Coronavirus Disease 2019NCT04401436
COVID-19 Associated Lymphopenia Pathogenesis Study in Blood
An observational study of Coronavirus Disease 2019, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in United States.
Trial summary
Background: COVID-19 is an acute respiratory syndrome. One symptom of COVID-19 is a reduction in the number of cells called lymphocytes in the blood. Lymphocytes are a type of white blood cell that fights infections. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Coronavirus Disease 2019
- How many people
- 240 participants
- Where
- 3 sitesUnited States
- Study dates
- 22 May 2020to 24 Feb 2025
- 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: COVID 19 positive and recovered patients from inpatient settings at the NIH CC and Georgetown University Medical Center, and the local community for COVID 19 recovered patients.
Who may be able to join
- Aged >=18 years.
- Diagnosis of COVID-19 via molecular assay or other commercial or public health assay.
- Meets one of the following criteria for COVID-19:
- Group A, mild clinical presentation: asymptomatic to oxygen requirements <-4L nasal cannula (NC).
- Group B, moderate clinical presentation: oxygen requirements >4L NC to <=50% fraction of inspired oxygen (FiO2) on high-flow oxygen devices.
- Group C, severe clinical presentation: non-invasive ventilation with oxygen requirements >50% FiO2 on high-flow oxygen devices, any other modality of non-invasive ventilation, or mechanical ventilation.
- Group D, recovered: meets CDC criteria for discontinuation of transmission-based precautions and disposition of patients with COVID-19 in healthcare settings. Enrollment will occur at least 30 days after the above criteria were met.
- Able to provide informed consent.
Who cannot join
- Individuals meeting any of the following criteria will be excluded from study participation:
- Documented history of hemoglobin from most recent blood draw <7g/dL if known.
- Any condition that, in the opinion of the investigator, contraindicates participation in this study.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007
MedStar Health Research Institute: Washington Hospital Medical Center
Washington D.C., District of Columbia, 20010
About this study
Official title: COVID-19-Associated Lymphopenia Pathogenesis Study in Blood
Background:
COVID-19 is an acute respiratory syndrome. One symptom of COVID-19 is a reduction in the number of cells called lymphocytes in the blood. Lymphocytes are a type of white blood cell that fights infections. With fewer lymphocytes, the body cannot effectively fight back against SARS CoV-2, the virus that causes COVID-19. Researchers want to better understand how SARS-CoV-2 affects these blood cells. This information may give them ideas for new treatments.
Read more
Objective:
To learn more about how SARS-CoV-2 affects lymphocytes, the immune, and the blood clotting system.
Eligibility:
Adults age 18 and older who either currently have COVID-19 or have recently recovered from it
Design:
Participants will give a blood sample. For this, a needle is used to collect blood from an arm vein. For participants who have a central line, blood will be collected through that instead.
Participants medical records related to COVID-19 will be reviewed.
Participants who have recovered from COVID-19 will be asked to undergo leukapheresis to collect white blood cells. For this, blood is taken from a needle placed in one arm. A machine separates out the white blood cells. The rest of the blood is returned to the participant through a needle placed in the other arm. This takes about 2-3 hours.
Recovered participants may have material collected from inside the nostrils and/or rectum. This is done by gently rubbing the area with a sterile cotton swab.
Recovered participants may have an echocardiogram to look at their heart. For this, a small probe is held against the chest to get pictures of the heart from different angles. This takes less than 30 minutes.
Participation lasts 1-2 days on most cases and may be split in a few visits for recovered patients if leukapheresis and echocardiogram are done.
...
Read the detailed description
Coronavirus disease 2019 (COVID-19) is an acute respiratory syndrome caused by the novel coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The emergence of SARS-CoV-2 has led to a pandemic with a wide range of manifestations. One of the hallmarks of severe illness is the presence of elevated levels of inflammatory biomarkers, coagulopathy, and lymphopenia. Lymphopenia is a robust and consistent predictor of mortality in COVID-19. Understanding the intersection of inflammation, complement activation, endothelial damage, and coagulation is critical to a better understanding of COVID-19 pathogenesis.
This is a multisite study that will conducted at the National Institutes of Health Clinical Center and other local hospitals. We will recruit patients with mild to severe COVID-19, as well as patients who have recently recovered from the disease. Participants will have blood drawn via venipuncture or available venous access and optional nasal and/or rectal swabs, with optional leukapheresis and echocardiogram for recovered patients. Leftover clinical specimens may also be used for research. Blood will be used for genetic testing, lymphocyte phenotyping, soluble biomarker analysis, and other research tests. Clinical and laboratory data from routine care
(eg, basic demographic information, vital signs, medications, clinical labs, and radiologic imaging) will also be collected and up to two follow up visits may be done for clinical purposes. Participants may re-enroll in the study after recovery from infection as recovered participants or if they experience a new infection.
- Conditions
- Coronavirus Disease 2019
- Keywords
- SARS-CoV-2, Lymphopenia, Coagulopathy, Cytokines, Natural History
- Medical subject headings
- COVID-19, Lymphopenia, Hemostatic Disorders
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 |
|---|---|---|
| COVID 19 patients | Study participants will be adults who either have COVID-19 or who have recently recovered from the disease(recovered per Centers for Disease Control and Prevention guidelines). |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of lymphocyte subsets in patients with COVID-19 at various stages of disease, including recovery.
To characterize lymphopenia and immunologic phenotypes and inflammatory responses including inflammasome responses and coagulopathy in patients with COVID-19.
Measured: Throughout the study
Secondary outcomes (1)
Evaluation of inflammatory pathways that may contribute to COVID-19 disease pathogenesis.
- Correlation of lymphopenia, immunologic phenotypes, and inflammatory responses with clinical outcomes. 2. Characterization of complement activation in patients with COVID-19. 3. Evaluation of activation-induced cell death and activated T cell autonomous death through measurement of intracellular reactive oxygen species in monocyte, natural killer (NK), and T cell subsets in peripheral blood and correlation with double stranded (ds)-DNA damage (gamma-H2AX), FAS/FasL, BCL-2, caspase-1 activation, and activation-induced proliferation. 4. Evaluation of homing receptors to lymphoid, skin, and mucosal surfaces on B and T cells and correlate with ACE2, bradykinin, and homing chemokine levels.
Measured: Throughout the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2020
- Study start22 May 2020
- Primary completion20 Feb 2025
- Study completion24 Feb 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Coronavirus Disease 2019Studies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 240 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Irini Sereti, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04401436
- Sponsor's protocol ID
- 200111
- Other IDs
- 20-I-0111
- Status last verified
- 8 Sep 2026
- First submitted
- 22 May 2020
- Last updated
- 10 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No plans at this time.
Publications
Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, Wang T, Zhang X, Chen H, Yu H, Zhang X, Zhang M, Wu S, Song J, Chen T, Han M, Li S, Luo X, Zhao J, Ning Q. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020 May 1;130(5):2620-2629. doi: 10.1172/JCI137244.
PubMed 32217835Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11.
PubMed 32171076Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W; China Novel Coronavirus Investigating and Research Team. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020 Feb 20;382(8):727-733. doi: 10.1056/NEJMoa2001017. Epub 2020 Jan 24.
PubMed 31978945Lucena Lage S, Rocco JM, Oguz C, Otaizo-Carrasquero F, Rupert A, Boswell KL, Epling BP, Cook L, Pinheiro Amaral E, Laidlaw E, Galindo F, Koup RA, Kumar P, Poon R, Wortmann GW, Lisco A, Manion M, Sereti I. Inflammasome Activation and Oxidative Stress in SARS-CoV-2 Infection and Symptomatic Rebound. J Infect Dis. 2026 May 15;233(5):e1285-e1297. doi: 10.1093/infdis/jiag037.
PubMed 41557260Epling BP, Rocco JM, Boswell KL, Laidlaw E, Galindo F, Kellogg A, Das S, Roder A, Ghedin E, Kreitman A, Dewar RL, Kelly SEM, Kalish H, Rehman T, Highbarger J, Rupert A, Kocher G, Holbrook MR, Lisco A, Manion M, Koup RA, Sereti I. Clinical, Virologic, and Immunologic Evaluation of Symptomatic Coronavirus Disease 2019 Rebound Following Nirmatrelvir/Ritonavir Treatment. Clin Infect Dis. 2023 Feb 18;76(4):573-581. doi: 10.1093/cid/ciac663.
PubMed 36200701
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- COVID-19-Associated Lymphopenia Pathogenesis Study in Blood
- ClinicalTrials.gov ID
- NCT04401436
- Acronym / sponsor ID
- 200111
- Conditions
- Coronavirus Disease 2019
- Keywords
- SARS-CoV-2, Lymphopenia, Coagulopathy, Cytokines, Natural History
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 240 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 22 May 2020 (actual)
- Primary completion
- 20 Feb 2025 (actual)
- Study completion
- 24 Feb 2025 (actual)
- First posted
- 26 May 2020 (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.
Background:
COVID-19 is an acute respiratory syndrome. One symptom of COVID-19 is a reduction in the number of cells called lymphocytes in the blood. Lymphocytes are a type of white blood cell that fights infections. With fewer lymphocytes, the body cannot effectively fight back against SARS CoV-2, the virus that causes COVID-19. Researchers want to better understand how SARS-CoV-2 affects these blood cells. This information may give them ideas for new treatments.
Objective:
To learn more about how SARS-CoV-2 affects lymphocytes, the immune, and the blood clotting system.
Eligibility:
Adults age 18 and older who either currently have COVID-19 or have recently recovered from it
Design:
Participants will give a blood sample. For this, a needle is used to collect blood from an arm vein. For participants who have a central line, blood will be collected through that instead.
Participants medical records related to COVID-19 will be reviewed.
Participants who have recovered from COVID-19 will be asked to undergo leukapheresis to collect white blood cells. For this, blood is taken from a needle placed in one arm. A machine separates out the white blood cells. The rest of the blood is returned to the participant through a needle placed in the other arm. This takes about 2-3 hours.
Recovered participants may have material collected from inside the nostrils and/or rectum. This is done by gently rubbing the area with a sterile cotton swab.
Recovered participants may have an echocardiogram to look at their heart. For this, a small probe is held against the chest to get pictures of the heart from different angles. This takes less than 30 minutes.
Participation lasts 1-2 days on most cases and may be split in a few visits for recovered patients if leukapheresis and echocardiogram are done.
...
Detailed description
Coronavirus disease 2019 (COVID-19) is an acute respiratory syndrome caused by the novel coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The emergence of SARS-CoV-2 has led to a pandemic with a wide range of manifestations. One of the hallmarks of severe illness is the presence of elevated levels of inflammatory biomarkers, coagulopathy, and lymphopenia. Lymphopenia is a robust and consistent predictor of mortality in COVID-19. Understanding the intersection of inflammation, complement activation, endothelial damage, and coagulation is critical to a better understanding of COVID-19 pathogenesis.
This is a multisite study that will conducted at the National Institutes of Health Clinical Center and other local hospitals. We will recruit patients with mild to severe COVID-19, as well as patients who have recently recovered from the disease. Participants will have blood drawn via venipuncture or available venous access and optional nasal and/or rectal swabs, with optional leukapheresis and echocardiogram for recovered patients. Leftover clinical specimens may also be used for research. Blood will be used for genetic testing, lymphocyte phenotyping, soluble biomarker analysis, and other research tests. Clinical and laboratory data from routine care
(eg, basic demographic information, vital signs, medications, clinical labs, and radiologic imaging) will also be collected and up to two follow up visits may be done for clinical purposes. Participants may re-enroll in the study after recovery from infection as recovered participants or if they experience a new infection.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| COVID 19 patients | – | –Study participants will be adults who either have COVID-19 or who have recently recovered from the disease(recovered per Centers for Disease Control and Prevention guidelines). |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- COVID 19 positive and recovered patients from inpatient settings at the NIH CC and Georgetown University Medical Center, and the local community for COVID 19 recovered patients.
Key inclusion criteria (8 listed)
Key exclusion criteria (3 listed)
- Individuals meeting any of the following criteria will be excluded from study participation:
- Documented history of hemoglobin from most recent blood draw <7g/dL if known.
- Any condition that, in the opinion of the investigator, contraindicates participation in this study.
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
Evaluation of lymphocyte subsets in patients with COVID-19 at various stages of disease, including recovery.
Time frame: Throughout the study
To characterize lymphopenia and immunologic phenotypes and inflammatory responses including inflammasome responses and coagulopathy in patients with COVID-19.
1 secondary outcome
Evaluation of inflammatory pathways that may contribute to COVID-19 disease pathogenesis.
Time frame: Throughout the study
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 10 Sep 2026.
- Background: PubMed 32217835Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, Wang T, Zhang X, Chen H, Yu H, Zhang X, Zhang M, Wu S, Song J, Chen T, Han M, Li S, Luo X, Zhao J, Ning Q. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020 May 1;130(5):2620-2629. doi: 10.1172/JCI137244.
- Background: PubMed 32171076Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11.
- Background: PubMed 31978945Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W; China Novel Coronavirus Investigating and Research Team. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020 Feb 20;382(8):727-733. doi: 10.1056/NEJMoa2001017. Epub 2020 Jan 24.
- Derived from this study: PubMed 41557260Lucena Lage S, Rocco JM, Oguz C, Otaizo-Carrasquero F, Rupert A, Boswell KL, Epling BP, Cook L, Pinheiro Amaral E, Laidlaw E, Galindo F, Koup RA, Kumar P, Poon R, Wortmann GW, Lisco A, Manion M, Sereti I. Inflammasome Activation and Oxidative Stress in SARS-CoV-2 Infection and Symptomatic Rebound. J Infect Dis. 2026 May 15;233(5):e1285-e1297. doi: 10.1093/infdis/jiag037.
- Derived from this study: PubMed 36200701Epling BP, Rocco JM, Boswell KL, Laidlaw E, Galindo F, Kellogg A, Das S, Roder A, Ghedin E, Kreitman A, Dewar RL, Kelly SEM, Kalish H, Rehman T, Highbarger J, Rupert A, Kocher G, Holbrook MR, Lisco A, Manion M, Koup RA, Sereti I. Clinical, Virologic, and Immunologic Evaluation of Symptomatic Coronavirus Disease 2019 Rebound Following Nirmatrelvir/Ritonavir Treatment. Clin Infect Dis. 2023 Feb 18;76(4):573-581. doi: 10.1093/cid/ciac663.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No. No plans at this time.
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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.
Irini Sereti, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Coronavirus Disease 2019, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in United States.
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 8 inclusion and 3 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 10 Sep 2026. 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 United States. 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?
Evaluation of lymphocyte subsets in patients with COVID-19 at various stages of disease, including recovery. (time frame: Throughout the study). 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 NCT04401436, which also lists 5 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 10 Sep 2026.