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<article xmlns:xlink="http://www.w3.org/1999/xlink">
  <front>
    <journal-meta>
      <journal-title-group>
        <journal-title>International Journal of Telemedicine and Applications</journal-title>
      </journal-title-group>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="doi">10.14218/ERHM.2021.00044</article-id>
      <title-group>
        <article-title>The COVID-19 Pandemic Dynamics and Incomes</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <string-name>Igor Nesteruk</string-name>
          <email>inesteruk@yahoo.com</email>
          <xref ref-type="aff" rid="aff0">0</xref>
          <xref ref-type="aff" rid="aff2">2</xref>
          <xref ref-type="aff" rid="aff3">3</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Oleksii Rodionov</string-name>
          <xref ref-type="aff" rid="aff1">1</xref>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <aff id="aff0">
          <label>0</label>
          <institution>Institute of Hydromechanics, National Academy of Sciences of Ukraine</institution>
          ,
          <addr-line>Kyiv</addr-line>
          ,
          <country country="UA">Ukraine</country>
        </aff>
        <aff id="aff1">
          <label>1</label>
          <institution>Private consulting office</institution>
          ,
          <addr-line>Kyiv</addr-line>
          ,
          <country country="UA">Ukraine</country>
        </aff>
        <aff id="aff2">
          <label>2</label>
          <institution>ProfIT AI 2024: 4</institution>
        </aff>
        <aff id="aff3">
          <label>3</label>
          <institution>SBIDER (Systems Biology &amp; Infectious Disease Epidemiology Research) Centre at University of Warwick</institution>
          ,
          <country country="UK">UK</country>
        </aff>
      </contrib-group>
      <pub-date>
        <year>2022</year>
      </pub-date>
      <volume>399</volume>
      <issue>10344</issue>
      <fpage>1205</fpage>
      <lpage>1211</lpage>
      <abstract>
        <p>Objectives. Large differences in the number of registered SARS-CoV-2 cases per capita in different countries encourage research into the causes of this phenomenon. In particular, the accumulated numbers of cases per million (CC) demonstrated strong linear correlations with the gross domestic product per capita (GDP) and the median age of populations. In this paper the possible correlations between GDP and numbers of cases CC and deaths (DC) per million, case fatality risks CFR=DC/CC, vaccinations and testing levels will be investigated. As well non-linear correlations of CC, DC and CFR values versus vaccinations and testing levels will be considered. Methods. A non-linear correlation and John Hopkins University (JHU) datasets for African and European countries corresponding to August 1, 2022 were used. Results. The numbers of CC, DC and CFR increase for richer countries, the same trends were revealed for DC and CFR values in Africa, but opposite ones in Europe. As expected, the testing and vaccination levels increase with the growth of GDP. Higher levels of testing probably allowed revealing more cases and COVID-19 related deaths in rich countries. CC values showed a very strong increasing trend with the increase of numbers of tests per capita (TC). Unexpectedly, the same increasing trend was revealed for CC and DC values versus percentage of fully vaccinated people (VC). Nevertheless, the decrease of CFR with the increase of VC demonstrates a positive effect of vaccinations. Conclusions. In some countries, the number of undetected COVID-19 cases may be tens or even hundreds of times higher than the number of registered ones due to the differences in testing levels and age structure. This fact increases the probability of the appearance of new dangerous SARS-CoV-2 strains and has to be taken into account in further investigations of impact of different factors on the pandemic dynamics.</p>
      </abstract>
      <kwd-group>
        <kwd>eol&gt;COVID-19 pandemic</kwd>
        <kwd>epidemic dynamics in Africa</kwd>
        <kwd>epidemic dynamics in Europe</kwd>
        <kwd>gross domestic product per capita</kwd>
        <kwd>non-linear correlation</kwd>
        <kwd>statistical methods</kwd>
        <kwd>1</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>Introduction</title>
      <p>Data, the non-linear regression and Fisher test
We will use the data sets regarding the gross domestic product per capita (GDP) based on
purchasing power parity (PPP) available in [19] and some COVID-19 characteristics reported by
John Hopkins University (JHU) as of August 1, 2022, [20]. The figures corresponding to the
versions of files available on September 4, 2022 are presented in supplementary Tables S1 and S2
and shown in the Figure for African (black markers) and European countries (blue markers).</p>
      <p>
        The following non-linear correlation will be applied:
y = a + b(x + с)g ; a ³ 0 , b&gt;0, x&gt;-c
(
        <xref ref-type="bibr" rid="ref1">1</xref>
        )
to find links between GDP, TC, and VC (variable x) and CC, DC, DC/CC, TC, and VC (variable y).
At γ =1 relationship (
        <xref ref-type="bibr" rid="ref1">1</xref>
        ) reduces to the linear one. It can be also reduced to the linear correlation by
using new random variables z and w≡log(x+c), [11, 14]:
z≡log(y-a)=log(b)+γlog(x+c)
(
        <xref ref-type="bibr" rid="ref2">2</xref>
        )
      </p>
      <p>
        The constant parameters γ, log(b) and corresponding best fitting lines can be found with the use
of standard linear regression formulas [21] for different values of constant parameters a and c.
Their optimal values correspond to the maximum of the correlation coefficient magnitude |r| or the
ratio of the Fisher functions F/Fc(k1,k2), (k1=1, k2=n-2, n is the number of observations, i.e., the
number of countries in datasets), [ 6, 11, 14]. The corresponding experimental values F can be
calculated with the use of formula (S1), [21], the critical values Fc(k1,k2) of the Fisher function at a
desired significance or confidence level can be found in [22]. If F/Fc(k1,k2)&lt;1, the hypothesis about
the relationship (
        <xref ref-type="bibr" rid="ref1">1</xref>
        ) is not supported by the results of observations. The highest values of F/Fc(k1,k2)
correspond to the most reliable hypotheses.
      </p>
    </sec>
    <sec id="sec-2">
      <title>Results</title>
      <p>
        The optimal values of parameters for different non-linear correlations (
        <xref ref-type="bibr" rid="ref1">1</xref>
        ) are listed in Table 1.
Corresponding best fitting lines are shown in the Figure by the black color for African datasets,
blue - for Europe and red - for complete datasets (Africa + Europe). Rows 1-3 of Table 1 and solid
lines in Figure illustrate that the accumulated numbers of cases per million CC always increase
with the increase of the incomes. Nevertheless, the number of deaths DC and case fatality risk CFR
decrease in richer European countries (see rows 5, 8 and blue dashed and dotted lines; the
correlation DC versus GDP is supported at confidence level 0.025; Fc (
        <xref ref-type="bibr" rid="ref1">1, 40</xref>
        ) =5.47). What is
surprising is the increase in DC and CFR values with increasing income in Africa and for the full
data sets (see rows 4, 6, 7, 9 and corresponding dashed and dotted lines; the correlation CFR versus
GDP for complete dataset is supported at confidence level 0.005; Fc(
        <xref ref-type="bibr" rid="ref1">1,94</xref>
        ) =8.33).
      </p>
      <p>
        As expected, the vaccination and testing levels (VC and TC) always increase with rising
incomes (see rows 10-15 and corresponding lines). Rows 16 and 18 represent the correlation of CC
values versus TC and VC, respectively. The strongest link between the number of cases and the
testing level (r=0.9496, and the highest F/Fc(k1,k2) ratio, see row 16) and the strong link between
TC and GDP values (see row 12) allows us to conclude that high CC values in rich countries are
probably connected with the higher testing level. Numbers of cases and deaths per capita for
complete dataset (Africa + Europe) increase with the increase of percentage of vaccinated people
VC (see rows 18 and 20). Opposite trend was revealed only for CFR values (row 22). Thus, the
positive effect of vaccinations is visible only in decreasing the probability to die for persons tested
positive. To eliminate the influence of the testing level the same correlations were investigated for
15 European countries with TC&gt;3. Corresponding CC, DC and CFR values demonstrate decreasing
trend with the increase of VC, but it was not supported even at the significance level 0.05 (Fc
(
        <xref ref-type="bibr" rid="ref1">1,13</xref>
        )= 4.67; see rows 19, 21 and 23).
      </p>
      <p>Table 1.</p>
      <p>
        Optimal values of parameters in eq. (
        <xref ref-type="bibr" rid="ref1">1</xref>
        ), correlation coefficients and the results of Fisher
test applications for Africa, Europe and complete datasets (Africa + Europe).
      </p>
      <p>
        The characteristics accumulated as of August 1, 2022 are: numbers of cases per million (CC,
“circles”), numbers of deaths per million (DC, “crosses”), percentage of fully vaccinated people (VC,
“dots”), numbers of test per capita (TC, “squares”). The case fatality risk was calculated with the
use of formula CFR=DC/CC and shown by “triangles. Lines represent the best fitting relationships
(
        <xref ref-type="bibr" rid="ref1">1</xref>
        ) with the optimal values of parameters listed Table 1: the black color corresponds to African
countries, the blue one – to European, the red one – to complete datasets (Africa + Europe).
      </p>
    </sec>
    <sec id="sec-3">
      <title>Discussion</title>
      <p>
        The large difference between the number of registered and real COVID-19 cases [23-33] has to
be taken into account to investigate the effects of different factors on the pandemic dynamics. In
particular, different healthcare infrastructures, public health policies, and social behaviors could
significantly change the pandemic dynamics and the analysis of these factors needs further
investigations. Here we will focus on some specific influence of the testing rate. In particular, the
TC values could approach some critical level, which allows revealing almost all COVID-19 cases.
To check this hypothesis, let us consider the countries with TC&gt;3. Their relatively large number
16 (all countries are located in Europe) - allows drawing some statistical conclusions (see row 17).
First, there is no correlation between CC and TC values even for significance level 0.1 (Fc (
        <xref ref-type="bibr" rid="ref1">1, 14</xref>
        )
=3.14). It means that 3 or more tests per person were enough to reveal the majority of cases before
August 1, 2022. Its average value CCa is approximately 460,834 and can be used to calculate the
visibility coefficient
b = ССa
      </p>
      <p>СС
as the ratio of real to registered number of cases.</p>
      <p>
        There are some theoretical and experimental estimations of the visibility coefficient for different
periods of COVID-19 pandemic [10, 23-25]. For example, a total testing in Slovakia (89.5% of
population was tested on October 31- November 7, 2020) revealed a number of previously
(
        <xref ref-type="bibr" rid="ref3">3</xref>
        )
undetected cases, equal to about 1.63% of the population [23, 24]. Taking into account that the
number of detected cases in Slovakia was approximately 1% of population [20], we can estimate
β≈2.63 for that period in Slovakia. As of August 1, 2022 the corresponding value CC=473,844 for
Slovakia (see Table S2) is slightly larger than CCa showing the good detection level in this country
with TC=9.41.
      </p>
      <p>
        A random testing in two kindergartens and two schools in the Ukrainian city of Chmelnytskii
[25] revealed the value 3.9 in December 2020. Theoretical estimations based on the generalized SIR
model [6, 10] yielded values from 3.7 to 20.4 for Ukraine and 5.4 for Qatar in different periods of
the COVID-19 pandemic. As of August 1, 2022 formula (
        <xref ref-type="bibr" rid="ref3">3</xref>
        ) yields the β values 3.8 for Ukraine and
3.0 for Qatar (CC=152,375.8, [20]). Corresponding visibility coefficients are: 4.4 in Japan; 1.7 in US
and 14.7 in India.
      </p>
      <p>
        The value CCa = 460,834 and formula (
        <xref ref-type="bibr" rid="ref3">3</xref>
        ) is probably not applicable for China and other
ZeroCOVID countries [34], where the total control and maximum suppression of the pandemic were
applied. For example, mainland China has achieved the testing level TC=6.46 already on April 11,
2022, [20]. The value CC=636 registered on August 1, 2022 is much lower than the CCa figure.
Nevertheless, CC values in Australia, New Zealand and South Korea (where the zero tolerance
policy was not as severe as in China) CC values vary from 317,619 to 384,572 (see [20]). The testing
levels in Hong Kong (TC= 6.59 as of May 24, 2022, [20]) and in mainland China are very close. The
huge difference in the registered numbers of cases per million (CC= 181,231 in Hong Kong as of
August 1, 2022, [20]) probably is connected with much higher values of the tests per case ratio in
mainland China, [14].
      </p>
      <p>The lack of appropriate testing makes it especially difficult to detect the first cases of a new
disease, which for SARS-CoV-2 probably appeared long before December 2019 [26]. In particular,
theoretical estimates give the date of the appearance of the first case at the beginning of August
2019, [6].</p>
      <p>The insufficient testing and high values of visibility coefficients can lead to controversial
conclusions about the influence of vaccinations. For example, for complete datasets, unexpected
upward trends for CC and DC values with the increasing VC were revealed at the very high
significance level (see rows 18 and 20). Similar correlations were also found in [11] for average
daily numbers of COVID-19 cases and deaths. In some countries (e.g., Israel, Japan, New Zealand),
high vaccination levels did not prevent new severe pandemic waves [10, 14] with record numbers
of cases and deaths, [10, 14]. Statistical studies support the fact that vaccinations diminished CFR,
but their ability to reduce infections should be questioned [10, 11, 13, 14] and needs further
investigation.</p>
      <p>It would also be interesting to investigate the reasons for the increase in CC and DC values with
the increase in incomes (see rows 3 and 6 in Table 1). One of them could be a lower mobility and
less number of contacts in poor countries [18]. The age of population is another important factor in
the visible COVID-19 pandemic dynamics [11, 35], since the percentage of asymptomatic (and
unregistered) patients is much higher in children [27-30]. In particular, a one-year increment in the
median year of population yields a 12-18 thousand increase in CC values and 52-83 increase in DC
values (both figures correspond December 31, 2022), [35]. Taking into account the 24 year
difference in the median age (18 in Africa and 42 in Europe, [36]) we can expect 288- 432 thousand
higher CC figures and 1.2-2 thousand higher DC figures in Europe. The huge number of undetected
COVID-19 cases increases the probability of the appearance of new dangerous SARS-CoV-2
variants.</p>
    </sec>
    <sec id="sec-4">
      <title>Conclusions</title>
      <p>Non-linear correlation analysis (using JHU datasets for Europe and Africa corresponding to
August 1, 2022) demonstrated that the numbers of COVID-19 cases CC and deaths DC per capita
and case fatality risks CFR=DC/CC increase for richer countries. The same trends were revealed
for DC and CFR values in Africa, but opposite ones in Europe. As expected, the testing and
vaccination levels increase with the growth of GDP. Higher levels of testing probably allowed
revealing more cases and COVID-19 related deaths in rich countries. CC values showed a very
strong increasing trend with the increase of numbers of tests per capita (TC). Unexpectedly, the
same increasing trend was revealed for CC and DC values versus percentage of fully vaccinated
people (VC). Nevertheless, the decrease of CFR with the increase of VC demonstrates a positive
effect of vaccinations.</p>
      <p>In some countries, the number of undetected COVID-19 cases may be tens or even hundreds of
times higher than the number of registered ones due to the differences in testing levels and age
structure. This fact increases the probability of the appearance of new dangerous SARS-CoV-2
strains and has to be taken into account in further investigations of impact of different factors on
the pandemic dynamics.</p>
    </sec>
    <sec id="sec-5">
      <title>Conflict of Interest</title>
      <p>The authors declare no conflict of interests</p>
    </sec>
    <sec id="sec-6">
      <title>Ethical Approval statement</title>
      <p>The study does not use any experiments with humans or animals. The data sources are available
on the Internet.</p>
    </sec>
    <sec id="sec-7">
      <title>Acknowledgments</title>
      <p>The authors are grateful to Robin Thompson, Matt Keeling, and Paul Brown for their support
and providing very useful information. Igor Nesteruk was supported by INI-LMS Solidarity
Programme at the University of Warwick, UK.
[29] Fowlkes A.L., Yoon S.K., Lutrick K., Gwynn L., Burns J., Grant L., Phillips A., Ellingson K.,
Ferraris M., LeClair M., et al. Effectiveness of 2-Dose BNT162b2 (Pfizer BioNTech) mRNA
Vaccine in Preventing SARS-CoV-2 Infection Among Children Aged 5-11 Years and
Adolescents Aged 12–15 Years -PROTECT Cohort, July 2021–February 2022. MMWR Morb.</p>
      <p>
        Mortal. Wkly. Rep. 2022;71:422–428. doi: 10.15585/mmwr.mm7111e1.
[30] Shang W, Kang L, Cao G, Wang Y, Gao P, Liu J, Liu M. Percentage of Asymptomatic
Infections among SARS-CoV-2 Omicron Variant-Positive Individuals: A Systematic Review
and Meta-Analysis. Vaccines (Basel). 2022 Jun 30;10(
        <xref ref-type="bibr" rid="ref7">7</xref>
        ):1049. doi: 10.3390/vaccines10071049.
      </p>
      <p>PMID: 35891214; PMCID: PMC9321237.
[31] Schreiber, P.W., Scheier, T., Wolfensberger, A. et al. Parallel dynamics in the yield of
universal SARS-CoV-2 admission screening and population incidence. Sci Rep 13, 7296
(2023). https://doi.org/10.1038/s41598-023-33824-6
[32] You Y, Yang X, Hung D, et al. Asymptomatic COVID-19 infection: diagnosis, transmission,
population characteristics. BMJ Supportive &amp; Palliative Care 2024;14:e220-e227.
[33] Kronbichler A, Kresse D, Yoon S, Lee KH, Effenberger M, Shin JI. Asymptomatic patients
as a source of COVID-19 infections: a systematic review and meta-analysis. Int J Infect Dis.
2020;98:180-186. doi:10.1016/j.ijid.2020.06.052
[34] https://en.wikipedia.org/wiki/Zero-COVID
[35] Igor Nesteruk, Matt Keeling. Population age as a key factor in the COVID-19 pandemic
dynamics. Preprint. Research Square. Posted November 30, 2023.
https://doi.org/10.21203/rs.3.rs-3682693/v1
[36] https://www.visualcapitalist.com/mapped-the-median-age-of-every-continent/. Retrieved</p>
      <p>September 30, 2023.</p>
    </sec>
    <sec id="sec-8">
      <title>Supplementary tables</title>
      <sec id="sec-8-1">
        <title>People</title>
        <p>fully</p>
      </sec>
      <sec id="sec-8-2">
        <title>Total</title>
        <p>Total
cases per</p>
        <p>deaths per
vaccinated
million CC,</p>
        <p>million, DC,
17.36418
12.7419
122.0629
67.6927
56.07519
10.89919
6061
3034
1779
18345
1778
1603
2575
6920
25043
9041
1439
10448
1435
5853
2808
4681
52.0226
27.1227
per hundred,
%, VC, [20]</p>
        <p>Fisher function
Switzerland
Ukraine
United
Kingdom</p>
        <p>The experimental values of the Fisher function can be calculated with the use of the formula:
F =</p>
        <p>
          r 2 (n - m)
(1- r 2 )(m -1)
(S1)
where n is the number of observations (number of countries and regions taken for statistical
analysis); m=2 is the number of parameters in the linear regression equation (
          <xref ref-type="bibr" rid="ref2">2</xref>
          ), [22].
no data
        </p>
      </sec>
    </sec>
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</article>