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Monocytes and NK Cells Activity in Covid-19 Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT04375176
Recruitment Status : Unknown
Verified May 2020 by Ietto Giuseppe, Università degli Studi dell'Insubria.
Recruitment status was:  Recruiting
First Posted : May 5, 2020
Last Update Posted : May 5, 2020
Information provided by (Responsible Party):
Ietto Giuseppe, Università degli Studi dell'Insubria

Brief Summary:

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.

Condition or disease Intervention/treatment
COVID-19 Severe Acute Respiratory Syndrome Coronavirus 2 Immunomodulation Diagnostic Test: Study of immune-mediated mechanisms in patients tested positive for SARS-CoV-2

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Study Type : Observational
Estimated Enrollment : 150 participants
Observational Model: Case-Only
Time Perspective: Prospective
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
Actual Study Start Date : April 27, 2020
Estimated Primary Completion Date : June 30, 2020
Estimated Study Completion Date : October 31, 2020

Group/Cohort Intervention/treatment
Tested positive for SARS-CoV-2
Patients, tested positive for SARS-CoV-2, will be recruited in E.R. of the "Ospedale Di Circolo - ASST Settelaghi" Teaching Hospital in Varese.
Diagnostic Test: Study of immune-mediated mechanisms in patients tested positive for SARS-CoV-2
Phenotypic and functional analysis of monocytes and NK cells

Primary Outcome Measures :
  1. Immune cells activity [ Time Frame: 6 months ]
    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.

Secondary Outcome Measures :
  1. Protective factors and new therapeutic strategies [ Time Frame: 6 months ]
    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.

Biospecimen Retention:   Samples With DNA
Venous blood sample (15 mL in EDTA solution test tube).

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients tested positive for SARS-CoV-2

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04375176

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Contact: Giuseppe Ietto, M.D. +393398758024
Contact: Domenico Iovino, M.D. +393407308867

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ATS Insubria Recruiting
Varese, Italy, 21100
Contact: Giuseppe Ietto, M.D.    +393398758024   
Principal Investigator: Giuseppe Ietto, MD         
Principal Investigator: Lorenzo Mortara, Professor         
Sub-Investigator: Domenico Iovino, MD         
Sub-Investigator: Daniela Dalla Gasperina, Professor         
Principal Investigator: Giulio Carcano, Professor         
Sub-Investigator: Andreina Baj, MD         
Sub-Investigator: Walter Ageno, Professor         
Sub-Investigator: Francesco Acquati, Professor         
Sub-Investigator: Angelo Genoni, Dr         
Sub-Investigator: Denisa Baci, PhD         
Sub-Investigator: Matteo Gallazzi, PhD         
Sub-Investigator: Annarosaria De Vito, PhD         
Sub-Investigator: Elisa Monti, MD         
Sub-Investigator: Andrea Vigezzi, MD         
Sub-Investigator: Caterina Franchi, MD         
Sub-Investigator: Valentina Iori, MD         
Sub-Investigator: Federica Masci, MD         
Sponsors and Collaborators
Università degli Studi dell'Insubria
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Study Chair: Giulio Carcano, Professor Università degli Studi dell'Insubria
Principal Investigator: Giuseppe Ietto, M.D. Università degli Studi dell'Insubria
Principal Investigator: Lorenzo Mortara, Professor Università degli Studi dell'Insubria

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Ietto Giuseppe, Adjunct Professor, M.D., Università degli Studi dell'Insubria Identifier: NCT04375176    
Other Study ID Numbers: 67/2020
First Posted: May 5, 2020    Key Record Dates
Last Update Posted: May 5, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Severe Acute Respiratory Syndrome
Respiratory Tract Infections
Pneumonia, Viral
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases