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.