What is new with the COVID-19 disease?

It has been about two months since the CoV outbreak in Wuhan, China.  We have learned a lot about the disease: the pathogen, transmission, symptoms, etc.  We have witnessed unprecedented efforts to curb the disease in China and around the world.  Well over 100 papers have been published on the subjects, as well as countless media reports.  Here are a few most prominent developments for the past 2 weeks.

1. In China, outside the Hubei province, new confirmed cases have dropped to 0 or close to 0 in most provinces.  The disease, thus, seems to be contained.  There will probably be rebounds here and there in the future, but the trend is established for now.  Zhong Nanshang was quoted as saying that now needs to distinguish between CoV and flu on Feb 23.  This is a backdoor saying we need to switch criteria to declare victory.  Because the drastic efforts currently still employed in China do not and cannot, and it is not even clear if the distinction is possible or doable at the population level.

2. Outside China the disease is spreading after a lull till about Feb 20.  During this time most infections occurred on the Diamond Princess cruise ship.  Now Japan, South Korea, and Italy have seen hundreds of cases.  Most new Japanese cases are linked to the ship, while in Korea linked to an infected patient attending many social events.  These cases complicated the health, social, and economic prospects of 2020, but perhaps it is also an opportunity to drive home the message: don’t panic over it, it will be here for a while, but just needs to be identified and treated properly.

3. There are still unknowns about the disease.  There are directly conflicting reports (scientific and media) in China about whether certain drugs are effective.  Maybe the treated cases have different severity, or we need more cases.  There are recommendations that glucocorticoids should not be used because of their side effects, also based on experience with SARS in 2003.  But many “younger” patients died from an overactive immune response, and some doctors have suggested that glucocorticoids could have saved their lives.  Another issue is virus carriers with no symptoms for a long time, and whether they are infectious.  People getting infected but staying healthy is actually common in most diseases, but it is also hard to say whether one has symptoms or not.  For one thing, we cough even without any infections.  And our body temperature fluctuates; even with a fever, we don’t stay hot all the time.  So a carrier may not realize he is infected or has symptoms.  Furthermore, with the stigma now associated: he gets blamed if he is infected, he gets more blame if he infects others (even though most likely he did not know he was sick), and he gets quarantined if he is confirmed, he has more reasons to lie about symptoms.  Thus, the current data or understanding is still up in the air.

4. Going back to Wuhan.  It has been estimated 5 million people left Wuhan, some carrying the virus outside.  We can now calculate how many of them infected others.  As of Feb 23, 2020, there are about 77000 confirmed cases, Wuhan 46000, Hubei outside of Wuhan 18000, rest of China 13000.  So 31000 cases from those 5 million.  Because there are secondary or tertiary infections, let’s assume 50% of the 31000 cases were directly from Wuhan carriers.  This leads to essentially about 1 in 300 of the people from Wuhan being infected.  Note that 50% is likely an overestimate, so percentage of the infected is likely even lower.  The media reports are filled with infections by people traveling from Wuhan, but absolutely nothing says that the vast, vast majority of those people are free of the virus.  This creates tremendous pressure and discrimination as well as brings about completely unnecessary social and economic costs.  

5. In the case of Wuhan, 46000 cases out of approximately 11 million people, a ratio also not alarming.  Remember, though, they can’t escape, so on the day of lockdown, Jan 23, infections must be much, much lower.  According to media reports, many people couldn’t get to the hospitals, because we know why, and had to stay at home, which led to the whole family eventually getting infected.  And they still couldn’t get to the hospital for many days, leading to a more serious disease.  When they finally got out, it might be too late to save them.  The same thing happens in the whole Hubei province.  In fact, the situation is exactly like that on the Diamond Princess ship: they are all sequestered, nobody escapes, so the virus is fermenting inside, with more and more people getting it. Here lies another reason why the fatality rate in Wuhan and Hubei is much higher than the rest of the country, which is linked to the other, previously blogs-stated reason: the health system was busted because of the panic.  In fairness to Wuhan, no city in the world can handle this.  The silver lining is now the tide is also turning in Wuhan.  With new hospitals built, and more patients getting discharged than admitted, most if not all patients can now get a bed in hospitals.  

With Wuhan and China improving, hopefully the other countries can also contain the smaller outbreaks quickly.  Then we can all come back to a still dangerous 2020.

Note on Feb 27, 2020: This latest article, quoting numerous experts, actually agreed very well with my blogs' arguments since Jan 26, 2020: https://www.yahoo.com/news/coronavirus-may-explode-u-overnight-101725466.html.

Updates on the Wuhan 2019-nCoV outbreak

The 2019-nCoV death toll surpassed 800 on Feb 9, making a prediction in the blog “Hyperbole, overreaction, and panicking in the Wuhan virus scare of 2020” wrong.  Between the Jan 26 blog and Feb 9, however, we have known a lot about the disease, initial cases, symptoms, Wuhan hospital and government responses, etc, based on real-time updates (https://news.sina.cn/zt_d/yiqing0121), media reports, and medical and scientific papers, and the principal ideas of the blog remain valid.

As of Feb 9, 2020, there are 37294 confirmed cases, 813 deaths.  Suspected cases (28942) might be less reliable because the criteria may have shifted, and the data collection too decentralized.   Quarantine numbers have been unavailable for days, because they are even more decentralized; estimates could be in hundreds of thousands but change every minute, with no meaningful standards.

In Wuhan, there are 14982 confirmed cases, 608 deaths, fatality rate is 4%.  In Hubei province outside Wuhan, about 12000 cases, 170 deaths, 1.5%.  Rest of China and the world, 10000 cases, 32 death, 0.3%.  Most cases obviously are people from Wuhan, so why the vast difference in mortality rates?  Reason #1 is that those patients (capable of) traveling out of Wuhan were less sick than those staying.  Reason #2 is that with the panicking in Wuhan and local hospitals flooded with patients, the healthcare system is overwhelmed, lowering the care for everybody.  One can assume that from Jan 20 to 26, hundreds of thousands of people went to the hospitals.  No city in the world can handle this.  Thus, it can be easily imagined that, say person A was just having a mild common cold, but because of nonstop, serious coverage of the virus and the lockdown, decided to go to a hospital to check.  There he joined hundreds or even thousands of similar patients, some with the 2019-nCoV, most without, in a crowded, closed environment.  After spending hours there, with all the blood work, CT, whatever, he was declared OK, but got infected with the virus on that day.  So he had a false sense of security with a “health certificate”, and went home to celebrate with family and friends.  Then several days later he developed symptoms, and many of his relatives and friends got infected.  This belief is not far-fetched: a JAMA paper (doi:10.1001/jama.2020.1585) showed that cases due to transmission in hospitals could be 40% (patient to patient 12%), during the earliest phase of the outbreak, when little was known, and protection was lacking.  Future analyses will determine the extent of this around Jan 23.  

The silver lining here is that with sufficient care, and treatment lessons learned, more cases will be confirmed but mortality rates in Wuhan will drop.  We also need to remember that throughout all history real infections are much higher than confirmed cases, as many people developed mild or no symptoms and did not check in.  While deaths could be undercounted as well, it is probable that some people had both common cold or seasonal flu, and 2019-nCoV, and it is the other infections that kill instead of 2019-nCoV.  In fact, having a 2019-nCoV epidemic doesn't mean the common cold/flu endemic is no more.  With the way people voluntarily or involuntarily check into Wuhan hospitals since the lockdown, one could die from a bad cold, or have a bad cold, contract the CoV at the hospital, and die, and both may count as death from CoV.  Since RNA test can yield false negatives, it is not essential in some diagnoses now.  If a suspected case dies quickly, he can be classified as a positive even without RNA test or time to confirm it.  And so far we haven't even mentioned the false positives.  Therefore, the death toll can be overcounted too.  

Another burning question is what Wuhan could have done better.  Based on the media reports and published articles in NEJM, Lancet, and JAMA, we have a clearer picture of what transpired in the early days.   The earliest case(s) could be traced back to early Dec 2019 or earlier, but the late Dec cluster cases (about 40) set off the alarms.  The first hospitals submitted the reports on Dec 26, Wuhan health authority warned all hospitals on Dec 30, national news (like Sina) reported it on Dec 31, WHO notified, a team of experts were sent from Beijing to Wuhan, and on Jan 1, 2020, the wet market in question was shut down.   In essence, within one week, a lot was done.  

The big problem, however, was we had a new virus.  Initial tests couldn’t find anything, not bacteria, known flu viruses, adenoviruses, or other coVs including SARS, MERS.   Moreover, we now know the incubation time for this virus can be long, and many patients don’t become sick for days, unlike SARS.  So the medical doctors and experts in Wuhan didn’t know what caused the diseases and who was infected unless he checked himself in.  At the time most quarantines, close relative of the patients showed no symptoms, so all the doctors could say was no apparent human-to-human transmission.  There are precedents: many bird flus go from birds like chickens to humans but not humans to human.  In fact, bird flus are often more dangerous than all the other viruses.  

The first problem was solved when the virus was sequenced: initial data was now known to be obtained on Jan 5, but they needed time to check data quality, confirmed in more samples, assembled and analyzed the data.  On Jan 7-8 WHO was notified, news reported that a new virus was identified. 

Finding a CoV should warn doctors about human-to-human transmission.  But at the time (Jan 8) it was still unclear what the virus could do.  For one thing, there weren’t known, secondary patients yet.  Another, unlike SARS and MERS, symptoms developed more slowly.  Lastly, there are other CoVs that present only mild problems.  So the doctors and experts were probably debating where the patients are and whether 2019-nCoV is like SARS, MERS, or the other CoVs.  Once the virus was known, PCR kits were designed to identify the infected.  Since it was new, detection was initially slow, taking 2-3 days out of town.  Unfortunately, there could still be false negatives: if you have mild symptoms, specimen may miss it.  These factors contributed to the undercounting of patients.    
     

But more patients eventually appeared: assuming the initial cases from late Dec 2019 infecting others in early Jan, and the latter started to show clear symptoms in mid Jan.  With more confirmed patients and better sampling and quicker PCR detection, the hospitals now had a sense of what really happened.  In mid Jan Wuhan stated could not rule out human-human spread, and on Jan 20 Dr Zhong Nanshan confirmed on major news human-human transmissions and advised travel freeze in Wuhan.  This sets the other responses in motion, and on Jan 23, lockdown began in Wuhan and elsewhere.

In retrospect, if the medical community had acted more forcefully once a CoV was identified, the situation might have been improved.  But a benefit of doubt is in order.  As mentioned, initially there were not many patients, how the symptoms evolved was unclear, the wet market was closed right away, secondary infections were not apparent for some time due to various reasons, CoV is not automatically very dangerous.  Based on sequence analyses alone, 2019-nCoV is 80% similar to SARS but believed likely less infectious or deadly.  All these influenced the thinking at the time and probably delayed a stronger recommendation or response.  This is really subjective, but I think sounding an alarm on Jan 15 is justified, but Jan 20 is understandable.  About a couple hundred of confirmed cases back then.

Sounding an alarm is, however, not the same as the subsequent lockdown, which is governments’ responsibility.  The lockdown as practiced is counterproductive.  It created panicking, likely leading to people getting unnecessarily infected and many more deaths in Wuhan.  In other places in China, it should reduce virus transmission, but there are other, less disruptive ways to do it.  The local measures are actually getting more extreme in recent days.  A few cities allow only one person from any family to get out shopping once every two days.  People buying OTC medicine for fever and cough may need registration.  You can’t visit any schools, residential areas of not your own.  There are instances of neighbors against neighbors, families against families, friends against friends.  Rumors are flying all over the place.  Stupidity and craziness are on full display.  These are completely self-harming and defeating.   

Perhaps panicking is inevitable, being on Jan 15 or Jan 23.  But the medical community and especially the governments should have done a better job discouraging or preventing mass hysteria.  For one thing, 80-90% of 2019-nCoV patients have only mild symptoms, 10-20% need ICU, but most make complete recovery with no residual effects.  Better life-supporting care should reduce the mortality rate further.   The virus is infectious, but not that bad compared to many other pathogens.  There are now 10 cases directly linked to air travel from China to the US.  During that period of time, there are over one hundred thousand passengers on the China to US flights.   In those ten flights there were maybe 3000 people packed in the environment.  Nobody else was infected.  It is not that a person can’t get infected through air or train transport or any other interactions with other people, but we need to remember the odd is low and can be lowered.  One can understand governments and airlines reducing flights, due to lower demands, but complete suspension is absolutely unjustifiable.  It feeds the worst of human nature, leading to xenophobia and racism.  Warren Buffett says: "Only when the tide goes out do you discover who's been swimming naked."  In the times of crises, you discover who's a bad human being.  There are a lot of them in the world.

Basic premises of the Jan 26 blog stand: Chinese governments’ response is really to fight a war against common cold and seasonal flu, not just 2019-nCoV, and many other governments’ are unreasonable.  The war can be won only when the nature helps (temperature increases) and the governments loosen the standards.  The virus will stay in the population for a while, even if not as an epidemic.  Later on, drugs and vaccines may be developed, which is the ultimate solution.  We are lucky that 2019-nCoV is no bird flu.