Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT04712448 |
| Other study ID # |
20/33 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
December 30, 2020 |
| Est. completion date |
December 30, 2024 |
Study information
| Verified date |
April 2024 |
| Source |
IRCCS San Raffaele Roma |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The first reports of infections caused by SARS-CoV-2 were released from Wuhan, China in
December 2019. From there, the infection quickly spread into a pandemic form. The clinical
manifestation of the infection varies enormously, from totally asymptomatic or mildly
symptomatic forms, with nonspecific and flu-like manifestations, to an acute respiratory
distress syndrome which, in patients requiring hospitalization in the ICU and mechanical
ventilation invasive, can lead to death, especially in elderly subjects and carriers of
co-morbidities. Recently, the association of blood groups ABO as possible biological markers
of susceptibility to COVID-19, has been evaluated, linking blood type O with a lower chance
of infection, blood type A with the highest risk, and blood group B with the greatest
complications.
In Italy, the first non "imported" case dates back to February 2020, although new evidence on
subjects tested positive for the antibody assay on serum samples suggests that the virus
started to circulate before the official date.
Few are the data relating to asymptomatic infections or with mild non-specific and nuanced
symptoms that have been quantified in about 85% of the total number of infected. Moreover,
thanks to the availability of serological tests that identify the presence of anti-SARS-CoV-2
antibodies, it emerged that a proportion of the population was infected by the virus and
developed an antibody response and that almost 30% of the people with antibodies were
asymptomatic. In order to evaluate the seroprevalence of COVID-19 infection among
asymptomatic subjects the investigators will conduct specific serological tests (total
antibodies) to identify the prevalence of SARS-2-CoV antibodies among healthy blood donors
who went to transfusion facilities of the DIMT in Venice during the pandemic (about 2500
periodic donors who referred to the Transfusion Center in the period between May and October
2019). Patients afferent to the Interinstitutional Multidisciplinary Biobank (BioBIM) of the
Research Center of the IRCCS San Raffaele Pisana in Rome, with or without concomitant
co-morbidities (about 1000 subject) will be also tested. All samples will be analyzed for any
association with sex, age group and blood group.
Description:
1. Title Serum prevalence of SARS-Cov-2 antibodies in pre-pandemic blood samples
2. Background The first reports of infections caused by SARS-CoV-2, a Beta Corona virus,
single-stranded RNA, were released from Wuhan, China in December 2019. From there, the
infection quickly spread into a pandemic form.
The clinical manifestation of the infection varies enormously, from totally asymptomatic
or mildly symptomatic forms, with nonspecific and flu-like manifestations, to an acute
respiratory distress syndrome which, in patients requiring hospitalization in the ICU
and mechanical ventilation invasive, can lead to death. The greater severity of the
course of the infection depends greatly on the general conditions of the patients, being
maximum in elderly subjects and carriers of co-morbidities. Recent studies have also
evaluated the association of blood groups ABO as possible biological markers of
susceptibility to COVID-19, suggesting that people with blood type O have a lower chance
of infection while individuals with blood type A are most at risk, and people with blood
group B have the greatest complications in the event of infection.
In Italy, the first non "imported" case dates back to February 2020 in a person residing
in Lombardy, in the province of Lodi. However, new evidence on subjects tested positive
for the antibody assay on serum samples suggests that the virus started to circulate
before the official date.
Initially, due to the sudden explosion of cases, epidemiological surveillance focused on
patients related to health facilities because they were symptomatic, suspicious and
high-risk contacts. Few are the data relating to asymptomatic infections or with mild
non-specific and nuanced symptoms that, data from China, would quantify in about 85% of
the total number of infected. Precisely on the role of person-to-person transmission in
the course of asymptomatic infection and in the subclinical phases of the disease,
epidemiological data are lacking despite they could prove to be very important. In fact,
thanks to the availability of serological tests that identify the presence of
anti-SARS-CoV-2 antibodies, it emerged that a proportion of the population was infected
by the virus and developed an antibody response and that almost 30% of the people with
antibodies were asymptomatic. Therefore, the understanding of the prevalence of the
disease and the prevalence of the antibody response appear to be of considerable
interest, as it seems to be established that asymptomatic subjects can transmit the
SARS-CoV-2 infection for a period that in some cases has proved greater than 14 days.
In order to evaluate the seroprevalence of COVID-19 infection among asymptomatic
subjects, thus obtaining a real estimate of the beginning of the circulation of the
virus in Italy, in the present study the investigators intend to conduct specific
serological tests (total antibodies) to identify the prevalence of SARS-2-CoV antibodies
among healthy blood donors who went to transfusion facilities of the DIMT in Venice
during the pandemic (about 2500 periodic donors who referred to the Transfusion Center
in the period between May and October 2019).
Samples belonging to healthy volunteers (about 500) who have agreed to donate their
blood will also be evaluated to establish a pool of control subjects belonging to the
Interinstitutional Multidisciplinary Biobank (BioBIM) of the Research Center of the
IRCCS San Raffaele Pisana in Rome. Finally, in order to evaluate the impact of
seroprevalence in subjects with chronic diseases (about 1000), such as cardiovascular,
oncological, respiratory and neurodegenerative ones, which represent settings of
COVID-19 positive patients with a poorer prognosis, patient samples with the listed
comorbidities, already present in BioBIM, will be analyzed. It has recently emerged that
seroprevalence increases with increasing age and that younger groups have a lower
susceptibility to infection. Therefore, all samples will be analyzed for any association
with sex, age group and blood group.
3. Promoter Prof.ssa Fiorella Guadagni
4. Sponsor/Promotor IRCCS San Raffaele Pisana
5. Site IRCCS San Raffaele Pisana
6. Study type Multicentric, retrospective, observational, non pharmacological, on
biological samples, conducted at the IRCCS San Raffaele Pisana, Rome, aimed at verifying
the seroprevalence of SARS-COV-2 antibodies in the population.
7. Objectives 7.1 PRIMARY Objective: The aim of the study is to determine the proportion of
people in the general population who developed an antibody response to antigenic
determinants of SARS-CoV-2 in the period preceding the spread of the virus in Italy.
7.2 SECONDARY Objective: Secondary objectives are represented by the possibility to
characterize the differences in prevalence between genders, age groups and blood groups,
also in relation to more unfavourable courses in subjects with other chronic diseases.
8. Participants
The study protocol will involve a total of 3500 subjects (3000 healthy subjects and 1000
patients with chronic diseases) aged> 18 years, of both sexes. The two groups will be
formed as follows:
A- Healthy subjects among periodic blood donors of the Transfusion Center and volunteer
donors of BioBIM B- Patients with chronic diseases including cardiovascular,
respiratory, oncological and neurodegenerative diseases related to BioBIM
9. Inclusion/exclusion Criteria 9.1 Inclusion criteria - Both sexes
- Age >18 years
- Signed informed consent for the donation / sample storage in the Biological Bank
9.2 Exclusion criteria
- for healthy subjects, all those who have shown any symptoms, albeit mild, in the 28
days prior to the donation.
- patients who have not signed the informed consent for the conservation of their
samples in the Biological Bank.
9.3 Drop out Not applicable.
10. Study design
The study will last 9 months, and includes 3 phases as follows:
Phase 1: identification of samples Phase 2: sample analysis Phase 3: statistical
analysis
11. Methods of contact with possible participants in the study Not applicable. The study
will be carried out only on samples stored in the Biobank.
12. Methods of acquisition, statistical analysis of data and storage of raw data, compliance
with privacy regulations Data collection will be carried out on a dedicated and
anonymized database by the Principal Investigator. Data will be stored on a dedicated
and protected server.
13. Statistical Methodology 13.1 Statistical analysis Statistical analysis of all parameters
will be conducted under the responsibility of the Biomarker Discovery and Advanced
Technologies (BioDAT) Unit of IRCCS San Raffaele Pisana.
Data analysis will be carried out using frequency and percentage for the categorical
variables, and mean and standard deviation for the quantitative variables. The t-test will be
used to compare means and a p-value less than 0.05 will be considered statistically
significant. All analysis will be performed on the SPSS Statistical Package for Social
Sciences.
13.2 Sample size The SPARE study is a pilot study, designed to verify the adequacy and
feasibility of the project, and to obtain preliminary data that allow to determine the size
of the sample of the final study. The sample size is therefore represented by a consecutive
number of subjects who donated blood in the period May-October 2019 (about 2500) and all
subjects (healthy and with chronic diseases) who referred to BioBIM in 2019 (about 1500 ).
14) Requirements of originality and scientific soundness of the study The SPARE study aims to
evaluate the seroprevalence of COVID-19 infection among asymptomatic subjects and thus obtain
a real estimate of the beginning of the circulation of the virus in Italy. The evidence
currently present in the literature refers mainly to the period of the actual pandemic, but
there are no data relating to the months prior to autumn 2019. Same for the official data
released by the Ministry of Health in collaboration with the National Institute of Statistics
(ISTAT). This study will allow us to define the spread of the SARS-2-CoV virus in a period
long before the date to which the pandemic began in Italy.
15) Expected Results
The main expected results are:
1. Identification of seroprevalence of anti-SARS-2-CoV antibodies in the population prior
to the date on which the beginning of the infection in Italy is officially traced;
2. Description of any associations with sex, age, blood group, outcomes of patients with
chronic diseases.
16) Progress report The proposers will submit a report on the progress of the study to the
Ethics Committee at the end of each year and at the end of the study.
17) Feasibility
- n. patient samples that may be included is consistent with the study design
- presence of the necessary equipment
- adequacy of personnel 18) Concomitant treatments Not applicable. The SPARE study is a
study on biological samples only 19) Cost/benefit ratio The study is supported by the
IRCCS San Raffaele Pisana. The inclusion of samples belonging to healthy donors and
patients in this clinical study may provide benefits in terms of more accurate
management and acquisition of indications on the spread of the Sars-COV-2 virus in the
asymptomatic population. There are no risks.
20) Ethical relevance The study is conducted on patient samples stored in the Biological
Banks, therefore there are no problems of an ethical nature to its execution.
21) Insurance The procedures provided for the study in this centre do not directly
involve patients, but the analysis of samples taken in the centres they enrol. The
researcher assigned to the analysis of the samples is covered by an insurance policy
included in the contract stipulated with the IRCCS San Raffaele Pisana.
22) Result publication In compliance with the provisions in force regarding the
confidentiality of sensitive data and patent protection, the results of the study will
be submitted for publication within 6 months of after the closure of the database.
23) Informed Consent The submission of specific informed consent for this study on
anonymized samples from biological banks or large collections does not apply.
24) Ethical aspects This protocol will be conducted in accordance with the ethical
principles that draw their origin from the Declaration of Helsinki, respects the GCP and
applicable regulatory provisions.
25) References
1. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. China Novel Coronavirus
Investigating and Research Team A Novel Coronavirus from Patients with Pneumonia in
China, 2019. N Engl J Med. 2020;382(8):727-33. 10.1056/NEJMoa2001017
2. World Health Organization (WHO). Novel coronavirus - China. Geneva: WHO; 12 Jan
2020. [Accessed 09 Oct 2020]. Available from:
https://www.who.int/csr/don/12-january-2020-novel-coronavirus-china/en/
3. Santos-Sánchez NF, Salas-Coronado R. Medwave. Origin, structural characteristics,
prevention measures, diagnosis and potential drugs to prevent and COVID-19. 2020
Sep 25;20(8):e8037. doi: 10.5867/medwave.2020.08.8037.
4. Luo L, Fu M, Li Y, Hu S, Luo J, Chen Z, Yu J, Li W, Dong R, Yang Y, Tu L, Xu X. The
potential association between common comorbidities and severity and mortality of
coronavirus disease 2019: A pooled analysis. Clin Cardiol. 2020 Oct 7. doi:
10.1002/clc.23465.
5. Zaho J, Yang Y, Huang H, Li D, Gu D., Lu X, et al. Relationship between the ABO
Blood Group and the COVID-19 susceptibility. 10.1101/2020.03.11.20031096
6. Zalba Marcos S, Luisa Antelo M, Galbete A, Etayo M, Ongay E, García-Erce JA.
Infection and thrombosis associated with COVID-19: Possible role of the ABO blood
group. Med Clin (Engl Ed). 2020 Sep 26. doi: 10.1016/j.medcle.2020.06.013.
7. Livingston E, Bucher K. Coronavirus Disease 2019 (COVID-19) in Italy. JAMA.
2020;323(14):1335. 10.1001/jama.2020.4344
8. Mizumoto K, Kagaya K, Zarebski A, Chowell G. Estimating the asymptomatic proportion
of coronavirus disease 2019 (COVID-19) cases on board the Diamond Princess cruise
ship, Yokohama, Japan, 2020. Euro Surveill 2020;25(10):2000180.
9. ISTAT. Primi risultati dell'indagine di sieroprevalenza sul SARS-CoV-2. Accessible
presso https://www.istat.it/it/archivio/246156
10. Oran DP, et al. Prevalence of Asymptomatic SARS-CoV-2 Infection - A Narrative
Review. Ann Int Med 2020; 173:362-376. doi.org/10.7326/M20-3012.
11. Pagani G, et al. Seroprevalence of SARS-CoV-2 significantly varies with age:
Preliminary results from a mass population screening. J Infect. 2020 Sep
19;S0163-4453(20)30629-0. doi: 10.1016/j.jinf.2020.09.021.
