Thursday, April 30, 2020

Day 90: Old-School Vaccines

On the world stage, cases are at 3.3 million and deaths at 233,000, with recoveries having finally hit one million. Spain is conflicted in its case count, only reporting PCR-based positive cases, while the counting sites include antibody-based test results, but even a disparity of more than 20,000 cases does not affect Spain's second-place standing. The UK is currently eyeing France's fourth-place spot, and Russia has jumped up to over 100,000 cases (including the Prime Minister), passing Iran to earn 8th place.

The US is at 1.07 million cases with 62,000 deaths, not to mention 30 million unemployed. New York is still its own country, with 309,000 cases and 23,730 deaths. Unfortunately, Massachusetts is firmly in 3rd place at 62,000 cases, despite being up only 3% again today. We also have about 1,000 patients currently in intensive care.

Science Mag reports on an "old-school" vaccine already in human trials in China after having worked in monkeys. The old-school approach consists of killing the virus and injecting it into people. (PlagueBlog notes that if you're really old school, you don't kill the virus first.)

On the new-school side, you genetically engineer a virus "vector" to include a target nucleotide sequence from the real virus. Oxford University has been working on one of these for a while. Today they announced an agreement with AstraZeneca for further development and production of the ChAdOx1 adenovirus vector vaccine.

The New York Times has a neat interactive report on all the time factors involved in making a vaccine (and how to squeeze them down), but it focuses more on the potential of new technology like mRNA vaccines, because they reduce the pipeline issues involved in various older-school approaches.

Also on the old-school vaccine front, yet another paper about the BCG vaccine is out in preprint. (For a bunch of previous papers, see Day 71.) This one seems much improved in that it breaks down vaccination status and COVID-19 outcomes by age group. (Plus, there's an app for playing with the numbers yourself.) Their somewhat counterintuitive conclusion is that a real correlation exists between BCG vaccination and improved pandemic outcomes, but it's not a correlation with historical vaccination of the susceptible elderly population. Instead, much more recent BCG vaccination would appear to be keeping the young people from spreading the virus to its eventual victims.

Wednesday, April 29, 2020

Day 89: Data Dump

Massachusetts' numbers are still "plateaued" at 3%, and the governor's office is still having trouble with basic youtubing. (Rumor has it you can catch the pressers live on Channel 25's livestream.) The exciting part of today's data is, instead, all the extras. For one, it's cities and towns day at the MDPH (see below). And, for the first time, all the data for the pretty dashboard is available in actually useful formats in a zip file.

For today, I've upped my cities and towns map to an interactive version. Last week both MassLive and Channel 5 put up the state's data using Leaflet.js, and I was inspired to try the R version. I redid last week's map with some tooltips of stats, but for this week I made something a bit more visual. (Open in a new tab.)



P.S. I also put the data up on Kaggle.

P.P.S. I also wrote up a tutorial about how I made the latest map.

Tuesday, April 28, 2020

Day 88: Even the Pug

In coronaveterinary news, WRAL reports that a North Carolina pug named Winston is the first American dog to test positive for COVID-19. The pug was tested as part of a study its owners volunteered for. Their other dog and their cat were negative. (Of the owners, two parents and a son were positive, but the daughter was negative.) Winston experienced mild symptoms for a few days and has since recovered.

PlagueBlog disapproves of a trial of female hormones on male COVID-19 patients reported in the New York Times, because female hormones (whether naturally elevated in pregnancy or administered, e.g., as birth control) pose a risk of thrombosis (clotting), which is already a problem for coronavirus patients. Though they've excluded patients with a history of clotting from the study, PlagueBlog does not consider this precaution sufficient, as the side-effect normally occurs in young people with no history of clotting, anyway. PlagueBlog recommends that, when grasping at straws, one try to avoid the extra-pointy ones.

The Guardian (AU) reports on an increase in toxic shock syndrome and Kawasaki disease in children in the UK. Kawasaki disease is an inflammation of the walls of blood vessels; the cause is unknown but it is suspected to be childhood infections, and genetic susceptibility may be involved. A firm connection to the coronavirus pandemic has yet to be established. The Independent (UK) and the NHS seem a bit more hesitant to peg the disease(s), instead calling the phenomenon "a multi-system inflammatory state requiring intensive care."

In other weird symptom news, ABC News reports on silent hypoxia in the wild, sometimes with crazy O2 levels:
Dr. Jeffrey Moon, medical director for the Hospital of the University of Pennsylvania's emergency department, said his department has seen "people coming in with COVID who are less symptomatic than we would expect given their low oxygen levels." Moon said he saw one patient Monday who was talking to him "in full sentences" despite having a pulse oxygenation level of just 55%.

"It's hard to believe what's in front of you at times. There is this subset of COVID patients where I don't believe my eyes," Moon said.
PlagueBlog speculates that one of those complete sentences was "I'm not dead yet!"

Time reports that "COVID toes" are getting more recognition, along with other minor dermatological symptoms like hives and rashes. There is some concern, however, that these conditions may be caused by generalized clotting, which may in turn be doing more significant damage under the surface.

LiveScience reports on the original weird coronavirus symptom, a "ruptured heart", observed in the autopsy of America's (retroactive) first death. (What actually ruptured was the left ventricle.)
This type of heart rupture occurs more typically in people with high cholesterol levels or abnormalities in the heart muscle, Melinek said. But Dowd's case was very unusual because her heart was a normal size and weight, she said.
Although LiveScience repeats rumors of the victim's alleged good health, the autopsy actually said that she was "mildly obese" with a "mildly" enlarged heart. In this context "mildly" obese is class 1 obesity, at a BMI of 31.2.

The Independent reports that the methanol poisoning death count in Iran has risen to 728, out of (apparently) a total of 5,011 poisoning cases.

P.S. Massachusetts' numbers are out; we are up 3% today. The governor describes us as on an unusual "plateau" and has closed the state for another three weeks, until May 18th. Middlesex County is also up only 3% (someone asked) and in no special need of masks at a distance outdoors, where the virus has never been shown to be transmissible.

In other mask news, the UK government and their scientific advisory committee have reiterated their complete rejection of masks for the public, in response to a belated attempt by Scotland to mask the populace merely on public transit and in shops.

Monday, April 27, 2020

Day 87: Who Was That Masked Man?

Today was a day of round numbers. The world is at 3 million cases and 211,000 dead, while the US is at a cool million with 56,000 dead. Italy is very close to 200,000 cases, and Russia has finally exceeded China's case count, with a significant leap to 87,000 cases. (Next up is Brazil, currently at 66,000 cases.) Massachusetts had a good day with a 3% rise, though our death count is now at 3,003, and the Boston Globe ran 21 pages of obituaries this Sunday.

It was a sad day in Middlesex County. We still retain our lead in cases, though this is due to no germy merit of our own but merely a consequence of a population twice the size of the next largest county. Our county case rate is a middling 800 per 100,000 cases, despite a few hotspots like Everett, Lowell, Medford, and Malden.

No, it's a sad day today because the mayor of Somerville will no longer let residents walk around outdoors at a safe distance from other people without a mask. Somerville, a city of over 80,000, has had only 415 cases for the entire pandemic. This is a rather low case rate of 512 per 100,000 residents (though not as low as Brookline, with 335 cases per 100,000 residents and a similarly severe mask policy). Sadly, Somerville residents will now need to commute to Cambridge, Arlington, or germy Medford just to take a walk in the fresh air in compliance with CDC and WHO recommendations for mask usage rather than panicked non-medical mayoral fiat. (Alternately, the internet notes that you are not required to carry ID to walk around Somerville, nor are you required to reveal what particular medical condition prevents you from wearing a mask.)

PlagueBlog reminds readers that cloth masks pose their own real dangers (unlike the imagined dangers of fresh air and sunshine), and that the below-average citizen is more qualified to judge a distance of six feet outdoors than to use a ersatz mask safely for unnecessarily long periods.

P.S. I updated the county map for the occasion:

P.P.S. In an after-hours show of counter-productivity, Cambridge joined Somerville in inventing unnecessary face covering requirements outdoors, rather than following the CDC or state guidelines. PlagueBlog notes that Cambridge's case rate is comparable to Somerville's.

Sunday, April 26, 2020

Day 86: Race and Ethnicity

Though the world, the US, and New York State are all approaching some very large, round, case numbers, today Massachusetts had its smallest uptick since we began ticking up in earnest in early March: only 3%. It is a Sunday and one apparently never knows what's up at Quest (especially since the state stopped breaking out testing by laboratory), but it's promising nonetheless.

Many statistics have gone by the wayside in the course of the state's reporting, and others have appeared to replace them. The state is quite concerned about race and ethnicity, although these are hard things to track and the results still lean quite heavily to "Unknown/Missing". (Race and ethnicity are unknown for the majority of both total cases and deaths, and for a full 40% of hospitalized cases.)

The Worcester Telegram reports that "Latinos" make up 30% of hospitalized COVID-19 patients in Worcester County, while being only 11% of the population there, and blacks are 10% of patients but only 5% of residents. The Telegram doesn't speculate about why, but elsewhere this phenomenon has been partly attributed to a disparity in pre-existing conditions. For example, PlagueBlog readers may recall that obesity is a major risk factor for hospitalization with COVID-19; Massachusetts obesity statistics from 2011 showed that "Black adults were 43% more likely to be obese, and Hispanic adults were 40% more likely to be obese than White adults."

California has observed an even more disturbing trend of young blacks and Latinos (that is, 18–49-year-olds) dying at higher rates not only than whites and Asians of the same age, but also than older people (65+) of their own race or ethnicity, respectively. Some added risk comes from pre-existing conditions:
Blacks have been found to have higher rates of diabetes, high blood pressure, obesity and smoking-related deaths than whites, according to the Centers for Disease Control and Prevention. They have a lower life expectancy and are more likely to not see a doctor because of the cost, CDC data show.

Latinos have a lower death rate overall than whites, but a 50% higher death rate from diabetes along with higher rates of poorly controlled high blood pressure and obesity, according to the CDC.
The article speculates that the reason younger blacks and Latinos are more affected than the old is that they are more likely to live in crowded conditions, to still be working in the service sector during the pandemic, and to distrust the healthcare system or lack health care coverage. (This argument may apply to Massachusetts as well.) The article mentions in passing that Pacific Islanders are the worst off of the groups considered, but without any comment as to why.

Saturday, April 25, 2020

Day 85: Ecuador

The world's case count stands at 2.92 million, with over 200,000 deaths. The US is at 960,000 cases and 54,000 deaths. Both Turkey and New Jersey have now exceeded 100,000 cases. Ecuador is on the list at 22,000 cases and 574 deaths, but the New York Times reports the suspected number of deaths is fifteen times higher, because there were approximately 7,600 excess deaths in March and early April.

With the Quest-inspired jump yesterday, Massachusetts has exceeded 50,000 cases, but today's numbers have settled down to the usual 5% rise. The governor still considers us (and Connecticut) to be in the middle of the surge, while Vermont and New Hampshire are leaving surge territory, and New York and New Jersey are (allegedly) completely past the surge. Only Rhode Island has yet to surge; he thinks it will happen in a week. (Those Massachusetts folks with houses straddling the state line should exercise caution when entering their living rooms next week.)

The San Francisco Chronicle reports that, according to her father, Patricia Dowd (the California woman who was retroactively declared the first coronavirus death in the US) showed no symptoms at the time, though earlier reports said she'd told her brother she was too sick to attend a funeral. There's still no confirmation or denial that she attended CES, only that she hadn't travelled internationally.

A thousand-year-old mill in England has gone back into operation due to the demand for flour.

Friday, April 24, 2020

Day 84: Vegas Flu and DIC

APM Reports reports on an attendee at CES 2020 (the Consumer Electronics Show in Las Vegas this January 7th through 10th) who has since tested positive for COVID-19 antibodies. He recalls getting sick immediately after CES with what was referred to on Twitter at the time as "Vegas flu" which, in hindsight, sounds exactly like COVID-19: "Weeks later, people were still posting about the lingering coughs they just couldn't seem to shake." International attendees had come from various already-infected places in China, and returned to homes and businesses all over the world, including Silicon Valley in Santa Clara County, CA.

On the topic of the flu, pre-COVID-19 research indicated that the flu vaccine actually increased recipients' susceptibility to other respiratory diseases (for example, this journal article from 2012). One study even found a particular risk of catching coronaviruses. A Canadian study postulates a couple of direct immune mechanisms for the problem, including antibody-dependent enhancement (ADE). Note that the anti-protective nature of the flu vaccine is already a potential explanation for the variable mortality by age and country that others have previously attempted to explain by differing rates of (protective) BCG or MMR vaccination.

Also on the topic of the flu, a 107-year-old Spanish woman who survived the Spanish flu as a child has apparently recovered from COVID-19.

There's been a bit of a ruckus in the news about "mysterious clotting" in COVID-19 patients: the Washington Post goes on at length about it, apparently from the springboard of this earlier Reuters article. But disseminated intravascular coagulation (DIC) is no mystery. It's a known symptom of ARDS (acute respiratory distress syndrome), regardless of the cause of the ARDS itself. The Journal of Thrombosis and Haemostasis already has an accepted report up about it, and MedPage Today reported on the problem and possible treatments for it over two weeks ago.
"What really has become clear in the discussions in the last 2 weeks is that the COVID-19 disease is much associated with thrombosis: large vessel clots, DVT/PE [deep vein thrombosis/pulmonary embolism], maybe arterial events, and potentially small vessel disease, microvascular thrombosis," said Stephan Moll, MD, of the University of North Carolina at Chapel Hill Hemophilia and Thrombosis Center.

As U.S. cases have skyrocketed, it has also become clear that hospitalized patients often develop blood clots despite being on prophylactic anticoagulation, he told MedPage Today.
P.S. PlagueBlog was experimenting with some pretty maps of the increase in cases between the state's two reports of case counts by city and town, and noticed that Milford had dropped precipitously in case count in the course of 8 days. (There were other negative rate changes, but they were much smaller and more explicable by individual case reclassifications and the like.) Google provided no explanation for the 71 evaporated cases, but did provide a local news report of Milford's new standing among its neighbors at the state's increased reported rate of 114 cases.

Going back to the state, I saw they revised their data, allegedly at 7pm on the day they reported. PlagueBlog wasn't the only outlet to pick up the original numbers and the Middlefield craziness; MassLive reports on the small town's brief moment in the hospital and their return to a zero case count, and on other errors in the data. They also have a decent map of the updated data. PlagueBlog will issue our own corrected map later today.

P.P.S. Speaking of data errors, the Massachusetts case count leapt skywards today due to an eleven-day backlog/correction of lab results from Quest. Apparently the dashboard charts for today have been updated to reflect retroactively corrected daily counts (so today's jump was really only 6%), but the archives and the town-by-town data have not.

Thursday, April 23, 2020

Day 83: Recounting China

China is once again a moving target in the coronavirus country counts, having locked down the northern city of Harbin (population 10 million). Accounts of why the city has been locked down vary, with some sources blaming an asymptomatic student "surnamed Han" ex New York City, while other sources only blame the 87-year-old super-spreader man "surnamed Chen" who actually spread the disease through two hospitals to 78 people, without any specific claims about where he got it. Sequencing the new cases would be quite helpful, but PlagueBlog does not expect to hear any such results, at least not anytime soon.

Some brave researchers at the University of Hong Kong have pulled an estimate of China's true case numbers by modeling results for the most accurate of their constantly fluctuating case definitions. Unfortunately the data they used for modeling dried up after February 20th, so their estimate is only of the case count as of that date. But it's still a doozy: 232,000 cases instead of the official count at that time of 55,508 cases. You can read more about it in their Lancet article.

On the cat watch, some suspect feline cases we've already mentioned have been confirmed. As part of the official confirmation of the two housecats from New York state, it came out that one of their owners was not actually sick. The cat appears to have caught COVID-19 through community spread. The CDC is now recommending social distancing for both dogs and cats, but (based on the research reviewed in previous posts) PlagueBlog recommends you not worry about the dogs unless you yourself are ill.

National Geographic reports that seven more large felines at the Bronx Zoo have tested positive; only one of the seven was asymptomatic and unsuspected back at the time their first tiger was tested. There's still no direct evidence that a zookeeper infected them; it's just "the only thing that makes sense."

The governor of California is planning to dig up more bodies more autopsies of possible early COVID-19 deaths like those revealed in Santa Clara county yesterday. Those patients have been identified, and had no obvious connection to Wuhan. A microbiologist involved in sequencing SARS-CoV-2 nevertheless believes that the two early deaths will prove to be from a strain imported from Wuhan to Santa Clara county early on.

Massachusetts' numbers are up 7% today, with about 3,000 new cases. The governor encourages people to seek treatment for other serious illnesses, because hospital visits are lower than expected (even taking the reduced accident rate into account) and the hospitals are safe to visit.

Wednesday, April 22, 2020

Day 82: Retroactive Deaths and Mutant Strains

SFGate reports on three deaths in the San Francisco area recently attributed to COVID-19 through autopsy. Two of them predeceased the first official American death in Kirkland, WA on February 28th, having died at home in Santa Clara County on February 6th and 17th, respectively. The third retroactive death occurred on March 6th, three days before the first known COVID-19 death in the county on March 9th. Neither the article nor the press release reveals how long the samples have been lingering at the CDC, though the fact that they sent them there at all would indicate it's been a while.

There's a new strain theory making the rounds. This is not your grandfather's L vs. S strain theory, but a more general look into the mutability of the virus and its effects. The authors sequenced virus samples from a small, apparently random sample of patients in Hangzhou, China, all of whom had had early contact with cases ex Wuhan. According to the preprint:
Taken together, despite only 11 patient-derived isolates being analyzed in this study, we observed abundant mutational diversity, including several founding mutations for different major clusters of viruses now circulating globally. This diverse mutational spectrum is consistent with their relatively early sampling time and relative proximity to Wuhan city, where the first viral strain was identified. The full mutational diversity of the virus in Wuhan city in the early days is still unknown to this day, due to limited sampling.
They infected a cell line with their 11 strains and observed significant variation in viral load and CPE (cytopathic effects such as cell death) between the strains. Due to the complexity of disease course they did not attempt to evaluate the pathogenicity of the strains directly in humans, but they did note that
[t]he tri-nucleotide mutation in ZJU-11 is unexpected; we note that this specific viral isolate is quite potent in our viral load and CPE assay, and its patient remained positive for an astounding period of 45 days and was only recently discharged from the hospital.
There is some discussion of the similarity of some of their samples to strains found in Washington State and Europe; in vitro, their Washington-like strains produced significantly less viral load than their Europe-like strain.

PlagueBlog complained about the weird county rate map in the state's new dashboard. Here is our less eye-bleeding version, thanks again to R:
Click to enlarge. Later today the new town-by-town numbers should be out (hopefully not in as inaccessible a format as the PDF dashboard, though R prevailed over the PDF in the end with the help of tabulizer) and mapped.

P.S. Massachusetts' numbers are out for today. We are again only up 4%, though there was a big jump in deaths: 221 new deaths for a total of 2,182. The new towns and cities data wasn't there at 4pm as promised, but it is there now:


Click (and zoom) to enlarge. Something's up in the small town of Middlefield, whose rate is about 19,000 cases per 100,000 residents (due to having 89 cases and only about 500 residents). That forced me to switch to a log scale for the case rates. Chelsea, while no longer the obvious hotspot it was, is still in the running at #3. The top 10 cities and towns by case rate are now Middlefield, Winthrop, Chelsea, Brockton, Everett, Randolph, Lynn, Lawrence, Topsfield, and Revere. Holyoke is still #11, but Littleton has dropped pretty far down the list. There are still 24 towns (in gray) with no cases.

P.P.S. Most of that news turned out to be bad data from the state. The actual results were much like last week's, with the top cities being Chelsea, Brockton, Everett, Randolph, Lynn, Lawrence, Topsfield, Revere, Holyoke, and Danvers, but it did still work better on a log scale.

Tuesday, April 21, 2020

Day 81: Crisis and Denial

The world has surpassed 2.5 million cases, with about 172,000 deaths. Only about 660,000 cases are considered recovered. The UK is close to 125,000 cases, Turkey has reached 90,000, and Russia has now exceeded 50,000. The US is fast approaching 800,000 cases, with a full quarter million of them in New York State.

Prisons are proving to be a breeding ground for cases, though they haven't yet led to a significant number of deaths. NPR reported 73% of inmates infected (with no deaths) at the Marion Correctional Institution, an Ohio state prison. Because Ohio is making an unusual effort to test prisoners and staff, "the prison system now accounts for more than 20% of the state's cases."

Etymonline explained the etymology of "crisis", originally a Greek medical term, and its relations, along with "epidemic", "virus", "corona", "quarantine", "sanitize", "variolation", "hospital", "draconian", and "hoard".

At STAT, Helen Branswell attributes the international failure to act more promptly against COVID-19 to denial, while complicating the matter by calling it "magical thinking". Real magical thinking requires some belief that your irrelevant actions or thoughts will actually affect the world. It is not merely a baseless hope that the world isn't about to go to hell in a handbasket.

Inspired by Trump's tweeted threat to temporarily suspend immigration to the US, Bloomberg promises (or perhaps bemoans) that coronavirus will end immigration as we know it.

P.S. Massachusetts' prettier numbers are out; cases are up only 5% again. They've also added a (rather weird) county rate map, but no city-level maps so far.

P.P.S. Also, school's out for the rest of the year. Presumably "fake school" (as the kids call it these days) continues.

Monday, April 20, 2020

Day 80: Obesity is an Underlying Condition

Today's title is a public service announcement for the BBC, which appears to believe otherwise. They reported that a 51-year-old obese male nurse from Northumberland "did not have any underlying health conditions" when he died at home of a seemingly mild case of coronavirus. His daughter described him as "slightly overweight, but otherwise fit and healthy."

PlagueBlog notes that "otherwise" fitness is not known to negate your pre-existing conditions, and obesity has been observed to be the most significant underlying factor after age in NYC hospital admissions:
"Prior to COVID-19, we already knew that obesity is a risk factor for infection in general and more severe complications, and this is particularly true for respiratory infections," Poland said.

During the 2009 H1N1 epidemic in 2009, adults with body mass indexes over 30 were 3.1 times more likely to die from the infection than people of lower weights, while adults with body mass indexes over 40 were 7.6 times more likely to die.
In other world news, Spain has exceeded 200,000 cases, and Iran has exceeded China's case count. Next up is Russia, which, while comfortably under 50,000 cases at the moment, seems to have some trouble brewing. Reuters reports they've quarantined about 15,000 troops as part of cancelling Victory Day celebrations on May 9th.

It's Patriots' Day here in Massachusetts, but it doesn't feel the same without the Boston Marathon or the annual reenactment of the Battle of Lexington. In even more depressing news, the Boston Globe published 16 pages of obituaries this Sunday (April 19th), a significant increase over last year's seven page spread. (Reports of only 15 pages are inaccurate.) The previous Sunday's count was 11 pages, and a week before that it was nine.

P.S. Reuters reports that one of two additional Ebola patients in Beni, DRC, has escaped the treatment center and has not yet been found. The current case count is six, though one patient is still only known from the WHO's case count. Besides Ebola, the Congo is also battling COVID-19, measles, and cholera outbreaks.

P.P.S. Since the Massachusetts Department of Public Health appears to be taking Patriots' Day off of coronavirus reporting, PlagueBlog instead brings you another pair of Germ Boats. Lucky #26 and #27 are the Royal Caribbean sister ships Oasis of the Seas and Symphony of the Seas, respectively. (The latter is the world's largest cruise ship.) Three weeks ago, Royal Caribbean Cruises started evacuating sick crew off both ships to hospitals on the Florida mainland, without actually admitting to the coronavirus outbreak among the crew still on board. Today, the death toll among the ships' crew reached 3 with the death of a 41-year-old Indonesian man who had been a waiter on #26. A Filipino man who had been a bartender aboard #26 died on Saturday; his age has not been reported, though apparently he died on his birthday.

Back on Easter Sunday, a 27-year-old Indonesian man from the crew of #27 apparently became the youngest person to die of coronavirus in Florida. Because all three victims were foreign nationals they have not been included in the Florida statistics, so some details of their cases remain unclear. Royal Caribbean has refused to comment on these deaths or on how many infected crew remain in Florida hospitals and offshore.

P.P.P.S. The state did eventually cough up a pretty, if inaccessible, PDF dashboard of the day's numbers: cases were up 4%, with 103 new deaths.

Sunday, April 19, 2020

Day 79: Cryptic Cases

In world stats, Turkey has surpassed China in cases, and Iran is very close now. In New York (City or state was not specified), two housecats appear to have caught coronavirus from their (respective) sick owners. Here in Massachusetts, our Sunday numbers are depressed as usual, going up only 5%. Note that tomorrow is still a holiday in Massachusetts despite the postponement of the Boston Marathon, and the numbers may continue to reflect the long weekend rather than the medical situation.

According to a somewhat arbitrary standard published in the New York Times, Rhode Island is the only state doing anything like enough testing to reopen.

Several more surveys of asymptomatic cases have come out recently, including a random, anonymous test of 200 people healthy enough to walk the streets of Chelsea (Mass.), of whom 32% proved to have antibodies to coronavirus. The Boston Globe also reports that half of the participants had had symptoms of COVID-19 in the past month, but none had previously tested positive. Chelsea is by far the most infected part of the state per capita, so PlagueBlog recommends not projecting these numbers across the state. Because the subjects were anonymous there was no way to give them their test results, but if they follow the news perhaps they will consider their odds and get tested elsewhere.

LiveScience reports on a similar study in Santa Clara County that "suggested that between 2.5% and 4.2% of people in the county have contracted COVID-19, which is 50 to 85 times greater than the number of cases being reported at the time." The study has been criticized for overestimating the rate, either through massaging the percentage up from its raw value of 1.5%, for the self-selection bias of the volunteers, for potential false positives on the antibody test (which is not yet FDA approved), and also for not being ethnically representative (the only criticism which implies the rate should be higher than the study estimated).

A similar study has been done in Wuhan, where the official infection rate was about half a percent, but more than 2% of hospital employees had antibodies. In Italy, most residents of the small town where their first death occurred (Vò) were tested twice. The preprint results show 43% of cases were asymptomatic, across all age groups, and that several asymptomatic patients spread the disease to others in the same household.

On the pretty picture front, I've updated last week's Massachusetts case rate map with better estimates of case rates in towns with fewer than 5 cases. I don't have the actual population numbers the MDPH seems to be using, so I used numbers from the census' population estimates API:

Saturday, April 18, 2020

Day 78: No Evidence of Immunity

The world stands at 2.33 million cases with 160,000 deaths. The US has exceeded 738,000 cases and 39,000 deaths. The situation in Spain seemed to have calmed down over Easter, but is active again now and may only take another day or two to hit 200,000 cases. The UK, at 114,000 cases, remains in sixth place but is still a contender to surpass the flattening continent. Both Turkey and Iran are looking to surpass China's revised numbers soon.

In the US, the Navajo Nation has made the news with 1,042 cases (none recovered) and 41 deaths, surpassing a handful of states although their total population, about 357,000, is less than that of any state.

If you were hoping for more pretty pictures today, I can only point you toward these charts of the Massachusetts data by something innocuous, who also posts them to Reddit daily. Massachusetts is up 6% today. While we remain in third place in case count, three states behind us have more active cases than we do. Pennsylvania in particular has over 3,300 more active cases despite having 4,600 fewer cases overall, so looks like it could catch up to us soonish.

The Telegraph reports that the WHO has cautioned against relying on serology to prove immunity to COVID-19:
There is currently no evidence to support the belief that people who have recovered from coronavirus then have immunity, the World Health Organisation has said.

Senior WHO epidemiologists warned despite the hopes governments across the world have piled on antibody tests, there is no proof those who have been infected cannot be infected again.
Germ Boat #25 is the nuclear-powered aircraft carrier Charles de Gaulle, flagship of the French navy, with more that 1,000 cases, nearly half of the ship's crew. The outbreak grew "exponentially" around April 4th, and the ship has now returned to its home port of Toulon for disinfection. Attempts to trace the outbreak to prior stops in Brest and Cyprus have not yet yielded a definitive answer.

Germ Boat #23, the USS Theodore Roosevelt, continues to make the news for its 60% rate of asymptomatic cases. There is little other test data for groups of young, healthy people.

Boston's Pine Street Inn homeless shelter made the news on Wednesday when testing of the entire population revealed a 38% positive rate (146 cases), all of them asymptomatic. One person was moved to a hospital, and the rest were isolated in temporary facilities. No news of symptoms has emerged since.

The hand-wringers are wringing extra hard about whether the virus came out of a lab, perhaps because Nobel laureate Luc Montagnier, discoverer of HIV, is in the made-in-a-lab camp. The suspect Wuhan lab has now denied it came from there.

PlagueBlog should note that the current Ebola outbreak in the Democratic Republic of the Congo remains current, due to the discovery of three or four new cases (two deceased, one receiving treatment, and one known only from the WHO case count) a full forty days after the last case had been resolved and two days before the outbreak would have been declared over.

Friday, April 17, 2020

Day 77: During the Peak

Massachusetts' numbers are up 7% today. The governor has been saying for a few days now that he considers us in the midst of the peak, and that due to our planning, there is still significant availability of beds for both COVID-19 patients and other emergencies. The IHME projections have also been updated, and they predict tomorrow as our peak (day).

In my non-disease blog, I wrote up a bit of a tutorial about making the Massachusetts cities and towns infection rate map from yesterday, and also how to map the absolute case counts using the same data set:
Click (and zoom in as desired) to enlarge. (This actually works now, after some Blogger tweaking.) The colors are on a log scale for visibility. Towns in gray have no cases. The top ten cities case-wise are Boston, Brockton, Worcester, Lawrence, Lynn, Chelsea, Lowell, Springfield, Cambridge, and Revere, in that order.

Thursday, April 16, 2020

Day 76: COVID In, COVID Out

Massachusetts' numbers are up 7.5% today. Yesterday the state promised some extra data (h/t MassLive), but of course it took some digging around the website to find it. The state's numbers for hospital infections [PDF] include Steward Health Care hospitals and also suspected cases, which is probably why they're so much higher than the numbers from the Globe the other day. Buried elsewhere, there's also a chart of bed occupancy and capacity [PDF] by "region", including the beds in alternate sites like Corey Hill the BCEC.

The new town-by-town data [DOCX] conveniently includes the rate scaled to 100,000 "residents". (The vast majority of cities in Massachusetts don't actually have 100,000 residents, never mind the towns.) There is a promise to update the town-by-town data weekly, but nothing about maintaining the hospital data.

An archive of the daily reports has also appeared. Finding them had previously required the Wayback Machine to discover their somewhat unpredictable and sometimes misspelled URLs. The archive also includes the previously missing DOCX for March 9th. (PlagueBlog has not yet checked the full archive against our own archives for changes.)

Here is a long-awaited pretty picture, of the town-by-town case rates (per 100,000) through April 14th:
Click to enlarge. The yellow hotspot near Boston is Chelsea. The top 10 cities ratewise are: Chelsea, Brockton, Randolph, Williamstown, Lawrence, Everett, Longmeadow, Braintree, Revere and Norwood, in that order. Holyoke is #11 and Littleton is #14, presumably due to their nursing home issues.

I made up the rates for the places with <5 but more than 0 cases; next time I will find population data for those places in order to estimate them properly (though it's unlikely to change the map much).

Wednesday, April 15, 2020

Day 75: Don't Be Alarmed

The world topped two million cases last night and now stands at 2,075,000, with 134,000 deaths. The standings are mostly unchanged, with the US at 641,000 cases and 28,000 deaths, and New York State now well ahead of Spain in cases (213,000 vs 177,000), though not deaths. Nevertheless, Dr. Fauci thinks we're finally flattening the curve.

ProPublica published a report on excess deaths in the US not yet attributed to coronavirus. It singled out Massachusetts and Detroit as particularly likely to be undercounting:
In Middlesex, Massachusetts’s most populous county and home to Cambridge, Somerville and Lowell, officials reported 317 at-home deaths in March. That’s about a 20% increase from the same time period for the past three years, in which deaths ranged from 249 to 265. [...]

Older people are particularly vulnerable to dying from COVID-19. In all of Massachusetts, deaths for people 65 and older increased by 3.6% in March from the same month, on average, during the previous three years. The comparison to 2019 was particularly dramatic, an additional 250 deaths across Massachusetts. At the same time, the data shows that increase can’t be accounted for by the official coronavirus tally alone: only 89 deaths statewide were attributed to the virus in March, according to state Health Department data.
Detroit had an increase of 110 "dead person observed" calls in early April. Other places are not necessarily doing any better; in many states vital records retrieval is difficult, slow, or entirely suspended, so the data is not available.

Massachusetts' numbers are up 6% today, with 151 new deaths. We are nearing 30,000 cases.

While early reports out of China indicated little risk to pregnant women, a couple of cases of death late in pregnancy hit the news today: a case study from Iran and an NHS nurse.

The coronavirus crisis seems to have led to many people discovering the Internet for the first time, at least judging from the amount of hand-wringing and alarm-sounding going on over "fake news" and "conspiracy theories". I don't mean Starving cannibal rats swarm deserted US streets amid Coronavirus lockdown. Some people might call that "fake news", but we already had yellow journalism. Giving it a new name only confuses the situation.

Instead I mean the sort of alarm expressed by a doctor on Medium about a non-doctor on Medium's hemoglobin theory. I came across the non-doctor's theory on reddit, where you can still find the archived link and other details, including the salient point that, despite sounding original, the non-doctor was summarizing existing research. Like other theories out there in preprint right now (several of which have been PlagueBlogged), it was interesting but not yet substantiated. There is always a pattern of people getting upset that someone dared suggest their particular misreading of a preprint because it's somehow vaguely dangerous or irresponsible to say something the original author usually didn't even say. (PlagueBlog is not suggesting that the Medium doctor is unique; he's just a well-written example not buried in a comments section.)

So, after a good deal of scare-quoting and gatekeeping, the alarmed doctor admits that the non-doctor's theory is clearly based at least in part on existing research (which the doctor also happens to find "seriously flawed"). His conclusion, far more unsubstantiated than any mistaken inference in the essay he's criticizing, is that somebody posting a scientific (if ultimately incorrect) theory on the internet "can genuinely put lives at risk". PlagueBlog eagerly awaits the mass graves and the death count websites devoted to victims of in silico speculation of this sort.

It's especially disappointing when an actual scientist can't abide by the process of science. It's not even a tiny bit surprising when the average journalist can't abide the average Joe. For example, Vox bemoans that 30% of Americans believe the coronavirus "conspiracy" theory that it originated in a lab, probably accidentally. Note that no conspiracy is involved; it's just a theory about the origins of the virus, as Vox reluctantly admits:
The belief that Covid-19 was created by humans stems from speculation by some scientists during the early days of the outbreak that the virus came from a laboratory.
Note that this theory has still not been disproven, though it may not be as fresh and appealing as it once was. There is no particular reason for Joe to change his mind about it, because it's still a free country no matter how alarmed you are. Vox thinks that Joe, being lower class, is in far more danger from coronavirus than the average alarmed middle class hand-wringer, but it's not his idea that the virus came from a lab that endangers him. If anything that would make him more cautious.

Vox also notes (referring to an older article and poll) that over 40% of Americans and even more Fox News viewers believed that the epidemic was being exaggerated. While it's clear how this opinion (finally!) could pose a danger to some people were it wrong, Vox hasn't actually established that it's wrong. Even PlagueBlog believes the pandemic is being exaggerated, because what else is left for the media to report about? Everything but coronavirus has been cancelled. This leads to a natural exaggeration of a disease that is, despite its rising death toll, still not the Spanish flu.

It is possible to hold an informed opinion that the economic toll of the cure is worse than the death toll of the disease (and various similar notions Vox might dismiss as "skepticism"). The easily alarmed may not like or agree with such opinions, but that doesn't make the alarmed opinion the truth and Joe's opinions a conspiracy.

Tuesday, April 14, 2020

Day 74: R0 and Rt

Today's numbers are edging ever closer to 2 million cases, hovering around 1,950,000 at the moment. A few numbers have leaked out of North Korea: four doctors and 180 soldiers have died of coronavirus. (These deaths are not included in the world total.)

The UK has joined Italy and New York City in hitting the news for its statistically suspicious death rate. Just by checking death certificates for mention of COVID-19, the Office for National Statistics picked up 15% more deaths than previously counted. A redditor noted even more of a death disparity in the ONS chart summary points:
The provisional number of deaths registered in England and Wales in the week ending 3 April 2020 (Week 14) was 16,387; this represents an increase of 5,246 deaths registered compared with the previous week (Week 13) and 6,082 more than the five-year average.

Of the deaths registered in Week 14, 3,475 mentioned “novel coronavirus (COVID-19)”, which was 21.2% of all deaths; this compares with 539 (4.8% of all deaths) in Week 13.
That's a difference of 2,607 unexpected deaths still not attributed to COVID-19. Unlike Italy and NYC, the health care system in England and Wales is not overwhelmed, so there's not a lot besides coronavirus to explain the extra deaths.

Circumstances have forced PlagueBlog to add the USS Theodore Rooosevelt to the germ boat list at #23, due to a death onboard from coronavirus. The unnamed sailor was found unresponsive last Thursday, two weeks after having tested positive, and died in intensive care on Monday. The case count aboard #23 is 585 positive out of a crew of 4,800. Rumor has it that four other infected sailors are in a hospital ashore; presumably the rest remain aboard.

Likewise, the USNS Mercy hospital ship has earned the title of Germ Boat #24 with its own outbreak. In this case they are combatting the outbreak not in the Diamond Princess way of Germ Boat #23, but by removing the seven infected sailors and their contacts to isolation ashore.

R0, the basic reproduction number, is a somewhat vaguely defined measure of the number of people one infected person will infect in a naive population taking no precautions. For example, R0 for measles, an extremely contagious and truly airborne disease, is generally estimated at 15. The CDC has estimated R0 for coronavirus at 5.7 (revising an initial estimate of 2.45).

R0 is contrasted with the effective reproduction number R (or Rt, or Re), which is the average number of people infected by one infected person in the current situation (of precautions, partial herd immunity, etc.). Gabriel Goh at OpenAI has written a fun tool for playing with these values and others to see how they affect "the curve". Kevin Systrom, cofounder of Instagram, has a writeup about Rt as a useful, local metric of how individual US states are doing. He's pretty pessimistic about Massachusetts and Rhode Island:
Which states have the epidemic least “under control?” To answer this, I plotted states where the best case (eg. low end of HDI) is above 1.0, indicating the true value of Rt is almost certainly above 1.0. Surprisingly, Rhode Island, Maryland and Massachusetts sit at the top. Part of this may be that Rhode Island is earlier in its infection curve, but seeing large states like Massachusetts and Texas above 1.0 is worrisome—especially because none of these states have hit the headlines as being trouble spots.
P.S. Massachusetts' numbers are up 5% again today. Hospitalization numbers have dropped out of the report for undocumented reasons. (Speaking of which, the Boston Globe published a hospital-by-hospital breakdown of coronavirus cases, though Steward Health Care hospitals are omitted.) Middlesex holds a commanding lead over Suffolk County, and at least one Middlesex County mayor has decided to confuse matters by issuing hiss own mask guidelines in contradiction of the CDC and state guidelines.

Monday, April 13, 2020

Day 73: Super-Spreading

The world is at nearly 1,925,000 cases, with 119,000 deaths and 445,000 recovered. The standings haven't changed much, although Massachusetts (up only 5% today due in part to a change in reporting times) has moved up to third place in the US in a general scramble of the 20,000+ states. PlagueBlog wonders whether there is a strain difference going on, as our coronavirus strains are predominantly from the disaster area that is Europe, while the west coast, like Asia in general, seems to be doing far better with their direct-from-China strains.

A few other theories about the strange pattern of contagion involve super-spreaders. A preprint from March postulated compound super-spreading: Do superspreaders generate new superspreaders? a hypothesis to explain the propagation pattern of COVID-19, by Pablo M. Beldomenico in Argentina. He believes that a sort of cascade of super-spreading through high viral loads is what led to the heterogeneity of sudden outbreaks in places like Italy versus slow burns in places where you wouldn't expect them, like Japan. He brings in some evidence from experiments with veterinary diseases to bolster the high viral load part of the theory. He concludes thus:
If superspreaders generate new superspreaders by exposing susceptible people to large viral loads, this mechanism should be immediately acknowledged and considered in the responses being undertaken. In particular, emphasis should be placed on the isolation or strict distancing of people of risk groups, as they would not only have more chances of developing a more severe disease (with the potential of overwhelming the health system), but they could also be source of high viral loads.
The New York Times reports (some more) about the super-spreading event at Biogen, and the New Yorker reports on a super-skiing event in Idaho. (Viral loads are not documented.)

Let us not forget South Korea's infamous Patient 31. While there are other clusters in South Korea, hers takes the super-spreading cake. Back in the US, Channel News Asia reports on a man in Chicago who super-spread at a February funeral and a subsequent birthday party, infecting at least fifteen people and killing three. Note that the article suggests coronavirus could be more contagious than measles; it is not. Nothing is as contagious as measles, with an R0 of about 15, and no one has suggested anything like that for COVID-19.

More on R0 tomorrow...

Sunday, April 12, 2020

Day 72: Coronascience

The numbers accelerate apace; most notably the UK has risen above the China mark to 84,000 cases and well over 10,000 deaths. (On the bright side, Boris Johnson is out of hospital.) In Massachusetts, we're up 2,615 cases (11%) to 25,475, with 70 new deaths. One notable death was of a whistleblower nurse at the Life Care Center of Nashoba Valley in Littleton, where ten residents have died and 67 have tested positive. (The surviving staff are still being tested.)

Non-pneumonia symptoms have been getting more attention lately. A 400% jump in at-home cardiac arrest deaths in New York City has been attributed to viral myocarditis or some other mechanism by which the virus is damaging the heart. JAMA Cardiology has a detailed case study of a healthy patient with cardiac complications. An autopsy study in New Orleans found cardiomegaly, right ventricular dilatation, and "scattered individual cell myocyte necrosis" in the heart muscle. (There's an interesting discussion of the autopsy results on reddit.)

Another non-pneumonia symptom that, like sudden cardiac arrest, may explain early rumors of people dropping dead in the streets is stroke. JAMA Neurology published a paper yesterday about neurological manifestations of coronavirus in patients in Wuhan. They noted that "[s]ome patients without typical symptoms (fever, cough, anorexia, and diarrhea) of COVID-19 came to the hospital with only neurologic manifestation as their presenting symptoms."
Seventy-eight patients (36.4% [of 214]) had nervous system manifestations: CNS (53 [24.8%]), PNS (19 [8.9%]), and skeletal muscle injury (23 [10.7%]). In patients with CNS manifestations, the most common reported symptoms were dizziness (36 [16.8%]) and headache (28 [13.1%]). In patients with PNS symptoms, the most common reported symptoms were taste impairment (12 [5.6%]) and smell impairment (11 [5.1%]).
Another new category of symptom to pop up is dermatological: a French medical society has published a press release claiming that rash unaccompanied by pulmonary symptoms may indicate asymptomatic COVID-19 infection.

On the reproduction front is a preprint out of England about anosmia as a predictor of infection. They used app data from Britain to "find that loss of smell and taste were present in 59% of COVID-19 positive individuals compared to 18% of those negative to the test [...] We also find that a combination of loss of smell and taste, fever, persistent cough, fatigue, diarrhoea, abdominal pain and loss of appetite is predictive of COVID-19 positive test with sensitivity 0.54, specificity 0.86".

On a different sort of reproduction front, South Korea reported a total of 91 relapses on Friday, up from 51 total on Monday. For some unknown reason, officials believe these cases are "reactivations" rather than reinfections, even though Korean patients must test negative twice before being counted as recovered.

There has been some progress combatting the cytokine storm with the CCR5 antagonist leronlimab. An Israeli treatment involving placental cell therapy and a stem cell therapy from Australia have also shown promise.

A drug target of interest is the bradykinin receptor type 1 (B1), according to a theory in preprint:
We propose it all starts with ACE2 and its role in the kallikrein-kinin system, which to date has not investigated in the pathogenesis of SARS or COVID-19. The kinin-kallikrein system is a zymogen system that after activation leads to the release of the nona-petide bradykin that after binding to the B2-receptor on endothelial cells leads to capillary leakage and thus angio-edema. The prototype diseases of local peripheral transient increased bradykinin release are hereditary or acquired angio-edema. The clinical picture of COVID-19 is in line with a single-organ failure of the lung that is due to edema at the site of inflammation.
In shorter words, the virus' use of ACE2 receptors on lung cells uses them up, causing them to fail at one of their important jobs: keeping fluid from leaking into the lungs.

P.S. PlagueBlog forgot to mention that John Conway died yesterday of coronavirus. He was 82 years old.

P.P.S. Another approach to the cytokine storm is cytokine blockers, as recently discussed in The Lancet.

Saturday, April 11, 2020

Day 71: BCG vs RCV1

Today's numbers are impressive: over 1.75 million cases worldwide, with well over 100,000 deaths. The US (with over 500,000 cases) has finally pulled ahead of Italy and exceeded 20,000 deaths. The UK probably won't hold on to its 7th place below China for long but remains there now, and Boris Johnson is out of the ICU.

New York State (at 180,000 cases) remains ahead of the major European hotspots. New Jersey is a distant second at 58,000 cases, and the remaining hotspots (Michigan, Pennsylvania, California, Massachusetts, Louisiana, Florida, and Illinois) are all hovering around 20,000 cases. Michigan has locked down for real this time, forbidding travel between homes and "public or private gatherings of any size."

Massachusetts' numbers are down again today, with 1886 new cases (up 9%) and 87 deaths. The state is now tracking deaths in long-term care facilities (304 total) along with infections (2645, which includes health care workers) and infected facilities (190). Also of note, the sidewalks of one street in Beverly have been declared one-way.

With Wyoming jumping on the bandwagon, all 50 states (plus 4 territories and the District of Columbia) have declared disasters simultaneously for the first time.

So, why us? You've heard this explanation here before, but since the media has picked up on another paper (apparently the fifth) about the correlation between tuberculosis vaccination and low case fatality rates from coronavirus, you're about to hear it four more times.

The Bacillus Calmette–Guérin (BCG) vaccine uses a live, attenuated strain of Mycobacterium bovis (yes, it's a real vaccine, perhaps even more so than vaccina). It protects against tuberculosis (Mycobacterium tuberculosis) and leprosy (Mycobacterium leprae and M. lepromatosis) to some extent, for a couple of decades. It has long been known to protect against other respiratory diseases indefinitely, by a still unknown mechanism; it is also sometimes used in the treatment of bladder cancer. Nevertheless, adoption of BCG vaccine varies by country, perceived risk of TB, and time; see the BCG World Atlas for lots of details.

1. Back in the day, PlagueBlog covered the first preprint on this topic, Correlation between universal BCG vaccination policy and reduced morbidity and mortality for COVID-19: an epidemiological study, by Aaron Miller, Mac Josh Reandelar, Kimberly Fasciglione, Violeta Roumenova, Yan Li, and Gonzalo H. Otazu, at several New York institutions. They said:
We compared large number of countries BCG vaccination policies with the morbidity and mortality for COVID-19. We found that countries without universal policies of BCG vaccination (Italy, Nederland, USA) have been more severely affected compared to countries with universal and long-standing BCG policies. Countries that have a late start of universal BCG policy (Iran, 1984) had high mortality, consistent with the idea that BCG protects the vaccinated elderly population. We also found that BCG vaccination also reduced the number of reported COVID-19 cases in a country.
They controlled for income and also charted start years of BCG vs. deaths for countries that do or did vaccinate.

2. Another early paper, BCG vaccination may be protective against Covid-19 by Paul K. Hegarty, Ashish Kamat, Helen Zafirakis, and Andrew DiNardo (two Brits and two Texans) quantified both the infection and death rates over a fifteen day period in March at almost 10 times lower with BCG vaccination. They did note that "[c]ountries that have a booster injection of BCG 7 to 14 years later had no better outcomes than those with a single inoculation only."

3. The story currently in the news is about a preprint by researchers at Johns Hopkins that estimated a death rate only 6 times lower with BCG: Differential COVID-19-attributable mortality and BCG vaccine use in countries, by Anita Shet, Debashree Ray, Neelika Malavige, Mathuram Santosham, and Naor Bar-Zeev. The mortality rate is 5.8 times lower in vaccinated populations than in the unvaccinated. The average death rate per 1 million people in vaccinated countries is 0.6, while in unvaccinated countries it is 8.6. (If you're curious about country by country data, take a look at this supplemental figure.)

4. An even more recent paper, Mandated Bacillus Calmette-Guérin (BCG) vaccination predicts flattened curves for the spread of COVID-19 by Martha K. Berg, Qinggang Yu, Cristina E. Salvador, Irene Melani, and Shinobu Kitayama at the University of Michigan, compared infection and death rates in the first 30 days of a country's outbreak to their BCG status. Countries with vaccination policies that did not last into this century (e.g., Spain, Germany) turned out to be equivalent to those who never vaccinated (e.g., the US, Italy). In the supplemental material, they "predict" the numbers for an alternate US with full BCG vaccination:
This analysis applied to the number of cases yielded a predicted value of 11.28, which translates to 79488.86 cases (compared to the actual 213372 cases reported in the US by April 1). This analysis applied to the number of deaths yielded a predicted value of 4.54, which translates to 93.97 deaths (compared to the actual 2467 deaths reported in the US by March 29).
5. There seem to be more than five such papers, so I'm picking a fifth from among the related preprints at medRxiv that contradicts the others: Association Between BCG Policy is Significantly Confounded by Age and is Unlikely to Alter Infection or Mortality Rates by Stefan Kirov of Bristol Myers Squibb. The title says quite a bit, but the author also notes a confounding correlation between BMI and BCG policy: countries with lower BMI also have BCG vaccination. (Obesity is a known risk factor for coronavirus.) He attempts to make a spurious connection between rubella vaccination and (poor) COVID-19 outcomes as a sort of cautionary example, but rubella vaccination dates back to 1964 at the earliest (while BCG is over a hundred years old) and thus is much more confounded by age than BCG coverage could possibly be. Rubella is also a poor choice of counterexample because rubella vaccine (RCV1) coverage has been fairly consistent across the western world (except, notably, in Italy), where the contrasts in outcome despite few cultural and biological confounders led to such a baroque theory as BCG in the first place.

One preprint from yesterday goes full on in the rubella direction with a study of the MMR vaccine: Homologous protein domains in SARS-CoV-2 and measles, mumps and rubella viruses: preliminary evidence that MMR vaccine might provide protection against COVID-19 by Robin Franklin, Adam Young, Bjoern Neumann, Rocio Fernandez, Alexis Joannides, Amir Reyahi, and Yorgo Modis (mostly in Cambridge, England). Though they accept the BCG theory at face value and postulate that adoption of the MMR vaccine might follow a pattern similar to that of BCG, for this paper the confounding element of age for BCG is the primary explanatory factor. Age is strongly correlated with MMR coverage because MMR only dates back to the early 70's, and its constituent vaccines only date to the late 60's. Because rubella vaccine was also given to women of childbearing age, immunity to COVID-19 would be increased differentially for women over 50 vs. men of the same age. (Unfortunately the figures for this in the paper are mostly unlabelled and inscrutable.)

They also found similarities in the viral genomes of SARS-CoV-2 and the measles, mumps, and rubella viruses; there are quite a few details there, but no wet results yet. However, they have collected rubella immunoglobulin data in severe vs. mild cases of COVID-19:
A further prediction of our hypothesis is that there should be a specific rise in rubella Immunoglobulin G (IgG) titres in COVID-19 patients, and that these should correlate with disease burden as a marker of immunogenicity against SARS-CoV2 [...]

Patients with a high severity illness had on average increased levels of rubella IgG (161.9+147.6 IU/ml) compared to patients with a moderate severity of disease (74.5+57.7 IU/ml) (Fig. 5). In comparison, Immunoglobulin M (IgM) levels were 0.21+0.16 IU/ml in severe disease and 0.26+0.21 IU/ml in moderate disease. Whilst we accept that it is possible that this trend could be representative of preinfection protection to rubella infection, it is not possible to determine this. In a study of 160 women of child bearing age, the IgG levels of non-infected patients measured between 24-143 IU/ml, suggesting that it is unlikely that those who developed severe symptoms of the disease had IgG levels far in excess of this prior to infection.

Day 70 Retrospective: Even the Ya̧nomamö

PlagueBlog apologizes for being unavailable for day 70. (We are not infected.) Massachusetts was down in absolute case numbers, and went up by only 11%. Also the Governor signed a bill waiving the MCAS testing requirements this year. It's unclear whether MCAS high school graduation requirements (of having passed the tests) will also be waived. CNN reports that the feds are also investigating the Holyoke Soldier's Home:
According to the state's Executive Office of Health and Human Services (EOHHS), which runs the facility, as of April 9, 69 residents and 68 staff had tested positive for coronavirus. Since March, 32 residents of the home have died with 28 of those testing positive for Covid-19.
On Friday, April 10th, Reuters reported that a fifteen-year-old Ya̧nomamö boy from Rehebe named Alvanei Xirixan died of coronavirus in a hospital in Boa Vista, Roraima, Brazil. (The YÄ…nomamö are an indigenous tribe in the north of Brazil.) Some attempt to isolate other infected villagers is underway. Reuters also reported four infections among the Kokama tribe.

Day 69 Retrospective: Making the Diamond Princess Look Good

PlagueBlog apologizes for being unavailable for day 69. (We are not infected.) Massachusetts numbers were up 13%. Also, someone's been testing our sewage and thinks we have 100,000 cases, not 18,941.

The Germ Boat of the Day on Thursday, April 9th was #22, the Aurora Expeditions ship Greg Mortimer, on a 21-day Antarctic cruise out of Ushuaia since March 15th. Though its original destination was Puerto Williams, Chile, both Chile and Argentina have closed their ports, so the plague ship instead anchored in the Rio de la Plata (between Argentina and Uruguay) on March 27th, hoping to eventually dock in Uruguay. The Uruguayan government, for its part, refused docking until all passengers died tested negative. Note that 128 passengers and crew out of 217 are infected, including the ship's doctor, but Uruguay is keeping their social distance from all 217.

A week ago Saturday six especially ill passengers were evacuated in a PPE-heavy Uruguayan naval operation. Two more such passengers were evacuated on Wednesday. This Saturday the ship finally docked in Montevideo, where about 110 Australian and New Zealander passengers were escorted "along a 'sanitary corridor'" to a waiting charter plane.

The crew of 80, along with 20 European and American passengers, remain aboard the ship waiting to die test negative.

Wednesday, April 08, 2020

Day 68: Death Panels

PlagueBlog believes Massachusetts' numbers are to pattern, but has been distracted by the governor's announcement at his presser today that we're taking some advice from Pennsylvania about allocating scarce resources. As our peak is still predicted to exceed capacity, PlagueBlog is duly alarmed.

P.S. The numbers were up 10%.

Tuesday, April 07, 2020

Day 67: 5G

Today the world hit 1,430,000 cases with 82,000 deaths and 301,000 recovered. The US hit 400,000 cases and is quickly approaching 13,000 deaths. Spain, nominally #2 at 141,000 cases, is now actually behind New York State (142,000 cases), though Spain continues to exceed in deaths. France has not only passed the 100,000 mark but has leapfrogged over Germany to fourth place. Iran is sixth and the UK seventh with 55,000 cases, among them Boris Johnson, spending his second night in the ICU.

Massachusetts' numbers were a bit late today (though not as late as this post): 1365 new cases (up 10%) for a total of 15202, with 96 new deaths. The excess deaths have something to do with reports over the weekend not being correlated with cases until now. Suffolk has leapt ahead of Middlesex County again. There are now 958 positives at long-term facilities, and 129 facilities reporting COVID-19 cases. We almost hit 5,000 tests today. The governor talked about his testing goals at his presser today, but didn't explain the cause of the fluctuations.

PlagueBlog has heard some third-hand rumors that 5G causes coronavirus. They somehow predate Representative Mark Green's allegations yesterday that China was making the delivery of medical supplies to France contingent upon their using Huawei to implement 5G.

P.S. Gothamist reports an unusual number of deaths at home in New York City, which are not being reported in the official counts when they are untested, presumptive cases:
The FDNY says it responded to 2,192 cases of deaths at home between March 20th and April 5th, or about 130 a day, an almost 400 percent increase from the same time period last year. (In 2019, there were just 453 cardiac arrest calls where a patient died, according to the FDNY.)

That number has been steadily increasing since March 30th, with 241 New Yorkers dying at home Sunday — more than the number of confirmed COVID-19 deaths that occurred citywide that day. On Monday night, the city reported 266 new deaths, suggesting the possibility of a 40% undercount of coronavirus-related deaths.
P.P.S. On the bright side, Hong Kong pandas Ying Ying and Le Le used their newfound privacy to make more pandas.

Monday, April 06, 2020

Day 66: Opportunities for Fresh Disasters

Boris Johnson, who seems to be on oxygen in hospital at the moment, is a spicier G. K. Chesterton so far as quotability goes:
My friends, as I have discovered myself, there are no disasters, only opportunities. And, indeed, opportunities for fresh disasters.
The world has some large number of cases that have exceeded PlagueBlog's buffer. Spain, still a strong second place to the US, is contemplating universal basic income as a response to the pandemic. Germany has crossed the 100,000 case barrier, putting it in fourth place among nations. New York State is at 123,000 cases, over a third of all 337,000 cases in the US, and looks likely to overtake third-place Italy (129,000) soon. (IHME updated its projections for the US yesterday, including state-by-state peaks.)

The Feds, in their endearing way, confiscated a shipment of 35,000 N95 masks destined for Somerset County, NJ. One, it hardly seems worth it, and two, let's hope this drives home the lesson of how important it is to field your own successful football team for end-runs around the federal government.

On the cancellation front, Tomorrowland, an electronic music festival scheduled to be held in Belgium this summer, is on the chopping block. Also Gamestop got their plastic-bag-covered hands slapped last week for operating a non-essential curbside pickup business in Boston. Hopefully they've really closed this time and won't just pop up again like a bad mall kiosk.

P.S. The Guardian reports that Boris Johnson has been moved to intensive care.

Massachusetts' testing numbers are down again today from Saturday's high of almost 6,000 tests. Today only 4,500 or so were tested, with 1337 new cases (up 11%) for a total of 13837. (Middlesex County is back in the lead.) There were 29 new deaths. Once again, it was a lack of Quest test results that kept the numbers down. PlagueBlog suspects the feds are confiscating our swab supplies now.

Sunday, April 05, 2020

Day 65: Summer is Cancelled

Today's Massachusetts numbers are suspiciously good: up only 764 new cases (7%) to 12500, with 15 new deaths. Upon closer examination, though, the drop seems to be due to a drop in tests completed (3137) to barely half of yesterday's 5838. The major Sunday vacationer was our major test provider, Quest, which completed under 1,000 tests today after having done over 3,000 on Saturday. So don't get your hopes up.

PlagueBlog is sad to report the first local cancellation of summer. Pinewoods Camp, Inc. has announced that it will remain closed all summer due in part to the difficulty of timing an opening for the camp in the current situation.

On the cat front, a tiger at the Bronx Zoo has tested positive for coronavirus, apparently due to exposure to an asymptomatic handler.
Zoo officials said Nadia, three other tigers, and three African lions have developed a dry cough, but are all expected to recover.

"Though they have experienced some decrease in appetite, the cats at the Bronx Zoo are otherwise doing well under veterinary care and are bright, alert, and interactive with their keepers," the zoo's release said.

Saturday, April 04, 2020

Day 64: Black Cats

Today in Massachusetts we had 1334 new cases (13% over yesterday), and 24 new deaths. The US has more that 311,000 total cases, and Spain has surpassed Italy to earn second place. (This is especially impressive because Spain has only three-quarters the population of Italy.) Worldwide the total is over 1,200,000 cases and 64,000 deaths.

PlagueBlog has been remiss in report on pet infections. A Belgian housecat was confirmed to be the first feline patient on March 27th. "A week after its owner, the animal presented symptoms such as diarrhea, vomiting, and difficulty in breathing." A second feline case was found Monday, March 30th in an asymptomatic domestic short-haired cat from Aberdeen, Hong Kong, sent to quarantine when its owner fell ill and tested there.

At first the only cat concern was for the poor animals catching the disease from overly affectionate humans, but a preprint by Hualan Chen reports that both cats and ferrets can spread the disease, and cats can do so with "respiratory droplets." In another preprint, Chinese scientists tested stray and domestic cats in Wuhan, and found antibodies to SARS-CoV-2 in 15% of the hundred or so animals tested after the outbreak.

On the plague ship front, the title of Germ Boat #21 goes to the Coral Princess, which managed to accumulate two dead passengers on its way into the Port of Miami today. Not unlike Germ Boat #18, the Coral Princess thought it could get away with a cruise to South America a month ago, but cut the junket short in mid-March and started searching for any old port in a storm. They managed to dock in Buenos Aires for a day to offload some lucky passengers, but they turned into a germ pumpkin at midnight on March 19th and had to set sail again, this time for Fort Lauderdale. They finally docked in Miami this morning and offloaded the sickest passengers. An unfortunate passenger delayed sickening until later this afternoon, at which time his family got the run-around for hours until they called 911.

P.S. PlagueBlog is saddened to report that the death toll from methanol poisoning in Iran has reached 300 (or, by some reports, 480), and the injured exceed 1,000 (or possibly 2,850), due to the false belief that alcohol is a cure for coronavirus, along with a fatal lack of education about potable vs. poisonous alcohols. Deep distrust in their government that initially downplayed the virus may also be a factor.

Friday, April 03, 2020

Day 63: A Tale of a Fateful Trip

NHK News reports the current numbers in Japan, which include three previously unaccounted-for deaths for Germ Boat #2, the Diamond Princess, for an official total of eleven. PlagueBlog is aware of one Australian (James Kwan of Perth, 78) who tested positive after returning home and died there; he has never been included in Japan's official plague ship death toll. Wikipedia, however, has sourced the other deaths: Two Japanese men in their 70's died on March 22nd, and one Hong Kong woman in her 60's died on March 28th.

PlagueBlog is long overdue for a full accounting of who's been cruising for a COVIDding. Lists of the plague ships have appeared in Business Insider, NTD and the Telegraph (unpaywalled version). Business Insider's list is the most complete, but Wikipedia's list is by far the best documented and ordered. (Note that multiple sailings of the same plague ship are listed separately, and there are also more boats at Wikipedia than in their main list.)
GB #ShipWI #BI #Confirmed
1World Dream2Yes
2Diamond Princess11Yes
3Anthem of the SeasNo
4MS Westerdam38No
5AIDAvitaNo
Voyager of the Seas5, 1030Yes (previous trips)
6Grand Princess62Yes
7Carnival PanoramaNo
8Regal Princess3No
9Costa Fortuna7No
10Caribbean Princess5No
11MS River Anuket/A'sara410Yes
12RV Bassac PandawYes
Ovation of the Seas1128Yes
13Ruby Princess1322Yes
14Costa Luminosa1217Yes
15Silver Shadow712Yes
16Silver Explorer813Yes
MS Braemar911Yes
Celebrity Solstice1427Yes
Costa Magica15Yes
Costa Favolosa16No
Costa Victoria17No
17Azamara Pursuit19No
18MS Zaandam1829Yes
19MS RotterdamNo
20MV Artania19Yes
(21)Coral Princess?Yes
MSC Meraviglia4Yes (previous trip)
Royal Princess6No (never sailed)
MSC Opera9Yes (previous trip)
Golden Princess14No
Norwegian Jewel15No
Pacific Princess16No
Celebrity Eclipse18No
Carnival Fascination20No
Freedom of the Seas21No
Azamara Quest23Yes (debated)
Majesty of the Seas24Possible
Norwegian Bliss25Yes
Celebrity Summit26No
MS Maasdam31No
Carnival Valor32Yes (previous trip)
(22)Greg MortimerYes
(23)USS Theodore RooseveltYes
(24)USNS MercyYes
(25)Charles de GaulleYes
(26)Oasis of the SeasYes
(27)Symphony of the SeasYes
(28)Norwegian GemYes (crew)
(29)Celebrity ApexYes (crew)
(30)MS Roald AmundsenYes
(31)m/s Paul GauguinYes (crew)
(32)SeaDream IYes (previous trip)
(33)Etchizen MaruYes (fishermen)
(34)HMS Queen ElizabethYes
(Germ Boat numbers in parentheses were assigned after this post went up.)

As you can see, there were a lot of promising candidates, but the title of Germ Boat #20 goes to the freshest face on Wikipedia's list, the MV Artania, flying a Bahaman flag and currently anchored off Western Australia. After offloading most passengers, all Aussies, and all known coronavirus patients in Perth last month, the remaining 16 passengers (including 12 who were too sick or frail to fly home from Perth) and the crew seem fated to sail all the way home. They have not set sail yet.

P.S. Massachusetts' numbers are in. We are up 1436 cases (16%), for a total of 10402 with 38 new deaths (192 total). Cases in long-term care facilities are up 94% over yesterday to 382, possibly due to the completion of testing at the Holyoke Soldiers' Home, for which the Governor reported 51 positives 160 negatives at his presser today. (Speaking of the presser, someone may have made Rupert the sign language interpreter a fan subreddit today.) After having lagged behind the city for several days, Middlesex County has pulled ahead of Suffolk with 2202 cases vs. 2183, and Essex has firmed up its lead over Norfolk County.

PlagueBlog cannot overlook the irony that, due to cerveza being declared a non-essential industry in Mexico, Grupo Modelo has shut down production of Corona beer.