.2015.10.006. Epub 2015 Oct 22.
- Background: PubMed 31488196Clohisey S, Baillie JK. Host susceptibility to severe influenza A virus infection. Crit Care. 2019 Sep 5;23(1):303. doi: 10.1186/s13054-019-2566-7.
- Background: PubMed 31919360Li B, Clohisey SM, Chia BS, Wang B, Cui A, Eisenhaure T, Schweitzer LD, Hoover P, Parkinson NJ, Nachshon A, Smith N, Regan T, Farr D, Gutmann MU, Bukhari SI, Law A, Sangesland M, Gat-Viks I, Digard P, Vasudevan S, Lingwood D, Dockrell DH, Doench JG, Baillie JK, Hacohen N. Genome-wide CRISPR screen identifies host dependency factors for influenza A virus infection. Nat Commun. 2020 Jan 9;11(1):164. doi: 10.1038/s41467-019-13965-x.
- Background: PubMed 30419337Chocron ES, Munkacsy E, Pickering AM. Cause or casualty: The role of mitochondrial DNA in aging and age-associated disease. Biochim Biophys Acta Mol Basis Dis. 2019 Feb 1;1865(2):285-297. doi: 10.1016/j.bbadis.2018.09.035. Epub 2018 Nov 9.
- European RadiologyLink provided by the sponsor.
- WHO Coronavirus Disease (COVID-19) DashboardLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Philippe Lambin, Prof. Dr. principal investigator
Head of Department of Precision Medicine, Maastricht University
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Covid19, run by Maastricht University at 3 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Greece, Italy, Portugal. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
COVID-19 Severity (time frame: When the patient is discharged from the hospital, up to 2 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04750330, which also lists 41 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2023.