Personalized Medicine in the COVID-19 Vaccination Amid the Wake of Diseases Comorbidity Using Nigeria as a Case Example

Mechanism of COVID-19 Pathogenesis and Diseases Comorbidity

The coronavirus disease 2019 (COVID-19) which accelerated to pandemic stage by March 2020 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Characteristic of coronaviruses, SARS-CoV-2 possesses a spike glycoprotein on its cell surface which acts as its primary antigen and accelerates entry into target cells by binding to receptors on host cell surfaces [1]. The virus is an enveloped beta coronavirus which has a single-stranded 30 kilobase positive-sense RNA that encodes the 4 structural proteins namely, the spike (S) protein, membrane “matrix” (M) protein, Nucleocapsid (N) protein, and the envelope (E) protein [2]. The SARS-CoV-2 infection can be transmitted via respiratory droplet such as those emitted when breathing, sneezing, normal speech, and coughing. Therefore, the maintenance of physical distancing is important in reducing the spread of the disease. The infection could also be transmitted through contaminated surface and objects, which is why the use of hand sanitizer is essential is fighting the pandemic [3]. Other studies have reported that the virus could be present in body fluids such as saliva [4].

In typical coronavirus fashion, SARS-CoV-2 binds to the angiotensin-converting enzyme 2 (ACE-2) receptor located on epithelial cells. This binding is mediated by the spike protein which has a strong affinity for ACE-2 receptor and the binding of both molecules signals the transmembrane protein serine 2 (TMPRSS-2) which mediates proteolytic cleavage and facilitates viral entry by priming the virus for interaction with ACE-2 [5, 6]. Upon entry into the host cell, the virus uncoats itself and then utilizes the host genetic and protein machinery to produce full-length antisense genome using its single stranded RNA as a template [7]. The spike protein is a trimer with 2 subunits namely SI and S2. The SI subunit contains 3 receptor-binding units including a receptor binding domain (RBD) which locks on to the ACE- 2 receptor, while the S2 contains heptapeptide sequence 2 and 1 [8, 9]. ACE-2 is a membrane-bound protein expressed in multiple human organs including the kidney, lungs, and in systems such as the central nervous system [10]. It is an important signal protein for the entry of SAR-CoV-2 into the host cell. Accelerated production of the receptor is reported in several pathological conditions. In diabetics there is an increased level of ACE-2 receptors followed by a proportionate increase in Furin levels [11, 12]. Furin is a type-1 membrane-bound proprotein convertase which activates the S protein by cleaving it into discrete S1 and S2 subunits thereby facilitating attachment to ACE-2 receptors and evasion of the host immune system [13].

Elevated levels of these proteins are also observed in patients with chronic obstructive pulmonary disorder (COPD) [14]. ACE-2 inhibitors, angiotensin receptor blockers (ARBs), and aldosterone receptor antagonists used in treating hypertension, cardiovascular and kidney disease result in upregulation of ACE-2 receptors [15]. The binding and entry of SARS-CoV-2 into a host is mediated by interaction of Spike protein with ACE2 receptor, this interaction depends on host protease (such as cathepsin B and L, TMPRSS2, and furin processing [5]. The mechanism used by those proteases in mediating host entry is unclear [16]. But some studies have suggested that the TMPRSS2 mediate cell entry by the activation of membrane fusion protein through irreversible conformational change. Therefore, the TMPRSS2 is one of the studied androgen-regulated genes associated with prostate cancer [17].

The mechanism of TMPRSS2 in the mediation of prostate cancer is by promoting oncogenic transcription. More than half of all prostate cancers in men of European ancestry harbor a gene fusion that juxtaposes the androgen receptor (AR) regulatory promoter/enhancer elements of TMPRSS2 in front of the ETS family transcription factors, most commonly ERG [18]. Even though the regulation of ERG is not mediated by androgen, but this somatic gene rearrangement results in oncogenic ERG expression under androgen receptor signalling. Through the activation of HGF, TMPRSS2 promotes metastatic prostate cancer [19]. The metalloprotease ACE2 receptor (zinc dependent) is expressed in heart, kidney, and testis at high level [10]. Hence, the mechanism of governing TMPRSS2 and ACE2 expression could shed light on the disparity of SARS-CoV-2 mortality and morbidity in men [20]. While this introduction highlights the relationship between the SAR-COV-2 and disease comorbidities, the specific aim of this article, however, is to review personalised medicine for COVID-19 vaccination in Nigeria.

Epidemiology of Common Chronic Diseases in Nigeria

The resolution of epidemiological data in Nigeria often suffers due to a paucity of national disease registries, high buy-in to traditional medicine in rural areas, difficulty accessing the limited available health centres, the state of medical records (analogue, non-searchable) and other systemic issues. These challenges notwithstanding, this paper integrates data from high quality sources including National System of Cancer Registries (NSCR), National survey of non-communicable diseases (NCDs), Federal Ministry of Health and global agencies like the World Health Organisation’s databases.

Global and Nigeria’s Vaccination Efforts

Globally, the development of effective vaccines against the coronavirus has been fast with an impressive growth rate of the vaccine having the effect of putting the pandemic on a tight rein [34]. Development of vaccine in several research centres and pharmaceutical companies was announced as soon as SARS-CoV-2 was known to be its causative agent [35]. The effectiveness of a vaccine may be abused on people’s strong preferences while a vaccine of low effect could also influence willingness of its acceptance by the population. To halt the COVID-19 pandemic, high vaccination coverage may be required hence the need to put into cognizance its demand in across countries where low- and middle-income countries (LMICs) or high-income countries [36]. By a year after the report of the first COVID-19 case, a minimum of 177 countries and territories had administered more than 878 million doses of a COVID-19 vaccine. Various strategies have been implored by countries with some vaccinating more of their citizens as fast as possible while others give precedence to populations more likely to be at risk making a sum of 879 million vaccines administered with 195 million fully vaccinated around the globe as at 15th April, 2021 [37].

Like any other African country, Nigeria had about 50 days or more to prepare for the pandemic since its outbreak in Wuhan, China. On March 12 2020, the Presidential Task Force on the fight against COVID-19 pandemic was inaugurated with the goal of National Response Strategy to help train healthcare workers on infection, prevention and control and respond to the pandemic [38]. Introduction of fiscal and monetary measures by the government coupled with partnerships from international agencies such as the World Bank, to mention a few are collaborating with the Taskforce to fight the coronavirus [39]. Despite disruptions associated with COVID-19 containment measures such as closure of borders, workplaces and educational institutions, restriction of movements (intra-urban/inter-urban transportation), negative responses have been recorded against the measures hence the reason for the continuous cases in the country. Nonchalant attitudes and failure to observe measures such as physical distancing and regular hand hygiene have caused a delay in flattening the curve of the pandemic hence birthing daily cases of infected individuals [40].

In March 2021, Nigeria received nearly 4 million doses of the AstraZeneca/Oxford vaccine shipped by COVAX facility from the Serum Institute of India (SII), Mumbai to Abuja, Nigeria with the aim to inoculate 70% of 200 million people by 2022 [41]. As at 15th of April, 2021, a total of 1.08 million doses have been administered to the citizens [37]. To support the vaccine procurement, MTN, a telecommunication company also delivered 300,000 doses of the vaccine. According to a poll by the National Primary Healthcare Development Agency (NPHCDA), various reactions have being recorded in term of ‘Vaccine hesitancy’ with 50% of the population showing interest in vaccine inoculation [42].

Before the arrival of the vaccine, vaccine accountability officers were appointed both in states and local government areas to ensure the vaccines are kept safe, potent and closely monitored through its management and utilization. The minimum criteria required for a vaccination program to hold include training, availability of data-gathering tools, cold storage, transport and logistics for healthcare workers [42]. Registration of people electronically for vaccination to ensure its efficiency and orderly schedule for its collection is being done in Nigeria through an e-registration portal under an electronic immunization data management scheme. According to pre-planned classifications which are in phases, frontline workers are prioritized for the vaccination followed by populations at high risk for severe diseases, essential workers and lastly the general public [43]. Being vaccinated does not mean that people can throw caution to the wind rather Nigerians need to continually adhere to other public health and social measures by wearing nose masks, washing of hands or use of hand sanitizers and maintenance of physical distancing to help curb the virus [41].

Advancing Precision Medicine in the Era Of COVID-19 Vaccination

With the passage of time medical practice has enjoyed increased efficiency and one of such processes currently being maximised in the interest of improved patient management is personalised medicine. The term implies the incorporation of the unique genomic composition of each individual as well as the variability of their environment and lifestyle choices into the diagnosis of their disease condition and management of the condition [44]. A most important element of precision medicine is that it takes cognizance of the patient’s pre- existing conditions while making recommendations for preferential treatment pathways that may be more effective. This is most applicable to the distribution of COVID-19 vaccines given the time sensitive nature of the pandemic. The application of precision medicine to the vaccine distribution process will help identify patient groups with pre-existing conditions that make them more vulnerable to more grave reactions to COVID-19. Several disease conditions result in the weakening of the patient’s immune system thus leaving them vulnerable to the SARS-COV-2.

Precision medicine affords the benefit of insight into what risk factors should have a greater weighting when considering who should be prioritised for COVID-19 vaccines. The most obvious groups of priorities are currently healthcare workers and people with debilitating disease conditions, but this prioritisation needs to be informed by factors other than physical assessment in order to ensure that the most vulnerable groups are adequately protected. Nigeria has high incidence of diabetes and hypertension which top the charts as comorbidities for COVID-19 [45]. The incidences of cancers in the country are also rapidly on the rise consistent with the global trend [46]. This makes it extremely expedient that a more specialised and bespoke approach be adopted to reflect these peculiarities.

Conclusion

Nigeria, with its characteristic high burden of disease comorbidities, will benefit immensely from personalized medicine in treatment or diseases prevention interventions such as vaccination. The emergence of COVID-19 and the need to vaccinate the adult population with various diseases comorbidities reemphasize the need to apply precision medicine to vaccination and disease treatment interventions. This is a wakeup call for Nigeria and other countries with high burden of disease to invest in precision medicine as there is no better time than now.