Thursday, April 16, 2020

Tunnels and Lights

An Italian bookstore, newly reopened

Treatment updates: the big guns
Convalescent serum: Since I last wrote the recruitment of recovered American covid-19 patients has proceeded apace, blood banks now vying with hospitals to find donors. The Red Cross has set up a donor website in addition to the National COVID-19 Convalescent Plasma Project one that I linked to last week. Patients with confirmed diagnoses are already donating plasma at the New York Blood Center, and they soon will be in at least another nine statesIn Italy, the Tuscan blood bank has begun sending letters to recovered covid-19 patients inviting them to donate plasma, withLombardy and Veneto soon to follow suit and Lazio, Campania, Marche and Molise the next comers.
Remdesivir: Some good preliminary news: the manufacturer has reported outcomes for the first 61 covid-19 patients given this antiviral on compassionate grounds. Most promisingly, with remdesivir only 18% of the patients on ventilators died. Compare that with the experience in New York City hospitals without remdesivir – 80% of covid-19 patients placed on ventilators died. This report is NOT a controlled trial, but its results encourage such trials to go forward.
Hydroxychloroquine: Its reputation is based on a single dubious study in France, and that study’s plausibiility slides from bad to worse. The society whose journal published it has said officially the article “Does not meet the society’s accepted standard.” And the first author, Didier Raoult, turns out to be a shady character. He was once temporarily banned from publishing, after being caught out falsifying research results, and the rest of his bibliography is nearly as dubious. In an as yet unreviewed paper, a different French group studying covid-19 patients with pneumonia has now reported hydrochloroquine to be useless. 
If you want to follow covid-19 treatment research for yourself and can handle technical language, here’s a constantly updated page.
Minor contenders touted in the media
Nitric oxide: a trial of this inhalant is now underway at the University of Alabama.
Heparin: Desperately ill patients sometimes develop Disseminated Intravascular Coagulation, widespread blood clotting, treated with blood thinners such as heparin. In a Chinese study, covid-19 patients with DIC supposedly died much less (40% vs. 64%) if they were given heparin. But this was a retrospective study, not a clinical trial, and heparin is standard therapy in any case. No magic bullet.
Ivermectin: This drug for head lice and pinworms turns out to block the growth of SARS-CoV-2 virus in test tubes and may soon be tested in human beings. Its chief promoter looks like a charlatan; I wouldn’t hold my breath.
BCG: Dubious statistics suggest that covid-19 takes less root in countries where this tuberculosis vaccine is widely used (which include China). Studies are underway to see whether BCG might give a general boost to the immune system  and help fight off covid-19 – “the equivalent of a Hail Mary pass.” 
Viagra: A pilot study is on in China. Lots of luck.
Snake oil department
Ozone: A quack treatment with no known efficacy, considered by the American Food and Drug Administration to be “a toxic gas with no known useful medical application,” being pushed as a treatment for covid-19. 
Colloidal silver: The FDA has issued warning letters to its manufacturers for fraudulently claiming effectiveness against covid-19. 
There is no evidence that any supplement or foodstuff, from zinc to elderberry to CBD to sauerkraut, can help prevent or treat covid-19.
Of the scores of research teams racing to develop one, four have already moved beyond animal testing to trials on human volunteers. But the timetable is all over the map.
-       Most experts continue to think a vaccine should be ready to roll out in autumn 2021.
-       Others are afraid it will take years.
-       The research team in Oxford, England, thinks theirs may be set for widespread use as early as this September.
-       One virologist has hinted that a vaccine could be obtained even faster if researchers overcame their moral scruples and deliberately infected volunteers with coronavirus.
Be aware that even a functioning vaccine may not eliminate the pandemic. We hope the winning entry will act like the measles vaccine, which gives permanent 97% protection after two doses. But it might instead turn out to be like the yearly flu vaccine, which only reduces infections by 50% or so. What we already know about immunity to coronaviruses is discouraging. Some coronaviruses cause the common cold, and immunity after you’ve had a case lasts only a couple of years, even though natural infection is better than vaccines at goosing the immune system.

Italy update
Italians are flexible, resourceful, and sensible. One friend writes, “The natives are observing with great dedication the lockdown and distancing rules, and – as if in tandem with the Easter season – we haven't seen so much hand washing in the Bel Paese since Pontius Pilate strode the dusty streets of Rome on his disgraced return from Judea. This shocking discipline reminds me a bit of the overnight adherence to the no-smoking regime, years ago, which no one would have predicted.” But another correspondent emphasizes the negative: neighbors having a drink together on the roof, biddies distributing olive branches door to door on Palm Sunday.
Much of the economic impact of the Italian epidemic is cushioned by generous sick pay, unemployment benefits, and universal health care without co-pays or deductibles. An emergency decree forbids layoffs, slashes rents, pays baby-sitters, etc. Self-employed workers are supposed to receive bonuses totalling $2500 over three months, supplemented by contributions from some professional societies. (My composer husband will get neither, because he receives an Italian pension – €124 ($136) a month!) But the millions who work off the books in Italy’s vast underground economy aren’t eligible for unemployment benefits or bonus payments, so the shutdown of the economy will cause real suffering. Two weeks ago a few people rolled their full shopping carts up to the checkout line in a Sicilian supermarket and refused to pay, and more serious unrest was widely anticipated. It never materialized.

Italy is shaking off covid-19, with the number of people in intensive care units now decreasing steadily:

New cases continue to be diagnosed, however, and there are still 500+ deaths every day, mostly in the ravaged North – likely new infections inside nursing homes, within patients’ families, and in factories that exploit legal loopholes to keep their workers crammed in. 
One Rome high-rise inhabited by 600 Eritrean squatters houses 18 definite and 33 suspected cases of covid-19. The authorities, instead of doing mass testing and moving people out as necessary to enable social distancing, have sent the army to keep the whole building under quarantine. They did, however, distribute milk, pasta, tomatoes…and chocolate Easter eggs.
Some Italian cities are now offering “drive in” covid-19 testing for people with relatively mild symptoms. In Rome, you start the process with a phone call to 06 3306.2738, 06 3306.4748, 06 3306.2847, or 06 3306.2707.
As of April 15th, 121 Italian physicians have died of covid-19.

Italy has taken initial baby steps toward reopening the economy, allowing a bizarre list of productive activities: dry cleaners, forestry, computer factories, and stores selling books, stationery, or baby clothes. But several regions where the fires of covid-19 are still burning, such as Lombardy, have declined the invitation.
Donald Trump and his buddies are chafing at the bit to do the same and more. The militia sorts are openly defying stay-at-home orders, some ministers held in-person Easter services… Is it time yet? And if and when, how?
In the United States it’s clearly too early, whether your chosen authority is Anthony Fauci or The Onion. Lacking consistent federal guidance, our shutdowns have been patchwork, in dribs and drabs. Every state experiences a different epidemic according to whether and how much it’s closed up shop, how well people are complying, and who is being tested. While California enters the downslope of the first-wave curve, New York still loses more than 700 people to covid-19 every day, and the death rate rises sharply in New Jersey, Georgia, Connecticut, and Michigan. How could guidelines be countrywide? I won’t go into details, just state a few principles:
First of all, when the number of active cases is low enough, we can finally do as we should have when the first cases appeared: test all suspected cases, isolate those who test positive, track down and test everybody who’s had contact with them, and quarantine the positives among those contacts. Germany was the only Western country to do this, under the exemplary leadership of Angela Merkel, and they have had 3800 deaths as compared with more than 13,000 in other European countries with comparable populations. 
Second, we need explicit criteria for determining restrictions. The Imperial College study that got social distancing going in both the US and the UK famously modelled the benefits of various mitigation strategies. But it also, less famously, modelled an ideal strategy over time, using the number of covid-19 patients in intensive care units as the indicator of when restrictions should stop and start:
A conservative model of an on-again off-again coronavirus lockdown

Based on an “on” trigger for the United Kingdom of 100 ICU cases in a week and an “off” trigger of 50 cases, and assuming testing, isolation, and quarantining, they calculated that while we wait for a vaccine, social distancing could be lifted a third of the time.
Now that we’ve gotten used to social distancing, though, I think we can accept some degree of it as the norm for the duration. With moderate social distancing, we should be able to lead a relatively normal life most of the time, as long as criteria are established and rigorously followed. Forget about packed baseball stadiums and sold-out Broadway shows, but there could be picnics, restaurants with proper table spacing, sports events and movie theatres with six feet between spectators, church services, dinner parties… Dinner parties!!! I can imagine drive-in stands where people can get swabbed for active infection, obtain their results in five minutes, and if negative be given a certificate good for a week’s freedom of movement. 
In addition to PCR swab tests for active disease, blood testing for antibodies against the coronavirus should play an important role. People with antibodies will probably be shown to be immune, at least temporarily, so they could work, socialize, and attend events with impunity. Some are hoping that mass blood testing will show that enough people are already immune to protect the rest by “herd immunity.” This is unlikely, since protection only seems to kick in when more than 90% of the population are immune, but we can hope.

Privilege and covid-19
Coronavirus is not an equal opportunity bug, with poor and minority populations suffering the most. This has been shown on a neighborhood level in New York, on a county level in Michigan, and on a statewide level both there – African-Americans make up 14% of the population but 40 percent of the dead – and in Louisiana, where the corresponding percentages are 33% and 70%. Many of the poorest states also have governors who resist stay-at-home orders, including South Dakota, where at least 350 workers at a single meat processing plant – largely immigrantsspeaking more than 80 languages – have tested positive for the coronavirus. 
As Charles Blow points out, African-Americans and impoverished populations are more likely to have underlying conditions and limited access to health care, more likely to be doing “essential” manual or service jobs without the luxury of working or sheltering at home, and more likely to share crowded living quarters; social conditions are at least as important a risk factor for severe covid-19 infection as medical conditions. 
The underprivileged, who rarely have adequate unemployment compensation, sick pay, or healthcare insurance, will also suffer more from the economic effects of a shutdown. Their children need those free school lunches, and often can’t attend virtual classes for lack of internet access. 
But the greatest tragedy due to socioeconomic discrepancies may be at the world level. When covid-19 hits the global South in force, the impact could be devastating. In the developed world the novel coronavirus seems to be more or less as contagious and deadly as the influenza virus that a century ago infected one-third of the people on the planet and killed 20 to 50 million. That pandemic hit at a moment when populations had been weakened by wartime suffering, and when there were no intensive care units, no ventilators, no oxygen therapy, no antivirals, not even antibiotics. 
This suggests that covid-19 is intrinsically much deadlier than the 1918-19 flu. In areas of Africa, South America, and Asia with few modern hospitals and high rates of chronic disease and malnourishment, it may well cause a holocaust.Statistics from many of those countries are unreliable, but the upswing may be starting now – India, despite fighting back early and hard, went from 1000 cases on March 29th to 12,000 on April 14th
For diseases with no pharmacological cure, such as covid-19 and Ebola, supportive care in modern ICUs is crucial. The death rate for Ebola was 74% in Africa, 18.5% in the US and Europe.
As the New York Times points out in an editorial entitled “The Global Coronavirus Crisis Is Poised to Get Much, Much Worse,” South Sudan – population 12 million – possesses exactly three ventilators. Already local quacks are touting useless nostrums: Benin’s Valentin Agon, whose apivirine has “successfully treated dozens of Covid-19 patients,” South Africa’s Kim Joachim Mvuselelo Cools, who peddles Magic of the Healers Juice. (American hucksters plug the likes of Superblue toothpaste.) While the economic devastation of anti-pandemic shutdowns in impoverished nations could kill more people than the virus.

Cutting through the crap
The Los Angeles Times was the first to circulate the claim that the novel coronavirus may have been around in California as early as the fall of 2019. There is no evidence this is true.
It has also been suggested that the way the coronavirus starves the body of oxygen is not by attacking the lungs but by binding directly to hemoblogin in the blood. This is, as Rachel Maddow might say, bullpucky.
I wouldn’t have thought anyone doubted the dangers of the pandemic any more, but wild theories still circulate that deaths from other causes are being falsely attributed to the coronavirus, it’s more common to die “with” the virus than “from” the virus, and so forth.
The respected journalist Fareed Zakaria has spread a version of this on CNN and in the Washington Post, suggesting that the reason fewer people than expected have died so far in the US is because the virus is not really very dangerous. His source is the contrarian epidemiologist Dr. John Ioannidis, who has written, and I quote, “If we had not known about a new virus out there, and had not checked individuals with PCR tests, the number of total deaths due to ‘influenza-like illness’ would not seem unusual this year.” 
This is utter nonsense. Here are the numbers of total deaths in northern Italy as compared with past years – not from “influenza-like illness” but from all causes. More than twice as many people than expected died, overall, during the pandemic.
Death rates from all causes in selected northern Italian cities: 2020 vs. predicted

It has been debated whether American covid-19 deaths have been overcounted or undercounted. But in New York Cityhundreds, perhaps thousands, of coronavirus victims who died at home alone didn’t make it into the official statistics, with a true death toll perhaps 70% higher than official reports. There’s no need to quibble over details – just look at this graph of total deaths in New York City since the year 2000. 

A horrendous spike, 2730 more deaths than expected, reflects the September 2001 terrorist attack. And an even more horrendous spike, 5330 more than expected, occurs between March 4th and April 4th of this year, with covid-19 the only possible reason. 

Zakaria and Ioannidis are right that many people infected with the novel coronavirus have few or no symptoms, and that the mortality rate of the coronavirus is therefore lower than it appears from diagnosed cases. So what? The reason covid-19 failed to decimate the US population is not that it is mild, but that prescient local politicians were relatively quick to enact stay-home orders, following the effective Italian model.
Forgive me for saying that those prescient politicians do not include Governor Andrew Cuomo of New York, despite his excellent leadership later on. My husband and I had been supposed to go to New York on March 13th, but we cancelled at the last minute, figuring the city would be too dangerous: once the coronavirus hit it would spread like wildfire, since the city’s iconic subway system would be a petri dish. Friends wrote that they tried to pick less crowded cars, hold the poles in the crook of their elbow, etc., but the virus seemed destined to win, as in fact it did, killing at least 10,899 people. 
Then, on March 16th, seven counties in and around San Francisco made the radical move of telling people to shelter in place. A lightbulb should have gone on instantly inside the head of Governor Cuomo and Mayor De Blasio, but it didn’t. If New York had issued a stay-at-home order on March 17th instead of waiting until March 22rd, hundreds if not thousands of lives would have been saved.

Personal notes from my gilded cage in Berkeley
You know how when you have laryngitis you hear a singer and can’t fathom how they’re doing it? Or when you have a sprained ankle and marvel at a passing jogger? I might have thought watching movies would be like that, night after stay-at-home night. But no, those scenes of crowded dance floors and hot kisses look perfectly normal. What did touch that nerve of unreality was reading an oldish New Yorker, writers all obsessed with unthinkables – art openings, restaurants, political rallies, trips to Europe – blessedly unaware that the world was about to, or could ever, grind to a halt.
A light now flickers at the end of my own refugee tunnel. Alitalia has kept up daily nonstop flights from New York to Rome, but they are nightmares. I’ve heard of people being abandoned in transit at JFK for days on end. I’ve read about repatriation flights taking off from New York and Madrid with every seat occupied. Other planes sat on runways for hours with hundreds of passengers packed cheek to jowl. Following scandalized interrogations in the Italian Parliament, Alitalia now claims it will start inflight social distancing… but even better, they’re promising a brand new nonstop flight from San Francisco to Rome. It will be inaugurated on June 1st, and my husband and I will be on it. 


  1. Thank you for your doctor's point of view of Italy's COVID-19 crisis. This is much better than: Why this pandemic is an indictment of socialized medicine by Marc A. Thiessen, Washington Post.
    This guy seems to chugged down the Trump Koolaid.

    1. Omigod, thanks so much for turning me on to this article by Marc Thiessen. Unbelievable crap.

  2. I can't thank you enough, Susan, for your constant postings and this overview. It obviously takes an enormous amount of time and effort to research all this and to write it up in a coherent and organized fashion. You have become my go to source for keeping abreast of covid developments. Bravissima!!

    1. Thanks so much! Yes, it takes a lot of time and effort, but I'd say that's all that's keeping me from going bonkers in this crazy time.


  3. Corriere della Sera

    Coronavirus, il segreto del Covid-19 «Il virus colpisce anche il cuore»
    Vaia (Spallanzani) spiega: «Le vittime muoiono per scompenso cardiorespiratorio»
    di Clarida Salvatori
    Coronavirus, il segreto del Covid-19 «Il virus colpisce anche il cuore»shadow

    «Da quello che abbiamo potuto riscontrare finora dagli esami autoptici condotti allo Spallanzani, le vittime di Covid-19 muoiono per scompenso cardiorespiratorio». A parlare dello studio condotto in collaborazione con Franca Del Nonno, responsabile di Anatomia patologica, e Nicola Petrosillo, direttore del Dipartimento clinico, è Francesco Vaia, direttore sanitario dell’Istituto Spallanzani, specializzato in malattie infettive. «A loro va il mio ringraziamento, anche per l’impegno quotidiano che stanno mettendo in questa emergenza».
    Quindi, secondo quanto è stato possibile osservare dalle autopsie, si muore per una grave coinvolgimento dei polmoni e del cuore?
    «Esatto. Tutti i pazienti presentano una polmonite bilaterale interstiziale associata ad una vasculite, ovvero una forte infiammazione dei vasi sanguigni. Inoltre sia il cuore che i polmoni vanno in fibrosi. Che vuol dire che si ispessiscono e si affaticano fino a che non reggono più».
    Ed è per questo che molti parlano dell’utilità di una terapia con l’eparina?
    Per quanto riguarda invece gli altri organi? Vengono intaccati in qualche modo dal virus ?
    «Finora non abbiamo mai trovato niente nell’encefalo. E altri organi, come reni o fegato, spesso erano già minati da patologie oncologiche».
    Quante autopsie sono state effettuate allo Spallanzani su pazienti affetti da coronavirus?
    «A oggi diciotto. Va considerato però che l’esame autoptico non si effettua su tutti i pazienti deceduti. Si fanno su indicazione della direzione sanitaria, dell’autorità giudiziaria oppure della famiglia. L’età media dei malati defunti sottoposti ad autopsia è di oltre 70 anni e, ad eccezione di due casi che sono il 50enne trasferito dal Policlinico Casilino e il 34enne di Cave che era un soggetto sano, tutti soffrivano di gravi patologie pregresse».
    È cambiato il vostro approccio terapeutico dall’inizio dell’epidemia a oggi?
    «Assolutamente sì. Ma voglio innanzitutto ricordare una cosa: che questo è un virus che stiamo studiando adesso e che la cosa importante è che le persone guariscano. Comunque all’inizio, con i primi pazienti che ci siamo trovati a trattare, ovvero i due turisti cinesi di Wuhan, abbiamo usato degli antivirali combinati e l’azitromicina che è un antibiotico, ma lo abbiamo utilizzato per la sua azione antinfiammatoria. Su chi è ricoverato in terapia intensiva è invece molto efficace il Remdesivir».
    E successivamente?
    «Abbiamo notato che la forte infiammazione che questo virus scatena produce interferone e interleuchina, che attivano i sistemi coagulativi. Per questo abbiamo introdotto dei farmaci che sono ora alla sperimentazione dell’Aifa: il Tocilizumab e Sarilumab. Sono medicinali anti-artrite».
    E come è andata?
    «I primi dati empirici sono favorevoli, ma serve approfondire».
    Ora state procedendo in questo modo?
    «Sui pazienti ricoverati procediamo anche così. La vera novità è quello che si sta facendo sul territorio, ovvero sui pazienti positivi in isolamento domiciliare. E su cui la direzione dello Spallanzani sta portando avanti uno studio. Stiamo cioé sperimentando l’uso di Clorochina e Idrossiclorochina, che sono antivirali e al tempo stesso antinfiammatori. Uno studio che finora sembra dare risultati promettenti. Ma che va monitorato perché sembra che possa dare effetti collaterali».