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Why does Japan have so few cases of COVID19?



There is a lot of interest brewing as to why Japan has such low numbers of confirmed infected cases of the COVID19 disease, caused by the SARS-COV-2 virus (Figure. 1), despite its high population density (over 6,100 persons/sqkm in Tokyo, 2.4 times higher than New York City) and large percentage of high-risk individuals over 65 years of age (about 26%, compared with 15% in the USA). In Singapore and Hong Kong, rapid and strict quarantine rules and contact tracing has helped to "flatten the curve".
Why does Japan have so few cases
of COVID-19?
Akiko Iwasaki
& Nathan D Grubaugh
Despite early exposure, its dense and aging
population, and little social distancing
measures, Japan reports low infection and
low death from COVID-19. Here, we specu-
late on and discuss the possible reasons
that may account for this anomaly.
There is a lot of interest brewing as to
why Japan has such low numbers of
confirmed infected cases of the
COVID-19 disease, caused by the SARS-CoV-
2 virus (Fig 1), despite its high population
density (over 6,100 persons/sqkm in Tokyo,
2.4 times higher than New York City) and
large percentage of high-risk individuals
over 65 years of age (about 26%, compared
with 15% in the USA). In Singapore and
Hong Kong, rapid and strict quarantine rules
and contact tracing have helped to “flatten
the curve”. In South Korea, mass testing and
quarantine measures appear to have reduced
the rate of new cases. However, Japan has
not engaged in expansive testing, contact
tracing, or strict quarantine measures and
yet is reporting a slow growth rate of
infected persons and a death rate that is
currently just 1/10
of world average. It is
difficult to make direct comparison of infec-
tion rates, because the number of tests per
capita varies dramatically between coun-
tries. However, this low death rate cannot
be simply explained by lack of testing or
reporting, as no surge in death from respira-
tory syndromes has been reported either.
So how has Japan dealt with COVID-19?
The Japanese Cluster Response Team of the
Ministry of Health set forth on March 9
three-pronged approach.
early detection of and early response to
infection clusters
early patient diagnosis and enhancement
of intensive care and the securing of a
medical service system for the severely ill
behavior modification of citizens (includ-
ing advise to refrain from holding large-
scale events, temporary school closures)
Note that none of these involve strict
social distancing measures taken by other
countries. Why is this? What can we learn
from Japan to help flatten the curve in other
Here, we discuss several hypotheses and
provide arguments for or against each
1 Japanese culture is inherently suited
for social distancing, and face mask
use prevents viral spread.
It is certainly true that the Japanese customs
do not involve handshaking, hugging, or
kissing when greeting. In addition, many
Japanese wear cloth or paper face masks
(not the N95 respirators required for exclu-
sion of aerosol viral particles) in the winter
to avoid transmission of respiratory infec-
tions. People use the mask to avoid spread-
ing the infection and also in an attempt to
prevent exposure to infection. However, we
are unconvinced that this is the main or only
reason why COVID-19 is so well contained in
Japan. There is no social distancing in rush
hour trains and buses, or when walking in
crowded streets to school or to work. The
use of face mask is also practiced in other
Asian countries that witnessed higher rates
of infection. A hint to whether this is a valid
hypothesis comes from looking at other
pandemic viral respiratory diseases. The
community R
rate for the 2009 pandemic flu
for Japan was 1.28 while USA was 1.72.0
(Boelle et al, 2011). Thus, R
in Japan was
somewhat lower than the global median R
of 1.47. In addition, an observational study
of elementary school children in Japan found
that wearing masks had significant protective
association (odds ratio of 0.859, 95% confi-
dence interval 0.7780.949) against seasonal
influenza (Uchida et al, 2017). Therefore,
the social practice culture of Japan and mask
use may explain to some extent the lower
number of observed COVID-19 cases, but is
unlikely the only explanation.
2 Japanese people were exposed to a
milder version of SARS-CoV-2 that
conferred herd immunity before the
spread of a more virulent strain of CoV2.
While possible, there is no current
evidence that milder strains of SARS-CoV-2
exist. Nor do we know what sort of antibody
response would develop as a result of expo-
sure to such a hypothetical variant. Phyloge-
netic analysis of SARS-CoV-2 of more than
3,500 SARS-CoV-2 genomes from around the
world, including 29 from Japan, suggests
that the outbreak in Japan was sparked by
several independent virus introductions
primarily from China (https://nextstrain.
org/ncov?f_country=Japan, accessed
7.4.2020) (Hadfield et al, 2018). Further-
more, all of the SARS-CoV-2 genomes are
highly similar; most contain no more than
10 mutations compared to the virus that
started the original outbreak. Thus, it is
highly unlikely that the virus has evolved a
significantly different phenotype, and even
less likely that it was introduced early into
1Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA. E-mail:
2Howard Hughes Medical Institute, Chevy Chase, MD, USA. E-mail:
3Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA
DOI 10.15252/emmm.202012481 | EMBO Mol Med (2020)12:e12481 | Published online 28 April 2020
©2020 The Authors. Published under the terms of the CC BY 4.0license EMBO Molecular Medicine 12:e12481 |2020 1of 3
Notably, early cases in Japan (January
February) were all linked to virus introduced
from China. Now, in March, the outbreaks
in Japan are linked to introductions from
Europe, and there is a large gap in between
those early introductions in January and the
recent ones in March. While the data are still
limited, this suggests that Japan was able to
control the early outbreaks, keeping cases
down, but is now experiencing a second
wave introduced more recently from
3 Japanese people have reduced suscep-
tibility due to ACE2 receptor expression.
SARS-CoV-2 utilizes ACE2 as a receptor
to enter cells. It is theoretically possible that
ACE2 expression in the respiratory tract is
somehow lower in the Japanese population,
though no direct evidence was identified
during studies investigating coronavirus S-
protein binding-resistant ACE2 mutants
among different populations. If anything,
East Asian populations were reported to
have higher allele frequency in the ACE2
variants associated with higher ACE2
expression in tissues (Cao et al, 2020).
However, the only way to find out whether
the expression of ACE2 is indeed different is
through surface protein staining of lung
tissues, which has yet to be done.
4 Japanese people have distinct HLA that
confers immune resistance to CoV2.
Genome-wide association studies
(GWAS) conducted on disease susceptibility
show that HLA is usually the top locus
associated with disease. This is true for
infectious diseases, autoimmunity, or
neurological disorders. HLA stands for
human leukocyte antigen and is also
known as MHC, or major histocompatibility
complex. These genes encode for proteins
that present antigenic peptides to T cells.
HLA class I presents antigenic peptides to
CD8 T cells, while HLA class II presents
peptides to CD4 T cells. HLA genes are the
most highly polymorphic genes in the
human genome. The variety in HLA
enables our immune system to survey for
maximal number of antigen peptides that
are present in pathogens, so as to elicit
robust cellular immune responses. Previous
studies have identified HLA-B*4601 to be
associated with higher risk of developing
SARS disease (Lin et al, 2003), based on a
small number of cases. However, whether
there are any HLA alleles that confer resis-
tance to COVID-19 and whether the allele
frequency is higher in the Japanese popula-
tion are unknown.
5 BCG vaccine used in Japan confers
protection against COVID-19.
Japan, like many other countries including
China, Korea, India, and the Russian
Figure 1. Cumulative number of cases, by number of days since February 1,2020.
Source:, accessed 6-4-2020, data based on European Centre for Disease Prevention and
2of 3EMBO Molecular Medicine 12:e12481 |2020 ª2020 The Authors
EMBO Molecular Medicine Akiko Iwasaki & Nathan D Grubaugh
Federation, have mandatory childhood BCG
vaccines against tuberculosis. These coun-
tries have so far a relatively low per capita
death rate from COVID-19 compared to coun-
tries that have no mandatory BCG vaccines
(USA, Spain, France, Italy, The Netherlands).
What further distinguishes Japan is that the
BCG vaccine strain used in Japan, Brazil, and
Russia is one of the original strains, while
further modified BCG strains are used for
ciation between BCG vaccination and appar-
ent low COVID-19 incidence in Japan has
spurred the idea that these two things may be
linked (for more discussions on this topic,
How would BCG, an attenuated bacterial
vaccine completely unrelated to COVID-19,
provide protection? Michai Netea and collea-
gues hypothesized that the vaccine may
boost “trained immunity” (Netea et al, 2016)
in other words, certain immune stimuli
may induce a prolonged state of resistance
against pathogens in general, by elevating
the expression levels of resistance factors.
Studies have shown that receipt of BCG
vaccine was associated with a reduction in
all-cause mortality within the first 1
60 months: The average relative risks were
0.70 (95% confidence interval 0.491.01)
from five clinical trials (Higgins et al, 2016).
Furthermore, Netea and colleagues showed
that BCG vaccination reduced the levels of
viremia caused by the yellow fever virus live
attenuated vaccine (Arts et al, 2018), and
post-BCG increase of IL-1bproduction
strongly correlated with lower viremia after
yellow fever virus administration. A placebo-
controlled randomized clinical trial of 1,000
healthcare workers in The Netherlands has
started, and a similar trial is planned to begin
at the Max Planck Institute (de Vrieze,
2020). The outcomes of these trials will help
us to understand whether and how BCG
confers resistance to other pathogens includ-
ing SARS-CoV-2.
There are many other theories to explain the
low number of COVID-19 cases in Japan, yet
we still do not have enough information to
determine the cause of this striking discrep-
ancy. Clearly, we do not understand what
causes these differences. Many of these
hypotheses can be tested as suggested
above, such as examining ACE2 expression
levels in the respiratory tract, GWAS data on
COVID-19 susceptibility, and whether BCG
vaccines indeed confer long-term innate
immune resistance to SARS-CoV-2. The
three-pronged approach by the Cluster
Response Team of the Japanese Ministry of
Health has thus far contained the spread of
COVID-19 by quickly identifying clusters of
infections, testing, and quarantine of the
infected individuals. A word of caution is
whether this approach will work in cases
where super-spreaders ignite a large-scale
transmission, or when there are multiple
clusters that occur throughout the country at
once. Perhaps one of the reasons for the low
number of cases in Japan might relate to lack
of super-spreader events to date. Just within
the last 24 h, Japan has declared the state of
emergency, as Tokyo faces more than 1,000
confirmed cases, more than double the
number a week ago. Perhaps stronger social
distancing measures are required to keep the
curve flattened in Japan.
We wish to thank Dr. Hiroshi Iwasaki for research
and providing key resources from Japanese media
and postings. We also thank Dr. Hironori Funabiki
for his informative Twitter postings on this subject.
Conflict of interest
The authors declare that they have no conflict of
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License: This is an open access article under the
terms of the Creative Commons Attribution 4.0
License, which permits use, distribution and repro-
duction in any medium, provided the original work
is properly cited.
ª2020 The Authors EMBO Molecular Medicine 12:e12481 |2020 3of 3
Akiko Iwasaki & Nathan D Grubaugh EMBO Molecular Medicine
... As previous studies have shown, the end of the first wave was achieved by people's selfrestraint from going out in public, which was attributed to increased public awareness and understanding of the risks of the current situation through media reports [35][36][37][38][39][40]. In addition, the characteristics of Japanese culture and customs-greeting without shaking hands, hugging or kissing, and wearing cloth or paper facemasks to prevent respiratory infections and pollen allergies-may have contributed to the lower number of new polymerase chain reaction (PCR) positive cases and deaths per population compared to other countries [41]. Watanabe and Mizuno attributed the decrease in the number of people going out in public during the first wave to government announcements, such as daily news releases of new PCR positive cases [42,43]. ...
... It is assumed that this information gave people a sense of urgency and encouraged them to refrain from going out [42,43]. This behavior is likely attributable to increased risk perception in the early stages of the epidemic, and when self-restraint in terms of staying home became widely practiced [35][36][37][38][39][40][41][42]. ...
... This result was likely attributable to the previous observation that the levels of people's anxiety and their preventive behaviors decrease as their perception of the seriousness and immediacy of the threat reduced [44,70]. The factors that encouraged people to stay at home during the first wave [35][36][37][38][39][40][41][42] have been recognized to some extent, and suggest that the sense of a crisis was not perceived beyond the first wave. In the second wave, the only change similar to that in the first wave was the index of web searches for going outside. ...
Full-text available
The suppression of the first wave of COVID-19 in Japan is assumedly attributed to people’s increased risk perception after acquiring information from the government and media reports. In this study, going out in public amidst the spread of COVID-19 infections was investigated by examining new polymerase chain reaction (PCR) positive cases of COVID-19 and its relationship to four indicators of people going out in public (the people flow, the index of web searches for going outside, the number of times people browse restaurants, and the number of hotel guests, from the Regional Economic and Social Analysis System (V-RESAS). Two waves of COVID-19 infections were examined using cross-correlation analysis. In the first wave, all four indicators of going out changed to be opposite the change in new PCR positive cases, showing a lag period of –1 to +6 weeks. In the second wave, the same relationship was only observed for the index of web searches for going outside, and two indicators showed the positive lag period of +6 to +12 weeks after the change in new PCR positive cases. Moreover, each indicator in the second wave changed differently compared to the first wave. The complexity of people’s behaviors around going out increased in the second wave, when policies and campaigns were implemented and people’s attitudes were thought to have changed. In conclusion, the results suggest that policies may have influenced people’s mobility, rather than the number of new PCR positive cases.
... Several hypotheses have been advanced to explain Japan's low SARS-CoV-2 burden, including its isolation as an island, higher baseline population immunity from previous coronavirus infections, a homogenous population with highly prevalent genetic human leukocyte antigen haplotype that differs from citizens of other countries, cultural differences in compliance with maskwearing, and earlier recognition by public health officials of aerosolized virus spread. [30][31][32] Future analyses should consider lessons we can learn from Japan, as well as countries such as New Zealand, which maintained very low COVID-19 burdens through a "Zero-COVID" approach in earlier phases of the pandemic. ...
... 7 Literatür çalışmaları karantinanın hem mortalite oranını düşürdüğü hem de salgından korunmak için en etkili yol olduğunu göstermektedir. 8 Dünyada çok sayıda insanın ölümüne sebep olmuş birçok salgın hastalık meydana gelmiştir. Veba, Kara Ölüm olarak da anılan ikinci büyük salgın, kolera, tüberküloz, çiçek hastalığı, tifüs, sifiliz, İspanyol gribi, AIDS, Ebola, SARS ve halen sürmekte olan COVID-19 en çok etki eden salgın hastalıklardır. ...
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ZET Amaç: Çalışmanın amacı COVID-19 salgınında bir nevi hastane işlevi gören öğrenci yurtlarının yerine getirdiği sağlık rollerinin tespit edilmesidir. Benzer başka büyük salgınlarda olduğu gibi öğrenci yurtlarının salgın yönetimin daha hazır ve daha kullanışlı hale getirebilmesi için mevcut deneyimlerden de hareket edilerek öneriler geliştirilmesi amaçlanmıştır. Materyal ve Metot: Araştırmada nitel araştırma yöntemi kullanıldığından evren ve örneklem tayinine gidilmemiştir. Bunun yerine 5-20 Nisan 2020 tarihlerinde çalışmanın gerçekleştirildiği yurtta, karantina için kalan 365 kişi arasından gönüllü olanlar çalışma grubu olarak belirlenmiştir. Araştırmanın çalışma grubunu karantina yurdunda kalan 17 gönüllü oluşturmaktadır. Çalışmada nitel veri toplama tekniklerinden yarı yapılandırılmış görüşme yöntemi kullanılmıştır. Elde edilen veriler içerik analizine tabi tutulmuştur. Bulgular: Karantina yurdunda kalanların sürece bakışları genel anlamda olumludur. Olumlu görüşlere rağmen katılımcıların çoğunluğu, seçenek sunulsa karantina dönemini evlerinde geçirmek istemektedir. Yine karantina dönemine dair en önemli eleştiri, kaldıkları süre boyunca yurtta sıkıldıkları konusudur. Yüksek memnuniyetin nedenleri arasında ise yurt şartlarının olumlu etkisinin yanında salgından kaynaklı korkunun etkisi de olabilir. Sonuç: Araştırmadan elde edilen bulgulara göre yurtların karantina dönemlerinde, "yurt-hastane" formatında sağlık hizmeti sunabileceği görülmüştür. Bu süreçte 'Yurt-Hastane'lerin mevcut sağlık sistemine yükü oldukça sınırlı olmuştur. İller bazında uygun yurtların tespit edilmesi ve bunların benzer salgınlarda kullanılması için gerekli düzenlemelerin yapılması önerilmektedir.
... As individuals age, several functional changes occur in both the innate and adaptive immune systems including dysfunction in the T cell compartment, [6][7][8][9] increasing chronic lowgrade inflammation (i.e., 'inflammaging') and diminished ability to fight infections. 10 Alterations to the innate immune system observed in older age include decreased leukocyte production and function, reduced phagocytic capability of neutrophils, elevated monocytes and macrophages, and a functional shift towards a proinflammatory phenotype. ...
Background The COVID-19 pandemic has highlighted the urgent need to understand variation in immunosenescence at the population-level. Thus far, population patterns of immunosenescence are not well described. Methods We characterized measures of immunosenescence from newly released venous blood data from the nationally representative U.S Health and Retirement Study (HRS) of individuals ages 56 years and older. Findings Median values of the CD8+:CD4+, EMRA:Naïve CD4+ and EMRA:Naïve CD8+ ratios were higher among older participants and were lower in those with additional educational attainment. Generally, minoritized race and ethnic groups had immune markers suggestive of a more aged immune profile: Hispanics had a CD8+:CD4+ median value of 0.37 (95% CI: 0.35, 0.39) compared to 0.30 in Whites (95% CI: 0.29, 0.31). Blacks had the highest median value of the EMRA:Naïve CD4+ ratio (0.08; 95% CI: 0.07, 0.09) compared to Whites (0.03; 95% CI: 0.028, 0.033). In regression analyses, race/ethnicity and education were associated with large differences in the immune ratio measures after adjustment for age and sex. For example, each additional level of education was associated with roughly an additional decade of immunological age, and the racial/ethnic differences were associated with two to four decades of additional immunological age. Interpretation Our study provides novel insights into population variation in immunosenescence. This has implications for both risk of age-related disease and vulnerability to novel pathogens (e.g., SARS-CoV-2). Funding This study was partially funded by the U.S. National Institutes of Health, National Institute on Aging R00AG062749. AEA and GAN acknowledge support from the National Institutes of Health, National Institute on Aging R01AG075719. JBD acknowledges support from the Leverhulme Trust (Centre Grant) and the European Research Council grant ERC-2021-CoG-101002587 Research in context Evidence before this study Alterations in immunity with chronological aging have been consistently demonstrated across human populations. Some of the hallmark changes in adaptive immunity associated with aging, termed immunosenescence, include a decrease in naïve T-cells, an increase in terminal effector memory cells, and an inverted CD8:CD4 T cell ratio. Several studies have shown that social and psychosocial exposures can alter aspects of immunity and lead to increased susceptibility to infectious diseases. Add value of this study While chronological age is known to impact immunosenescence, there are no studies examining whether social and demographic factors independently impact immunosenescence. This is important because immunosenescence has been associated with greater susceptibility to disease and lower immune response to vaccination. Identifying social and demographic variability in immunosenescence could help inform risk and surveillance efforts for preventing disease in older age. To our knowledge, we present one of the first large-scale population-based investigations of the social and demographic patterns of immunosenescence among individuals ages 50 and older living in the US. We found differences in the measures of immunosenescence by age, sex, race/ethnicity, and education, though the magnitude of these differences varied across immune measures and sociodemographic subgroup. Those occupying more disadvantaged societal positions (i.e., minoritized race and ethnic groups and individuals with lower educational attainment) experience greater levels of immunosenescence compared to those in less disadvantaged positions. Of note, the magnitude of effect of sociodemographic factors was larger than chronological age for many of the associations. Implications for practice or policy and future research The COVID-19 pandemic has highlighted the need to better understand variation in adaptive and innate immunity at the population-level. While chronological age has traditionally been thought of as the primary driver of immunological aging, the magnitude of differences we observed by sociodemographic factors suggests an important role for the social environment in the aging human immune system.
... A review of the related literature showed that quarantine is an effective way to reduce the disease. [8,9] It was suggested to be effected in all countries upon the emergence of the disease. The results reported in 20 relevant works of research revealed that the number of afflicts was reduced from 81% to 41%, and the mortalities were also reduced from 61% to 31%. ...
Full-text available
Background: One way to reduce the burden of early detection of COVID-19 disease is in vulnerable and high-risk groups. The aim of this study was to diagnose and evaluate the disease in the homeless in Southern Iran Bandar Abbas. Materials and methods: The target group of this study was 234 homeless people. Census sampling included all homeless residents of Isin camp Bandar Abbas. People were individually examined, and their information was recorded. COVID-19 sampling was done for all as outpatients this year. Results: Eight percent of people were able to answer the questions of awareness about symptoms, ways of transmission, and ways of prevention of COVID-19 disease. Nine percent of the homeless people in the target group stated that they used to wash their hands before settling in the camp. Six percent of homeless people stated that they used face masks before settling in the camp. Fifteen participants showed similar symptoms to COVID-19, yet their test result was negative. However, six people who were asymptomatic ended up afflicted. The mean duration of time (since the emergence of symptoms to the sampling date) was 3 days. The minimum duration of time from the emergence of symptoms to the sampling date was 3 h, and the maximum time was 7 days. Conclusion: Considering the spread of the disease, certain social measures need to be taken in society to help take care of these people and transfer them from streets to safe places and provide for their essentials. Diagnostic tests should be done periodically among these people at regular intervals.
... Therefore, if cases of infection had been missed due to lack of testing or undetected asymptomatic cases, there should have been a large increase in the number of cases of COVID-19 once testing was increased. 17 This was not the case. ...
The first case of coronavirus disease 2019 (COVID-19) in Japan was confirmed on 16 January 2020. The first wave of cases peaked on 10 April 2020 (n = 710) and the second on 7 August 2020 (n = 1595). Iwate Prefecture in north-eastern Japan was the last prefecture to confirm a case of COVID-19, on 29 July 2020, 110 days after all other prefectures had confirmed cases. No cases were reported during the first wave.1 As of 21 September 2021, there had been 3469 cases (282.8/100 000 population) and 52 deaths (1.50% fatality rate) in Iwate and 1.7 million cases (1333.2/100 000 population) and 17 294 deaths (1.03% fatality rate) in Japan overall. This article discusses possible reasons for the low number of COVID-19 cases in Iwate.
... Despite the early exposure, dense and aging population, and minimal social distancing measures, Japan has reported low infection and mortality rates from COVID-19. 34 We were unable to evaluate a larger cohort. The power of this study might have been inadequate. ...
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Aim: Awake prone positioning (PP) in patients with coronavirus disease 2019 (COVID-19) can improve oxygenation. However, evidence showing that it can prevent intubation is lacking. This study investigated the efficacy of awake PP in patients with COVID-19 who received remdesivir, dexamethasone, and anticoagulant therapy. Methods: This was a two-center cohort study. Patients admitted to the severe COVID-19 patient unit were included. The primary outcome was the intubation rate and secondary outcome was length of stay in the severe COVID-19 unit. After propensity score adjustment, we undertook multivariable regression to calculate the estimates of outcomes between patients who received awake PP and those who did not. Results: Overall, 108 patients were included (54 [50.0%] patients each who did and did not undergo awake PP), of whom 25 (23.2%) were intubated (with awake PP, 5 [9.3%] vs. without awake PP, 20 [37.0%]; P < 0.01). The median length of stay in the severe COVID-19 unit did not significantly differ (with awake PP, 5 days vs. without awake PP, 5.5 days; P = 0.68). After propensity score adjustment, those who received awake PP had a lower intubation rate than those who did not (odds ratio, 0.22; 95% confidence interval, 0.06-0.85; P = 0.03). Length of stay in the severe COVID-19 patient unit did not differ significantly (adjusted percentage difference, -24.4%; 95% confidence interval, -56.3% to 30.8%; P = 0.32). Conclusion: Awake PP could be correlated with intubation rate in patients with COVID-19 who are receiving remdesivir, dexamethasone, and anticoagulant therapy.
... In Japan, the government declared a state of emergency, which is not legally binding, which significantly restrained people from going out [21,25,39]. It is widely considered to have been more successful in controlling the number of infections than in other OECD countries [20,28]. How many people in Japan refrain from going out under the non-binding declaration of a state of emergency? ...
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Social stigma can effectively prevent people from going out and possibly spreading COVID-19. Using the framework of replicator dynamics, we analyze the interaction between self-restraint behavior, infection with viruses such as COVID-19, and stigma against going out. Our model is analytically solvable with respect to an interior steady state in contrast to the previous model of COVID-19 with stigma. We show that a non-legally binding policy reduces the number of people going out in a steady state.
COVID-19 is a respiratory tract infection caused by a novel corona virus strain. Mild manifestations widely observed are flu-like symptoms, fever, malaise, and fatigue. Left untreated, this results in disease progression manifested by chest pain, dyspnoea, chest tightness, and death of the patients. COVID-19 has spread to every part of the world due to lack of specific treatment strategies regarding Corona Virus disease, treated symptomatically and an emergency call for vaccine development was initiated globally. In accordance, preventive measures were taken to control the spread of the corona virus. They include the implementation of the use of face masks, hand hygiene, respiratory hygiene, social distancing, lockdown, curfew, closing educational institutes, closing borders, awareness programmes, safety programmes, and advancements in the medical field. High risk groups were handled sensitively to head off the COVID-19 incident. Patients with psychological distress during lockdown were supported psychologically, airlines closed to prevent entry of new cases, and all passengers were screened and quarantined to prevent the spread of the disease. Due to the implementation of the lock down, almost all businesses, small-scale industries, and travel agencies were closed temporarily, leading to an economic crisis globally. Many countries with tourist spots were closed resulted in a lack of financial support in those countries. In that regard, many organisations have come forward to provide financial support. This review mainly focuses on the preventive strategies implemented by each country, their contingency plans, and financial measures assisted by various organisations to prevent the spread directly or indirectly.
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Understanding the spread and evolution of pathogens is important for effective public health measures and surveillance. Nextstrain consists of a database of viral genomes, a bioinformatics pipeline for phylodynamics analysis, and an interactive visualisation platform. Together these present a real-time view into the evolution and spread of a range of viral pathogens of high public health importance. The visualization integrates sequence data with other data types such as geographic information, serology, or host species. Nextstrain compiles our current understanding into a single accessible location, open to health professionals, epidemiologists, virologists and the public alike. Availability and implementation: All code (predominantly JavaScript and Python) is freely available from and the web-application is available at Contact:,,
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The tuberculosis vaccine bacillus Calmette-Guérin (BCG) has heterologous beneficial effects against non-related infections. The basis of these effects has been poorly explored in humans. In a randomized placebo-controlled human challenge study, we found that BCG vaccination induced genome-wide epigenetic reprograming of monocytes and protected against experimental infection with an attenuated yellow fever virus vaccine strain. Epigenetic reprogramming was accompanied by functional changes indicative of trained immunity. Reduction of viremia was highly correlated with the upregulation of IL-1β, a heterologous cytokine associated with the induction of trained immunity, but not with the specific IFNγ response. The importance of IL-1β for the induction of trained immunity was validated through genetic, epigenetic, and immunological studies. In conclusion, BCG induces epigenetic reprogramming in human monocytes in vivo, followed by functional reprogramming and protection against non-related viral infections, with a key role for IL-1β as a mediator of trained immunity responses.
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Measures of seasonal influenza control are generally divided into two categories: pharmaceutical and non-pharmaceutical interventions. The effectiveness of these measures remains unclear, because of insufficient study sample size and/or differences in study settings. This observational epidemiological study involved all elementary schoolchildren in Matsumoto City, Japan, with seasonal influenza during the 2014/2015 season. Questionnaires, including experiences with influenza diagnosis and socio-demographic factors, were distributed to all 29 public elementary schools, involving 13,217 children, at the end of February 2015. Data were obtained from 10,524 children and analyzed with multivariate logistic regression analysis. The result showed that vaccination (odds ratio 0.866, 95% confidence interval 0.786–0.954) and wearing masks (0.859, 0.778–0.949) had significant protective association. Hand washing (1.447, 1.274–1.644) and gargling (1.319, 1.183–1.471), however, were not associated with protection. In the natural setting, hand washing and gargling showed a negative association, which may have been due to inappropriate infection control measures or aggregating infected and non-infected children to conduct those measures. These results may indicate a pathway for influenza transmission and explain why seasonal influenza control remains difficult in school settings. The overall effectiveness of vaccination and mask wearing was 9.9% and 8.6%, respectively. After dividing children into higher (grades 4–6) and lower (grade 1–3) grade groups, the effectiveness of vaccination became greater in the lower grade group, and the effectiveness of wearing masks became greater in the higher grade group. These results may provide valuable information about designing infection control measures that allocate resources among children.
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Objectives To evaluate the effects on non-specific and all cause mortality, in children under 5, of Bacillus Calmette-Guérin (BCG), diphtheria-tetanus-pertussis (DTP), and standard titre measles containing vaccines (MCV); to examine internal validity of the studies; and to examine any modifying effects of sex, age, vaccine sequence, and co-administration of vitamin A. Design Systematic review, including assessment of risk of bias, and meta-analyses of similar studies. Study eligibility criteria Clinical trials, cohort studies, and case-control studies of the effects on mortality of BCG, whole cell DTP, and standard titre MCV in children under 5. Data sources Searches of Medline, Embase, Global Index Medicus, and the WHO International Clinical Trials Registry Platform, supplemented by contact with experts in the field. To avoid overlap in children studied across the included articles, findings from non-overlapping birth cohorts were identified. Results Results from 34 birth cohorts were identified. Most evidence was from observational studies, with some from short term clinical trials. Most studies reported on all cause (rather than non-specific) mortality. Receipt of BCG vaccine was associated with a reduction in all cause mortality: the average relative risks were 0.70 (95% confidence interval 0.49 to 1.01) from five clinical trials and 0.47 (0.32 to 0.69) from nine observational studies at high risk of bias. Receipt of DTP (almost always with oral polio vaccine) was associated with a possible increase in all cause mortality on average (relative risk 1.38, 0.92 to 2.08) from 10 studies at high risk of bias; this effect seemed stronger in girls than in boys. Receipt of standard titre MCV was associated with a reduction in all cause mortality (relative risks 0.74 (0.51 to 1.07) from four clinical trials and 0.51 (0.42 to 0.63) from 18 observational studies at high risk of bias); this effect seemed stronger in girls than in boys. Seven observational studies, assessed as being at high risk of bias, have compared sequences of vaccines; results of a subset of these suggest that administering DTP with or after MCV may be associated with higher mortality than administering it before MCV. Conclusions Evidence suggests that receipt of BCG and MCV reduce overall mortality by more than would be expected through their effects on the diseases they prevent, and receipt of DTP may be associated with an increase in all cause mortality. Although efforts should be made to ensure that all children are immunised on schedule with BCG, DTP, and MCV, randomised trials are needed to compare the effects of different sequences.
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The human leukocyte antigen (HLA) system is widely used as a strategy in the search for the etiology of infectious diseases and autoimmune disorders. During the Taiwan epidemic of severe acute respiratory syndrome (SARS), many health care workers were infected. In an effort to establish a screening program for high risk personal, the distribution of HLA class I and II alleles in case and control groups was examined for the presence of an association to a genetic susceptibly or resistance to SARS coronavirus infection. HLA-class I and II allele typing by PCR-SSOP was performed on 37 cases of probable SARS, 28 fever patients excluded later as probable SARS, and 101 non-infected health care workers who were exposed or possibly exposed to SARS coronavirus. An additional control set of 190 normal healthy unrelated Taiwanese was also used in the analysis. Woolf and Haldane Odds ratio (OR) and corrected P-value (Pc) obtained from two tails Fisher exact test were used to show susceptibility of HLA class I or class II alleles with coronavirus infection. At first, when analyzing infected SARS patients and high risk health care workers groups, HLA-B*4601 (OR = 2.08, P = 0.04, Pc = n.s.) and HLA-B*5401 (OR = 5.44, P = 0.02, Pc = n.s.) appeared as the most probable elements that may be favoring SARS coronavirus infection. After selecting only a "severe cases" patient group from the infected "probable SARS" patient group and comparing them with the high risk health care workers group, the severity of SARS was shown to be significantly associated with HLA-B*4601 (P = 0.0008 or Pc = 0.0279). Densely populated regions with genetically related southern Asian populations appear to be more affected by the spreading of SARS infection. Up until recently, no probable SARS patients were reported among Taiwan indigenous peoples who are genetically distinct from the Taiwanese general population, have no HLA-B* 4601 and have high frequency of HLA-B* 1301. While increase of HLA-B* 4601 allele frequency was observed in the "Probable SARS infected" patient group, a further significant increase of the allele was seen in the "Severe cases" patient group. These results appeared to indicate association of HLA-B* 4601 with the severity of SARS infection in Asian populations. Independent studies are needed to test these results.
The general view that only adaptive immunity can build immunological memory has recently been challenged. In organisms lacking adaptive immunity, as well as in mammals, the innate immune system can mount resistance to reinfection, a phenomenon termed "trained immunity" or "innate immune memory." Trained immunity is orchestrated by epigenetic reprogramming, broadly defined as sustained changes in gene expression and cell physiology that do not involve permanent genetic changes such as mutations and recombination, which are essential for adaptive immunity. The discovery of trained immunity may open the door for novel vaccine approaches, new therapeutic strategies for the treatment of immune deficiency states, and modulation of exaggerated inflammation in autoinflammatory diseases.
The new influenza virus A/H1N1 (2009), identified in mid-2009, rapidly spread over the world. Estimating the transmissibility of this new virus was a public health priority. We reviewed all studies presenting estimates of the serial interval or generation time and the reproduction number of the A/H1N1 (2009) virus infection. Thirteen studies documented the serial interval from household or close-contact studies, with overall mean 3 days (95% CI: 2·4, 3·6); taking into account tertiary transmission reduced this estimate to 2·6 days. Model-based estimates were more variable, from 1·9 to 6 days. Twenty-four studies reported reproduction numbers for community-based epidemics at the town or country level. The range was 1·2-3·1, with larger estimates reported at the beginning of the pandemic. Accounting for under-reporting in the early period of the pandemic and limiting variation because of the choice of the generation time interval, the reproduction number was between 1·2 and 2·3 with median 1·5. The serial interval of A/H1N1 (2009) flu was typically short, with mean value similar to the seasonal flu. The estimates of the reproduction number were more variable. Compared with past influenza pandemics, the median reproduction number was similar (1968) or slightly smaller (1889, 1918, 1957).
License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited
License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. ª 2020 The Authors EMBO Molecular Medicine 12: e12481 | 2020