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
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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
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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
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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 |
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