Monocytes and NK Cells Activity in Covid-19 Patients

NCT04375176 | Unknown

• 1 other identifier: 67/2020
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

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.

Conditions

COVID-19; Severe Acute Respiratory Syndrome Coronavirus 2; Immunomodulation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Protective factors and new therapeutic strategies

  6 months

Study Arms (1)

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

Interventions

Study of immune-mediated mechanisms in patients tested positive for SARS-CoV-2 DIAGNOSTIC_TEST

Phenotypic and functional analysis of monocytes and NK cells

Tested positive for SARS-CoV-2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients tested positive for SARS-CoV-2

You may qualify if:

• Age: ≥ 18
• SARS-CoV-2 documented infection

You may not qualify if:

• Refusal to the sign the agreement (informed consent);
• Inability to sign the agreement;
• HIV, HCV, HBV (positive to HBsAg) infection.

Sponsors & Collaborators

• Università degli Studi dell'Insubria: lead

Study Sites (1)

ATS Insubria

Varese, 21100, Italy

RECRUITING

Related Publications (11)

• Ietto G. SARS - CoV-2: Reasons of epidemiology of severe ill disease cases and therapeutic approach using trivalent vaccine (tetanus, diphtheria and Bordetella pertussis). Med Hypotheses. 2020 Aug;141:109779. doi: 10.1016/j.mehy.2020.109779. Epub 2020 Apr 22.

  PMID: 32387756 BACKGROUND

• Netea MG, Dominguez-Andres 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 Jun;20(6):375-388. doi: 10.1038/s41577-020-0285-6. Epub 2020 Mar 4.

  PMID: 32132681 BACKGROUND

• 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.

  PMID: 25035950 BACKGROUND

• 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. doi: 10.1007/s10555-007-9108-5.

  PMID: 18087678 BACKGROUND

• 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.

  PMID: 29507865 BACKGROUND

• 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.

  PMID: 23680130 BACKGROUND

• 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. doi: 10.1593/neo.121758.

  PMID: 23441128 BACKGROUND

• 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.

  PMID: 29763380 BACKGROUND

• 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):461. doi: 10.3390/cancers11040461.

  PMID: 30939820 BACKGROUND

• 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.

  PMID: 26091716 BACKGROUND

• Ietto G, Mortara L, Dalla Gasperina D, Iovino D, Azzi L, Baj A, Ageno W, Genoni AP, Acquati F, Gallazzi M, Spina G, Coco G, Pierin F, Noonan D, Vigezzi A, Monti E, Iori V, Masci F, Franchi C, Di Saverio S, Carcano G. Immune-Mediated Mechanisms in Patients Testing Positive for SARS-CoV-2: Protocol for a Multianalysis Study. JMIR Res Protoc. 2022 Jan 25;11(1):e29892. doi: 10.2196/29892.

  PMID: 34854818 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Venous blood sample (15 mL in EDTA solution test tube).

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Giulio Carcano, Professor

  Università degli Studi dell'Insubria

  STUDY CHAIR

• Giuseppe Ietto, M.D.

  Università degli Studi dell'Insubria

  PRINCIPAL INVESTIGATOR

• Lorenzo Mortara, Professor

  Università degli Studi dell'Insubria

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Giuseppe Ietto, M.D.

CONTACT

+393398758024; giuseppe.ietto@gmail.com

Domenico Iovino, M.D.

CONTACT

+393407308867; domenico.iovino@ASST-Settelaghi.it

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Adjunct Professor, M.D.

Study Record Dates

• First Submitted: May 3, 2020
• First Posted: May 5, 2020
• Study Start: April 27, 2020
• Primary Completion: June 30, 2020
• Study Completion: October 31, 2020
• Last Updated: May 5, 2020

Record last verified: 2020-05

Locations

IT (1)