Beruflich Dokumente
Kultur Dokumente
A severe respiratory disease emerged in the Whether it will be contained or not, this Many SARS-related coronaviruses are widely
city of Wuhan, Hubei province, China, in outbreak is rapidly becoming the first true prevalent in bats. It has been suspected that
December 2019. As of early February 2020, at pandemic challenge that fits the disease X one such bat coronavirus had jumped into civet
least 28,088 diagnosed and 24,702 suspected category, listed to the WHO’s priority list of dis- or other mammals and adapted to cause the
cases have been reported, including at least eases for which we need to prepare in our cur- 2003 SARS epidemic. Thus, we again suspect
564 deaths. Unfortunately, the disease has rent globalized society. Initial resemblances that this time, too, wild animals should be the
spread globally. The etiologic agent, a novel co- with the SARS outbreak in terms of its origin, source, though the exact animal host has not
ronavirus, now called SARS-CoV-2, was imme- the disease associated with infection, and the yet been identified. Many speculate that this is
diately identified and characterized in China. ability to spread are clear. But since 2003, another SARS epidemic, but epidemiologically
Although we know the presence of unprece- global air travel has increased more than 10- and clinically, this outbreak appears different
dented genetic diversity of viruses in nature, fold, and the efforts needed to try to contain from the 2003-SARS in terms of higher trans-
this outbreak further indicates that there is the epidemic are daunting. There have been missibility with efficient intra-familial spread
considerable uncertainty in predicting when, great advances since 2003, with the coordi- and a lower crude mortality. The key question
where, and how novel disease-causing patho- nated efforts of WHO and funders focusing on is to find the molecular determinant that allows
gens emerge. the priority threats. But unfortunately, as in transmission from animal to human and then
Phylogenetic analyses reveal that SARS- past outbreaks, key knowledge gaps and med- human to human. It is notable that the nucleo-
CoV-2 is closely related to a group of SARS- ical countermeasures need to be assessed on tide identity of SARS-CoV-2 genome, espe-
like coronaviruses. However, it remains unclear the fly, and scientists and public health experts cially at the external ectodomain of the receptor
where the virus comes from and how it was alike are wasting precious time writing grant ap- binding domain (RBD) of spike protein, is quite
transmitted to humans in the first place. Unlike plications to do what we long know needs to be different from that of the SARS coronavirus.
with other zoonotic agents such as hantavirus done but which is not part of routine investment Knowing the exact biophysical mode of proteo-
and arenavirus, thus far we haven’t found a in science and (global) public health prepared- lytic activation of this novel spike protein and
SARS virus in animals that is the same as that ness. In my birth town, we used to watch the the interaction between this RBD with the host
in humans. Fortunately, SARS virus has not ap- rivers flood inevitably every winter, with some receptor ACE2 at physiological and endosomal
peared in humans since 2004. In contrast, this people losing their homes because ‘‘that is pH would reveal how this virus overcame the
new virus seems to have stronger transmission what a happens.’’ Now, there are modern flood species barrier between animals and humans.
capabilities among people. Compared to the barriers built to channel the river, based on for- Such information would enable us to under-
primary virus in humans, we still know less ward-looking investments in the past decades. stand pathogenesis, to design effective antivi-
about whether, what, and how the virus has Our ways of dealing with outbreaks is a mixture rals, and to develop safe vaccines.
changed and the effect of the changes for their of modern floodwalls in some parts of the world
epidemics in humans. Control and prevention while relying on sandbags in others. Needless
of the disease is especially difficult in China to say where the weakest links will be. Time
and elsewhere if there are infected individuals will tell whether the consolidated efforts of the
with no clinical signs. Chinese authorities and the international public
health and research community will succeed.
But we also need to understand how we make
this model of preparedness future-proof.
Sequencing and Beyond Understanding the Virus Basic and Public Health Questions
Science has moved with blazing speed during The SARS-CoV-2 epidemic that began in The recent emergence of SARS-CoV-2 and its
this epidemic. Within weeks of authorities Wuhan, China, and has spread to several coun- rapid, continuing spread across China and
recognizing a novel outbreak, the virus had tries throughout the world has led to intensive movement around the world raise many scien-
been identified, isolated, and sequenced. Pub- efforts by healthcare, public health, and tific and public health questions and chal-
lic sharing of data rapidly allowed for the crea- governmental authorities. The epidemic has lenges.
tion of diagnostic tests and validation of ACE2 had enormous impacts economically and so- From the basic science view, we must be for-
as the receptor for the virus. cially in China, and while first efforts must be ward looking to address questions about the
Sequencing of this coronavirus has espe- to control the epidemic, limit virus spread, and interplay between coronaviruses and their
cially moved at a rapid pace, with currently provide appropriate patient care, several ques- hosts. SARS-CoV-2 is the third recently
more than 50 sequences shared openly. This tions need to be addressed. First, why is this vi- emerged zoonotic coronavirus. Genomic se-
sequencing information has allowed us to learn rus more transmissible than other CoV that quences support that these viruses are closely
critical features of the virus and epidemic, cause severe respiratory disease (SARS-CoV related to bat coronaviruses. Given the large
including (1) guiding design of diagnostics, and MERS-CoV)? Does this virus replicate number of novel coronaviruses identified in
drugs, and vaccines; (2) identifying bats as the more readily in the upper airway than these bat populations, we likely will continue to have
likely reservoir; (3) showing that the epidemic other viruses and more similarly to HCoV- spillover to humans. What factors drive this?
was the result of a single spillover event; (4) NL63, which causes croup and the common Are there genomic signatures in bat viruses
that the epidemic is sustained by human-to-hu- cold (but not pneumonia)? Is virus spread pri- that may help predict which viruses will eventu-
man transmission, which has been ongoing marily by droplet, as was true for SARS-CoV ally emerge? Do the emerging viruses need to
since the beginning; and (5) that the beginning and MERS-CoV? How much transmission route through an intermediate host prior to in-
of the epidemic was likely in mid-November to occurs when patients exhibit the earliest signs fecting humans? What accounts for the spec-
mid-December of 2019. of disease or even have subclinical disease? trum of disease outcomes when this happens,
As the epidemic expands, it is important that Second, is the virus mutating to better infect and what drives human-to-human spread?
virus sequencing and open data sharing con- humans, like SARS-CoV, but not MERS- Are there viral and/or host genetic factors
tinues. Critical questions that sequencing will CoV, did? How well does the virus bind to its involved in disease outcome?
help to address include an understanding putative cellular receptor (angiotensin convert- From the public health perspective, the
of how effective intervention strategies are, ing enzyme-2), and if the binding is not strong, development of effective vaccine and antiviral
whether we are missing transmission chains, is the virus adapting to bind better? Third, therapeutics and how rapidly these can be
how locations of virus transmission are con- what is the zoonotic source for the virus? Bats available are pressing. Previous work with
nected, and what environmental and human may be the ultimate source, but is an intermedi- pathogenic severe acute respiratory syndrome
factors may contribute to spread. In addition, ate host involved? Finally, what are the unique (SARS-CoV) and Middle East respiratory syn-
we also need to understand how easily the virus molecular attributes of the virus that contribute drome (MERS-CoV) coronaviruses provides
spreads between people, including the level of to its pathogenicity? insight and platforms that can help expedite
asymptomatic spread and transmission during the process, but none has moved beyond
the incubation period. While development of phase 1 trials. The rapid availability of genomic
new vaccines and therapeutics is unlikely to sequences of SARS-CoV-2 isolates might
affect the trajectory of this epidemic, repurpos- move things along quickly, possibly on a
ing of preexisting drugs could offer new faster-than-normal track for vaccine develop-
opportunities for treating people infected with ment. The availability of the virus and animal
SARS-CoV-2. models will also help. This will become a more
critical priority if the SARS-CoV-2 continues to
spread and becomes embedded in the respira-
tory virus disease landscape. Much remains to
be learned about the SARS-CoV-2 and its inter-
play with its human host and what will consti-
tute the most effective, safe vaccine strategy.
Isabella Eckerle
Centre for Emerging Viral Diseases, University
Hospital Geneva and University of Geneva