Wednesday, April 8, 2020

Drug Dreams, Italian Realities

Piazza Navona reverting to wilderness
Treatment Update 
I was going to put this section at the end, but so much has happened in the week since my last post that I will lead with it instead.
Convalescent serum – exciting news
Several preliminary steps have been whizzed through. A blood test capable of telling who’s had covid-19 has gone in a week from a hope to a reality. An antibody-rich preparation from recovered patients’ blood has proved effective in both China and northern Italy. The Food and Drug Administration has classified covid-19 convalescent serum as an investigational drug, allowing American hospitals to start administering it. Now not only are large studiesunderway, but the National COVID-19 Convalescent Plasma Project has set up a dedicated website to recruit potential donors. If you are in the United States and think you have had covid-19, even if you were never tested, or if you know someone in that situation, please go to the NCCPP website to get more information, and sign up. One blood donation treats one sick patient – you might save a life!
Antiviral drugs
Remdesivir: This new antiviral, widely available on a compassionate basis, might see the first results of clinical studies as early as next week from China and at the end of April from the United Kingdom. Fingers crossed. The patent-holder, Gilead Science, tried to get its monopoly extended by having remdesivir declared an “orphan drug,” causing such an outcry that it had to back off.
Favipiravir (Avigan): the report of one of the two published trials, which was in any case seriously flawed, has been abruptly withdrawn by the researchers. We’ll see what the better ongoing studies will show.
Lopinavir/ritonavir (Kaletra): A small trial had found no benefit, and now a second, larger one has proved just as disappointing. This medication is probably a dead end.
Leronlimab: An experimental drug with antiviral as well as antiinflammatory properties, which very recently began testing. It’s far too early to say much. 
Hydroxychloroquine (Plaquenil)
Trump went on Saturday from “It will be wonderful” to “I really think they should take it,” and two more reports now claim Plaquenil is good for treating covid-19. HOWEVER. One is a repeat performance from the French researchers whose study I panned last week, and the new one is methodologically even worse. The other, a Chinese study pre-published by its authors without going through any kind of review, is just as fishy: poorly written, peculiar methods, and unclear results. My doubts remain unallayed.
Between the strange new Plaquenil study, the older ones whose great results evaporated when the results were actually examined, and the mysterious favipiravir story, I have to admit I’m getting a bit skeptical of any covid-19 research that comes out of China.
A possible covid-19 vaccine coming out of Pittsburgh has now been tested in mice, and the mice produced antibodies. This is good. Volunteers in China, the United Kingdom, and Seattle have already received doses of three other vaccines, so we’ll soon know whether people will produce antibodies too. Even if they do, though, it doesn’t shorten the 12-18 month timeline before a useful vaccine may be available. Two weeks ago there were already 44candidate vaccines, being studied in 500 centers spread across a dozen countries.

Covid-19 in Italy: Facts and Flimflam
Origin stories
The wildfire spread of the pandemic in northern Italy is still not fully understood. One factor was likely the return of many Chinese immigrants from New Year’s celebrations in Wuhan. Not everybody, especially outside Italy, realizes that the virus’s choice of its first known victim was also particularly clever. Mattia (who was on a respirator for weeks but survived) was a previously-healthy man of 38, with absolutely no Chinese connections, who in the week before he fell ill had gone to work every day in a large building, run two races, played soccer, and partied at least three evenings. He went several times to his local Emergency Room, exposing myriad people, before he was admitted with pneumonia to a non-isolation ward, and spent several more days infecting patients and staff before a brilliant anesthesiologist broke protocol and tested him for the novel coronavirus.
The death rate “scandal”
China is known to have vastly underreported its covid-19 death toll. Ten days ago it came out in the Italian press, then the international press, that Italy did too. In hard-hit Bergamo and Brescia, in particular, a suspiciously low number of deaths were being attributed to covid-19 in proportion to the increase in overall death rate. Many deaths were being classified as influenza or pneumonia, without coronavirus testing. 
The reality is neither scandalous nor nefarious. True, at the peak of the epidemic, the health system was so overwhelmed and test kits so lacking that many elderly people with probable covid-19 were left at home to die undiagnosed. But just a week after Italy’s lockdown the epidemic began improving continuously and steadily, suggesting that underreporting of deaths likely happened only in limited areas and for limited periods without greatly impacting the overall statistics. Daily deaths are now down by at least a third, and every region of Italy now has ICU beds to spare – partly because the absolute number of very sick covid-19 patients has dropped, partly because the country succeeded in expanding those beds from 5324 to 9284. 
Now the New York Times writes that the same underreporting is happening in the United States: “Hospital officials, public health experts and medical examiners say that official tallies of Americans said to have died in the pandemic do not capture the overall number of virus-related deaths, leaving the public with a limited understanding of the outbreak’s true toll.” So it wasn’t the Italians being Italians, after all.
The sickest patients
I have been tracking the number of covid-19 patients in intensive care units at my Facebook page as a good way of following the pandemic, and the curves are looking great:

Unfortunately, no comparable figures are available for the United States. Diagnosed cases and death toll, yes, but not how many patients are hospitalized, in ICUs, or in home isolation – all data published daily in Italy. Yet another reason to be grateful to the Italian National Health Service. 
All I can tell from meagre data is that there are now at least 7200 covid-19 patients in ICUs in New York, California, and Louisiana. Since those three states have accounted for 51% of the deaths in the US, we can guess the total number of covid-19 patients in American ICUs at about 14,400 – more times as many as in Italy.
When I write about the pandemic I generally ignore data on diagnosed covid-19 cases, because they are so dependent on how many tests are being done, and on whom. But I’ll break that rule now for Italy, because for four weeks the criteria for coronavirus testing have been pretty stable: all people sick enough to need hospitalization, and only those people, are tested. So we can probably trust the steady drop during that period in the daily rate of increase in total Italian cases, from 23% on March 11th to 2% today.
Terrible rationing choices had to be made in the worst-hit hospitals in northern Italy at the peak of the epidemic. Right-wing American media outlets have been spinning them as “socialized medicine” running “death panels.” Ignorant, dangerous nonsense, as even those know-nothings will realize if and when American hospitals find themselves similarly overwhelmed.
Doctor patients
In Italy an outsized proportion of diagnosed covid-19 cases have been in health care workers – 11,252 cases as of Friday, 8% of the total. As of today 94 Italian physicians have died, most of them over 65 years old, many retirees who heroicially volunteered to man the front line; here is a heartbreaking if incomplete list of names, cities, specialties, and birthdates. Interestingly, the Spallanzani Hospital in Rome, which specializes in infectious diseases and has treated vast numbers of covid-19 patients, has reportedly had no cases among its own doctors and nurses. And in the United States, where the death toll is now up to three-quarters of the Italian total, only one physician has died from the disease. Why so much variation? In part, it’s due to varying degrees of training in the care of contagious patients. But in part it is surely related to the horrific conditions in northern Italy at the height of the epidemic. In Lombardy, where the vast majority of those doctors died, staff in some ICUs were intubating seven covid-19 patients a day and working 14-hour shifts for weeks on end, while family physicians with no protective equipment went door to door signing death certificates for patients who died at home. 
Life under lockdown
In Italy, ads for malpractice lawyers are burgeoning in the middle of the covid-19 epidemic. In the United States, Republicans are using the epidemic as an excuse for reducing access to abortions. To each country its con.
My Italian friends tell me the famous evening balcony songfests have mostly petered out . But it’s spring, and everybody with a personal or rooftop terrace is hanging out there – one friend wrote she’ll be  “walking, reading, eating a sandwich among the sheets hung out to dry – it’s like being in a movie by Scola.” 
Cuba sent 52 doctors and nurses to help out in the Northern Italian city of Cremona. The right-wing regional government welcomed them with open arms.
Pallets of medical supplies donated by the Chinese consumer electronics company Xiaomi arrived in Italy bearing labels that quoted the Roman stoic philosopher Seneca: “We are waves of the same sea, leaves of the same tree, flowers of the same garden.”
Yesterday a guy yelled at me in a California supermarket for not wearing a mask: “It’s the law!” (Actually it’s not, at least not yet.) That’s no surprise in Berkeley but it is in Italy where, a friend says, “Everybody’s turned into carabinieri.”
Carabinieri maybe, but generous ones. Signs are popping up all around Italy, on tables or baskets laden with pasta, milk, tomato sauce, olive oil, crackers…, labelled with variations on, “Chi ha metta, chi non ha prenda,” “If you have, contribute. If you don’t have, take.”

Fake news

I think I’ll end with a romp through the nonsense about covid-19 that has been flying around Italian social media. Some is international:
-       The coronavirus was created in a Wuhan laboratory by NATO to help elect Trump
-       The coronavirus was created in a Wuhan laboratory by China as a bioweapon
-       500 lions are roaming the streets of Moscow to keep people indoors
-       Swarms of helicopters fly over cities at night spraying disinfectant
-       Eat garlic, take vitamina C, and drink plenty of water and you’ll be immune
And some is home-grown:
-       The coronavirus was created by the Italian government, to save money by killing off old folks
-       The coronavirus was created by Bill Gates, so he could make billions off a vaccine
-       People living in Rome but officially resident elsewhere are to be expelled
-       Public servants earning over $60,000/year are to have their salaries slashed to $10,000
-       Pensions are to be cut by 50%

-       Only Italians have had covid-19, immigrants are immune


  1. Thanks for the update! Always like to hear your professional point of view, Dr. Levenstein. There are rays of light ahead! Be well!

    1. Thanks to you, Luke! (Luke from Rome?) Indeed there's glimmers of light at the end of the Italian tunnel, but I weep for my home town, New York, which is being laid low by its subway system.

  2. Great article Susan!!!! Enjoy California

    1. thank you my dear, and stay safe. We're so lucky that our place to be stranded happened to be Berkeley!

  3. Dear Dr.Levenstein, thanks for the update which is more readable than official sites about COVID-19 clinical trials.

    If you happen yo have interest and time to take a look at an augmented hypothesis of COVID-19 and arginine-NO-pathway, please click my name above.

    I shall tell Finnish newspapers about Your superior website, so that also Finnish people can start to see some light ahead. Stay safe.

    1. Dear Dr. Pellinen, thank you for the kind words about my blog. I know there are trials underway testing inhaled nitric oxide as a treatment for covid-19. Are you suggesting that trials of breathing techniques and diet also be performed?

    2. Thank You for Your reply. First I have to emphasize that I am a non-specialist without medical education still thinking that those clinical trials might be useful in order to increase resistance against COVID-19 in the near future - especially among the risk groups and within the medical staff.

      My friends with medical background have told me that it is not easy to get allowance for such clinical trials, but I anyhow with crossed fingers go on trying to find institutes and scientists all around the world who might be interested in implementing those tests asap.

      By the way nitrite is produced also in the salivary glands so maybe chewing gum will rescue our planet :)

  4. Excellent. I will be very interested in your adventure to get back. I need to return to Oregon at some point, but find the logistics daunting, and the thought of close quarters in a plane terrifying. I am glad you at least live in Rome, so the flight will get you home.

    1. If Alitalia is starting a new nonstop between San Francisco and Rome on June 1st - as you'll see from my latest blog post, my husband and I will be on it - maybe they'll be restarting other flights too. And they swore to me over the phone that they now for the first time have started putting space between passengers on the plane.

  5. Thank you for another interesting article and helpful insights. Did you consider commenting on the role of WHO? Would love to hear your thoughts! Best, Peggy Nelson

    1. I haven't gone deeply into the WHO question, just enough to feel sure the only reason the Orange Wonder is harping on it is to distract from his own failings. I think China has behaved pretty badly, between covering up at the onset, probably underreporting covid-19 deaths by an order of magnitude or more, and publishing and self-publishing ("pre-print") useless/dangerous/misleading research reports. But WHO has been if anything less gullible than the rest of us. I think this article has it pretty right:

    2. Kristof is always sensible ... good article. Thank you.

    3. To tell the truth I've always found him a bit goody-goody. But he's smart, and his heart is definitely in the right place.

  6. Susan, You are one helluva good writer/reporter.