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\begin{document}

\title{Large-scale Synchronized Replacement of Alpha strain by the Delta Strain}



\author[1]{Yuan Liu}%
\author[1]{Anyin Feng}%
\author[2]{Shi Zhao}%
\author[1]{Daihai He}%
\affil[1]{The Hong Kong Polytechnic University}%
\affil[2]{The Chinese University of Hong Kong}%


\vspace{-1em}



  
  \date{June 14, 2024}


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\selectlanguage{english}
\begin{abstract}
In this letter, we report a large-scale synchronized replacement pattern
of the Alpha strain by the Delta strain. We argue that this phenomenon
is associated with the invasion timing and transmissibility advantage of
the Delta strain. Alpha strain skipped some countries/regions, e.g.
India and neighboring countries/regions, which led to a mild first wave
before the invasion of the Delta strain, in term of reported
COVID-deaths per capita.%
\end{abstract}%



\sloppy


Large-scale Synchronized Replacement of Alpha strain by the Delta Strain

(Running title: \textbf{Replacement of Alpha by Delta} )

Yuan Liu\textsuperscript{1}, Anyin Feng\textsuperscript{1}, Shi
Zhao\textsuperscript{2,3}, Daihai He\textsuperscript{1,\#}

\textsuperscript{1} Department of Applied Mathematics, The Hong Kong
Polytechnic University, HKSAR, China

\textsuperscript{2} JC School of Public Health and Primary Care, Chinese
University of Hong Kong, Hong Kong, China

\textsuperscript{3} CUHK Shenzhen Research Institute, Shenzhen, China

Email of all authors:

YL: 21039899R@connect.polyu.hk

AF: anyin.feng@connect.polyu.hk

SZ: zhaoshi.cmsa@gmail.com

DH: daihai.he@polyu.edu.hk;

\# Correspondence author: Daihai He, Department of Applied Mathematics,
The Hong Kong Polytechnic University, Hong Kong China. Email:
daihai.he@polyu.edu.hk

\textbf{Abstract}

In this letter, we report a large-scale synchronized replacement pattern
of the Alpha strain by the Delta strain. We argue that this phenomenon
is associated with the invasion timing and transmissibility advantage of
the Delta strain. Alpha strain skipped some countries/regions, e.g.
India and neighboring countries/regions, which led to a mild first wave
before the invasion of the Delta strain, in term of reported
COVID-deaths per capita.

\textbf{Keyword:} variants of concern, Delta strain, Alpha variant,
synchronization

Dear Editor:

The coronavirus disease 2019 (COVID-19), caused by severe acute
respiratory syndrome coronavirus 2 (SARS-COV-2) has seriously affected
public health worldwide. As of February 2021, more than 100 million
people had been diagnosed with SARS-COV-2 and more than 2 million deaths
have been attributed to COVID-19 \textsuperscript{1}. The virus evolved
rapidly and several variants have emerged. In March 2021, the Alpha
variant began to spread in Cambodia and Thailand, in some clusters in
Thailand, the positive rate of SARS-CoV-2 testing is as much as
60-90\%.\textsuperscript{2} According to \textsuperscript{3}, besides a
higher transmissibility than the previous wild strain, patients infected
with the Alpha COVID-19 variant were at a higher risk of hospitalization
than those infected with the previous wild strain, reflecting the
increased virulence of the Alpha variant.

At the same time, Kappa (B.1.617.2) and Delta (B.1.617.2) variants
appeared in Maharashtra, India and resulting in a resurgence of cases in
the country. Different from Alpha variant, the Delta variant lineage is
defined by eight non-synonymous mutations in S protein. The Delta
variant which spread around 200 countries/regions has been classified as
a variant of concern by the CDC. \textsuperscript{4} Besides a higher
transmissibility than Alpha strain, patients with the Delta variant were
more than twice as likely to be hospitalized as those with the Alpha
variant, according to\textsuperscript{5}. The Delta variant is replacing
all the other SARS-COV-2 variants.

Starting from June 2020, India has implemented 11 stages of unlocking,
phase 11 of which was announced at the end of March, 202 and remains in
effect until April 30, 2020. But since mid-April, 2020, India has seen a
severe surge in the pandemic. As of May 10, 2020, more than 388,000
people had been affected.\textsuperscript{6} And according to another
report \textsuperscript{7}, characteristic mutations of the Delta
variant were observed in sequences obtained in India in April and May
2021, and the Delta variant became the dominant transmission variant in
May and June, 2021 in India.

In this letter, we visualize the replacement of previous strain with
Alpha strain and the replacement of Alpha strain with Delta strains
globally. We find that the Alpha strain only dominated for a short
period of 3-4 months and the replacement of Alpha with Delta show
surprisingly synchronous pattern in a large number of countries/regions.

\textbf{Hosted file}

\verb`image1.emf`  available at \url{https://authorea.com/users/737041/articles/712297-large-scale-synchronized-replacement-of-alpha-strain-by-the-delta-strain}

\textbf{Figure 1.} Timing of the confirmations of Delta strain exceeding
Alpha strain (the first time that the proportion of Delta \textgreater{}
the proportion of Alpha), denoted as \(T_{\alpha\rightarrow\sigma}\)in 71
countries/regions, versus timing of the confirmations of Alpha strain
exceeding the previous strain \(T_{w\rightarrow\alpha}\). (a) countries/regions
are ordered from left to right according to\(T_{\alpha\rightarrow\sigma}\). (b)
countries/regions are ordered from left to right according to
\(T_{w\rightarrow\alpha}\).

From Figure 1, we can see that Delta strain was first found in India and
spread first in neighboring countries/regions, gradually to other
countries/regions. Alpha strain was first found in United Kingdom and
spread first in neighboring countries/regions, gradually to the rest of
the world. \(T_{\alpha\rightarrow\sigma}\) (Black circle) has a surprisingly
synchrony patten across a large number of countries/regions (ie, a
horizontal line across a large number of countries/regions in July
2021). This synchrony pattern is less evident in the\(T_{w\rightarrow\alpha}\)
(red squares). In other words, the timing of Delta strain replacing
Alpha strain occurred simultaneously in many countries/regions. In
contrast, the timing of Alpha strain replacing the previous wild strain
did not show a strong synchronous substitution trend. This could be
related to a higher transmissibility of Delta strain compared to other
previous strains. Delta strain also possesses shortened incubation
period and increased viral load. In particular, the viral load is about
1000 times higher in patient who was infected with Delta strain than
patient who was infected with the original strain. And the first
detectable time for Delta strain is 4 days after infection which is
longer than the average detectable time of original strain (6 days)
\textsuperscript{8}

Also, the invasion time of Delta strain happened at the tail of the wave
of Alpha strain and coincided with a relax of social distancing in many
countries (see Figure S1 in supplementary).

The dominance time of the Alpha strain is between\(T_{w\rightarrow\alpha}\) and
\(T_{\alpha\rightarrow\sigma}\). In South and Southeast Asia, e.g. India, the Alpha
strain failed to dominate, which could be associated to a mild first
wave (with low deaths per capita in India in 2020).

In Scotland, BNT162b2 and Astrazeneca vaccines were 79\% and 60\%
effective at preventing SARS-COV-2 Delta infection after two doses,
respectively. However, the Pfizer-Biontech and Astrazeneca vaccines
maintain a high degree of protection against any infection similar to
Alpha strain \textsuperscript{9}.

In summary, we reported a large-scale synchronized replacement of Alpha
strain by the Delta strain which could be due to the invasion timing of
Delta strain and its relatively high transmissibility. Also, we note
that these countries/regions in South and Southeast Asia experienced a
mild 2020 year was largely skipped by the Alpha strain.

\textbf{Declarations}

\textbf{-Ethics approval and consent to participate}This study only
reanalyzed publicly available data which were carried out in accordance
with relevant guidelines and regulations.

\textbf{-Consent for publication}Not applicable.

\textbf{-Availability of data and materials}

All data are publicly available.
https://ourworldindata.org/grapher/covid-variants-area \textbf{Competing
interests}

The authors declare that they have no competing
interests.\textbf{-Funding} The work described in this paper was
partially supported by a grant from the Research Grants Council of the
Hong Kong Special Administrative Region, China (HKU C7123-20G).

\textbf{-Authors' contributions}All authors conceived the study, carried
out the analysis, wrote the draft, revised the manuscript critically,
and approved it for publishing.

\textbf{Funding} The work described in this paper was partially
supported by a grant from the Research Grants Council of the Hong Kong
Special Administrative Region, China (HKU C7123-20G).

\textbf{-Acknowledgements}None.

\textbf{Reference}

1. Wang C, Wang Z, Wang G, Lau JY-N, Zhang K, Li W. COVID-19 in early
2021: current status and looking forward. \emph{Signal Transduction and
Targeted Therapy} 2021; \textbf{6} (1): 1-14.

2. Chookajorn T, Kochakarn T, Wilasang C, Kotanan N, Modchang C.
Southeast Asia is an emerging hotspot for COVID-19. \emph{Nature
Medicine} 2021: 1-2.

3. Vassallo M, Manni S, Klotz C, et al. Patients admitted for variant
alpha COVID-19 have poorer outcomes than those infected with the old
strain. \emph{Journal of clinical medicine} 2021; \textbf{10} (16):
3550.

4. Farinholt T, Doddapaneni H, Qin X, et al. Transmission event of
SARS-CoV-2 Delta variant reveals multiple vaccine breakthrough
infections. \emph{BMC medicine} 2021; \textbf{19} (1): 1-6.

5. Liu Y, Gayle AA, Wilder-Smith A, Rockl\selectlanguage{ngerman}öv J. The reproductive number
of COVID-19 is higher compared to SARS coronavirus. \emph{Journal of
travel medicine} 2020.

6. Ghosh N, Saha I, Sarkar JP, Maulik U. Strategies for COVID-19
Epidemiological Surveillance in India: Overall Policies Till June
2021.\emph{Frontiers in Public Health} 2021; \textbf{9} .

7. Shrivastava S, Mhaske ST, Modak MS, et al. Emergence of Two Distinct
Variants of SARS-CoV-2 and Explosive Second Wave of COVID-19: An
Experience From A Tertiary Care Hospital, Pune, India. 2021.

8. Reardon S. How the Delta variant achieves its ultrafast
spread.\emph{Nature} 2021; \textbf{21} .

9. Cevik M, Grubaugh ND, Iwasaki A, Openshaw P. COVID-19 vaccines:
Keeping pace with SARS-CoV-2 variants. \emph{Cell} 2021.

\textbf{Supplementary Figures}

\textbf{Figure S1.} The population standardized daily reported COVID-19
deaths in these countries/regions listed in Figure 1.

\textbf{Hosted file}

\verb`image2.emf`  available at \url{https://authorea.com/users/737041/articles/712297-large-scale-synchronized-replacement-of-alpha-strain-by-the-delta-strain}

Figure S1. The countries/regions skipped by Alpha strain (e.g., India)
had a mild 2020 year. The synchronized \(T_{\alpha\rightarrow\sigma}\)coincided by a
trough of deaths in European countries. Here we show population
standardized daily data (daily reported COVID-19 per 1 million
population). A bright band (low deaths) can be seen in June-July 2021,
when Delta invaded. Data are obtained from
https://covid19.who.int/info/.

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