Clinical trial NCT05038475: Clinical and Immunological Responses After SARS-CoV-2 Infection Causing COVID-19
Official title: Longitudinal Observation of Clinical and Immunological Profiles After SARS-Cov-2 Infection
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Covid19
SARS-CoV2 Infection
Olfactory Disorder
COVID-19
Smell Loss
Smell Disorder
Keywords: Antibody responses
olfaction
smell
sars-cov-2
covid-19
IgG
IgM
serology
immune response
humoral response
Lead sponsor: Association "Naso Sano" Onlus
Sponsor class: OTHER
First posted: 2021-09-09
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Detailed description: Study design: A monocentric pilot longitudinal observational study

Study subjects: patients recovered from SARS-CoV-2 infection in March 2020 (detected by RT-PCR)

Study method: The study was conducted after written informed consent for voluntary participation. The antibody titers were longitudinally analyzed by sequential serological tests at different time points (TPs) 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 the treatment undertaken using a standardized questionnaire.

From May 2020 to January 2021:

Anti-Nucleocapsid (NCP) antibodies were analyzed using FDA-approved CLIA immunoassay through sequential serum samples.

Time was treated as a factor and six different time points (TPs) were defined (T0-T5). The first blood sample was collected in the month of May 2020, 2 months after the month of infection (March), and was defined as T0. Consecutive serological samples were analyzed at different TPs; three months (T1), five months (T2), seven months (T3), eight months (T4), and ten months (T5) post-infection in June, August, October, November of 2020 and January 2021 respectively.

At this point, a more specific immunoassay was adopted to detect neutralizing antibodies against the Spike-Receptor binding domain 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 and 6 male) were gradually vaccinated from mid-March 2021 and hence excluded from the original cohort, making the revised final sample size as n=32.

The presence of antibodies was analyzed The study continues to actively enroll patients for future analysis.

with vaccination in progress, the antibody titers of the recovered and then vaccinated patients will also be analysed separately.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. No acute respiratory infection or active SARS-CoV-2 infection.
3. Informed consent of the adult participant.

Exclusion Criteria:

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

Primary outcomes:
measure: Analysis of demographic profile (Age) of recovered COVID-19 patients [at inclusion]
timeFrame: At inclusion
measure: Analysis of demographic profile (Gender) of recovered COVID-19 patients [at inclusion]
timeFrame: At inclusion
measure: Analysis of demographic profile (occupation) of recovered COVID-19 patients [at inclusion]
timeFrame: At inclusion
measure: Analysis of clinical profile of recovered COVID-19 patients [at inclusion]
timeFrame: At inclusion
measure: Analysis of associated co-morbidities in recovered COVID-19 patients [at inclusion]
timeFrame: At inclusion
measure: Analysis of immunological profile recovered COVID-19 patients [at inclusion]
timeFrame: At inclusion
measure: Seroprevalence of IgM and IgG against Nucleocapsid of SARS-CoV-2 (in AU/ml) [from T0 to T5]
timeFrame: 8 months
measure: Seroprevalence of IgM and IgG against spike-receptor binding domain of SARS-CoV-2 (in AU/ml) [from T6 to T8]
timeFrame: through study completion, an average of 2 years
measure: Seroprevalence of IgM and IgG against spike-receptor binding domain of SARS-CoV-2 (in AU/ml) for vaccinated individuals
timeFrame: through study completion, an average of 2 years
Secondary outcomes:
measure: 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 ]
timeFrame: 8 months
measure: 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 ]
timeFrame: 4 months
measure: 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 ]
timeFrame: at inclusion and within the observational period (8 months)
measure: 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 ]
timeFrame: at inclusion and within the observational period (4 months)
measure: Co-relation of co-morbidities and antibody titer levels with respect to disease severity [ at inclusion]
timeFrame: at inclusion and within the observational period (8 months)
measure: Co-relation of co-morbidities and antibody titer levels with respect to disease severity [ at inclusion]
timeFrame: at inclusion and within the observational period (through study completion, an average of 2 years)
measure: Co-relation of antibody titer levels and smell and taste dysfuntion with respect to disease severity [ at inclusion]
timeFrame: at inclusion and within the observational period (through study completion, an average of 2 years)
Other outcomes:
Locations:
city: San Mariano
country: Italy
facility: Associazione Naso Sano
state: Perugia
Study officials:
affiliation: Associazione Naso sano, Italy
name: Puya Dehgani-Mobaraki, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.