Abstract:
COVID-19 pandemic has started in December 2019 in China and quickly
extended to become a worldwide health and economic emergency issue. It
is caused by the novel coronavirus; SARS-CoV-2. COVID-19 patients’
clinical presentations vary from asymptomatic infection or flu like
symptoms to serious pneumonia which could be associated with multiple
organ failure possibly leading to death. It is understood that the
immune response to SARS-CoV-2 includes all elements of the immune system
which could altogether succeed in viral elimination and complete cure.
Meanwhile, this immune response may also lead to progression of disease
and could be responsible for the patient’s death. Many trials have been
done recently to create therapies and vaccines against human coronavirus
infections such as MERS or SARS, however, till now, no effective
antiviral drugs or vaccines have been approved to treat or prevent this
disease and its management depends mainly on supportive care. The spike
glycoprotein or protein S of SARS-CoV-2 is the main promoter that
induces development of neutralizing antibodies; hence, many attempts of
vaccines and antiviral drugs development have been designed to be
directed specifically against this protein. While some of these attempts
have been proved to be efficient in in vitro settings, only few of them
have been proceeded to randomized animal trials and human studies which
makes Covid-19 prevention an ongoing challenge.
This review describes the natural immune response scenario during
COVID-19 and the vaccines development trials to create efficient
vaccines thus helping to build more effective approaches for prophylaxis
and management.
Keywords: Novel coronavirus, COVID-19, SARS COV-2, immune
response, cytokine storm, vaccines
Introduction:
COVID-19 was announced as a pandemic on March 11, 2020 with more than 23
million confirmed cases and 809.484 reported deaths all over the world
by August 24, 2020(1). The origin of this viral infection was in Wuhan
city, Hubei province, China, where a series of cases were first
discovered in December 2019 (2).
The etiology was immediately determined as beta coronavirus with high
sequence homology to bat coronaviruses (CoVs) which uses the
angiotensin-converting enzyme 2 (ACE2) receptor as the main cell entry
process(3). Its human to human transmission was confirmed following
possible zoonotic spillover. SARS-CoV-2 is also closely linked to SARS
(previously named SARS-CoV-1) and Middle Eastern Respiratory Syndrome
(MERS) CoVs, which resulted in zoonotic and local outbreaks in 2003 and
2012, respectively. Covid-19 patients present clinically with wide range
of symptoms varying from no or mild symptoms like influenza clinical
picture to more severe forms of pyrexia, cough, dyspnea, sometimes
followed by respiratory failure and multi system failure then death(4).
Whereas SARS-CoV-2 is less deadly than SARS or MERS; its lethality rate
is estimated to be 2.7% versus 9.6% for SARS and 35% for MERS(5),
however its global extension has led to immense uncertainty and
devastating effects in many countries due to its high infectivity rate
requiring specialized medical care in intensive care units (ICU) (6) and
revealing the unseen vulnerabilities of health systems and the
importance of global health cooperation.
The most seriously affected population is the old age group, especially
those suffering from chronic diseases as well as the immunocompromised
patients. Additionally, there are some regional differences in Covid-19
infection patterns whose causes are not clearly understood(7) .
Although a fast and coordinated immune response exerts the first line of
defense in Covid-19, exaggerated production of inflammatory cytokines
during the innate response could result in tissue injury either at the
site of infection or systemically. Moreover, a dysregulated cell
mediated and humoral response may worsen the condition. It was reported
that significant changes occur in both the innate and adaptive immune
response while encountering SARS-CoV-2 leading to enormous release of
cytokines or the “cytokine storm” which represents the ongoing
hysterical activation of the immune system(8).
There is no fully effective therapy till now particularly for the less
immunocompetent patients which makes evading complications a real
challenge. Most of the suggested therapies for Covid-19 are derived from
those used previously in treatment of related viruses such as SARS and
MERS or other viruses as Zika or Ebola. Examples of treatments that
showed some success till now are remdesivir (adenosine analogue) ,
lopinavir/ritonavir (protease inhibitors) alone or combined with
interferon-β, chloroquine, hydroxychloroquine and plasma therapy(9).
The diminished commercial production of effective therapies and vaccines
for Covid-19 and related Corona viruses could be in part due to
decreased interest of the pharmaceutical corporations. Usually, during
epidemics, the requirement for developing a therapeutic drug or a
vaccine lasts only for short period which is the stay of the infection
as there might be no patients available for clinical trials by the time
the new therapy is produced(10).
Since there is limited control of the pandemic even by physical
distancing and good hygiene measurements and there is minimal
understanding of the cytokine storm nature and the changes that occur in
the signaling pathways stimulated by SARS-CoV-2, thus, better
identification of the immune response scenario in Covid-19 patients
especially at the molecular level could help finding the molecular
targets either for therapy or vaccines.
The aim of this review is to focus on the main aspects of both the
innate and adaptive immune responses as well as the effective vaccines
strategies for SARS-CoV-2.