COVID-19 Clinical Trial
Official title:
Study of Immune-mediated Mechanisms in Patients Tested Positive for SARS-CoV-2: Phenotypic and Functional Analysis of Monocytes and NK Cells in the Blood of Subjects Affected by Covid 19
NCT number | NCT04375176 |
Other study ID # | 67/2020 |
Secondary ID | |
Status | Recruiting |
Phase | |
First received | |
Last updated | |
Start date | April 27, 2020 |
Est. completion date | October 31, 2020 |
SARS-CoV-2 belong to beta-coronavirus family and its transmission route and symptoms follow
those of all community-acquired coronaviruses. The main difference of the novel Coronavirus
is the higher mortality rate, that is around 3%.
Death rate is over 1% only for patients over 50 years old, whereas until 40 years old is
under 0,4%. No fatalities are declared among children under 10 years old to date. Death rate
is almost double for male rather than female. This distribution of mortality rate according
to age of infected patients could be only partially ascribed to other comorbidities in
addition to great age. In fact, patients with no pre-existing conditions have however a case
fatality rate of 0,9%.
The almost null rate of severe illness in children and generally in patients younger than 40
years old is quite un-explicable. Infant, children and young people could be infected but
infection is rapidly self-limited or without symptoms. Older patients undergo severe lung
injury as consequence of an immune response that is late in coming.
Possible explanation of these phenomena could be something, which assure ability to prompt
response to SARS-CoV-2 in younger people independently from the novelty of the virus itself.
It would seem to be that younger people are already sensitized to the antigens of the virus
without a previous contact.
This immunity is not really specific, but "partially specific" for many antigens of the
virus, however able to limit the infection in the organism. Something stimulated the immune
system and it scattered immunity against more and more antigens present. Children are the age
group mostly exposed to all community-circulating viruses.
This immunity is not persistent but progressively fade out. It protects from the age of two,
when the hypothetical stimulation occurs, to the fifth decade because of its slow decrease.
The only external stimulation, which healthy people receive are vaccines. All vaccinations
and especially tetanic, diphtheria toxoids and inactivated bacteria as pertussis could
stimulate immune system. They develop the specific immunity but generate also a sprouting
immunity against antigens in transit, as coronaviruses and other community-circulating
viruses.
The developed immunity gives some protection against multiple viral infection for years until
the natural fade out.
After the fifth decade, that immunity is slower to be recall and reactivated. Additionally,
transplant recipients and HIV infected patients, which have an immune system inhibited,
unexpectedly, do not seem to suffer the worst complications of SARS-CoV-2 infection. An
immune system imbalance could be play a pivotal role during the reaction to the virus,
limiting destructive consequences of excessive inflammation.
According to the medical hypothesis on which the protocol is based on, young people could
benefit from a functional adaptation of innate immune cells induced through epigenetic
reprogramming and, especially, a pre-existing "partially specific" immunity to the community
viruses caused by "bystander effect" of preceding vaccinations. In this study, we will
explore the main differences existing among patients infected by SARS-CoV-2 who experience
the illness at different degree of severity. We suppose to recognize different populations of
patients, each one with a specific immunological pattern. It could differ in terms of
cytokines, soluble factors serum level and immune cells activity both of the innate
compartment and of the acquired one. The proof of a role of these immunological phenomena in
the pathogenesis of Covid-19 are bases for implementation of therapeutic immunomodulatory
treatments. In addition, the definition of an immunological risk profile could tailor
established therapies to each kind of patient.
Status | Recruiting |
Enrollment | 150 |
Est. completion date | October 31, 2020 |
Est. primary completion date | June 30, 2020 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: - Age: = 18 - SARS-CoV-2 documented infection Exclusion Criteria: - Refusal to the sign the agreement (informed consent); - Inability to sign the agreement; - HIV, HCV, HBV (positive to HBsAg) infection. |
Country | Name | City | State |
---|---|---|---|
Italy | ATS Insubria | Varese |
Lead Sponsor | Collaborator |
---|---|
Università degli Studi dell'Insubria |
Italy,
Bassani B, Baci D, Gallazzi M, Poggi A, Bruno A, Mortara L. Natural Killer Cells as Key Players of Tumor Progression and Angiogenesis: Old and Novel Tools to Divert Their Pro-Tumor Activities into Potent Anti-Tumor Effects. Cancers (Basel). 2019 Apr 1;11(4). pii: E461. doi: 10.3390/cancers11040461. Review. — View Citation
Benn CS, Netea MG, Selin LK, Aaby P. A small jab - a big effect: nonspecific immunomodulation by vaccines. Trends Immunol. 2013 Sep;34(9):431-9. doi: 10.1016/j.it.2013.04.004. Epub 2013 May 14. Review. — View Citation
Bruno A, Bassani B, D'Urso DG, Pitaku I, Cassinotti E, Pelosi G, Boni L, Dominioni L, Noonan DM, Mortara L, Albini A. Angiogenin and the MMP9-TIMP2 axis are up-regulated in proangiogenic, decidual NK-like cells from patients with colorectal cancer. FASEB J. 2018 Oct;32(10):5365-5377. doi: 10.1096/fj.201701103R. Epub 2018 May 15. — View Citation
Bruno A, Focaccetti C, Pagani A, Imperatori AS, Spagnoletti M, Rotolo N, Cantelmo AR, Franzi F, Capella C, Ferlazzo G, Mortara L, Albini A, Noonan DM. The proangiogenic phenotype of natural killer cells in patients with non-small cell lung cancer. Neoplasia. 2013 Feb;15(2):133-42. — View Citation
G. Ietto, SARS - CoV -2: reasons of epidemiology of severe ill disease cases andtherapeutic approach using trivalent vaccine (tetanus, diphtheria and Bordetella pertussis), Medical Hypotheses(2020), doi: https://doi.org/10.1016/j.mehy.2020.109779
Morandi F, Horenstein AL, Chillemi A, Quarona V, Chiesa S, Imperatori A, Zanellato S, Mortara L, Gattorno M, Pistoia V, Malavasi F. CD56brightCD16- NK Cells Produce Adenosine through a CD38-Mediated Pathway and Act as Regulatory Cells Inhibiting Autologous CD4+ T Cell Proliferation. J Immunol. 2015 Aug 1;195(3):965-72. doi: 10.4049/jimmunol.1500591. Epub 2015 Jun 19. — View Citation
Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW, Goerdt S, Gordon S, Hamilton JA, Ivashkiv LB, Lawrence T, Locati M, Mantovani A, Martinez FO, Mege JL, Mosser DM, Natoli G, Saeij JP, Schultze JL, Shirey KA, Sica A, Suttles J, Udalova I, van Ginderachter JA, Vogel SN, Wynn TA. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity. 2014 Jul 17;41(1):14-20. doi: 10.1016/j.immuni.2014.06.008. — View Citation
Netea MG, Domínguez-Andrés J, Barreiro LB, Chavakis T, Divangahi M, Fuchs E, Joosten LAB, van der Meer JWM, Mhlanga MM, Mulder WJM, Riksen NP, Schlitzer A, Schultze JL, Stabell Benn C, Sun JC, Xavier RJ, Latz E. Defining trained immunity and its role in health and disease. Nat Rev Immunol. 2020 Mar 4. doi: 10.1038/s41577-020-0285-6. [Epub ahead of print] Review. — View Citation
Noonan DM, De Lerma Barbaro A, Vannini N, Mortara L, Albini A. Inflammation, inflammatory cells and angiogenesis: decisions and indecisions. Cancer Metastasis Rev. 2008 Mar;27(1):31-40. Review. — View Citation
Parisi L, Gini E, Baci D, Tremolati M, Fanuli M, Bassani B, Farronato G, Bruno A, Mortara L. Macrophage Polarization in Chronic Inflammatory Diseases: Killers or Builders? J Immunol Res. 2018 Jan 14;2018:8917804. doi: 10.1155/2018/8917804. eCollection 2018. Review. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Immune cells activity | Scientists' hypothesis is that monocytes, NK, CD4 AND CD8 T cells, in patients with severe infection to SARS-CoV-2, show an impairment in their function: cells reveal an overpowering hyperactivity that provokes a pathologic inflammatory response with a massive production of proinflammatory cytokine, edema and pulmonary fibrosis. | 6 months | |
Secondary | Protective factors and new therapeutic strategies | The secondary objectives are to correlate clinical data and vaccination history with laboratory immune pattern to identify protective factors for Covid 19 and open paths for new therapeutic strategies. | 6 months |
Status | Clinical Trial | Phase | |
---|---|---|---|
Withdrawn |
NCT06065033 -
Exercise Interventions in Post-acute Sequelae of Covid-19
|
N/A | |
Completed |
NCT06267534 -
Mindfulness-based Mobile Applications Program
|
N/A | |
Completed |
NCT05047601 -
A Study of a Potential Oral Treatment to Prevent COVID-19 in Adults Who Are Exposed to Household Member(s) With a Confirmed Symptomatic COVID-19 Infection
|
Phase 2/Phase 3 | |
Recruiting |
NCT04481633 -
Efficacy of Pre-exposure Treatment With Hydroxy-Chloroquine on the Risk and Severity of COVID-19 Infection
|
N/A | |
Recruiting |
NCT05323760 -
Functional Capacity in Patients Post Mild COVID-19
|
N/A | |
Completed |
NCT04537949 -
A Trial Investigating the Safety and Effects of One BNT162 Vaccine Against COVID-19 in Healthy Adults
|
Phase 1/Phase 2 | |
Completed |
NCT04612972 -
Efficacy, Safety and Immunogenicity of Inactivated SARS-CoV-2 Vaccines (Vero Cell) to Prevent COVID-19 in Healthy Adult Population In Peru Healthy Adult Population In Peru
|
Phase 3 | |
Recruiting |
NCT05494424 -
Cognitive Rehabilitation in Post-COVID-19 Condition
|
N/A | |
Active, not recruiting |
NCT06039449 -
A Study to Investigate the Prevention of COVID-19 withVYD222 in Adults With Immune Compromise and in Participants Aged 12 Years or Older Who Are at Risk of Exposure to SARS-CoV-2
|
Phase 3 | |
Enrolling by invitation |
NCT05589376 -
You and Me Healthy
|
||
Completed |
NCT05158816 -
Extracorporal Membrane Oxygenation for Critically Ill Patients With COVID-19
|
||
Recruiting |
NCT04341506 -
Non-contact ECG Sensor System for COVID19
|
||
Completed |
NCT04384445 -
Zofin (Organicell Flow) for Patients With COVID-19
|
Phase 1/Phase 2 | |
Completed |
NCT04512079 -
FREEDOM COVID-19 Anticoagulation Strategy
|
Phase 4 | |
Completed |
NCT05975060 -
A Study to Evaluate the Safety and Immunogenicity of an (Omicron Subvariant) COVID-19 Vaccine Booster Dose in Previously Vaccinated Participants and Unvaccinated Participants.
|
Phase 2/Phase 3 | |
Active, not recruiting |
NCT05542862 -
Booster Study of SpikoGen COVID-19 Vaccine
|
Phase 3 | |
Withdrawn |
NCT05621967 -
Phonation Therapy to Improve Symptoms and Lung Physiology in Patients Referred for Pulmonary Rehabilitation
|
N/A | |
Terminated |
NCT05487040 -
A Study to Measure the Amount of Study Medicine in Blood in Adult Participants With COVID-19 and Severe Kidney Disease
|
Phase 1 | |
Terminated |
NCT04498273 -
COVID-19 Positive Outpatient Thrombosis Prevention in Adults Aged 40-80
|
Phase 3 | |
Active, not recruiting |
NCT06033560 -
The Effect of Non-invasive Respiratory Support on Outcome and Its Risks in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2)-Related Hypoxemic Respiratory Failure
|