Atiyya Varachia

GENE330 Assignment- The relevance and application of genomics to the molecular diagnosis of
SARS-CoV-2 in South Africa.

[email protected]

Introduction

In Wuhan, China cases of an unknown pneumonia fever was reported in late December of 2019.
By May 2020, this virus was classified as SARS-CoV-2 and a pandemic was declared due to the
severity of this virus (Krammer, 2020). Covid-19 is a severe respiratory disease that is caused by
severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is a beta coronavirus that
belongs to the subgenus Sarbecovirus. The emergence of SARS-CoV-2 in 2019 unleashed a
global pandemic, with profound impacts on public health worldwide. By the end of 2020, over
80 million cases of COVID-19 had been recorded, resulting in more than 1.7 million deaths. This
relentless spread of the virus, coupled with varying degrees of success in implementing public
health measures, led to the generation of numerous virus lineages. To combat this evolving
threat, the scientific community leveraged open sharing of genomic surveillance data and
collaborative online platforms to track these lineages in real time (Hadfield et al., 2018).
Globally, the COVID-19 pandemic has resulted in a high death toll as well as negative economic
and societal effects. The main route of transmission of Covid-19 is from person-to-person
contact, through respiratory droplets, aerosols and fecal-oral contamination (Shi et al., 2020).
The COVID-19 pandemic has prompted the scientific community to quickly develop highly
reliable diagnostic methods to effectively and accurately diagnose the disease and prevent its
spread. Initially, the structural and molecular characteristics of SARS-CoV-2 were unknown, but
various diagnostic strategies that have been developed by private research laboratories and
biomedical companies to make an accurate diagnosis of COVID-19 enabled the biological and
molecular understanding of this virus (Falzone et al., 2021).

With over 80,000 additional natural deaths anticipated by the end of 2020, South Africa was one
of the African nations that has been severely impacted by the COVID-19 epidemic, with a
fatality rate of over 1,400 per million people. A lineage with numerous nonsynonymous spike
mutations has been discovered, including mutations in the RBD that may have functional
importance. This is in addition to the proliferation of several SARS-CoV-2 lineages across the
nation. (Tegally et al., 2021). In this essay the application of genomics and the role it played in
the diagnosis and management of Covid-19 globally and in South Africa will be discussed.

Discussion

The continuous, uncontrolled spread of Covid-19 in many regions has created conditions that
were favorable for evolutionary changes, which led to the development of multiple Covid
variants (Tegally et al., 2021). Due to the emergence of various Covid-19 variants, the methods
of diagnostic testing had to greatly improve for the efficient detection and control the spread of
Covid-19 (Fernandes et al., 2022). The methods for detection of SARS-CoV-2 focus on the
antibodies by serological testing, antigen-specific viral proteins by antigen testing, and certain
viral nucleic acids by molecular methods such as PCR. However, the type of testing method used
depends on the stage of infection as the antibodies, viral nucleic acid, and antigens present differs
at different times of the infection (Tegally et al., 2021). During the early stages of infection,
highly sensitive and specific tests are carried out to detect the presence of viral RNA by
molecular methods and viral proteins by Antigen rapid detection test. After the onset of
symptoms occur, the preferred method of detection includes Antibody tests, molecular tests, and
antigen rapid detection tests as these tests are able to produce results within 15 to 20 minutes and
provide a retrospective diagnosis (Peeling et al., 2021). Serological assays are important for the
detection of antiviral antibodies in infected individuals. An example of antibody-based tests is to
detect the production of antibodies in response to a viral infection or antigen, which can be
determined by Enzyme-linked immunosorbent assays (ELISA). These antibody tests were
proven to be efficient in diagnosing Covid-19, as they can detect the presence of the antibodies
within 3-6 days as well as previous and current infections of the same virus (Rai et al., 2021). To
detect early infection, Nucleic acid amplification tests (NAAT) such as reverse transcriptase real-
time PCR tests (RT-qPCR), microarray tests, and loop-mediated isothermal amplification-based
assays (RT-LAMP) (Chu et al., 2020). LAMP has been classified as a point-of -care test for
SARS-CoV-2 as it explicitly amplifies the sequence of interest (target sequence) under
isothermal conditions in order to detect specific viral RNA genes. However, mutations that occur
at the primer binding site can affect the accuracy of LAMP results, therefore the sites of mutation
should be avoided to ensure effective detection (Chu et al., 2020). Real-time PCR tests, such as
RT-qPCR, aims to detect if viral RNA from the ORF1ab region, Nucleocapsid, spike, and viral
envelope domains are present, however mutations can hinder the accuracy of this testing method
by producing false-negative results (Chu et al., 2020). Samples for NAAT’s are obtained through
nasal swabs, saliva, and throat swabs (Fernandes et al., 2022).

The detection and monitoring for mutations of SARS-CoV-2 is crucial for identify new variants
that could be more contagious and severe. Since the discovery of Covid-19, the virus went
through genetic variations such mutations, horizontal gene transfer, and gene duplication which
led to development of many variants such as Alpha, Beta, Gamma, Delta, and Omicron, which
displayed unique characteristics, levels of severity, and resistance factors to specific vaccines or
treatment methods (Vasireddy et al., 2021). To detect the occurrence of mutations that can lead to
variants, the genetic changes of the viral genome can be identified using sequencing technologies
such as Next generation sequencing (NGS), Amplicon sequencing, and shotgun sequencing to
identify ancestral variants, differences and similarities amongst the different variants by genomic
surveillance as well as to detect mutations such as single nucleotide polymorphisms (SNP)
(Bagabir et al., 2022). Detection of these variants and mutations provides information that will
enable scientists to understand the biology of the virus which is useful for the development of
treatments and vaccines as well as other preventative measures that will effective and control the
transmission of Covid-19 (Chavda et al., 2022).

In South Africa, the rate of infection drastically increased from March 2020 to December 2020,
with several hotspots and superspreading events that occurred in different provinces of the
country. According to a study done by Arashi et al., 2022, the major hotspots of Covid-19 in
South Africa was discovered to be Gauteng, Eastern Cape, and Western Cape with Gauteng
having the highest rate of infection and Limpopo having the lowest rate of confirmed infections
of Covid-19. It was observed that the bordering provinces are advantageous to each other, which
indicated that the provinces that were adjacent to the infectious hotspot regions were more
vulnerable to an increase in infection rate (Arashi et al., 2022). The major issue during the
Covid-19 pandemic in South Africa that led to superspreading events was that individuals did not
strictly follow the rules of lockdown that was implemented as means to control the spread of the
infection. Other factors that could have possibly contributed to the superspreading event in South
Africa was poor hygiene conditions and poor health-seeking behavior and it was observed that
the superspreading event contributed to up to 80% of confirmed infections (Made et al., 2021).

In order to manage and reduce the transmission of Covid-19 globally and in South Africa
professionals such as the World Health Organization (WHO) provided the government with
strategies and rules that should be implemented by pharmaceutical and non-pharmaceutical
interventions. Non-pharmaceutical interventions includes travel restrictions to avoid the spread
of Covid-19 from one country or province into another (Lai et al., 2020). Other non-
pharmaceutical interventions that were implemented were social distancing between people of
approximately 2 meters, the cancellation of all social gatherings, washing hands regularly as well
as sanitizing yourself and surfaces that could be exposed to the virus, the use of face masks and
the implementation of nationwide and global lockdown (Perra, 2021). By preventing and limiting
the size of the epidemic's peak, these strategies aim to stop the spread of the virus. This will give
the healthcare system abundant time to prepare for future transmission and infections and
enables the use of vaccinations and medications in the future (Perra, 2021). In South Africa, the
implementation of different levels of lockdown played a major role in reducing the spread of
Covid-19. The effectiveness of various lockdown alert levels in curbing community movement
was observed, with Alert Level 5 showing a substantial reduction, while Alert Level 4 had fewer
restrictions due to exceptions like walking, running, and cycling, impacting movement. Similar
trends were noted between Alert Levels 3 and 4, influenced by relaxed policies such as
permitting business operations and interprovincial travel, with the grocery, pharmacy, and
workplaces being most affected locations. Alert Levels 1 and 2 had comparable effects on
community movement, while Alert Level 3 had a notably higher impact compared to Alert Level
2 across all studied locations, echoing similarities between Alert Levels 5 and 4, and 4 and 3 in
movement pattern (Mabuka et al., 2023). Pharmaceutical interventions includes the
administration of DNA and RNA vaccines, the use of anticoagulants such as heparin to treat the
blood clots of patients that have a severe Covid-19 infection. Other strategies also include the
consumption of antivirals such as Remdesivir and Molnupiravir which will prevent the virus
from undergoing replication during the early stages of infection. Oxygen therapy or ventilators
are also used as a pharmaceutical strategy to assist the severe patients that have underlying
respiratory conditions (Zong et al., 2022). These various pharmaceutical interventions For
Covid-19 exhibited a promising rate of effectiveness for treatment during the early stages and
during the course of the infection (Rathore et al., 2020).

The battle against COVID-19 has greatly benefitted from the use of genomic technologies which
enabled the possibility of identifying the complete genetic sequence of the Covid-19 virus and
allowed for the development diagnostic tools and vaccines. Thus, genomics holds the promise of
greatly continuing to enhance the public health in South Africa as well as globally. Public health
genomics, which integrates genomic data with established public health practices, offers the
potential to improve infectious and non-communicable disease prevention, management, and
monitoring (Moyo et al., 2022).

Conclusion

In conclusion, the application of genomics has played a crucial role in both the global and South
African response to the COVID-19 pandemic. Genomic surveillance and sequencing have
enabled scientists to track the evolution of the SARS-CoV-2 virus in real-time, identifying
various lineages and mutations. This has been instrumental in understanding the virus's
transmission dynamics, including the emergence of more contagious variants. In South Africa,
genomics played a vital role in monitoring the spread of the virus and identifying hotspots, such
as Gauteng, Eastern Cape, and Western Cape. This information helped public health authorities
target interventions and allocate resources more effectively. Additionally, genomic analysis
revealed the presence of lineages with significant spike mutations, which raised important
questions about vaccine efficacy and potential treatment options. The ability to rapidly sequence
and analyze the virus's genome has also facilitated the development of diagnostic tools, allowing
for accurate and timely COVID-19 diagnosis. Genomic data has provided insights into the virus's
structural and molecular characteristics, aiding in the design of reliable diagnostic methods.

In essence, genomics has been an indispensable tool in the fight against COVID-19, enabling
scientists and healthcare professionals to better understand, diagnose, and manage the disease. As
the pandemic continues to evolve, genomics will remain a critical asset in the efforts to control
and mitigate its impact on public health. The COVID-19 pandemic has imparted several crucial
personal lessons. Early and accurate detection through various testing methods, like PCR and
antibody tests, is paramount for controlling the virus's spread, especially with the emergence of
variants. Vigilance in monitoring mutations through genomic surveillance is vital for
understanding the virus's evolution. Strict adherence to public health measures, such as social
distancing and mask-wearing, plays a pivotal role in reducing transmission. Embracing vaccines
and pharmaceutical interventions while staying updated on available treatments is essential.
Recognizing the importance of global collaboration and organizations like the WHO in
managing pandemics is a lesson in unity. Public health genomics holds promise for enhancing
disease prevention. Superspreading events underscore the need for responsible behavior, and
adaptation and preparedness are key for future health crises. Continuous learning and staying
informed are essential in navigating the ever-evolving landscape of infectious diseases.
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