MBE, 19(11): 11324–11344.

DOI: 10.3934/mbe.2022527
Received: 02 May 2022
Revised: 26 July 2022
Accepted: 02 August 2022
http://www.aimspress.com/journal/mbe Published: 09 August 2022

Research article
Mathematical modeling of SARS-nCoV-2 virus in Tamil Nadu, South India

Avinash Shankaranarayanan1 and Hsiu-Chuan Wei2, *

1
International School of Technology Management, Feng Chia University, 100 Wen Hua Road, Xitun
District, Taichung 40724, Taiwan
2
Department of Applied Mathematics, Feng Chia University, Taichung 40724, Taiwan

* Correspondence: Email: [email protected]; Tel: +8864245172505118.

Abstract: The purpose of this paper is to build a mathematical model for the study of the roles of
lock-down, social distancing, vaccination, detection efficiency, and health care capacity planning of the
COVID-19 pandemic taking into account the demographic topology of the State of Tamil Nadu, India.
Two mathematical models are proposed for the evolution of the first and second wave of COVID-19
pandemic. The model for the first wave considers lock-down orders, social distancing measures, and
detection efficiency. The model for the second wave considers more sub-populations and incorporates
two more elements, vaccination and health care capacity. Daily reported data on the evolution of the
COVID-19 pandemic are used to determine the parameter values. The dynamics produced by the
mathematical model closely follow the evolution of COVID-19 in the State of Tamil Nadu. Numerical
simulation shows that the lock-down effect is limited. Social distancing implementation and detection
of positive cases are relatively ineffective compared with other big cities. Shortage of health care
resources is one of the factors responsible for rapidly spreading in the second wave in Tamil Nadu.

Keywords: COVID-19; mathematical modeling; numerical simulation; epidemic

1. Introduction

In December 2019, a new coronavirus infection, called corona virus disease (COVID-19) by the
World Health Organization, was found in Wuhan, Hubei, China [1] and soon spread outside of China.
Although two rather effective antivirals have been approved by the FDA and monoclonal antibody
treatment has been in use for some time and is extremely effective, this viral contamination continues
to spread rapidly across globe [2, 3]. In March 2020 [1, 2, 4–7] the emergency arrived at the
pandemic stage as the overall effect was accelerated. The number of cases and deaths with COVID-19
have reached 506 million and 6.2 million worldwide, respectively, as of 21 April 2022. Currently,
only vaccines can attenuate the COVID-19 pandemic. Several vaccines, such as Pffizer-BioNtech,
 11325

Moderna, AstraZeneca, etc., had been developed and approved via Emergency Use Authorization
(EUA) worldwide [8]. On December 2, 2020, UK became the first country to approve the
Pffizer-BioNtech COVID-19 vaccine, and several vaccines were approved under EUA by different
countries in early 2021 [8].
Mathematical modeling is a useful technique to understand the dynamics of infectious diseases.
Mathematical models of evolution of COVID-19 pandemic have been proposed to predict the spread
of Covid-19 pandemic such as the peaks, total numbers of infections, and the ending time of COVID-19
epidemic in different countries [9–13]. Balasubramaniam et al. [9] used a stochastic epidemiological
model (SEM) along with a machine learning technique to compute the infection rates in populations.
Yadav [10] employed the well known SIR model, consisting of deterministic ODEs, to predict the peak
and ending time of COVID-19 pandemic in India. Hassen et al. [11] also employed the SIR model
to predict the evolution of COVID-19 cases in the Maghreb Central countries. Bhardwaj [12] used
the natural exponential function with a time dependent growth rate to estimate the peak dates and the
number of total infections in several countries. Jamshidi et al. [13] proposed a computational algorithm
to predict the number and locations of new epicenters.
Santosh [14] pointed out that complex models were needed to study the spread of COVID-19
which depends on many factors such as hospital capacity, testing rate, demographics, population
density, poverty, etc. Furthermore, as COVID-19 continues to spread, mathematical models studying
pharmaceutical or non-pharmaceutical factors, which can help with reducing effect of the spread and
devising the control strategies for fighting COVID-19 pandemic, are as important as the models
attempting to predict the future evolution of COVID-19 pandemic [15–17]. Dawoudi [18] proposed a
computational algorithm to study coronavirus DNA sequences for discovery of new drugs. Based on
the SIR model, Wanjau, Ndam, and Asempapa et al. [19–21] proposed mathematical models with
more sub-populations such as susceptible, exposed, infectious, isolated, and recovered individuals.
Asempapa et al. [21] further divided some of the above sub-populations into high-risk and low-risk
sub-populations. These complex models contain many coupled ODEs with many parameters.
However, daily information of these sub-populations, such as the number of isolated individuals,
high-risk and low-risk sub-populations, or the number of exposed individuals, is not available in many
countries/regions. Estimation of parameters and the plausibility of the model may be hindered by lack
of information in many countries/regions.
Rojas-Vallejos [22] suggested that mathematical models should not be simpler than necessary, but
also not more complex than needed to provide helpful insight. Recently, Alvarez et al. [23] have
proposed a simple yet novel mathematical model of COVID-19 epidemic to study the effect of social
distancing and detection of positive cases in urban areas. The mathematical model considered two
populations, population of the cumulative confirmed cases and population of recovery/death. Daily
reported data of the number of cumulative cases and the number of recovered or died individuals are
available for most countries, making the model plausible for their study. The computational results
are interesting. However, the mathematical model has not been correctly formulated. Motivated by
the model in [23], the purpose of this paper is to build a mathematical model to study the impacts of
pharmaceutical factors (vaccination, detection efficiency, and health care capacity) and
non-pharmaceutical factors (lock-down and social distancing) on COVID-19 pandemic.
To provide details, the mathematical model is presented in Section 2. Parameter fitting and
numerical simulation are performed in Section 3. Finally, a brief conclusion is made in Section 4.

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2. Mathematical model

2.1. The first-stage model

In this paper, a two-stage model is to be constructed. The first-stage model contains two state
variables, X and R, and the impacts of lock-down, social distancing, and testing intensity. The
variable X represents the cumulative COVID-19 cases. The variable R represents the number of
individuals who have been infected but removed from the population and thus do not contribute to the
propagation of COVID-19. The construction of first-stage model is motivated by the model proposed
by Alvarez et al. [23]. However, the mathematical model proposed by Alvarez et al. [23] was not
correctly formulated nor consistent with the implementation of the solutions in Excel spreadsheets
(Supplemental File F1 in [23]). The model given in [23] is as follows:

dX/dt = µ0 (1 − σ)(X − R)(1 − X/P0 ), (1)

Z t=t−delay q Z t=t−delay r
dR/dt = α dX/dt + (1 − α) dX/dt, (2)
t=0 t=0

where P0 is the population of the region, which may be a country, state, or urban area, and µ0 is
the intrinsic infection rate. Both σ and α were modeled by nondecreasing functions of t [23]. The
function σ represents the effect of social distancing. The infection rate is reduced by σ due to social
distancing effect. In [23], Eq (2) describes the rate at which infected patients are retrieved from the
general population. It has been assumed in [23] that a fraction (α) of infected individuals is effectively
removed from the general population with a delay of delay q days from the onset of virus to positive
diagnosis. These individuals do not contribute to the propagation of COVID-19. Another fraction
(1−α) of infected individuals is not effectively removed from the general population until their recovery
or death after delay r days. It was stated in [23] that the second term was formulated by the integral of
all infected individuals recovered or died from the onset of the epidemic episode in the region with a
delay of delay r days. Apparently, Eq (2) and the above statement do not describe the rate of change
of R. Furthermore, Eqs (1) and (2) were converted into equations of differences in [23]:

∆X = (µ0 (1 − σ)(X − R)(1 − X/P0 ))∆t, (3)

( Z t=t−delay q Z t=t−delay r )
∆R = α dX/dt + (1 − α) dX/dt ∆t. (4)
t=0 t=0

Using the fact that X(t) is nondecreasing, Eq (4) is equivalent to

∆R = (αX(t − delay q) + (1 − α)X(t − delay r))∆t

≥ (αX(t − delay r) + (1 − α)X(t − delay r))∆t
= X(t − delay r)∆t (5)

if delay r ≥ delay q. The left hand side of Eq (5) represents the increment of the population R over a
time span [t, t + ∆t] while the right hand side uses the cumulative infected cases over the whole time
span with a delay of a few days [0, t − delay r], multiplied by ∆t. This shows that Eq (2) was not
correctly formulated in [23]. Nevertheless, the elements and terms considered in the mathematical
model in [23] are novel and can be easily applied to construct a modified model to study the evolution
of the desease.

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Following the construction concept of Eqs (1) and (2) with modification and incorporation of the
lock-down effect, the first-stage model proposed in this paper is given by a deterministic system of
ODEs with time delays:

dX/dt = µ1 (1 − σ(t))(X(t) − R(t) + K(t))(1 − X(t)/P0 ), (6)

dR/dt = α(t − τ1 )dX(t − τ1 )/dt + (1 − α(t − τ2 ))dX(t − τ2 )/dt, (7)

where µ1 is the intrinsic infection rate and K is the number of infected individuals who reside outside of
the region and travel to the region. The functions σ(t) and α(t) represent the same effects as in Eqs (1)
and (2). The notations delay q and delay r are replaced by shorter notations τ1 and τ2 , respectively.
Equation (6) describes the rate of change in cumulative COVID-19 cases. Assume that it is of
similar status of COVID-19 outbreak in neighboring regions. This assumption leads to K(t) = β1 (X(t)−
R(t)). Thus X(t) − R(t) + K(t) = (1 + β1 )(X(t) − R(t)) where β1 represents the unlock-down factor. At
the stage of implementation of the lock-down orders, β1 = 0.
Social distancing involves the change of behavior [24] and it is difficult for individuals to stick to
the social distancing guidelines [25]. Implementation of social distancing policy can become effective
after people have learned the importance of social distancing [26]. This behavioral change can be
related to the S-shaped learning curve, measuring an individual who is new to a task [27]. The bottom
of the S curve indicates slow progressing initially as it requires more time to master new skills. The S
curve also describes the strongest resistance to adoption of a change [28]. After the learner becomes
proficient in the skills, it requires less time to complete the task. The curve eventually levels off,
indicating a plateau or new challenges [27]. Alvarez et al. [23] reported that using a linear ramp
between two values over a time period for σ could reproduce the actual progression of COVID-19.
The behavioral change of social distancing described above and the formulation of σ given in [23]
suggest that a sigmoid function, which is regularly used in mathematical modeling, is a good fit for σ.
The effect of social distancing σ(t), shown in Figure 1(a), is modeled as follows:
L1
σ(t) = , 0 ≤ L1 ≤ 1, (8)
1 + e−k1 (t−t1 )
where k1 represents the steepness of the curve, t1 is the time point at which the learner reaches the
maximum growth rate, and L1 represents the maximum performance measure. When a learner develops
new skills required for a new task through previous experience, the bottom of the curve might not start
with zero performance. In this case, Eq (8) is modified as follows:
L1
σ(t) = M1 + , 0 ≤ M1 + L1 ≤ 1, (9)
1 + e−k1 (t−t1 )
where M1 is the previous-experience factor. Note that Eq (9) becomes Eq (8) when M1 = 0. Thus
Eq (9) is used in this paper as it represents a more general case than Eq (8). Figures 1(a),(b) give
examples of S-shaped learning curves without and with prior experience, respectively.
Equation (7) describes the rate of change of the removed population R. At the initial stage of
COVID-19 outbreak, most countries faced a shortage of testing kits [29]. As a result, infected
individuals were tested only after the onset of symptoms. The function α has the same meaning as in
Eq (2). Recall that τ1 is the delay from the onset of symptoms to positive diagnosis. The delay takes
about 2–5 days [23]. We use τ1 = 4 in this paper. It has been reported that the median time to

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1
1
Performance Measure
0.8 0.8

0.6 0.6

0.4 0.4

0.2 0.2

0 0
0 20 40 60 0 20 40 60
t (time) t (time)

(a) (b)

Figure 1. S-shaped learning curves, plotted using Eq (9), (a) without prior experience (M1 =
0, t1 = 30, k1 = 0.2, and L1 = 0.8) and (b) with prior experience (M1 = 0.3, t1 = 30, k1 = 0.2,
and L1 = 0.6).

recovery is 13.5 days [30]. We assume that these individuals are removed from the general population
after their recovery or death with a delay of τ2 = 14 days. From Eq (7), 0 ≤ α(t) ≤ 1, X(t) = 0 for
t < 0, and dX(t)/dt = 0 for t < 0, we have
Z t
R(t) = (dR(ξ)/dξ) dξ
0
Z t
= α(ξ − τ1 )dX(ξ − τ1 )/dξ + (1 − α(ξ − τ2 ))dX(ξ − τ2 )/dξ dξ
 

Z0 t−τ1 Z t−τ2
= α(ξ) (dX(ξ)/dξ) dξ + (1 − α(ξ)) (dX(ξ)/dξ) dξ
0 0
Z t−τ2 Z t−τ1 Z t−τ2
= α(ξ) (dX(ξ)/dξ) dξ + α(ξ) (dX(ξ)/dξ) dξ + (1 − α(ξ)) (dX(ξ)/dξ) dξ
0 t−τ2 0
Z t−τ1
= X(t − τ2 ) + α(ξ) (dX(ξ)/dξ) dξ (10)
t−τ2
≤ X(t − τ1 ) ≤ X(t).

Equation (10) shows that R(t) includes the cumulative infected individuals over the time span [0, t − τ2 ]
and the removed individuals over [t − τ2 , t − τ1 ]. The expression X(t) − R(t) represents the infected
individuals who are capable of infecting susceptible individuals in the region. Equation (10) also
shows that X(t) − R(t) includes the individuals contracted the disease over [t − τ1 , t] and the individuals
contracted the disease over [t−τ2 , t−τ1 ] who have not been removed from the general population. Since
X(t) is a differentiable, nondecreasing function and bounded above by P0 , the limit limt→∞ X(t) exists
and limt→∞ (dX/dt) = 0. Thus, Eq (10) implies limt→∞ R(t) = limt→∞ X(t); all the infected individuals
will be included in the population R eventually.
The outbreak of COVID-19 is an unprecedented public health crisis affecting all countries
worldwide. Testing and treatment strategies are new tasks for health-care workers. Thus, it is

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reasonable to expect an improvement in effective diagnosis with time. Here, the removal factor α(t) is
also modeled by an S-curve,
L2
α(t) = M2 + , 0 ≤ M2 + L2 ≤ 1. (11)
1 + e−k2 (t−t2 )
The first-stage model becomes

dX/dt = µ1 (1 + β1 )(1 − σ(t))(X(t) − R(t))(1 − X(t)/P0 ), (12)

dR/dt = α(t − τ1 )dX(t − τ1 )/dt + (1 − α(t − τ2 ))dX(t − τ2 )/dt, (13)

where σ(t) and α(t) are given as in Eqs (9) and (11), respectively. Figure 2 gives a schematic of Eqs (12)
and (13).

P 0- X X-R R

Figure 2. Schematic of Eqs (12) and (13). P0 − X, X − R, and R represent the susceptible,
infectious, and removed populations, respectively.

2.2. The second-stage model

COVID-19 vaccines had been approved by many countries in early 2021 [8]. In the second-stage
model, four state variables X1 , X2 , Y1 , and R are considered. The variables X1 and X2 represent the
cumulative COVID-19 cases in unvaccinated and vaccinated sub-populations, respectively. The
variable Y1 represents the unvaccinated uninfected sub-population. The practical meaning of R is the
same as in Eqs (12) and (13). Many countries have experienced the second wave of COVID-19, and
the second wave has caused a dramatic increase in COVID-19 cases which exceed health care
capacity [31–34]. The second-stage model further considers the factor of health care capacity and is
given as follows:

dX1 /dt = µ1 (1 + β1 )(1 − σ(t))(X1 (t) + X2 (t) − R(t))(Y1 (t)/P0 )

γ(t)X1 (t)
− , (14)
h1 + X1 (t)
dX2 /dt = µ2 (1 + β1 )(1 − σ(t))(X1 (t) + X2 (t) − R(t))(Y2 (t)/P0 )
γ(t)X1 (t)
+ , (15)
h1 + X1 (t)
dY1 /dt = −µ1 (1 + β1 )(1 − σ(t))(X1 (t) + X2 (t) − R(t))(Y1 (t)/P0 )
γ(t)Y1 (t)
− (16)
h1 + Y1 (t)
dR/dt = (1 − H(t))(α(t − τ1 ))dX(t − τ1 )/dt
+(1 − α(t − τ2 ))dX(t − τ2 )/dt
+H(t − (τ2 − τ1 ))α(t − τ2 )dX(t − τ2 )/dt (17)

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where X(t) = X1 (t) + X2 (t) represents cumulative infected cases and Y2 (t) = P0 − X1 (t) − X2 (t) − Y1 (t)
represents the vaccinated uninfected sub-population. The function
 L3 
γ(t) = β2 M3 + (18)
1 + e−k3 (t−t3 )
is a factor related to vaccination rate with the maximum vaccination rate β2 . Note that γ(t) is modeled
by an S-curve. Vaccination plays an important role in controlling the spread of the disease. Due to rapid
development of COVID-19 vaccines, doubts and worries of vaccination safety lead to hesitancy or
refusal initially [35]. Many people preferred to wait until others have taken the vaccine [36]. However,
vaccination willingness changed over time, where vaccination refusal was reported from >70% in
March 2020 to <50% in October 2020 [36]. Another research study reported an increase in vaccine
acceptance during a study period from February to September 2020 [37]. The behavioral response to
vaccination acceptance can be related to adoption and diffusion of technology which is often described
by the S-curve [28]. The vaccination rate depends on the size of unvaccinated sub-populations X1
and Y1 . A factor X1 /(h1 + X1 ) is incorporated into the term of vaccination rate. This factor describes
the situations that the rate of change of vaccination is determined by vaccination willingness, γ(t), if
a considerable population is unvaccinated (X1 >> h1 or X1 /(h1 + X1 ) ≈ 1). The rate of change of
vaccination decreases and becomes small as majority of the population are vaccinated (X1 << h1 or
X1 /(h1 + X1 ) ≈ 0). Furthermore, the factor X1 /(h1 + X1 ) can also prevent the solutions from becoming
negative.

X + X - R
1 2

Y1 Y R
2

Figure 3. Schematic of Eqs (14) and (17). X1 , X2 , Y1 , and Y2 represent the numbers
of unvaccinated infected, vaccinated infected, unvaccinated susceptible, and vaccinated
susceptible individuals, respectively. R and X1 + X2 − R represent the removed and infectious
populations.

Let τ3 be the average number of days that a COVID-19 patient is hospitalized for. The function
H(t) ∈ [0, 1] represents the utilization factor of health care resources. Due to limited health care
resources available for COVID-19 patients, we assume that the portion of COVID-19 patients who
can be admitted to hospital depends on H(t). When H(t) << 1 (1 − H(t) ≈ 1), ample health care
resources are available for COVID-19 patients; the patients with positive test results can be admitted to
hospital. In contrast, H(t) ≈ 1 represents the situation when available health care resources have been
fully employed. In this case, few or none COVID-19 patients can be admitted to hospital. Let Hτ3 (t)

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represent the number of patients being hospitalized. For simplicity, we shall assume that these patients
do not contribute to the propagation of the disease. Since (1 − H(t))(α(t − τ1 ))(dX(t − τ1 )/dt) represents
the rate of change of these individuals,
Z t
Hτ3 (t) = (1 − H(ξ)α(ξ − τ1 )(dX(ξ − τ1 )/dξ)dξ (19)
t−τ3

represents the number of patients being hospitalized at t. We model the utilization factor of health care
Hτ (t)
resources using H(t) = h2 +H3 τ (t) which depends on the number of patients being hospitalized at t. Thus
3

Z t
Hτ3 (ξ)
Hτ3 (t) = (1 − )α(ξ − τ1 )(dX(ξ − τ1 )/dξ)dξ. (20)
t−τ3 h2 + Hτ3 (ξ)

Since τ2 represents the average time period it requires to recover from the disease, we use τ3 = τ2 in
this paper.

3. Parameter fitting and numerical simulation

The parameter values in the mathematical model are fitted using the daily reported data of Tamil
Nadu of India. The dataset is taken from [38], a repository supported by Center for Systems Science
and Engineering (CSSE) at Coronavirus Resource Center of John Hopkins University (JHU) through
GitHub. The features, in daily reported data, related to Eqs (12) and (13) are “Confirmed”, “Deaths”,
‘’Recovered” and “Active”, where Confirmed equals the sum of Deaths, Recovered, and Active. The
data for the feature Confirmed is used to fit the cumulative cases X(t). Figure 4 shows that the sum of
Deaths and Recovered in daily reported data follows the same progression as Confirmed with a delay
of roughly 10 days. Note that the mathematical analysis (Eq (10)) agrees with this property. The sum
of Deaths and Recovered is used to fit R(t). In the second-stage model, X2 (t) + Y2 (t) represents the
number of individuals who received at least one dose of vaccine in the data. The vaccination data for
Tamil Nadu is not available. To work around this, the daily vaccination data for India is downloaded
from [39]. Consider populations of 7.8 × 107 persons and 1.4 × 109 persons in Tamil Nadu and India,
respectively [40]. The India Express reported that over 76% of eligible population have received at
least one dose of COVID vaccine on 25 November 2021. Daily vaccination data for India shows
that 776,515,911 individuals (about 55.5% of the population) in India had received at least one dose of
COVID vaccine by 25 November 2021. Let f = (0.76 · 7.8 × 107 )/(0.555 · 1.4 × 109 ) = 0.076, and let
N(t) be the number of individuals in India that had been vaccinated. Then, f N(t) is used to estimate
the number of individuals in Tamil Nadu who had been vaccinated. The lock-down dates are taken
from lock-down orders posted in https://www.tn.gov.in/go view/dept/26 by Tamil Nadu government.
Two periods of lock-down orders took place in 2020, 8 April 2020 through 15 September 2020 and 28
October 2020 through 30 November 2020.

3.1. Parameter values for the first-stage model

The daily reported data of COVID-19 cases from 6 March 2020 to 28 February 2021 (359 days)
along with the lock-down information is used to estimate the parameter values for the first-stage model,
Eqs (12) and (13). Let T = 359 be the number of days from 6 March 2020 to 28 February 2021. Let X̃i

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106
3
Data: Confirmed
Data: Recovered+Deaths

X and R
1

0
r-2
0
l-2
0 20 21 -2
1 21
p Ju ct- an- pr J ul-
1 -A 1- 1-
O
1-
J 1-
A 1 -
Days (6 Mar. 2020 thru 4 Aug. 2021)

Figure 4. The removed population R follows the dynamics of the infected population X with
a delay of roughly 10 days.

and R̃i , i = 0, 1, · · · , T be Confirmed and the sum of Deaths and Recovered from the daily reported data,
respectively. Equations (12) and (13) are integrated over [0, T ] using Euler’s method with ∆t = 0.01
day. Ten parameters listed in Table 1 are to be fitted using q 360 data points. qThe parameter values
i=0 (X(i) − X̃i ) +
PT 2
PT 2
are determined by solving the minimization problem min i=0 (R(i) − R̃i ) . The
Nelder Mead simplex method [41] is employed to solve the least square error of the fitting. The Nelder
Mead simplex method is an iterative method. The Matlab build-in functions fminsearch can also fulfill
the tasks. In the fitting process, we set 200 for the maximum number of iteration. The fitting process is
executed a few times until the q evolution of X(t) andqR(t) agrees with the daily reported data. Figure 5
i=0 (X(i) − X̃i ) + i=0 (R(i) − R̃i ) = 1.3 × 10 (persons) and with
PT 2
PT 2 5
shows the fitting results with
the parameter values determined and summarized in Table 1. The parameter fitting result shows that
the intrinsic infection rate in Tamil Nadu is 0.2053 day−1 which is between the growth rates initially
and after measures for the regions studied by Alvarez et al. [23].
Parameter estimation of dynamical systems is often associated with parameter uncertainty due to
data errors and computational errors in parameter fitting processes. The analysis of parameter
uncertainty is important as it determines how reliable the model outputs are. Bootstrap method is a
popular technique for assessment of parameter uncertainty due to its simplicity. A bootstrapping
sampling was proposed for assessment of parameter uncertainty of a mathematical model of
population dynamics [42]. This method can be directly applied to the analysis of parameter
uncertainty in this paper. A random sample with replacement of size T + 1 is drawn over
{0, 1, · · · , T }. After discarding the repeated numbers, we have 0 ≤ t1 < t2 < · · · < tI ≤ T . The
parameter values are estimated using the datasets X̃ti and R̃ti , i = 1, · · · , I with the parameter values
listed in Table 1 as the initial guess. The Nelder Mead simplex method is performed for 500 iterations
to obtain the bootsrtap estimates of parameter values. The above parameter estimation process with
resampling is repeated 1000 times. The bootstrap statistics are shown in Table 2. As about 95% of the

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105 105 103

10 10
Data: cumulative cases Data: Removal population Data: Daily new cases
Simulation using Eqs. (12) and (13) Simulation using Eqs. (12) and (13)
8 Simulation using Eqs. (12) and (13)
8 8

New cases
6 6

R
X

4
4 4

2 2 2

0 0 0
0 0 20 21 0 0 20 1 0 0 0 21
r-2 l-2 t- n- r-2 l-2 t- n-2 r-2 l-2 t-2 n-
Ap 1-
Ju Oc -Ja Ap -Ju Oc -Ja Ap 1-
Ju Oc Ja
1- 1- 1 1- 1 1- 1 1- 1- 1-
Days (6 Mar. 2020 thru 28 Feb. 2021) Days (6 Mar. 2020 thru 28 Feb. 2021) Days (6 Mar. 2020 thru 28 Feb. 2021)

(a) (b) (c)

Figure 5. Population dynamics for Eqs (12) and (13) with parameter values shown in Table 1.
X and R represent the infected and removed populations, respectively. The number of new
cases are computed using Xi − Xi−1 and X(i) − X(i − 1), i = 1, 2, · · · T , for the observations
and simulation, respectively.

Table 1. Parameter values in Eqs (12) and (13).

Parameter Brief Description Value Units Reference

P0 7.8 × 107 Population of Tamil Nadu State, India individual [40]
µ1 0.2053 Intrinsic infection rate Day−1 fitted with data [38]
β1 0.0484 Unlock-down factor Dimensionless fitted with data [38]
M1 0 Pre-experience in σ Dimensionless fitted with data [38]
t1 29 Time parameter in σ Day fitted with data [38]
k1 0.1935 Steepness of σ Day−1 fitted with data [38]
L1 0.4533 Maximum increase in σ Dimensionless fitted with data [38]
M2 0 Pre-experience in α Dimensionless fitted with data [38]
t2 105 Time parameter in α Day fitted with data [38]
k2 0.0248 Steepness of α Day−1 fitted with data [38]
L2 0.6405 Maximum increase in α Dimensionless fitted with data
τ1 4 Delay in detection Day [23]
τ2 14 Recovery time Day [30]

data values of a distribution usually fall within 2 standard deviations from the mean. The intervals
[Mean - 2Std,Mean + 2Std] are given in Table 2. These narrow intervals and small standard
deviations show that the bootstrap estimates of parameter values closely distributed around the mean
values. The parameter values used for the first-stage model (Table 1) are rather close to these mean
values of bootstrap estimates and lie within the intervals of Mean ± 2 × Std. Further investigation of
correlations between parameters has shown that the correlation coefficients of µ1 and L1 and of t2 and
L2 are 0.77 and –0.96, respectively. Figure 6 shows the plots of their distributions. These plots also
show that these bootstrap estimates are densely distributed around the mean values. All other
parameters show no correlation or weak correlation with each other.

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 11334

Table 2. Bootstrap statistics, first wave, 1000 bootstrap samples.

Parameter µ1 M1 t1 k1 L1
Mean 0.2064 0 29.3 0.1786 0.4565
Std 0.004 0 0.9 0.0233 0.0081
Mean ± 2Std [0.1984, 0.2144] [0,0] [27.5,31.1] [0.1320,0.2252] [0.4403,0.4727]
Parameter β1 M2 t2 k2 L2
Mean 0.0485 0 105.7 0.0249 0.6395
Std 0.0017 0 2 0.0004 0.0076
Mean ± 2Std [0.0451,0.0519] [0,0] [101.7,109.7] [0.0241,0.0257] [0.6243,0.6547]

0.52 0.7

0.68

L2
0.48
0.66
L1

0.44 0.64

0.62
0.4
0.2 0.22 0.24 0.26 90 100 110
1 t2
(a) (b)

Figure 6. Two dimensional distributions, using 1000 bootstrap samples, for (a) µ1 and L1 ,
and (b) t2 and L2 .

3.2. The effect of lock-down, social distancing, and detection of positive cases
The parameter β1 is related to the lock-down effect. The infection rate is reduced by 1 − 1/(1 + β1 ) =
4.6% during lock-down, where β1 = 0.0484. The effect for lock-down is considered insignificant in
this paper. The functions σ(t) and α(t) are plotted in Figure 7 to show the effect of social distancing
and efficiency of detection of COVID-19 positive cases, respectively. Figure 7(a) shows that the social
distancing factor starts with 0 initially, implying social distancing is considered a new concept in Tamil
Nadu during the first wave. The social distancing factor reaches the plateau of 0.4533 around Day 50.
Alvarez et al. [23] used social distancing factors increasing form 0 on March 10 to 0.75 on March 23,
2000, for New York City (NYC) in their simulation. They also showed that a social distancing factor
of about 70% in Mexico City. Compared with the social distancing effect in NYC and Mexico City,
our simulation result shows that the social distancing effect in Tamil Nadu increases relatively slowly
and levels off at a relatively low level. Chakraborty et al. [43] have pointed out that the first wave
of COVID-19 infection in India took off in March 2020, and the lack of the use of face covering and
compliance with social distancing measures are among significant factors that cause the fast spread of
COVID-19 in India.
Figure 7(b) shows that detection of positive cases does not start with zero performance meaning
that although COVID-19 is a novel disease, health care professionals adopt new skills through prior

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 11335

experience. The function α(t) starts with a low level of 0.05 and slowly increases to a plateau of 0.64
over several months. In the simulation example for NYC, Alvarez et al. [23] used α values from 0
to 0.76 in two weeks, from March 20 to April 7, 2020. They also reported that South Korea
implemented widespread testing with α ≈ 0.98 in controlling the spread of the disease whereas
Mexico City suffered from a low level of testing with α = 0.1. Compared with NYC and South Korea,
the detection of positive cases in Tamil Nadu is relatively ineffective.

0.5 0.6

0.4 0.5

0.4
0.3

(t)
(t)

0.3
0.2
0.2
0.1
0.1

0 0
0 0 0 1 0 0 20 21
r-2 l-2 ct-2 n -2
pr
-2 l-2 ct- n-
Ap Ju O Ja A Ju O Ja
1- 1- 1- 1- 1- 1- 1- 1-
t: Days (6 Mar. 2020 thru 28 Feb. 2021) t: Days (6 Mar. 2020 thru 28 Feb. 2021)
(a) (b)

Figure 7. The functions (a) σ(t) and (b) α(t) in Eqs (12) and (13) with parameter values
given in Table 1 for M1 , t1 , k1 , L1 , M2 , t2 , k2 , and L2 .

To study the effect on the evolution of COVID-19 cases caused by the change in σ, we enhance
L1 by 10%. Let L1 = 0.498 and all parameter values are kept the same as in Table 1. Figure 8(a)
shows the evolution of cumulative cases X(t); the spread of COVID-19 can be effectively controlled by
improving social distancing behaviors. Next, we enhance L2 by 10%. Let L2 = 0.704 which increases
the detection rate. Figure 8(b) shows that the number of cumulative cases X(t) decreases dramatically.
Comparing Figures 8(a) and (b), the effectiveness in controlling the spread of COVID-19 by enhancing
detection rate is not as significant as that by improving social distancing measures. The simulation
suggests that implementing non-pharmaceutical interventions may be an effective method to slow the
spread of COVID-19.

3.3. Parameter values for the second-stage model

It has been reported that the efficacy of all COVID-19 vaccines exceeds 70% [44], and the RNA
based vaccines are highly efficacious, with an efficacy over 92% [44, 45]. The vaccine efficacy varies
over time [45]. The vaccination data used in this study contains individuals who have received one
or two doses. Based on the above reported efficacy of COVID-19 vaccines, we assume a collective
vaccine efficacy of 80% and let µ2 = 0.2µ1 in the parameter fitting process. We also assume that the
vaccination willingness is the main factor determining the vaccination rate; a relatively small value
h1 = 104 (persons) is used in this paper, compared with the population P0 in Tamil Nadu. For the
utilization factor of health care resources, h2 = 5 × 105 (persons) is assumed, which is about one

Mathematical Biosciences and Engineering Volume 19, Issue 11, 11324–11344.

 11336

105 105
10 10
Data: cumulative cases Data: cumulative cases
Simulation using Eqs. (12) and (13) Simulation using Eqs. (12) and (13)
8 8

6 6
X

X
4 4

2 2

0 0
0 0 20 21 0 0 0 21
r-2 ul-
2
ct- n- r-2 l-2 t-2 n-
-A
p
1-
J -O -Ja -A
p
1-
Ju Oc J a
1 1 1 1 1- 1-
Days (6 Mar. 2020 thru 28 Feb. 2021) Days (6 Mar. 2020 thru 28 Feb. 2021)
(a) (b)

Figure 8. The evolution of the cumulative cases produced using Eqs (12) and (13) with all
parameter values kept the same as in Table 1 except for (a) L1 = 0.498 and (b) L2 = 0.704. X
represents the infected population.

percent of P0 . The daily reported data of COVID-19 cases and vaccination from 1 March 2021 to 4
August 2021 (156 days) are used to estimate the parameter values for the second-stage model.
Let X̃i , i = 0, 1, 2, · · · , 156, be the cumulative COVID-19 cases from daily reported data. We fit
X1 (t) + X2 (t) to X̃i . Note that X1 (t) + X2 (t) represents the cumulative COVID-19 cases in the
mathematical model. Let Ṽi , i = 0, 1, 2, · · · , 156, be the number of vaccinated individuals from the
vaccination dataset. We fit P0 − (X1 (t) + Y1 (t)), which represents the number of vaccinated individuals
in the mathematical model, to Ṽi . Let R̃i , i = 0, 1, 2, · · · , 156, be the sum of Recovery and Deaths from
daily reported data. The removed population R(t) is fitted to R̃i . The fitting process is the same as that
used for the first-stage model. Equation (20) is approximated by the left-hand sum with dξ = 0.01
day. Fourteen parameters listed in Table 3, including µ1 , β2 , Li , Mi , ki , ti , i = 1, 2, 3, are to be fitted.
The
q parameter qvalues are qdetermined by minimizing
i=0 (X1 (i) + X2 (i) − X̃i ) + i=0 (R(i) − R̃i ) + 0.3 × i=0 (V(i) − Ṽi ) , where T = 156. Figure 9
PT 2
PT 2
P T 2

shows
q the q fitting q results with
i=0 (X1 (i) + X2 (i) − X̃i ) + i=0 (R(i) − R̃i ) + 0.3 × i=0 (V(i) − Ṽi ) = 3.6 × 10 (persons) and
PT 2
P T 2
P T 2 6

with the parameter values determined and summarized in Table 3. The infection rate µ1 = 0.227 day−1
is higher in the second wave than that in the first wave. India scientists have reported mutant variants
which are more infectious in the second wave, and India experienced the exponential growth of
COVID-19 infection beginning in March 2021 [43, 46]. Figure 4 shows that in the first and second
waves, the number of COVID-19 cases was growing exponentially in March 2020 and March 2021,
respectively.
The bootstrap statistics for the parameters of the second-stage model are shown in Table 4.

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 11337

106 106
3 3
Data: Daily new cases Data: Daily new cases
Simulation using Eqs. (14)-(17) Simulation using Eqs. (14)-(17)
2.5 2.5

2 2

R
X

1.5 1.5

1 1

0.5 0.5
1 1 21 1 1 1
-2 -2 l- -2 y-2 l-2
ar ay -Ju ar Ju
-M M 1 -M Ma 1-
1 1- 1 1-
Days (1 Mar. 2021 thru 4 Aug. 2021) Days (1 Mar. 2021 thru 4 Aug. 2021)

(a) (b)

104 107
3
Data: Daily new cases Data: Daily new cases
4 Simulation using Eqs. (14)-(17) Simulation using Eqs. (14)-(17)
2.5
Daily new cases

3 2
Vaccination

1.5
2
1
1
0.5

0 0
1 1 21 1 1 1
r -2 -2 l- -2 y-2 l-2
Ma ay -Ju ar a Ju
1- 1-M 1 1 -M 1-M 1-
Days (1 Mar. 2021 thru 4 Aug. 2021) Days (1 Mar. 2021 thru 4 Aug. 2021)

(c) (d)
Figure 9. Population dynamics for (a) the infected population (X = X1 + X2 ), (b) the removed
population (R), (c) new cases (X(i) − X(i − 1), i = 1, 2, · · · , T ), and (d) the vaccinated
population (P0 − X1 − Y1 ) with simulation using Eqs (14)–(17) and parameter values given in
Table 3.

Similarly, small standard deviations for bootstrap estimates are found for the second-stage model. The
parameter values used for the second-stage model (Table 3) are rather close to these mean values. The
bootstrap statistics show no correlation or weak correlation between all parameters except for µ1 and
t1 with a correlation coefficient of –0.9 (Figure 10).

3.4. The effect of social distancing and detection of positive cases for the second wave
During the second wave, major hospitals faced a shortage of hospital beds, medicines, oxygen and
ventilator supplies, leading to high mortality [43, 46]. The detection rate α(t), shown in Figure 11(a),
is lower compared with that in the first wave (Figure 7(b)). The parameters k2 and t2 are negative
indicating that the detection rate α(t) is decreasing and α(t), for t ≥ 0, contains only the lower part

Mathematical Biosciences and Engineering Volume 19, Issue 11, 11324–11344.

 11338

Table 3. Parameter values in Eqs (14)–(17). HSC represents half saturation constant. HCR
represents health care resources.

Parameter Value Brief Description Units Reference

P0 7.8 × 107 Population of Tamil Nadu State, India individual [40]
µ1 0.227 Intrinsic infection rate Day−1 fitted with data [38, 39]
µ2 0.0454 Infection rate after vaccinated Day−1 assumed, based on [44, 45]
β1 0.0484 Unlock-down factor Dimensionless fitted with data [38]
h1 104 HSC of vaccination Individual assumed
M1 0.43 Pre-experience in σ Dimensionless fitted with data [38, 39]
t1 83.9 Time parameter in σ Day fitted with data [38, 39]
k1 0.2421 Steepness of σ Day−1 fitted with data [38, 39]
L1 0.265 Maximum increase in σ Dimensionless fitted with data [38, 39]
h2 5 × 105 HSC of HCR Individual assumed
M2 0.3491 Pre-experience in α Dimensionless fitted with data [38, 39]
t2 -5.8882 Time parameter in α Day fitted with data [38, 39]
k2 -0.6178 Steepness of α Day−1 fitted with data [38, 39]
L2 0.5406 Maximum increase in α Dimensionless fitted with data [38, 39]
M3 0.0216 Pre-experience in γ Dimensionless fitted with data [38, 39]
t3 282.2 Time parameter in γ Day fitted with data [38, 39]
k3 0.0163 Steepness of γ Day−1 fitted with data [38, 39]
L3 0.7209 Maximum increase in γ Dimensionless fitted with data [38, 39]
β2 3155833 Maximum vaccination rate Individual Day−1 fitted with data [38, 39]
τ1 4 Delay in detection Day [23]
τ2 14 Recovery time Day [30]
τ3 14 Hospitalization time Day [30]

Table 4. Bootstrap statistics, second wave, 1000 bootstrap samples.

Parameter µ1 M1 t1 k1 L1
Mean 0.2339 0.4304 82.2 0.2363 0.2658
Std 0.01 0.0011 2.6 0.0391 0.0082
Mean ± 2Std [0.2139,0.2539] [0.4282,0.4326] [77,87.4] [0.1581,0.3145] [0.2494,0.2822]
Parameter M2 t2 k2 L2
Mean 0.3574 -5.53 -0.6341 0.5625
Std 0.0219 0.52 0.0803 0.0318
Mean ± 2Std [0.3136,0.4012] [-6.57,-4.49] [-0.7947,-0.4735] [0.4989,0.6261]
Parameter M3 t3 k3 L3 β2
Mean 0.0221 282 0.0165 0.7264 3.1757 × 106
Std 0.0015 7 0.0007 0.0528 1.872 × 105
Mean ± 2Std [0.0191,0.0251] [268,296] [0.0151,0.0179] [0.6208,0.832] [2.8013, 3.5501] × 106

Mathematical Biosciences and Engineering Volume 19, Issue 11, 11324–11344.

 11339

85

80

t1
75

70
0.22 0.24 0.26 0.28
1

Figure 10. Two dimensional distributions for µ1 and t1 using 1000 bootstrap samples.

of the curve. The detection rate decreases quickly initially, levels off soon, and remains at a low
level. Combining this effect with shortage of health care resources, Figure 11(b) shows that the overall
rate of hospitalization of the positive cases continue to decrease over time. Shortage of health care
resources is one of the factors responsible for fast increased number of cases in Tamil Nadu [46]. Jain
et al. [46] suggested that prevention was better than cure for this disease and the implementation of
social distancing and the use of face masks was able to help with controlling the disease. Figure 11(c)
shows that during the first two months of the second wave, implementation of social distancing is not
effective and remains at the same level as that in the first wave. Then, the social distancing effect
increases during May and Jun 2021 and levels off at about 0.7 which is much higher than that during
the first wave. Chakraborty et al. [43] pointed out that social distancing was not strictly implemented
during the first wave in India due to crowded style of living arrangement. Our study shows that people
in Tamil Nadu may have learned their lessons and follow social distancing measures after some time in
the second wave. Nevertheless, a factor of 0.7 for social distancing measures is not effective compared
with other cities studied in [23].

0.44 0.45 0.7

0.42 0.4
0.6
0.4
(t)

(t)
(1-H)

0.35
0.38
0.5
0.3
0.36

0.34 0.25 0.4

1 1 21 1 1 1 1 1 1
r-2 y-2 l- r -2 y-2 l-2 r-2 y-2 l-2
Ma Ma -Ju Ma Ma -Ju Ma Ma 1-
Ju
1- 1- 1 1- 1- 1 1- 1-
t: Days (1 Mar. 2021 thru 4 Aug. 2021) t: Days (1 Mar. 2021 thru 4 Aug. 2021) t: Days (1 Mar. 2021 thru 4 Aug. 2021)
(a) (b) (c)

Figure 11. The functions (a) α(t), (b) α×(1−H), and (c) σ(t) in Eqs (14)–(17) with parameter
values given in Table 3.

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 11340

4. Conclusions

In this paper, mathematical models using deterministic ODEs with time delays are proposed for
the study of impacts of pharmaceutical and non-pharmaceutical factors on the COVID-19 pandemic
for the state of Tamil Nadu, India. The first-stage model, designed for the first wave in the region,
considers two populations, the population of infected individuals and the population of removed
individuals. The second-stage model, designed for the second wave, considers four populations,
unvaccinated infected population, vaccinated infected population, unvaccinated uninfected
population, and removed population. Some factors such as social distancing, detection efficiency, and
vaccination willingness are modeled by learning curves. Daily reported data supported by CSSE at
Coronavirus Resource Center of JHU are used to fit the model [38, 39] and to determine the
parameter values. The model produces a close match to the evolution of COVID-19 in Tamil Nadu
(Figures 5 and 9).
The preliminary results obtained from the simulation indicate that the lock down contributed limited
effects on controlling the spread of the disease in Tamil Nadu. The social distancing implementation
and detection of positive cases are relative ineffective compared with some big cities studied by Alvarez
et al. [23] in the first wave. These observations are in agreement with the research report that social
distancing was not strictly implemented during the first wave in India [43]. The implementation of
social distancing remains at a low level during the first half period of the second wave but is improved
after some time in the second wave (Figure 11(c)). The detection efficiency and hospitalization rate
decrease rapidly and remains at low levels over the second wave (Figure 11(a),(b)). Jain et al. [46]
pointed out that Tamil Nadu faced shortage of health care resources during the second wave of COVID-
19. The impacts of other factors will also need to be considered and is currently under future research
directions of the authors.

Acknowledgments

A Shankaranarayanan was supported by the Ministry of Science and Technology (MOST) of Taiwan
under the grant no. MOST 110-2222-E-035-002; H.-C. Wei was supported by the MOST of Taiwan
under the grant no. MOST 110-2115-M-035-004.

Conflict of interest

The authors declare there is no conflict of interest.

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