Archives of Academic Emergency Medicine. 2020; 8(1): e54

LET TER TO EDITOR

Cross-Protection Induced By Encephalitis Vaccines
against COVID-19 Might be a Reason for Relatively Lower
Mortality Rate in Some Countries
Shojiro Katoh1,2, Toshihiko Obayashi2, Jegatheesan Saravana Ganesh3, Masaru Iwasaki4, Senthilkumar
Preethy5, Samuel JK Abraham4,6∗

1. Edogawa Evolutionary Lab of Science, Edogawa Hospital Campus, 2-24-18, Higashi-Koiwa, Edogawa, Tokyo 133-0052, Japan.

2. Edogawa Hospital, 2-24-18, Higashi-Koiwa, Edogawa, Tokyo 133-0052, Japan.

3. Waikato District Health Board, Hamilton 3204, New Zealand.

4. Yamanashi University-Faculty of Medicine, 1110, Shimokato, Chuo, Yamanashi 409-3898, Japan.

5. The Fujio-Eiji Academic Terrain (FEAT), Nichi-In Centre for Regenerative Medicine (NCRM), PB 1262, Chennai 600034, Tamil Nadu, India.

6. The Mary-Yoshio Translational Hexagon (MYTH), Nichi-In Centre for Regenerative Medicine (NCRM), PB 1262, Chennai 600034, Tamil
Nadu, India.

Received: April 2020; Accepted: April 2020; Published online: 21 April 2020

Abstract: COronaVIrus Disease 2019 (COVID-19) is an on-going pandemic attributed to a novel virus named SARS-CoV-2.
Comparing the statistics of incidence and death rates between nations reveals that there is discrepancy amongst
countries in these regards, even between countries that share borders. We herein present information from the
literature indicating how cross-protection against COVID-19 conferred by the encephalitis vaccine could be the
reason for lower fatality rate in the countries where immunization against encephalitis is widespread or included
in national programs. This may pave the way for arriving at efficient prevention strategies as well as vaccine
development.

Keywords: COVID-19; immunity, heterologous; encephalitis; vaccines; japanese encephalitis vaccines

Cite this article as: Katoh S, Obayashi T, Ganesh JS, Iwasaki M, Preethy S, Abraham S. Cross-Protection Induced By Encephalitis Vaccines

against COVID-19 Might be a Reason for Relatively Lower Mortality Rate in Some Countries. Arch Acad Emerg Med. 2020; 8(1): e54.

COVID-19, an acronym for COronaVIrus Disease 2019, pre-

viously 2019-nCoV, is an on-going pandemic attributed to

a novel virus that belongs to the coronavirus (CoV ) fam-

ily, SARS-CoV-2. As of April 20t h , 2020, the infection has

spread to 210 countries with a total of 2,314,621 confirmed

cases and 157,847 deaths worldwide, according to the World

Health Organization (WHO) (https://covid19.who.int/). The

CoVs are a large family of single-stranded RNA viruses (+ss-

RNA) that can cross species barriers and cause illnesses in

humans ranging from the common cold to more severe dis-

eases such as Middle East respiratory syndrome (MERS) and

severe acute respiratory syndrome (SARS) (1). Coronaviruses

∗Corresponding Author: Samuel JK Abraham; Yamanashi University-Faculty
of Medicine, 3-8, Wakamatsu, Kofu – 400-0866, Yamanashi Prefecture, Japan.
Tel: +81 (0)55-235-7527, Fax: +81 (0)55-235-7569, Email: drsam@nichimail.jp;
drspp@nichimail.jp

were first described in 1966 by Tyrell and Bynoe who named

them based on the crown-like morphology of the spherical

virion with surface projections that resemble a solar corona.

Among the four CoV sub-families (alpha-, beta-, gamma-,

and delta-coronaviruses), SARS-CoV-2 belongs to the B lin-

eage of beta-CoV and is closely related to the SARS-CoV. The

widely reported initial clinical sign for case detection is pneu-

monia but gastro-intestinal and asymptomatic infections are

also being reported in children (2).

With the death toll increasing daily, we considered the mor-

tality rates reported by the European Centre for Disease Pre-

vention and Control (3) as of April 20t h , 2020 wherein re-

ported deaths are provided in parentheses after a country’s

name: Africa: the five countries reporting most deaths are

Algeria (375), Egypt (239), Morocco (141), South Africa (54)

and Cameroon (42). Asia: the five countries reporting most

deaths are Iran (5,118), China (4,636), Turkey (2,017), Indone-

sia (582) and India (543). America: the five countries re-

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Sh. Katoh et al. 2

porting most deaths are United States (US) (40,682), Brazil

(2,462), Canada (1,580), Mexico (686) and Ecuador (474).

Europe: the five countries reporting most deaths are Italy

(23,660), Spain (20,453), France (19,718), United Kingdom

(16,060) and Belgium (5,683). Oceania: the four countries

reporting most deaths are Australia (70), New Zealand (12),

Guam (5) and Northern Mariana Islands (2). Interestingly,

countries like the US, Spain and Italy have more fatalities

than China, the epicentre of the outbreak with a much big-

ger population. In addition to several factors such as the

preparedness of countries like South Korea and Japan due

to their earlier fight against SARS and MERS, the empha-

sis these countries put on developing in vitro diagnostics

and therapeutics against the disease (4), co-operation of the

public (5), small but significantly contributing factors such

as sense of Life Worth Living (Ikigai) in Japan (which actu-

ally has been proven to decrease the risk of mortality (6))

etc., which potentially decreased fatalities in these countries

compared to Italy, Spain, USA etc., cross-protection against

COVID-19 conferred by the encephalitis vaccine also seems

to be a key parameter worthy of further investigation. This

connection is well illustrated by comparing the large number

of fatalities in Italy with the small number of deaths in their

neighbouring country, Austria (452 deaths) (3), where, un-

like Italy, encephalitis vaccination is included in its national

immunization schedule (7). This hypothesis is further sup-

ported by several additional reports.

Viral-induced encephalitis is associated with four different

kinds of viruses i. Arboviruses (e.g., eastern equine en-

cephalitis, Japanese encephalitis ( JE), La Crosse encephalitis,

St. Louis encephalitis, western equine encephalitis, West Nile

virus encephalitis), ii. Enteroviruses (e.g., coxsackievirus, po-

lioviruses), iii. Herpes viruses and iv. Other viruses such as

measles, mumps, and rubella, which cause secondary en-

cephalitis (8). Of these, JE is the leading cause of viral en-

cephalitis worldwide, with an estimated 50,000 cases and

15,000 deaths annually. It is a member of the genus Fla-

vivirus, which also includes the dengue, yellow fever and

West Nile viruses and is transmitted by Culex mosquitoes. In

northern Europe and northern Asia, flaviviruses causing en-

cephalitis have evolved to use ticks as vectors because of their

abundance in cooler climates and hence the encephalitis

caused by flavivirus is termed tick-borne encephalitis (9). It is

interesting to note that CoVs, though primarily recognized as

respiratory pathogens, are also encephalitis-inducing infec-

tious agents; especially, HCoV-229E, HCoV-OC43, and SARS-

CoV, which possess neuroinvasive properties and their viral

RNA has been detected in human brains. A few years after the

2002-2003 SARS-CoV epidemics, associated viral particles

were identified in the brain tissue of infected individuals with

central nervous system (CNS) issues associated with oedema,

neurodegeneration, and gliosis. The viruses accessed the

brain through the olfactory bulbs, where they infected neu-

ronal cells, and induced a lethal disease in an area of the

body with restrained immune infiltration (8). Immunization

with inactivated JE vaccine (INV ) and live attenuated vac-

cine (LAV ) induces a cross-immune response that confers

cross-protection against dengue viruses (DENVs) (10). Tri-

partite motif-containing (TRIM) proteins are active players

in antiviral innate immunity and overlapping molecular de-

terminants govern the antiviral activities of TRIM56 against

infections by yellow fever virus (YFV ), dengue virus serotype

2 (DENV2) and human CoV (HCoV-OC43) (11). The neuroin-

vasive properties of SARS-CoV2 may also underlie respiratory

failure in patients with COVID-19 (12). Furthermore, a case

of meningitis was recently attributed to COVID-19 in Japan

(13).

Next, we considered countries where JE immunization is

widespread or included in national programs namely, Japan,

Laos, Malaysia, Nepal, South Korea, Thailand, Sri Lanka, and

Vietnam. Again, in all of these countries, the fatality rate

due to COVID-19 is very low (3) compared with countries

that don’t immunize against JE. In China, the epicentre of

the COVID-19 outbreak where the JE vaccine is included in

its national immunization schedule, the fatality rate is 2.3%

compared to 7.3% in Italy where the JE vaccine is not rou-

tinely administered (14).

Therefore, the implications and applications of the immuno-

logical cross-protection conferred by the JE vaccine ought to

be considered in design and development of vaccines against

COVID-19 as well as other antiviral therapeutic approaches,

so that development of efficient and effective CoV vaccine

and therapy is ensured.

1. Declarations

1.1. Acknowledgment

The authors wish to acknowledge the staff of Edogawa Hos-

pital & JBM Inc., Tokyo, Japan for their secretarial assistance

and Loyola ICAM College of Engineering Technology (LICET)

Chennai, India for their support to our research work.

1.2. Authors Contributions

Concept, Design & Definition of intellectual content - Shojiro

Katoh

Concept & Review- Toshihiko Obayashi

Literature search - Jegatheesan Saravana Ganesh

Manuscript preparation - Senthilkumar Preethy

Manuscript review -Masaru Iwasaki

Concept, Design, Definition of intellectual content, editing

and review - Samuel JK Abraham

Authors ORCIDs
Shojiro Katoh: 0000-0002-8355-9074

Toshihiko Obayashi: 0000-0001-9774-0133

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3 Archives of Academic Emergency Medicine. 2020; 8(1): e54

Jegatheesan Saravana Ganesh: 0000-0003-1385-3099

Masaru Iwasaki: 0000-0003-3766-8744

Senthilkumar Preethy: 0000-0002-9333-0361

Samuel JK Abraham: 0000-0003-2646-2687

1.3. Funding

None.

1.4. Conflict of Interest

None.

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	Declarations
	References