Clinical and Immunological Responses After SARS-CoV-2 Infection Causing COVID-19

NCT05038475 | Unknown DMC

• 1 other identifier: ANS-2020/001
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

There are very few long-term studies that analyze the immune responses in patients recovered from COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The main aim of this study is to analyze the clinical profile and immune responses of recovered COVID-19 patients in a representative cohort of people in the Umbria region of Italy. The participants had a history of testing positive for SARS-CoV-2 in March 2020 by Reverse Transcriptase- Quantitative Polymerase Chain Reaction (RT-qPCR). The participants were invited for voluntary participation in a seroprevalence study. This study analyzes longitudinally the presence of antibodies against SARS-CoV-2 by sequential serological tests at different time points using two FDA-approved Immunoassays. At the first serum sample collection, the participants were asked to provide information about their COVID-19 clinical history including clinical profile, co-morbidities, and treatment undertaken using a standardized questionnaire. Successive sequential serological assessments were conducted to understand the immune responses in these recovered patients. Moreover, stage two of the study involves, analysis of antibody titers in recovered vaccinated individuals and their follow-up.

Conditions

COVID-19; SARS-CoV2 Infection; Olfactory Disorder; Smell Loss; Smell Disorder

Keywords

Antibody responses; olfaction; smell; sars-cov-2; covid-19; IgG; IgM; serology; immune response; humoral response

Outcome Measures

Primary Outcomes (9)

• Analysis of demographic profile (Age) of recovered COVID-19 patients [at inclusion]

  Demographic profile included Age at presentation (in years)

  At inclusion

• Analysis of demographic profile (Gender) of recovered COVID-19 patients [at inclusion]

  Demographic profile included Sex (gender) at presentation (male/female/other)

  At inclusion

• Analysis of demographic profile (occupation) of recovered COVID-19 patients [at inclusion]

  Demographic profile included occupation at presentation (healthcare-worker/non-healthcare)

  At inclusion

• Analysis of clinical profile of recovered COVID-19 patients [at inclusion]

  Clinical profile included clinical symptoms experienced at the time of presentation. The participant completed a questionnaire with "Yes" or "no" for each symptom. The symptoms were namely: Fever, Rhinorrhea, Dry cough, Sore throat, Shortness of breath, fatigue, Headche, Muscle ache, skin eruptions, diarrhoea, conjunctivitis, loss of smell, loss of taste, chest pain or any other symptom (please specify).

  At inclusion

• Analysis of associated co-morbidities in recovered COVID-19 patients [at inclusion]

  Participants completed a questionnaire with "Yes" or "no" for history of comorbidities namely: Asthma/seasonal allergies, Diabetes Mellitus, Hypertension, cardiovascular disease or any other co-morbidity (please specify).

  At inclusion

• Analysis of immunological profile recovered COVID-19 patients [at inclusion]

  The participants were questioned about their respective blood groups.

  At inclusion

• Seroprevalence of IgM and IgG against Nucleocapsid of SARS-CoV-2 (in AU/ml) [from T0 to T5]

  From May 2020 to January 2021, anti-nucleocapsid (NCP) antibodies developed against SARS-CoV-2 were analysed using n-CoV IgM/IgG CLIA assay through sequential serological tests in n=30 patients. Time was treated as a factor and six time points were defined. The first blood sample was collected in May 2020 (2 months after infection) and was defined as T0. Consecutive samples were analysed at 3 months (T1), five months (T2) , seven months (T3) and eight months (T4) and ten months (T5) post infection in June, August, October, November of 2020 and January 2021 respectively.

  8 months

• Seroprevalence of IgM and IgG against spike-receptor binding domain of SARS-CoV-2 (in AU/ml) [from T6 to T8]

  A more specific immunoassay (CLIA) against SARS-CoV-2 S-RBD was adopted for future assessments. From late February 2021, an additional n = 12 patients (8 female and 4 male), who met the eligibility criteria for participation, were enrolled in the study and added to the original cohort (n = 30). These patients (n=12), similar to the original cohort, had a history of testing positive for SARS-CoV-2 by RT-qPCR in March 2020, updating the sample size to n = 42. Since the legal provisions adopted by the Italian Ministry of Health advised mandatory vaccination for all Healthcare Workers, irrespective of previous disease status,n=10 patients (4 female, 6 male) were gradually vaccinated from mid-March 2021 and excluded from the original cohort, making the revised final sample size,n = 32.

  through study completion, an average of 2 years

• Seroprevalence of IgM and IgG against spike-receptor binding domain of SARS-CoV-2 (in AU/ml) for vaccinated individuals

  The vaccinated recovered individuals continued to report for follow-up for antibody analysis

  through study completion, an average of 2 years

Secondary Outcomes (7)

• Co-relation of demographic profile with antibody titers against NCP of SARS-CoV-2 with respect to disease severity [ Time Frame: at inclusion and within observational period ]

  8 months

• Co-relation of demographic profile with antibody titers against spike- RBD of SARS-CoV-2 with respect to disease severity [ Time Frame: at inclusion and within observational period ]

  4 months

• Co-relation of symptoms and antibody titer levels against Nucleocapsid of SARS-CoV-2 with respect to disease severity [ Time Frame: at inclusion and within observational period ]

  at inclusion and within the observational period (8 months)

• Co-relation of self reported symptoms and antibody titer levels against spike-RBD with respect to disease severity [ Time Frame: at inclusion and within observational period ]

  at inclusion and within the observational period (4 months)

• Co-relation of co-morbidities and antibody titer levels with respect to disease severity [ at inclusion]

  at inclusion and within the observational period (8 months)

Study Arms (2)

Mild group

As per the WHO guidelines, the patients were divided into two groups based on disease severity: Mild and Moderately severe. This was based on the self-reported symptoms experienced by the patients during the infection period (March 2020). Intervention: COVID-19 Antibody testing at different time points

Diagnostic Test: COVID-19 antibody test

Moderately-severe group

As per the WHO guidelines, the patients were divided into two groups based on disease severity: Mild and Moderately severe. This was based on the self-reported symptoms experienced by the patients during the infection period (March 2020). Intervention: COVID-19 Antibody testing at different time points

Diagnostic Test: COVID-19 antibody test

Interventions

COVID-19 antibody test DIAGNOSTIC_TEST

FDA-approved Immunoassays were used in the study. At the beginning of the study, up to 3 months, ELISA and CLIA immunoassays were adopted to analyze the antibody titers. Thereafter, CLIA was used for longitudinal analysis of antibody titers for consecutive months. Anti

Mild group; Moderately-severe group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Individuals who tested positive for SARS-CoV-2 in March 2020 and are not vaccinated till date, within the age range of 18-80 years, with no active respiratory infection / active COVID-19 infection and willing to give informed consent were invited to take part in the study.

You may qualify if:

• Individuals who tested positive for SARS-CoV-2 in March 2020. These patients will be divided into two groups and followed up over time. The first group will include patients who have recovered and have not received the vaccine. The second group will include patients who have recovered and have received the vaccine.
• No acute respiratory infection or active SARS-CoV-2 infection.
• Informed consent of the adult participant.

You may not qualify if:

• Individuals \<18 years or \>80 years.
• No informed consent by the adult participant.
• Suspicion of acute COVID-19 infection

Sponsors & Collaborators

• Association "Naso Sano" Onlus: lead

Study Sites (1)

Associazione Naso Sano

San Mariano, Perugia, 06073, Italy

Location

Related Publications (4)

• Abu-Raddad LJ, Chemaitelly H, Coyle P, Malek JA, Ahmed AA, Mohamoud YA, Younuskunju S, Ayoub HH, Al Kanaani Z, Al Kuwari E, Butt AA, Jeremijenko A, Kaleeckal AH, Latif AN, Shaik RM, Abdul Rahim HF, Nasrallah GK, Yassine HM, Al Kuwari MG, Al Romaihi HE, Al-Thani MH, Al Khal A, Bertollini R. SARS-CoV-2 antibody-positivity protects against reinfection for at least seven months with 95% efficacy. EClinicalMedicine. 2021 May;35:100861. doi: 10.1016/j.eclinm.2021.100861. Epub 2021 Apr 28.

  PMID: 33937733 RESULT

• Piccoli L, Park YJ, Tortorici MA, Czudnochowski N, Walls AC, Beltramello M, Silacci-Fregni C, Pinto D, Rosen LE, Bowen JE, Acton OJ, Jaconi S, Guarino B, Minola A, Zatta F, Sprugasci N, Bassi J, Peter A, De Marco A, Nix JC, Mele F, Jovic S, Rodriguez BF, Gupta SV, Jin F, Piumatti G, Lo Presti G, Pellanda AF, Biggiogero M, Tarkowski M, Pizzuto MS, Cameroni E, Havenar-Daughton C, Smithey M, Hong D, Lepori V, Albanese E, Ceschi A, Bernasconi E, Elzi L, Ferrari P, Garzoni C, Riva A, Snell G, Sallusto F, Fink K, Virgin HW, Lanzavecchia A, Corti D, Veesler D. Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology. Cell. 2020 Nov 12;183(4):1024-1042.e21. doi: 10.1016/j.cell.2020.09.037. Epub 2020 Sep 16.

  PMID: 32991844 RESULT

• Suthar MS, Zimmerman MG, Kauffman RC, Mantus G, Linderman SL, Hudson WH, Vanderheiden A, Nyhoff L, Davis CW, Adekunle O, Affer M, Sherman M, Reynolds S, Verkerke HP, Alter DN, Guarner J, Bryksin J, Horwath MC, Arthur CM, Saakadze N, Smith GH, Edupuganti S, Scherer EM, Hellmeister K, Cheng A, Morales JA, Neish AS, Stowell SR, Frank F, Ortlund E, Anderson EJ, Menachery VD, Rouphael N, Mehta AK, Stephens DS, Ahmed R, Roback JD, Wrammert J. Rapid Generation of Neutralizing Antibody Responses in COVID-19 Patients. Cell Rep Med. 2020 Jun 23;1(3):100040. doi: 10.1016/j.xcrm.2020.100040. Epub 2020 Jun 8.

  PMID: 32835303 RESULT

• Sette A, Crotty S. Adaptive immunity to SARS-CoV-2 and COVID-19. Cell. 2021 Feb 18;184(4):861-880. doi: 10.1016/j.cell.2021.01.007. Epub 2021 Jan 12.

  PMID: 33497610 RESULT

MeSH Terms

Conditions

COVID-19; Anosmia; Olfaction Disorders

Interventions

COVID-19 Serological Testing

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; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

COVID-19 Testing; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Serologic Tests; Immunologic Tests; Investigative Techniques; Immunologic Techniques

Study Officials

• Puya Dehgani-Mobaraki, MD

  Associazione Naso sano, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 10, 2021
• First Posted: September 9, 2021
• Study Start: May 1, 2020
• Primary Completion: November 1, 2023
• Study Completion: May 1, 2024
• Last Updated: April 14, 2023

Record last verified: 2023-04

Locations

IT (1)