Professional's Health in Epidemiological Crisis Covid-19 (ProHEpiC-19)

• ClinicalTrials.gov Identifier: NCT04885478
• Recruitment Status: Unknown
• First Posted: May 13, 2021
• Last Update Posted: May 21, 2021
• Sponsor: Fundacio d'Investigacio en Atencio Primaria Jordi Gol i Gurina
• Collaborators: Fundació Institut Germans Trias i Pujol; IrsiCaixa; Institut Catala de Salut
• Information provided by (Responsible Party): Pere Toran, MN, Fundacio d'Investigacio en Atencio Primaria Jordi Gol i Gurina

Study Description

Brief Summary:

Introduction: Coronavirus Disease 2019 (COVID-19) has caused a global pandemic. Epidemiological and clinical inter-individual differences, symptomatology, recovery and humoral response against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are key factors to better understand and predict the course of the pandemic. As Health Care Workers (HCWs) are caring for infected patients they are more susceptible to infection, which not only is critical for their own health but also because it results in a shortage of HCWs that seriously affects health services. Thus, maintaining the health and welfare of HCWs and enabling their rapid return to work is vital to overcome this crisis. The ProHEpiC-19 cohort presents data on the immune response of HCWs infected with SARS-CoV-2. This dynamic cohort was started in March 2020 and still continues including participants.

Condition or disease	Intervention/treatment
COVID-19; SARS-CoV-2	Other: Immune response monitoring , blood samples

Detailed Description:

Objectives:

Primary: To consolidate a prospective cohort of Health Care Workers (HCWs) to generate epidemiological and clinical high quality data. This information will be relevant to improve health policies and clinical COVID-19 protocols. This cohort will also be used as an ongoing platform to implement SARS-CoV-2 research projects with particular emphasis on incidence rate, reinfection, vaccines, and long term immune response.

Secondary:

1. To determine the kinetics of SARS-CoV-2 antibodies and cellular immune response in early, mid, and long periods of immunization.
2. To assess the relation between clinical variables and initial RT-PCR results with the interindividual differences in the immune response in early, mid, and long periods of immunization.
3. To analyze differentially expressed cytokines as biomarkers of disease progression in early, mid, and long periods of immunization.

Methods and analysis: Longitudinal, dynamic, prospective cohort study with a 12-month follow-up, which is being conducted in 4 primary-care centres and one hospital of Northern Metropolitana Nord of Barcelona (Spain). For now, the study consists of 1350 participants divided into 2 cohorts: 1) Healthy-Exposed HCWs: 675 not infected by SARS-CoV-2 (RT-PCR with a negative result and negative SARS-CoV-2 antibodies at baseline) and 2) Infected HCWs: 675 symptomatic participants (those with new persistent cough, temperature ≥37.5°C, anosmia, or ageusia or other compatible symptoms with COVID-19) or asymptomatic participants diagnosed by positive RT-PCR test and/or SARS-CoV-2 antibodies (IgM, IgG at baseline). Primary outcomes include: humoral and cellular immune response, quantitative antibodies to SARS-Cov-2, SARS-CoV-2 antibody levels related to progression phenotype, clinical spectrum of SARS-Cov-2, symptomatology, demographics and other variables that may be predictive of immune response.

Follow-up: baseline, 15 days, 1, 3, 6, 9 and 12 months. Findings to date: Current literature has shown that the immune response is maintained for a minimum of 2 months. Nevertheless little is known about the association between the immune response and the progression phenotype of COVID-19 .

Future plans: This prospective cohort offers the possibility to study associations between immune response and progression phenotype according to age and gender as well as long-term immune response. In turn, we will be able to examine possible cumulative effects, taking into account several clinical variables. The study is ongoing and we plan to extend it to increase the size of the cohort until 2024.

Study Design

• Study Type: Observational
• Estimated Enrollment: 1350 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: SARS-CoV-2 Infection Among Healthcare Professionals: Demographic Characteristics and Serological and Immune Responses Related to Progression's Phenotype (ProHEPiC-19)
• Actual Study Start Date: March 30, 2020
• Estimated Primary Completion Date: June 30, 2022
• Estimated Study Completion Date: June 30, 2022

Groups and Cohorts

Group/Cohort	Intervention/treatment
Healthy health care workers; ≥ 18 years of age Accept to take part in the study and sign the informed consent according to the Declaration of Helsinki. To be a health care professional worker infected or exposed to SARS-CoV-2 RT-PCR (SARS-CoV2), negative at baseline or follow up Anti-SARS-CoV-2 IgG and IgM antibodies (Nucleopcapside), negative positive at baseline or follow up	Other: Immune response monitoring , blood samples; In both cohorts: -SARS-CoV-2 IgG and IgM antibodies, ( Nucleocapside, Spike) in 8 visits during a year. Infected HCW: Cytokines and T-Cell determination at baseline, 30, 60,180 days, 365 after positive test ( RT-PCR or SARS-CoV-2 antibodies ); Covid-19 Symptoms, clinical monitoring
Infected health care workers; ≥ 18 years of age Accept to take part in the study and sign the informed consent according to the Declaration of Helsinki. To be a health care professional worker infected or exposed to SARS-CoV-2 RT-PCR (SARS-CoV2), positive at baseline or follow up Anti-SARS-CoV-2 IgG and IgM antibodies (Nucleopcapside), positive at baseline or follow up	Other: Immune response monitoring , blood samples; In both cohorts: -SARS-CoV-2 IgG and IgM antibodies, ( Nucleocapside, Spike) in 8 visits during a year. Infected HCW: Cytokines and T-Cell determination at baseline, 30, 60,180 days, 365 after positive test ( RT-PCR or SARS-CoV-2 antibodies ); Covid-19 Symptoms, clinical monitoring

Outcome Measures

Primary Outcome Measures :

1. Creation prospective cohort of health care workers [ Time Frame: Baseline, to 12 months after the beginning of the study ]
   Include 675 exposed HCW participants and 675 infected HCW participants againts SARS-CoV-2, cohorts will be compared at each time point in terms of sociodemographic, epidemiological, clinical, and immunological information available. an exploratory bivariate analysis will be performed using the tests of Chi Square, ANOVA, Kruskall-Walis, depending on the application conditions assumptions.
2. Cohort description demografics ( age, sex, academic level, housing characteristics, work variables ) [ Time Frame: Baseline, to 12 months after the beginning of the study ]
   Descriptive analysis of the participants will be performed using the number and percentage for categorical variables, and mean and standard deviation or median and quartiles 1 and 3 for quantitative variables, an exploratory bivariate analysis will be performed using the tests of Chi Square, ANOVA, Kruskall-Walis, depending on the application conditions assumptions.
3. Cohort description clinical spectrum (asymptomatic, mild-moderate Illness, severe-critical) [ Time Frame: Baseline, to 12 months after the beginning of the study ]
   Cohort comparison , an exploratory bivariate analysis will be performed using the tests of Chi Square, ANOVA, Kruskall-Walis, depending on the application conditions assumptions.

Secondary Outcome Measures :

1. Kinetics of SARS-CoV-2. IgM Nucleocapside [ Time Frame: Baseline, 7 days, 15 days, 3, 6, 9 and 12 months after the beginning of the study ]
   IgM (nucleocapside) ELISA kits (Inmunodiagnostic Limited ©). Positivity thresholds were provided by the assay manufacturers and were considered positive with an index value greater than 1.1, indeterminate from 0.9 to 1.1 and negative if <0.9 index units
2. Kinetics of SARS-CoV-2. IgG Nucleocapside [ Time Frame: Baseline, 7 days, 15 days, 3, 6, 9 and 12 months after the beginning of the study ]
   IgG (nucleocapside) ELISA kits (Inmunodiagnostic Limited ©). Positivity thresholds were provided by the assay manufacturers and were considered positive with an index value greater than 1.1, indeterminate from 0.9 to 1.1 and negative if <0.9 index units
3. Kinetics of SARS-CoV-2. IgG Spike [ Time Frame: Baseline, 7 days, 15 days, 3, 6, 9 and 12 months after the beginning of the study ]
   IgG (spike). ELISA kits DECOV1901 (Demeditec Diagnostics GmbH©). Positivity thresholds were provided by the assay manufacturers and were considered positive with an index value greater than 40, indeterminate from 32 to 40 and negative if <32 Ul/ml
4. Kinetics of SARS-CoV-2. T-Cell [ Time Frame: Baseline, 7 days, 15 days, 3, 6, 9 and 12 months after the beginning of the study ]
   SARS-CoV-2 specific CD4+ and CD8+ T-cell responses we performed an IFNγ ELISPOT assay. Wells will be considered positive if they contained at least 50 spot-forming cells per 106 PBMCs above the background level (2X mean + 3Xstandard deviation).
5. To assess the relation between clinical variables and initial RT-PCR results in the whole sample and by sex. [ Time Frame: Baseline, to 12 months after the beginning of the study ]
   To study the differences between clinical spectrums and initial RT-PCR we will use ANOVAs or Kruskal-Wallis tests, after checking normality assumption using a Shapiro-test
6. To analyse the relation between clinical variables and the interindividual differences in the immune response in early, mid, and long periods of immunization in the whole sample and by sex [ Time Frame: Baseline, 7 days, 15 days, 3, 6, 9 and 12 months after the beginning of the study ]
   To study the differences between clinical spectrums and immune response in early period we will use ANOVAs or Kruskal-Wallis tests, after checking normality assumption using a Shapiro-test . Similarly, to look for differences in antibody levels between sex, either a t-test or a Mann-Whitney test will be performed.
7. Cytokines as biomarkers of disease progression in early, mid, and long periods of immunization. [ Time Frame: Baseline, 7 days, 15 days, 3, 6, 9 and 12 months after the beginning of the study ]
   Cryopreserved plasma samples will be used in a 45-plex assay of soluble mediators. The plates will be read with a Luminex instrument (Luminex 200, Austin Luminex, USA).Appropriate statistical tests (i.e. t-test or Mann-Whitney to compare between sexes and ANOVA or Kruskal-Wallis to compare between clinical spectrums) will be used after checking for normality (Shapiro-test)

Biospecimen Retention:   Samples With DNA

Blood, Serum , plasma, nasopharyngeal swabs.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

This is a multicenter study (public primary care centers set in Mataró, Sabadell and Santa Perpètua and the public third level hospital Hospital Germans Tries i Pujol located in Badalona) with HCW cohorts recruited from Gerència Territorial Metropolitana Nord of the Catalan Institute of Health (ICS), which consists of 7,776 HCW, including physicians, nurses, COVID-19 researchers, medical residents and other essential workers in direct contact with patients during present and future pandemic waves.

Criteria

Inclusion Criteria:

• ≥ 18 years of age
• Accept to take part in the study and sign the informed consent according to the Declaration of Helsinki.
• To be a health care professional worker infected or exposed to SARS-CoV-2.

Exclusion Criteria:

• < 18 years old
• Not to accept to take part in the study and/or not to sign the informed consent according to the Declaration of Helsinki.
• Not to be a health care professional worker exposed to SARS-CoV-2

Contacts and Locations

Contacts

Contact: Concepción Violán Fors, MD, PhD; +34 629566936; cviolanf.mn.ics@gencat.cat

Contact: Pere Monteagudo Zaragoza; +3493 482 42 53; ugp@idiapjgol.info

Locations

Spain

Jordi Gol i Gurina Foundation; Recruiting

Mataró, Barcelona, Spain, 08303

Contact: Concepción Violán Fors +34 629566936

Contact: Pere Monteagudo Zaragoza +34 93 482 42 53 ugp@idiapjgol.info

Sponsors and Collaborators

Fundacio d'Investigacio en Atencio Primaria Jordi Gol i Gurina

Fundació Institut Germans Trias i Pujol

IrsiCaixa

Institut Catala de Salut

Investigators

• Principal Investigator: Concepción Violán Fors, MD, PhD; Fundacio d'Investigacio en Atencio Primaria Jordi Gol i Gurina

  Study Documents (Full-Text)

Documents provided by Pere Toran, MN, Fundacio d'Investigacio en Atencio Primaria Jordi Gol i Gurina:

Study Protocol, Statistical Analysis Plan, and Informed Consent Form  [PDF] May 18, 2021

More Information

Publications of Results:

Garcia-Sierra RM, Badia Perich E, Manresa Dominguez JM, Moreno Millan N, Sabate Cintas V, Romero Martinez M, Moreno Gabriel E, Pera G, Seda Gombau G, Montella Jordana N, Violan Fors C, Argerich Gonzalez MJ, Bonet Simo JM, Prat Gil N, Toran Monserrat P. [Descriptive study of the health service workers of a Primary Care Department confined by Covid-19.]. Rev Esp Salud Publica. 2020 Sep 3;94:e202009106. Spanish.

Huang AT, Garcia-Carreras B, Hitchings MDT, Yang B, Katzelnick LC, Rattigan SM, Borgert BA, Moreno CA, Solomon BD, Trimmer-Smith L, Etienne V, Rodriguez-Barraquer I, Lessler J, Salje H, Burke DS, Wesolowski A, Cummings DAT. A systematic review of antibody mediated immunity to coronaviruses: kinetics, correlates of protection, and association with severity. Nat Commun. 2020 Sep 17;11(1):4704. doi: 10.1038/s41467-020-18450-4.

Other Publications:

Chen ZM, Fu JF, Shu Q, Chen YH, Hua CZ, Li FB, Lin R, Tang LF, Wang TL, Wang W, Wang YS, Xu WZ, Yang ZH, Ye S, Yuan TM, Zhang CM, Zhang YY. Diagnosis and treatment recommendations for pediatric respiratory infection caused by the 2019 novel coronavirus. World J Pediatr. 2020 Jun;16(3):240-246. doi: 10.1007/s12519-020-00345-5. Epub 2020 Feb 5.

Liu W, Fontanet A, Zhang PH, Zhan L, Xin ZT, Baril L, Tang F, Lv H, Cao WC. Two-year prospective study of the humoral immune response of patients with severe acute respiratory syndrome. J Infect Dis. 2006 Mar 15;193(6):792-5. doi: 10.1086/500469. Epub 2006 Feb 9.

Callow KA, Parry HF, Sergeant M, Tyrrell DA. The time course of the immune response to experimental coronavirus infection of man. Epidemiol Infect. 1990 Oct;105(2):435-46. doi: 10.1017/s0950268800048019.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Violan C, Toran-Monserrat P, Quirant B, Lamonja-Vicente N, Carrasco-Ribelles LA, Chacon C, Manresa-Dominguez JM, Ramos-Roure F, Dacosta-Aguayo R, Palacios-Fernandez C, Roso-Llorach A, Pujol A, Ouchi D, Monteagudo M, Montero-Alia P, Garcia-Sierra R, Armestar F, Dolade M, Prat N, Bonet JM, Clotet B, Blanco I, Boigues-Pons M, Moreno-Millan N, Prado JG, Caceres EMM; ProHEpiC-19 study. Kinetics of humoral immune response over 17 months of COVID-19 pandemic in a large cohort of healthcare workers in Spain: the ProHEpiC-19 study. BMC Infect Dis. 2022 Sep 3;22(1):721. doi: 10.1186/s12879-022-07696-6.

• Responsible Party: Pere Toran, MN, Family Physician, Fundacio d'Investigacio en Atencio Primaria Jordi Gol i Gurina
• ClinicalTrials.gov Identifier: NCT04885478
• Other Study ID Numbers: 4R20-105
• First Posted: May 13, 2021
• Last Update Posted: May 21, 2021
• Last Verified: May 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Pere Toran, MN, Fundacio d'Investigacio en Atencio Primaria Jordi Gol i Gurina:

COVID-19; Serological test; Kinetics; T cell; Citokines

Additional relevant MeSH terms:

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases