COVID-19 origin and cases

Nothing in history had consumed global efforts as intensively as COVID-19 in the last 7 months.  A lot has been learned: the pathogen, transmission routes, the symptoms, and patients.  Since late Feb 2020 the understanding has been mostly in the areas of immunity and what treatments might or might not help.  

An important question which is unlikely to get answered any time soon nonetheless continues to be explored, indirectly and directly: how did COVID-19 arise?  All arguments in my 3/28/2020 blog stand, further strengthened by the new data emerging in the past 3-4 months.

When Wuhan identified ~ 40 COVID-19 cases by early Jan 2020, 2/3 were connected to the Huanan Seafood Market, prompting the idea that it started there in late Dec 2019, perhaps jumping from an animal to humans in the Market.  This idea, while popular, had a couple of holes.  First is that 1/3 of the first cases were not connected to the Market.  While it is always hard to interpret negative data, e.g., these 1/3 might still be connected to the market somehow, no links have been established since.  Second is that subsequent analyses found the virus in the environment, but not in animals from the Market.  Again, negative data, not theory disproving, but not confirmatory either.  So since Jan no holes have been filled indicating the Market as the origin.  A tall task in itself anyway, but it suggests that people should be as critical about “positive” data as about negative data too.

Circumstantial evidence hints at the Market not being the origin.  The best example is probably another market in Beijing, China found to be a source of local infections in June 2020 (https://news.sina.com.cn/c/2020-06-26/doc-iirczymk9080051.shtml).  Both Wuhan and Beijing markets sold the same things: vegetables, seafoods, lamb, pork, beef, and other meats, often frozen, and their environments were similarly cold and damp.  The consensus now is that both markets are the places of superspreading events because of the environment, as virus likes low temperature, and large crowds.  Upon reflection, thinking of the Wuhan market as the origin was always based more on the urge for a quick answer than solid evidence.  In fact, while there were pictures, at least some deemed fake later, showing exotic animals in the Wuhan market, such animals were extremely rare if ever present, and nobody had seen bats there. 

   

The negative data in themselves can’t say the Wuhan market is not the origin, even though one must admit the first impression was never well grounded either.  But other data weakened the idea more directly.  COVID-19 cases have been identified in countries outside China in Dec 2019 or earlier, and virus RNA found in wastewater in Italy, Spain (6/28/2020 blog) and Brazil (https://www.news-medical.net/news/20200701/SARS-CoV-2-circulating-in-Brazil-back-in-November-2019.aspx).  While waste water needs more sampling and confirmation, the abundance of data indicates that even if one or two datapoints might be wrong, collectively they show COVID-19 more widespread and earlier than we thought.  For example, if Italy had virus RNA in its wastewater in mid Dec 2019 or Brazil in Nov 2019, it is impossible that COVID-19 originated in the Wuhan market in mid Dec 2019.  One can still argue that the animal-to-human transmission occurred in Oct 2019, but such an idea, itself lacking any evidence, still needs to jump through a lot of tough hoops to be even remotely feasible.  And it must be stressed that the Wuhan market received attention only because 2/3 of the first 40 cases worked or shopped there, and nothing else.  

It is expected that more waste water analyses will identify positives in more 2019 samples around the world, which likely depends on how well countries saved their waste water samples.  But even if, e.g., Spain found RNA in March 2019, it doesn’t mean COVID-19 originated in Spain.  Live viruses won’t be recovered from waste water, so the best one can get is small pieces of virus RNA/DNA, and little chance much of the 30k nt COVID-19 viral genome.  With such partial data, nobody can be certain it is COVID-19, not its parents, for instance.  In other words, all the evidence in the world so far can’t rule out this scenario mentioned numerous times already, e.g., in my 3/28/2020 blog: either COVID-19, or its predecessors, might have infected humans “silently” for months or years in or before 2019.  They didn’t get identified until Wuhan because the symptoms were none or similar to cold/flu, and/or because the transmission was short-lived, absent a superspreading event, or doctors and patients not present in the right place at the right time.  

Thus, Spain, Brazil, Italy, China, and other places might have infections of COVID-19 or its prior version earlier in 2019.  Especially if the COVID-19 predecessors were not so infectious or pathogenic.  Then the virus mutated to yield COVID-19, somewhere, some time.  How can all COVID-19 sequences around the world so far be almost identical, if there are independent evolutions?  It could be convergent evolution, newly introduced viral species overwhelming the existing species, or simply people not looking hard enough.  That the first COVID-19 seq was identified in Wuhan undoubtedly makes it the reference for everybody, but remember that random chances and superspreading could mask or supersede earlier events.   

Two more issues to consider.  The first is that we still don’t know when and how COVID-19 or predecessors jumped from animals to humans.  At this moment the next closest CoV sequence is 96% identical to COVID-19, >1000 nt differences, and decades to evolve.  Since nobody knows whether there is another, closer CoV, with bats all over the Earth, here lies the vast difficulty in identifying the origin of any disease (3/28/2020 blog).   The CoV of 96% identity was found in Yunnan, China.  Yunnan is a province with a great deal of ecological diversity, animals, plants, mountains, and forests, forming a continuous mass with SE Asia.  Like the Amazon jungle, with multiple countries sharing the geology.  What is present in Yunnan is in SE Asia (and other countries) as well, so placing a blame on any countries is both scientifically incorrect and morally corrupt.  Besides, say a person was infected with a COVID-19 predecessor, which then mutated to COVID-19 in his body, leading to the pandemic, should he get stigmatized, when this happened unknowingly and completely out of his control?   Going one step further, unlike the Hitler analogy (3/28/20 blog), COVID-19 predecessors can be as “guilty” as COVID-19 itself, so we would have an endless list of people and places, looking long back into history, to blame. 

The second issue concerns Ab tests.  Countries are using Ab tests to find out how many people are/were truly infected with COVID-19, for most infections might not get RNA tested because they didn’t realize they were infected or felt little discomfort.  A common conclusion is that Ab tests uncover ~10x cases as RNA tests (6/6/2020 blog, https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31483-5/fulltext).  Yet despite what the Ab test suppliers say, the specificity of Ab remains uncertain, especially in light of the recent waste water and early case data, whose logical explanation is they indicate early COVID-19 or predecessor infections.  Does immunity against COVID-19 predecessors protect against COVID-19 and/or interfere with the current Ab tests?  Can the Ab tell the differences between COVID-19 and its predecessor?  Unlikely to the last question, since the closest disease the suppliers can test for specificity is SARS, 80% identical.  COVID-19 predecessors could be 99% or even higher.  Japan found positive Ab in blood samples from May 2019: was it COVID-19, or predecessors, or some other false positive?  Most of this remains speculative, but it could explain the waste water results and early cases in 2019, and perhaps some of the Ab test results as well.  

At this time, there is no hope for a magic pill to cure COVID-19, so most work will be focused on: How long does Ab last in the body?  Is the Ab protective?  How long is the protection?  Cellular immunity?  And Vaccines.  There is evidence that Ab lasts only weeks or months in some former COVID-19 patients (https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31483-5/fulltext, and other, earlier reports), but it doesn’t mean they become susceptible again.  We still don’t know for sure if former patients can get re-infected, although animal studies and the lack of reporting of re-infection so far strongly suggest that they are immune, albeit without a definite time frame.  In the grand scheme of things, finding earlier COVID-19 cases is irrelevant to stemming the current pandemic but still of immense scientific value, not least because it shows how little is known about COVID-19 and the world.

PS: WHO is sending a team back to China on the subject of COVID-19 origin, according to the headlines by the media.  This purpose is 100% valid, absent of politicizing.  What will happen is that the Chinese and WHO doctors will review and discuss the earliest cases and samples, including the raw data and Wuhan market results, and perhaps other things as well.  Just don’t get your hopes up.  40 years later, do we know how exactly AIDS originated?  Scientists have a clue, but still not precisely: the first recognized outbreak was in the US around 1980, but the earliest cases could be traced to at least around 1900 in Africa (3/28/2020 blog).  No reason why COVID-19 is any easier: both were animal-to-human jumps, (is there any infectious disease that wasn’t?) but COVID-19 is much harder to track than AIDS, and bats are everywhere in the world, unlike our closest primates that are in Africa only.