The New Coronavirus: More Cases, More Deaths, Unclear Transmission

Lung tissue containing the original SARS coronavirus (CDC, 2003)

There’s lots of news to catch up with regarding the new coronavirus that emerged last summer in the Middle East and has been causing concern to international health authorities all autumn: additional cases, additional deaths, and new lab evidence that is more than a little concerning.

First: The case count has now risen from six to nine. One of those cases, we knew about already; it is the remaining person in the Saudi family cluster announced last month, whose case analysis was pending. But the other two are newly uncovered, and interesting: They are from a group of 11 health care workers and patients who fell ill in Jordan back in April. A correspondent to the mailing list ProMED actually raised a question about this cluster when the first known cases were disclosed. At the time, the cases were ruled to be not caused by coronavirus — but as the new virus had not yet been recognized, the test used was for known coronaviruses. The victims were negative on that test, but positive when a retest on their stored samples, using the new assay, was done recently.

Sadly, all three of these new cases died — so not only has the case count risen, but the fatality count has also, to 5 out of 9. Though we have only a few cases, that is still a case-fatality rate of more than 50 percent. By contrast, the case-fatality rate of SARS, the last novel coronavirus to trouble public health, was less than 10 percent.

In addition, the recognition of these cases expands the outbreak geographically, and even more important, lengthens it in time as well, since the previously presumed first case was the Saudi resident who was treated in Jiddah in June and announced to ProMED in September. And because the health care workers who died were part of a local cluster — which all together included seven nurses and one doctor at the Zarqa Public Hospital, two patients there, and a brother of one of the nurses — it raises the same question as the recently announced Saudi family cases: Is human-to-human transmission happening with this virus?

A parallel question: Is transmission (and amplification) happening among species we have not recognized? This possibility is raised by findings just published in the journal mBio, written by a multinational group of investigators who include the two authors of that first ProMED post, an Egyptian physician (then working in Saudi Arabia) and a Dutch virologist. The group says that — unusually for coronaviruses — this virus can grow in the cells of more than one species:

…[T]he virus is capable of infecting human, pig, and bat cells. This is remarkable, as human CoVs normally cannot replicate in bat cells as a consequence of host adaptation. Our results implicate that the new virus might use a receptor that is conserved between bats, pigs and humans suggesting a low barrier against cross-host transmission.

The issue here (clearly explained yesterday by the always-excellent Helen Branswell) is that coronaviruses such as SARS are usually in one species at a time: for instance, they might arise from bats, jump to humans, adapt to humans, and then — having become a human infection — stop there, and not jump back again. But what this group is suggesting is that this new coronavirus might move horizontally among species. If that is the case, then tracking its spread could become much more difficult.

This paper makes the point not only that the virus can replicate in multiple species, but also that it does so by using a different receptor than its relative, the SARS virus of 2003, did. That’s important because that receptor (angiotensin-converting enzyme 2 , or ACE2) lies deep in the lungs. That meant SARS infections therefore occurred in the lower respiratory system; lower respiratory infections are generally more serious than upper-respiratory ones, and therefore these made their unlucky victims very ill. But, because the infections  were in the lower respiratory system, the replicating viruses were less likely to be coughed out toward new victims.

In this paper, the authors do not establish which receptor the new coronavirus — formally, hCoV-EMC — uses, but they have established that it does not use ACE2. And they raise the possibility that, whichever receptor is used, it might be higher up in the respiratory tract, and because of that location might allow the new virus to be more infectious.

In a third piece of news, the European Centre for Disease Prevention and Control (Europe’s CDC) has posted an updated risk assessment for the new virus, its third version since cases were discovered. The agency is clearly concerned that patients from the Middle East may enter the European Union for treatment (as the second known case, a Qatar resident, did; his illness was identified by physicians in London). The risk assessment urges awareness of patients’ travel history and origin and strict infection control for cases of unexplained pneumonia. Implicitly, the agency warns of human-to-human transmission:

Healthcare workers caring for confirmed cases should be monitored for early symptoms of infection. This includes healthcare workers who provided direct clinical or personal care, or performed examination of the cases while they were symptomatic. Close contacts of confirmed cases must be monitored for symptoms as well.

Fourth — sorry, there has been a lot of news in a few weeks — a year-old research consortium called ISARIC (the International Severe Acute Respiratory and Emerging Infection Consortium) has proposed an international collaborative plan, open to both clinicians and investigators, that could quickly generate research results on many of the questions posed by this new virus (for which, remember, diagnostics are very new, and no vaccine or antivirals exist).

And finally, if this is all becoming confusing, Nature reporter Declan Butler has put together an excellent interactive timeline that makes the back-and-forth chronology of this virus’s emergence much more comprehensible. Find it here.


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