Fractal Signatures in the Dynamics of an Epidemiology An
Analysis of COVID 19 Transmission, 1st Edition
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iv Fractal Signatures in the Dynamics of an Epidemiology
with an FR4-epoxy substrate of 1.6 mm thickness. The printed prototype measured parameters, including
S-parameters, polarization, and radiation pattern show a good agreement with simulated results.
The fourth chapter aims to validate the design of a novel unique microstrip fractal patch antenna and
its array with a COVID-19 shape designed for wireless applications. The single element patch is a compact,
miniature size, multiband, low weight, and low cost patch antenna; the demonstrated patch antenna and
its array are simulated using the High-Frequency Structure Stimulator software program. This chapter has
productively used the fractal geometry and the COVID-19 shape in order to create a miniature antenna for
the implementation of dual-band wireless, satellite, and radar applications (when it is a part of an array) and
civil commercial services.
The World Health Organization on Jan 30, 2020 has declared this genomic-virus a ‘public health
emergency of international concern’. But with time, this phenomenon further spread like a wildfire with no
possible anti-viral treatment at the moment due to which it began to be referred as pandemic on 11th March,
2020. Gradually, it has been studied that the entire genomic-sequencing indicated that these viral cells were
not at all recombinant. Although, it has been analyzed that relatively much recent corona genomic viral of
group-1 category was prevalent. The fifth chapter of the book studies the outbreak of coronavirus towards
major parts of United States. With usage of multifractality, self-affinity, narrowing to fractality for time
series, the complexity of the situation was dealt with to understand the scenario known as pandemic. Hurst
exponent values, multi-fractal, and waveform signal analysis indicate a similar pattern. This study is required
as the outliers, or the inaccuracies may keep away the actual picture of the situation. Therefore, it was
required to capture this essence related to the pandemic as it had been affecting millions everyday beginning
from January in this case of the United States. From the data-driven hybrid analysis, it is observed that Herd
immunity started increasing in the society.
In the sixth chapter of this book, the multifractality concepts on the infected cases, death cases, and
vaccinated cases of COVID-19 for highly affected countries are investigated through the multifractal detrended
fluctuation analysis. This analysis helps us to examine the COVID-19 diffusion process extensively by
multifractal spectrum. Further, it may help us to take further actions and also we can increase the vaccinations
based on the results obtained from the infected cases and death cases for the representative countries to
reduce the rate of infections and the death ratio.
In order to help society towards resilience in the environmentally sustainable public health care system, the
seventh chapter focus to provide an integrated fractal based prognostic analysis on the coronavirus transitivity
rate. The achievable reconstruction of the epidemic curves based on the fractal interpolation function with
variable scaling parameter to construct the predicted data is indulged in this proposed scheme by using the
sample COVID-19 datasets with infected and death cases. The improved generalized fractal dimensions
of COVID-19 time series are figured out and also the comparative analysis is premeditated between the
predicted data interpolated by the fractal interpolation function with the two types of scaling factors. Based
on the forecasting results with the sample data set in this integrated research study, the COVID-19 data on
any time interval can be taken for the investigation in the similar way. Further, the results suggest the public
health care sectors to take effective control measures in order to control the deadly coronavirus diffusion and
attain sustainable environment.
The eighth chapter has proposed and analyzed a mathematical model to study the epidemic and
economic consequences of novel coronavirus, with special emphasis on the interplays between the disease
transmission, the management of pandemic and the socio-economic perspective. Both the asymptomatic and
symptomatic individuals are considered and include the effectiveness of disease control into the respective
disease transmission rates. The proposed model is analyzed to discuss the feasibility as well as stability of the
disease-free and endemic steady states, and an epidemic threshold in the form of basic reproduction number
is obtained. Performed as the global asymptotic stability of the disease-free and endemic steady state of the
Preface v
proposed system by constructing suitable Lyapunov function. Through numerical simulations, we observed
that to mitigate the direct contacts between susceptible and infected individuals the population must have to
maintain the social distances.
The ninth chapter intends to provide a fractal-based approach to analyze a Covid-19 data set in India
from June 2020 to May 2022. The entire study period is divided into four half-years, and the analysis is to
be carried out separately for each half-year. Covid-19 data analysis begins with the reconstruction of the
curves representing the number of daily confirmed cases and the curves for the number of daily tests through
the fractal interpolation technique. A linear iterated function system is formulated using the considered data
set with a proper vertical scaling factor. Then, the attractor of this iterated function system is the required
fractal interpolation curve. Fractal interpolation offers the benefit of minimizing data loss when creating
curves. In addition to the reconstruction of the curves, this chapter proposes a more straightforward method
to find the cumulative number of Covid-19 cases during each half-year by calculating the area under the
curve using fractal numerical integration. It is easier to compute the number of cumulative cases using fractal
numerical integration instead of adding up each day’s number of cases separately. By determining the ratio
of cumulative cases to the entire population, this chapter the analysis the virus’ growth rate in the nation.
The tenth chapter discusses the COVID-19 cases from 2020 to 2023 that employ the fractal dimension.
This chapter classifies the time series of positive newly confirmed COVID-19 cases, fatality COVID-19
cases from January 2020 to January 2023, and vaccinated and boosted cases from 2021 to 2023 for the world
and most affected countries, including the United States, India, the United Kingdom, France, and China. The
analysis process has performed by identifying fractal dimension through the Hurst exponent. The year-wise
comparison of the aforementioned data is described for both raw data and outcomes.
The countries of the world are still struggling to get rid of the impact of SARS CoV-2. As if this is
not enough, different variants of Corona are continuously evolving. These are discovered by analyzing the
genetic sequence of the particular virus. Consequently, the eleventh chapter focuses on the various graph
interpretations of spike proteins in variants and genetic sequences in subvariants. Furthermore, the variation
between the variants and sub-variations of the SARS Cov-2 is investigated by determining the fractal
dimension and similarity measures in this chapter.
In the twelfth chapter, a model based on Lambert W function is proposed for analyzing the growth rate
of multicellular tumor spheroid. The model is validated with multicellular tumor spheroid data such as 9L,
U-87MG and Rat1-T1. Also the model discriminate the growth rate changes in three stages of each tumor
data. The obtained results reveal our proposed method is very much suitable for approximating the tumor
growth rate for the data which preserves the properties of Gompertz curve.
Contents
Preface iii
1. Analysis of the Current, Past, and Future Evolution of COVID-19 1
Reza Elahi, Parsa Karami, Mahsa Bazargan, Shahrzad Ahmadi, Arash Azhideh
and Abdolreza Esmaeilzadeh
1.1 Introduction 1
1.2 An Overview of the Evolution of SARS-CoV-2 2
1.3 An Overview of the Evolution of COVID-19 6
1.4 Future Evolution of COVID-19 based on Fractal Models 8
1.5 Conclusion 12
Conflicts of Interest 12
References 12
2. A Fractal Viewpoint to Covid-19 Infection 19
Oscar Sotolongo-Costa, José Weberszpil and Oscar Sotolongo-Grau
2.1 Introduction 19
2.2 Fractal Model 20
2.3 Results and Discussion 22
2.4 Conclusions and Outlook for Further Investigations 26
References 27
3. Design of Covid-19 Fractal Antenna Array for 5G and mm-WAVE Wireless Application 29
J.S. Abdaljabar, M. Madi, A. Al-Hindawi and K. Kabalan
3.1 Design of COVID-19 Antenna Array for Centimeter Wave Band 29
3.2 Antenna Fabrication and Measurements 36
3.3 Design of COVID-19 Antenna Array for Millimeter Wave Band 37
3.4 Conclusion 45
References 45
4. Design of Fractal COVID-19 Microstrip Patch Antenna Array for Wireless Applications 47
J.S. Abdaljabar, M. Madi, A. Al-Hindawi and K. Kabalan
4.1 Introduction and Preliminaries 47
4.2 Fractal Geometry 48
4.3 Antenna Configuration 49
4.4 Some of Related Formula 52
4.5 Results and Discussion 53
4.6 Antenna Array Design Using Miniaturized Patch Element 56
4.7 Conclusion 67
References 67
Contents vii
5. Fluctuation Analysis Through Multifractals for the Pathogenesis of SARS-CoV-2 aka 70
nCoV-19 Community Spread in USA
Aashima Bangia and Rashmi Bhardwaj
5.1 Introduction 70
5.2 Dataset Collection 71
5.3 Multi-fractal Analysis 72
5.4 Hurst Rescaled R/S Analysis 73
5.5 Discrete Waveform Signal Analysis (DWS) 73
5.6 Results and Discussions 73
5.7 Conclusion 81
References 81
6. Multifractal Detrended Fluctuation Analysis on COVID-19 Dynamics 84
M. Dhanzeem Ahmed, D. Easwaramoorthy, Bilel Selmi and Sara Darabi
6.1 Introduction 84
6.2 Mathematical Methods 85
6.3 Data Description 87
6.4 Results and Discussion 87
6.5 Conclusion 100
References 100
7. An Integrated Perspective of Fractal Time Series Analysis for Infected Cases of COVID-19 103
A. Gowrisankar, D. Easwaramoorthy, R. Valarmathi, P.S. Eliahim Jeevaraj, Christo Ananth and
Ilie Vasiliev
7.1 Introduction 103
7.2 Methods 107
7.3 Clinical Data 108
7.4 Results and Discussion 110
7.5 Conclusion 114
References 114
8. A Mathematical Model for COVID-19 Pandemic with the Impact of Economic Development 118
Jayanta Mondal, Subhas Khajanchi and Md Nasim Akhtar
8.1 Introduction 118
8.2 Mathematical Model 120
8.3 Mathematical Analysis 121
8.4 Numerical Illustrations 128
8.5 Conclusion 132
References 132
9. Growth Analysis of Covid-19 Cases Using Fractal Interpolation Functions 135
M.P. Aparna and P. Paramanathan
9.1 Introduction 135
9.2 Preliminaries 136
9.3 Methodology 139
viii Fractal Signatures in the Dynamics of an Epidemiology
9.4 Results 141
9.5 Conclusion 145
References 145
10. Classification of COVID-19 Time Series Through Hurst Exponent and Fractal Dimension 147
C. Kavitha, M. Meenakshi and A. Gowrisankar
10.1 Introduction 147
10.2 Methodology 149
10.3 Data Description 151
10.4 Result and Discussion 153
10.5 Conclusion 159
References 159
11. A Study on the Variants and Subvariants of a Solitary Virus 162
A.A. Navish and R. Uthayakumar
11.1 Introduction 162
11.2 Preliminaries 163
11.3 Analyzing Chaotic Characteristics of SARS Cov-2 Variants and Subvariants 164
11.4 Results and Discussion 171
11.5 Conclusion 174
References 174
12. Mathematical Modelling of Multicellular Tumor Spheroid Growth Using Lambert Function 176
C. Aishwarya and P. Paramanathan
12.1 Introduction 176
12.2 Materials and Methods 177
12.3 Model Formulation 178
12.4 Results and Discussion 180
12.5 Conclusion 189
References 190
Index 193
Chapter 1
Analysis of the Current, Past, and Future
Evolution of COVID-19
Reza Elahi,1,* Parsa Karami,1 Mahsa Bazargan,2 Shahrzad Ahmadi,3
Arash Azhideh4 and Abdolreza Esmaeilzadeh5
1.1 Introduction
Since December 2019, the coronavirus disease (COVID-19) pandemic has been a worldwide health concern.
COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV 2), which is a virus
from the betacoronaviridae family [1]. As of November 2022, COVID-19 has spread to most countries
causing more than 626 million confirmed cases and more than 6.5 million deaths (https://covid19.who.int/
accessed 30 October 2022). Due to the rapid spread and serious health problems caused by the disease, on
March 11, 2020, this disease was declared a global pandemic of worldwide importance by the world health
organization (WHO) (https://www.who.int/emergencies/diseases/novel-coronavirus-2019).
Major clinical symptoms of COVID-19 include a sore throat, cough, dyspnea, and muscle weakness. In
some cases, COVID-19 could also have more aggressive respiratory signs and progress to severe disease
with pulmonary distress [2]. Imaging of COVID-19 patients shows patchy ground glass opacifications;
however, these signs were reversible and often disappear after recovery [3]. Moreover, other symptoms
including vomiting, diarrhea, and mild abdominal discomfort could also be seen [4]–[9]. Major cases of
COVID-19-associated mortality are older patients with chronic conditions, including chronic kidney disease,
hypertension, diabetes mellitus type II, or cardiopulmonary disease [10]–[12]. Studies have discussed that
the mortality rate could increase in the first episodes of a COVID-19 outbreak due to the potential of the virus
to infect patients more aggressively and was more pathogenic in first exposures. However, further efforts
for a better comprehension of the SARS-CoV-2 pathogenicity, immunization of the population, and proper
hygiene observations have led to a significant reduction in mortalities [13].
1 School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
2 Virology Research Center, the National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Masih
Daneshvari Hospital, Allergy and Immunology Subspecialty Lab, Tehran, Iran.
3 Department of Immunology, School of Medicine, Sahid Beheshti University of Medical Sciences, Tehran, Iran.
4 Skull Base Research Center, Sahid Beheshti University of Medical Sciences, Tehran, Iran.
5 Cancer Gene Therapy Research Center (CGRC), Zanjan University of Medical Sciences, Zanjan, Iran.
2 Reza Elahi, Parsa Karami, Mahsa Bazargan, Shahrzad Ahmadi, Arash Azhideh and Abdolreza Esmaeilzadeh
After being declared a pandemic, COVID-19 spread rapidly to most countries around the world. The
COVID-19 pandemic has gone through several changes and has experienced an evolutionary process since
2019. Some of these changes could be attributed to the natural behavior of the pandemic, while others are
related to worldwide anti-viral vaccination [14]. Mathematical models can study the behavior of a specific
disease and can predict its behavior in the future. Understanding the spikes of the COVID-19 pandemic in
different countries is a good example of this. Different mathematical models have been proposed for viral
spread and other features of the disease [15]–[18]. Based on regression analysis, such models can be used for
both monitoring the policies of the governments against the pandemic as well as setting proper policies to
control it [19]. Understanding the evolution of past and present evolution of COVID-19 can help predict the
future evolution of the disease. In this chapter, we overview the evolution of the SARS-CoV-2 and discuss
how new variants affect the pandemic, overview the evolution of the COVID-19 pandemic, and finally discuss
the future evolution of COVID-19 based on known mathematical models.
Understanding the evolution of past and present evolution of COVID-19 can help predict the future
evolution of the disease. In this chapter, we overview the evolution of the SARS-CoV-2 and discuss how
new variants affect the pandemic, overview the evolution of the COVID-19 pandemic, and finally discuss the
future evolution of COVID-19 based on known mathematical models.
1.2 An Overview of the Evolution of SARS-CoV-2
In understanding the emergence and evolution of SARS-CoV-2 it is necessary to understand the evolution
of COVID-19. In this section, we aim to discuss the current data on the origin of SARS-CoV-2 and its
different variants. The Sarbecovirus subgroup of Betacoronavirus contains the coronaviruses that have
recently caused pandemic/epidemic outbreaks of infection in human populations. Coronaviruses belonging
to this family can be found in large numbers in bats and other animals. This subgroup includes the endemic
and low pathogenic coronaviruses, such as HCoV-HKU1, HCoV-NL63, HCoV-OC43, and HCoV-229E,
which cause mild symptoms in humans, and SARS-CoV-2, middle-east respiratory coronavirus (MERS-
CoV), and severe acute respiratory syndrome coronavirus (SARS-CoV), which cause more severe symptoms
[20]. Although the zoonotic transmission mechanism for SARS-CoV-2 is unknown, it is thought to have
arisen from Rhinolophus bats [21]. Due to the consistent population growth of coronaviruses (CoVs) and
the widespread finding of varied CoVs, bats are thought to be the fundamental hosts for all CoV lineages, in
contrast to the epidemic-like growths found in other species [22].
There are beliefs regarding the origin of SARS-CoV-2 that it could be from a seafood market in Wuhan,
Hubei Province, China. It is hypothesized that Rhinolophus bats are the natural reservoirs of SARS-CoV-2
[23]. SARS-CoV-2 genomic research uncovered several recombination occasions [24]. Due to the potential
for SARS-CoV-2 recombination, virologists have a lot to be concerned about regarding the spread of new
and potentially more harmful virus strains. Studies have investigated that SARS-CoV-2 came from the
recombination of a coronavirus of bat called RaTG13, although the similarity of these viruses strengthens
our guesses about the origin of SARS-CoV-2 the real origin of this virus is still unclear. Viruses could change
their genomic structures after their exposure to a new cell, which could improve our hypothesis of several
conversions of a bat virus or an unknown-origin virus over the decades turned into the brutal SARS-CoV-2
that cause the recent pandemic and a great number of mortalities around the world [25]. There is a piece of
interesting evidence that has been investigated that the flu pandemic that occurred between 1889 and 1891
and caused over a million deaths caused by a member of coronaviruses families was a beta coronavirus
called HCoV-OC43 same as the MERS, SARS, and SARS-CoV-2, but it belongs to other subgroups of
coronaviruses [26].
An Overview of the Evolution of SARS-CoV-2 3
Variable changes in transmissibility and virulence follow the formation of a new disease. Regarding SARS-
CoV-2, this unpredictability is exacerbated by the fact that it is a unique human illness that has undergone
multiple periods of uncontrolled spread throughout the world. It is often wrong to consider that viruses will
eventually evolve to become less infectious [24]. Lower virulence of some viruses that have infected humans
may be owing to the death of susceptible individuals and/or the survivors’ acquisition of partial or complete
immunity [27].
Viral variations result from nucleotide alterations that occur spontaneously in the viral genetic sequence
along replication, particularly RNA viruses, which exhibit a greater frequency of these changes than DNA
viruses [28]. Every time a virus replicates, its genetic material undergoes mutations or changes, producing
variations. However, the amount of these nucleotide alterations in coronaviruses is substantially underneath
other viruses with RNA genes, due to the presence of a replication-correcting enzyme [29]. The activity of
exoribonuclease (ExoN) within SARS-CoV-2 non-structural protein 14 (nsp14) has a “proofreading” impact,
and inactivating ExoN is deleterious for the replication of SARS-CoV-2 [30]. The impact of these changes on
viral transmission and pathogenicity must be understood. The fact that the identical SARS-CoV-2 mutation
has arisen independently in other countries suggests that it may improve the virus’s fitness. In addition, there
are many mutations across all variations, which points to rapid evolution over brief periods [31].
SARS-CoV-2, similar to other Coronaviruses family members, has a 30kb genome that is responsible for
the formation of 4 key structural proteins, including a spike protein (S), an envelope protein (E), a membrane
protein (M), and a nucleocapsid protein (N), some other nonstructural genomes. Several recombinations of
the genome of coronaviruses are the main cause of the recent global pandemic. S protein is affected by
several recombinations in the genome that find a greater ability to bind to its specific receptor in humankind,
angiotensin-converting enzyme 2 (ACE2) [20]. The ACE2 receptors on the alveolar epithelial cells, laryngeal,
and tracheal epithelial cells are the most host cells for SARS-CoV-2, of which alveolar type II pneumocytes
are affected the most [32], [33]. After the entrance of the virus, the viral genome induces replication and
production of viral particles, which are released to infect other cells after the host cell death [34]. These
events activate the immune response against the virus. The normal activity of the immune system is to
prevent the virus from infecting more cells and to recover the damaged organs. However, in some conditions,
the self-regulation of the body could be affected by the rapid progression of the disease and the great viral
load, which leads to the hyperactivity of the immune response and releasing proinflammatory cytokines and
chemokines from the immune and damaged cells, a process called the cytokine storm. The cytokine storm is
the leading cause of respiratory distress and death in many cases [35]. Moreover, SARS-CoV-2 can suppress
immune activity, which causes severe manifestations of rapid progression disease [36]. These events together
caused great waves of mortality around the world during the primary phases of the COVID-19 pandemic
(Figure 2) [37].
The WHO divides SARS-CoV-2 strains into two categories: variants of interest (VOI) and variants of
concern (VOC). The Centers for Disease Control and Prevention (CDC) characterizes a VOC as an infectious
disease exhibiting high transmission and virulence rates, resistance to vaccines and acquired immunity, and
the capacity to evade diagnostic identification. Since the initial outbreak in December 2019, the original
wild-type strain discovered in Wuhan has given rise to several VOCs (https://www.cdc.gov, cited 2022 Oct
30). Since VOCs have evolved separately in the human population, each pursuing various paths to better
achievement relative to early 2020 variations. Although, there is still the risk of new VOCs with distinct
virulence features in the future.
Since its emergence, SARS-CoV-2 has undergone many changes, which has led to the development of
several variants. Since early 2020, the virus had rapidly evolved into various strains before we were concerned
about COVID-19 variations. As COVID-19 began to undergo more powerful mutations, the WHO decided to
name each significant variant using the Greek alphabet, beginning with Alpha. Variant Alpha (B.1.1.7) was
4 Reza Elahi, Parsa Karami, Mahsa Bazargan, Shahrzad Ahmadi, Arash Azhideh and Abdolreza Esmaeilzadeh
identified for the first time in late September 2020 and was appointed the prevalent subtype in the UK almost
immediately [38]. Nevertheless, the fraction of the Alpha variant exhibited a considerable decrease from
April 2021 to June 2021, most notably because Delta variant strains had dramatically grown since April. The
Alpha variant has an enormous viral load and is 43 − 90% more contagious than the original wild virus. As
a result, those infected with COVID-19 have a 61% − 64% higher chance of death [39], [40]. The B.1.351
lineage, or its Beta form, 20H/501Y.V2, was initially identified in October 2020 in South Africa and has since
spread throughout the continent, dominating the second wave in South Africa [41]. The receptor binding
domain (RBD) region of the Beta version is mutated in three locations: K417N, E484K, and N501Y. It also
has L18F, D80A, D215G, R264I, and A701V alterations in its spike protein. Neutralizing antibodies and
vaccinations are less effective due to the presence of mentioned mutations [42]. The Beta version contains
1% of globally found SARS-CoV-2 genomes. Between October 2020 and April 2021, the Beta version spread
alarmingly. Like the Alpha type, the Beta variant has declined since April 2021 [43].
On January 6, 2021, the Gamma variant (also called P.1 lineage or the 501Y.V3) was discovered in
four Japanese nationals returning to Tokyo after visiting the Brazilian Amazon [44]. The Gamma variant’s
hallmark collection of distinctive amino acid alterations in the spike protein includes E484K, K417T, and
N501Y, among others. The N501Y mutation is shared by the Alpha and Beta versions, whereas the E484K
mutation is shared by the Beta and Gamma variants. Human transmission of the Gamma version led to
further evolution and the emergence of other variations [45]. Instead of accumulating in a single chronically
infected patient, the Gamma variation was acquired through a series of infections, suggesting that it resulted
from population-level selection pressure. The global distribution and rapid evolutionary development of the
Gamma variant are consistent with a process driven by natural selection under host-virus interaction [46].
There have been about 3% Gamma variant strains in circulation as of September 2021 [43].
Variant Delta (B.1.617.2), initially found in December 2020, caused a significant increase in cases that
resulted in the second peak in India and the outbreak of diseases at various events in the United States [47],
[48]. Besides the RBD mutations, the Delta version is distinguished from other VOCs by the presence of
numerous amino acid changes in the N-terminal domain (NTD) region. B.1.617 is the ancestor of the Delta
variety, which evolved into B.1.617.3, B.1.617.2, and B.1.617.1. Due to its fast global spread, the Delta
strain was declared a VOC by the WHO on May 11, 2021 [49]. As of September 2021, 29% of all viral
genomes uploaded worldwide have been the Delta variety. The majority of documented occurrences of the
Delta variation were found in India and Turkey. Delta is also found in Vietnam, the United Kingdom, and
Russia. Until June 20, 2021, 76.7 percent (49,407 out of 64,449) of all Delta variations found in the world
originated in the UK. Moreover, the new Delta plus variant (B.1.617.2.1 Delta-AY.1) emerged in Louisiana,
US, sending infection rates soaring [43]. The replication and spike-mediated entrance rates of the Delta
variant are higher than those of B.1.617.1, allowing it to spread more quickly than the Alpha and Kappa
variants. These two changes also boost the infectiousness of the virus, facilitate cell fusion, and speed up
viral reproduction [50]. In England, Delta variant infections are more likely to result in hospitalization or
the need for urgent medical attention [51]. According to data from Public Health England (PHE), the case
fatality rate for the Delta version is 0.4% as of September 2021, which is around one-third that of the Alpha
form [52].
The most recently recognized VOC is Omicron (B.1.1.529), which was detected for the first time in
November 2021 in South Africa and has since been identified in several countries [53]. On November 11,
2021, the first detection of the new Omicron strain (B.1.1.529) occurred in Botswana. Subsequently, it was
found in Hong Kong. It was primarily ascribed to the increase in monitoring that the number of cases in these
nations climbed dramatically from one week to the next following the disease’s identification. The deletions
and mutations of the Omicron are linked to improved transmissibility via enhancing the affinity of the S protein
for ACE2, as well as host immune evasion and decreased potential of antibodies produced by the vaccine
An Overview of the Evolution of SARS-CoV-2 5
to neutralize the virus [54], [55]. According to studies, Pfizer/BioNTech and Moderna mRNA vaccine’s
third dosage effectively neutralizes the Omicron variant. However, these vaccinations’ first and second doses
produced negligible to no neutralization against this variation [56]. Generally, Omicron type infection tends
to produce less severe symptoms than other variations. In nations with advanced immunization programs, it is
possible to establish wide protection against the virus by vaccination. Nevertheless, in countries with limited
vaccination, according to the Omicron variant’s low virulence, the dissemination of the Omicron variation
can lead to an increase in infection cases but not in fatality rates. Moreover, due to its ineffective cleavage by
the host protease, the in vitro and in vivo replication capacity of Omicron is significantly decreased compared
to other SARS-CoV-2 variants such as Delta, Beta, Alpha, and WT [57], [58].
BA.1, BA.2, and BA.3 are Omicron’s three separate sub-lineages that were identified nearly simulta-
neously [59], [60]. Initially, BA.1 was the most prevalent sublineage discovered internationally; however,
BA.2 (and it is component sublineages) is currently surpassing BA.1 as the primary form worldwide [60],
[61]. Recently, two additional sublineages, BA.5 and BA.4 have been identified in South Africa and have
subsequently been recognized in nations such as Australia, Germany, Botswana, China, France, and Belgium
[61], [62]. In August of 2022, the Omicron subvariant XBB, a recombinant of the BA.2.75 and BA.2.10.1,
was found for the first time. It has produced a minor increase in cases in Singapore and Bangladesh, among
other places, and is described as “immune-evasive”. However, the severity of the new mutations is unclear
(https://fortune.com/2022/10/11/what-is-xbb-variant-covid-singapore-immune-evasive, cited 2022 Nov 1.)
[63]. Soumya Swaminathan, a senior scientist at the WHO, issued a warning on October 20, 2022, that
the XBB subvariant has been detected in parts of India, including Kerala [64]. BA.5 has two brand-new
subtypes: BQ.1 and BQ.1.1 [65]. Two subvariants were detected in the state of New York. BA.2.12.1 (or
B.1.1.529.2.12.1) and BA.2.12 (or B.1.1.529.2.12) have 23–27% more growth potential than BA.2 and con-
tributed to an increase in infections in central New York, which dominated by May 24, 2022, in the United
States [66]. The emergence of Omicron is expected to have significant consequences for existing measures
to manage the SARS-CoV-2 pandemic.
VOIs are variants that probably do not have as much spread and importance, compared to VOCs. Several
reports of VOIs are only projected to affect vaccine immunity, transmission, pathogenicity, or acquired
immunity. Epsilon (B.1.427/B.1.429) which was found in California is among the VOIs being monitored.
Before September 2021, the Epsilon variant included two percent of all SARS-CoV2s and was mostly found
in the United States. The Epsilon variation is around 20% more contagious than other variants. However,
its pathogenic mechanism is yet unknown [67]. The variant Iota (B.1.526/B.1.526.1) was discovered in
New York, Eta (B.1.525) in Nigeria and the United Kingdom, Zeta (P.2) in Brazil, and Theta (P.3) in the
Philippines. In August 2020, Lambda (C.37) was discovered for the first time. Since mid-June 2021, the
number of Lambda variations has been declining and from April to June 2021, the number of Lambda
variants climbed dramatically. As of September 2021, less than 0.5% of all viruses have the Lambda form,
mostly disseminated in South America [68]. Delta Plus (B.1.617.2.1) and Kappa (B.1.617) were detected
in India. BA.2.75 was discovered in India, and the community of BQ.1 is unclear. Additional research
is necessary to understand their effect on the present COVID-19 (cited 2022 Oct 30]. Available from:
https://www.who.int/activities/tracking-SARS-CoV-2-variants) [69]. The Kappa variation accounts for fewer
than 0.5% of known strains as of September 2021 and is mostly spread in India [70].
It is still being determined if the new variations are more likely to infect children than adults, even though
the number of infected youngsters appears to be greater in the UK. It would indicate that both ancient and
novel varieties are having an impact on the younger generation. In contrast, younger children and females of
Asian origin were shown to be less severely affected by the condition and less susceptible to developing it.
This trend may be attributable to increased ACE2 expression among Asians. Children’s immune systems are
likely to be more robust, which might play an impact. More research is required to pinpoint the transmission’s
6 Reza Elahi, Parsa Karami, Mahsa Bazargan, Shahrzad Ahmadi, Arash Azhideh and Abdolreza Esmaeilzadeh
mechanism and its origins. Schools have not been proven to have a role in the viral interpersonal transfer.
Therefore, the fact that children continued to attend despite the rest of the area being placed back on lockdown
after reopening might be a possible reason [71], [72].
SARS-CoV-2 is regarded as atypical since new human diseases discovered in the last several decades
frequently exhibit increased virulence due to a lack of host protection. As the transmission rate of SARS-
CoV-2 was already high, it was considered that there was no selection benefit for a drop in virulence. In the
case of Omicron, despite its high transmissibility rate, there has been an unexpected and fortunate decrease
in the severity of infections due to a shift in the prevalence of upper respiratory infections [73]. Due to the
unpredictable nature of SARS-CoV-2 development, it is uncertain whether future variants will be a “milder”
version of SARS-CoV-2 or whether a new VOC with unique features and virulence factors will arise [74].
Another crucial concern arises from the ongoing evolutionary trajectory of SARS-CoV-2, given that the
virus has been circulating in the human population for over a year and has seen a tremendous population
increase by infecting tens of millions of individuals. It has been questioned whether during the epidemic,
there have there been any signs of adaptation to human hosts in the SARS-CoV-2 genome. Population genetic
investigations of SARS-CoV-2 genomes provide insight into this subject. Such information is still being
produced as part of the worldwide effort to comprehend the dynamics of SARS-CoV-2. Since extensive
SARS-CoV-2 genome sequence datasets are now available, researchers may track the virus’s history in
humans to see if any particular locations have undergone adaptive evolution since it was first introduced. In
addition to finding targets and candidates for vaccines and treatments, such research will help us distinguish
the dynamics of CoVs dissemination and its influence on public health. There is little doubt that this is a
vibrant frontier of the current study, with many new understandings likely to be revealed in the weeks and
months ahead [75], [76].
1.3 An Overview of the Evolution of COVID-19
The rate at which we are using up the resources of the globe is unsustainable the world’s population grew
6 billion in the last century. By the end of the twenty-first century, it is anticipated to be between 14 and
18 billion (https://www.unhcr.org/globaltrends.html, accessed November 5th, 2022) [77], [78]. With over
637,074,723 infected cases and 6,602,220 fatalities (as of 3 November 2022), SARS-CoV-2 has already
spread to 216 nations, regions, and territories. The majority of COVID-19-related fatalities happened in
countries including Spain, Italy, the United States, the United Kingdom, France, Germany, Brazil, Turkey,
Belgium, Iran, etc. [79], [80].
In this section, we aim to overview the past and present evolution of the COVID-19 pandemic
(Figure 1). Analysis of the prior outbreaks of other coronaviruses, including SARS and MERS, with math-
ematic models, showed us the possibility of investigating a pattern of how the disease spreads among the
population according to its exposure time. Current findings could consider that by studying and analysing the
pattern of infection in the evolution of disease history, we could prevent future catastrophes and improve our
decision makings and disease management. Since its evolution, COVID-19 has undergone several changes,
which are both related to the physiologic features of the viruses as well as the anti-pandemic policies taken
by the governments [81]. Reproductive number (R0) is an epidemiologic determinant of the number of indi-
viduals that can be infected by an infected patient. Initial studies on the transmission dynamics of COVID-19
showed that the R0 was 1.4–3.9 (13). Proper vaccination, isolation of patients, and rapid diagnosis of the
patients helped to reduce the R0 to less than one [82].
As shown in Figure 1, since the first outbreak of COVID-19 in December 2019, the world has experienced
five different peaks. The first peak occurred between October 2020 and February 2021 with the most cases in
An Overview of the Evolution of COVID-19 7
Fig. 1.1: The number-time chart of COVID-19 cases (https://covid19.who.int/).
January 2021. This spike occurred due to inaccessibility to effective protections, medications, and effective
vaccines. At the beginning of the outbreak, cases of pneumonia in Wuhan, China, were reported on 8th
December 2019. The center for disease control and prevention (CDC) in china enounced the pathogen as a
novel coronavirus on 7th January 2020. The first death was reported on 9th January 2020, the first case out
of China was reported in Thailand on 13th January 2020, and after one week, WHO reported 282 confirmed
positive cases of novel coronavirus disease and 6 deaths. The rapid spread of the disease showed the potential
for distribution and severity of the disease. Finally, after one month, on 11th March 2020, the downhill first
peak. Later, on December 2020 and January 2021, the 3 most effective vaccines included (Pfizer, Moderna,
and AstraZeneca) were used in the UK, Europe, USA, and other countries, which changed the situation and
played a key role in future controls of the outbreak [83]–[85].
The second spike occurred between march 2021 and June 2021, during which most cases were found in
April 2021. The third one happened between July 2021 and September 2021 and the peak was in august
2021. Due to vaccination and the global protection protocols, the peak number of cases was lower in the
third peak. The most dramatic peak was the fourth peak between December 2021 and May 2022. The top
peak happened in January 2022, when 23,789,141 cases of COVID-19 around the world were reported.
Despite global vaccination, this peak happened due to the new subtype of the virus, named Omicron, which
had more transferability but less severity. Therefore, despite the higher number of cases, the mortality was
lower than before the peaks. Compared to the first peak, the deaths were lower, and the number of cases
decreased faster. The faster decrease of the fourth spike proves that the fourth peak could have predictable
data of the finishing downhill of COVID-19 [86]. The final peak of COVID-19 occurred between June 2022
and September 2022. The top spike was in July 2022 which showed a drastic reduction in cases compared
with the fourth peak of the disease. During the last two years, researchers have investigated antiviral drugs,
anti-inflammation treatments, and alternative medications used for severely ill patients in intensive care units
(ICU). Importantly, global efforts to develop vaccines and the efforts made to vaccinate most of the population
around the world are other factors contributing to the downhill of COVID-19. Moreover, the restrictions made
by the governments, such as the compulsion to use masks and the lockdowns were also other causes of the
COVID-19 downhill [87].
8 Reza Elahi, Parsa Karami, Mahsa Bazargan, Shahrzad Ahmadi, Arash Azhideh and Abdolreza Esmaeilzadeh
Fig. 1.2: The chart showing the number of COVID-19 deaths per time (https://covid19.who.int/).
Figure 2 presents the death chart of COVID-19. Since 2019, there have been eight spikes which show
decreasing trend up to the recent spikes. The first spike occurred between March 2020 and May 2020, the
second wave was between June 2020 and august 2020, and the third spike occurred. between October 2020 and
February 2021, a dramatic increase happened. This was due to disease spreading, inaccessibility to effective
medications for the severe and progressive conditions of disease, and unknown life-saving operations. The
fourth spike happened one month after the first one, between March 2021 and June 2021, and because of
the similar conditions of inaccessibility to effective disease prevention functions, the second dramatic spike
of death occurred similar to the third one. After the fourth wave, the death chart experienced a significant
decrease due to the production of vaccines and effective medications for severely ill patients in the ICU. The
fifth spike occurred between July 2021 and October 2021, the sixth wave was even lower than the previous
wave between October 2021 and December 2021, and the seventh spike happened due to the Omicron and
showed a significant increase in death chart between December 2021 and April 2022. Based on the death
chart, the duration of this peak was lower than the first high spikes which is because of the higher immunity
of the population and the pace of the vaccine production. The last spike occurred between June 2022 and
September 2022, which was the lowest spike and showed the effectiveness of the methods of dealing with
this disease during these two years.
1.4 Future Evolution of COVID-19 based on Fractal Models
The fractal dimension of the epidemiological curve can help to select the datasets for predicting the behavior of
the pandemic. Moreover, the reproduction rate has been shown to have a sensible fractal pattern. Interestingly,
Pacurar and colleagues found a correlation coefficient of 0.386 between the new daily cases of COVID-19
and daily global radiation [88]. A supervised learning model can be created to make a prediction based on an
unknown input instance. To train the regression model in this learning approach, a dataset of input instances
and their matching regressors are used. After that, the trained model makes a forecast for the test dataset
