Clinical trial NCT04520880: Antibodies Responses to COVID-19 Infection in Hospitalized Patients
Official title: Antibodies Responses to SARS-CoV 2 Infection (COVID-19) in Hospitalized Patients. A Prospective Observational Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV 2 Infection)
Hospitalized Patients
Laboratory-confirmed SARS-CoV 2 Infection
Lead sponsor: Imam Abdulrahman Bin Faisal University
Sponsor class: OTHER
Collaborators: name: Dammam Medical Complex
name: Institute for Research and medical consultations (IRMC)
First posted: 2020-08-20
Enrollment: 158
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Symptomatic inpatients (ICU and none ICU) patients with laboratory-confirmed SARS-CoV 2 infection admitted to the participating centers will be screened, eligible patients will be consented then assessed for the timing of the onset of symptoms.

Patients will be included for testing of the virus-specific antibodies levels if they spend at least 2 weeks from symptoms onset.

Brief summary: 1.5. Why this clinical study?

The prevalence of seropositivity following SARS-CoV 2 infection might have its own potential benefits in terms of predicting the end of pandemic and the validity of herd immunity. It is not clear if SARS-CoV 2 infection would have a long-lasting antibody-mediated immunity, and if the antibodies' persistence is dependent on disease severity.depends on the severity of illness. If evidence is provided about the persistence of antibodies that is reflective of the protective immune response, serodiagnosis will be an important tool to identify individuals with various risk for infection, and those who are in need of receiving the forthcoming vaccines.

The here proposed prospective clinical study will test the prevalence of seropositivity following SARS-CoV 2 infection in critically ill patients compared to those who do not require intensive care unit (ICU) admission or invasive ventilation with respect to the IgM and IgG levels.

Detailed description: 1.1. Prevalence of Coronavirus infection:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused an ongoing pandemic where the first case was reported in Wuhan china earlier in December 2019 then spread exponentially to the rest of the world.

The disease has a wide spectrum of severity where most of the cases have caused mild or no symptoms, 15-20% require hospitalization, and severe cases that need intensive care unit admission account for approximately 3-5% which varies across countries with reported mortality ranged from 30-80% for mechanically ventilated patients.

1.2. Immune response to coronavirus infection.

The immune system responds to infection with coronaviruses primary by developing humoral antibodies responses, in which S-specific and to a lesser extent N-specific antibody are typically elicited in infected individuals. Previous studies conducted during severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) epidemics identified an S and N-specific antibodies that are elicited 2-3 weeks after infection and persisted several weeks to months. During this SARS-CoV-2 pandemic, studies have revealed evidence of seroconversion in those patients who were recovered SARS-CoV-2 infections with a variable degree of response.

1.3. Immune response to SARS-CoV 2 infection.

A case series reported antibodies response to SARS-CoV-2 in some patients and health care workers in a pediatric dialysis unit after contact with a seropositive patient where most of them were asymptomatic.

Some studies showed different seroconversion sensitivity and titer changes over time-based on the degree of symptoms where those who were symptomatic had higher and more sustainable S-specific antibodies (IgM/IgG) response in their sera compared to asymptomatic patients.

Another study of 149 patients who were recovered from mild SARS-CoV-2 illness whom blood was collected after an average of 39 days after the onset of symptoms had variable neutralizing titers: less than 1:50 in 33% and below 1:1,000 in 79%, while only 1% showed titers above 1:5,000 and they conclude that most convalescent plasmas obtained from individuals who recover from SARS-CoV-2 do not contain high levels of neutralizing antibodies activity.

1.4. Immune response to SARS-CoV 2 infection and severity of the disease.

Other investigators reported that in the asymptomatic group, the median duration of viral shedding was 19 days (interquartile range (IQR),15-26 days). The shortest duration of viral shedding in the asymptomatic group was 6 days and the longest was 45 days. In patients with mild symptoms, the median duration of viral shedding was 14 days (IQR, 9-22 days). Interestingly, 81.1% of the asymptomatic patients tested positive for (antigen: S-specific?) IgG 3-4 weeks post-exposure and 83.8% of the symptomatic group tested positive for (antigen: S specific?) IgG 3-4 weeks post-exposure. In the acute phase, (antigen to be specified) IgG levels in the asymptomatic group (median S/CO, 3.4; IQR, 1.6-10.7) were significantly lower (P = 0.005) relative to the symptomatic group (median S/CO, 20.5; IQR, 5.8-38.2). Of note, 93.3% of the asymptomatic group saw a decline in IgG levels during the convalescent phase (8 weeks post-hospitalization) compared with 96.8% of the symptomatic group - the median percentage of decrease was 71.1% (range, 32.8-88.8%) and 76.2% (range, 10.9-96.2%) respectively.

Other investigators published online in medRxiv, and not yet peer-reviewed, reported that 40% of asymptomatic individuals became seronegative and 12.9% of the symptomatic group became negative for (antigen) IgG in the early (8 weeks) convalescent phase.

SARS-Cov2 patients who survived critical illness expected to have a maximum immune response which helped them to survive their illness, whether this response has the prolonged-lasting effect or not compared to other hospitalized none critically ill patients with less disease severity is to be investigated,

Objectives

Given the evidence available on this area, the investigators would measure the S specific and N specific binding antibody levels as well as N neutralizing antibodies of COVID-19 patients with different severity of illness at the different time periods.

The overall objectives of this prospective observational parallel clinical trial are to test the persistence of humoral antibody responses measured by the levels of binding and neutralizing antibodies after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hospitalized patients with different severity of illness over different time intervals.

Here, the investigators aim to measure the proportion of patients with positive S-specific and N-specific antibodies during at 4 to 6 and at least 16 weeks after the onset of symptoms of SARS-Cov2 infection in ICU and non-ICU hospitalized patients.

The investigators would provide information for the scientific community to predict the short-term herd immunity of the disease.

Hypothesis

The investigators hypothesize that, compared with symptomatic hospitalized patients, the critically ill patients might be likely to produce long-lasting protective antibodies against this virus following SARS-CoV-2 infection.

STUDY DESIGN

A multi-center, prospective observational, longitudinal study in patients with SARS-CoV 2. The study will be conducted according to Good Clinical Practice (GCP) Guidelines and comply with the principles of the Declaration of Helsinki. The study will be registered in a public registry.

Eligibility criteria: Inclusion Criteria:

* Symptomatic infection with at least 2 weeks' time interval since the symptom's onset.
* Laboratory-confirmed COVID-19 with positive SARS-CoV-2 real-time polymerase chain reaction (RT-PCR) testing of nasopharyngeal or oropharyngeal swabs.
* Inpatients in either isolated wards or ICU.
* Agreement for blood sampling during the course of the study.

Exclusion Criteria:

* Decline consent to participate.
* Pregnancy.
* Asymptomatic patients, who are PCR positive during routine screening upon admission
* Administration of immunoglobulins within the 3 proceeding months including Covid-19 convalescent plasma.
* Patients with Don't resuscitate orders
* Patients with terminal illnesses regardless of the severity of SARS-CoV 2 infection.

Primary outcomes:
measure: Changes in the levels of S specific antibodies in severely ill patients compared to mild cases.
timeFrame: Changes from baseline (4 to 6 weeks) at 16 weeks after the onset of symptoms of SARS-Cov2 infection
measure: Changes in the levels of N specific antibodies in severely ill patients compared to mild cases.
timeFrame: Changes from baseline (4 to 6 weeks) at 16 weeks after the onset of symptoms of SARS-Cov2 infection
Secondary outcomes:
measure: S specific binding antibodies of SARS-CoV-2
timeFrame: 4 to 6 weeks and 16 weeks after the onset of symptoms of SARS-Cov2 infection
measure: N specific binding antibodies of SARS-CoV-2
timeFrame: 4 to 6 weeks and 16 weeks after the onset of symptoms of SARS-Cov2 infection
measure: Neutralizing antibodies directed against S protein of SARS-CoV-2
timeFrame: 4 to 6 weeks and 16 weeks after the onset of symptoms of SARS-Cov2 infection
measure: The severity category of critically ill
timeFrame: Day 0, 4 to 6 weeks and 16 weeks after the onset of symptoms of SARS-Cov2 infection
measure: Length of ICU
timeFrame: For 16 weeks after the onset of symptoms of SARS-Cov2 infection
measure: Length of hospital stays
timeFrame: For 16 weeks after the onset of symptoms of SARS-Cov2 infection
measure: Alive status at 28-days
timeFrame: For 28 days after the onset of symptoms of SARS-Cov2 infection
measure: Alive status at 90-day
timeFrame: For 90 days after the onset of symptoms of SARS-Cov2 infection
measure: Correlation between the levels of S neutralizing antibodies and disease severity
timeFrame: For 16 weeks after the onset of symptoms of SARS-Cov2 infection
measure: Correlation between the levels of N neutralizing antibodies and disease severity
timeFrame: For 16 weeks after the onset of symptoms of SARS-Cov2 infection
Other outcomes:
Locations:
city: Dammam
country: Saudi Arabia
facility: Imam Abdulrahman Bin Faisal University
state: Eastern
Study officials:
affiliation: Critical Care and emergency Department, Associate Professor, College of Medicine, Imam Abdulrahman Ben Faisal University
name: Mohammed S Alshahrani, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Associate Professor, Department of epidemic disease research, IRMC, IAU
name: Iman Almansour, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Anesthesiology Department, Associate Professor, College of Medicine
name: Mohamed R El Tahan, MD
role: STUDY_DIRECTOR
References: