Antibodies Responses to COVID-19 Infection in Hospitalized Patients

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.