COVID19 update, June 25, 2020: Greek colchicine trial; Dr. Campbell on long-term sequelae and home antibody testing

(1) It seems that steroids are not the only low-cost anti-inflammatories that reduce COVID19 aggravation and mortality. In two previous posts, back in April and again last week, I mentioned clinical trials with the ancient anti-inflammatory colchicine. 

Results from a randomized clinical trial in Greece were just published in JAMA (the Journal of the American Medical Association). The sample is small (since fortunately for them, Greece had a pretty mild COVID19 season) but there are some statistically significant results.

http://doi.org/10.1001/jamanetworkopen.2020.13136 

In this prospective, open-label, randomized clinical trial (the Greek Study in the Effects of Colchicine in COVID-19 Complications Prevention), 105 patients hospitalized with COVID-19 were randomized in a 1:1 allocation from April 3 to April 27, 2020, to either standard medical treatment or colchicine with standard medical treatment. The study took place in 16 tertiary hospitals in Greece.

Intervention  Colchicine administration (1.5-mg loading dose followed by 0.5 mg after 60 min and maintenance doses of 0.5 mg twice daily) with standard medical treatment for as long as 3 weeks.

Main Outcomes and Measures  Primary end points were (1) maximum high-sensitivity cardiac troponin level; (2) time for C-reactive protein to reach more than 3 times the upper reference limit; and (3) time to deterioration by 2 points on a 7-grade clinical status scale[*], ranging from able to resume normal activities to death.[…]

Results  A total of 105 patients were evaluated (61 [58.1%] men; median [interquartile range] age, 64 [54-76] years) with 50 (47.6%) randomized to the control group and 55 (52.4%) to the colchicine group. […] The clinical primary end point rate was 14.0% in the control group (7 of 50 patients) and 1.8% in the colchicine group (1 of 55 patients) (odds ratio, 0.11; 95% CI, 0.01-0.96; P = .02). Mean (SD) event-free survival time was 18.6 (0.83) days the in the control group vs 20.7 (0.31) in the colchicine group (log rank P = .03). Adverse events were similar in the 2 groups, except for diarrhea, which was more frequent with colchicine group than the control group (25 patients [45.5%] vs 9 patients [18.0%]; P = .003).

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This is a small-sample study, but with definitely a promising result. [Full disclosure: I’ve taken colchicine on and off for gout (its primary indication), for which it is very effective — I have had essentially no side effects from the drug.]

(2) Dr. John Campbell here discusses long-term sequelae for people who survive not-so-mild cases of COVID19.

But at 22:10, he also shows a demonstration of a home antibody testing kit.

 

[*] Elsewhere in the paper, the 7-step ordinal scale is defined as follows:

1, ambulatory, normal activities;

2, ambulatory but unable to resume normal activities;

3, hospitalized, not requiring supplemental oxygen;

4, hospitalized, requiring supplemental oxygen;

5, hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both;

6, hospitalized, requiring extracorporeal membrane oxygenation, invasive mechanical ventilation, or both;

7, death.

COVID19 update, April 21, 2020: Colchicine; more on COVID19-related pneumonia and “stealth hypoxia”; community testing in Los Angeles; Belgium as seen from Germany

(1) Via Mrs. Arbel, here is info on a clinical trial of the ancient-as-dirt drug colchicine. This has been in use since Antiquity for the treatment of gout (full disclosure: I have been taking it for a while, when a low-carb, high-protein diet intended to lose weight gave me a painful bout of this “rich man’s disease”): this clinical trial investigates whether its early administration to COVID19 patients may prevent “cytokine storm”. (More here at Physician’s Weekly) https://www.physiciansweekly.com/anti-inflammatory-drug-colchicine-on-deck-for-covid-19/

I am wondering more than ever whether the vast majority of dead from COVID19 aren’t killed by the patients’ own immune systems going amok. (This was what caused most deaths during the 1918 “Spanish” Flu: the main difference with the present epidemic — other than the causative agent which was an influenza virus then, a coronavirus now — is that in COVID19 the severe disease picture seems to be the exception rather than the rule, statistically speaking.

How rare? Consider Israel, which tests reasonably broadly and is conservative about diagnoses, albeit admittedly has a “younger” population pyramid than most Western countries. The screenshot below is from the daily report by its Ministry of Health: https://govextra.gov.il/ministry-of-health/corona/corona-virus/  

As of the time of writing, we have 13,883 verified cases (read: people testing positive for the virus): 9,072 of them in mild condition, 135 in moderate condition, just 142 in severe condition of which 113 on respirators, 181 deceased (of course, 181 too many), and 4,353 verified recoveries — defined here as previously diagnosed, now without symptoms and testing negative for the virus. (The “170” at the top of the graph are new cases added.) Moderate+severe+dead together is 4% (four percent) of the total infected. (Probably closer to 8% or 10% of symptomatic/overt cases — since anecdotally, it seems that about half of Israel’s verified “cases” [read: verified infections] are completely asymptomatic.)

(2) “masgramondou” Emailed me this one from the NYT (original link: https://www.nytimes.com/2020/04/20/opinion/coronavirus-testing-pneumonia.html?action=click&module=Opinion&pgtype=Homepage archived here http://archive.is/QSBfc) in which an emergency physician named Richard Levitan MD at Bellevue Hospital in NYC talks about “stealth hypoxia” in COVID19 patients. Unlike the usual fodder at the NYT, this is a factual report with no obvious political axe to grind. Some moneygrafs:

And here is what really surprised us: These patients did not report any sensation of breathing problems, even though their chest X-rays showed diffuse pneumonia and their oxygen was below normal. How could this be?

We are just beginning to recognize that Covid pneumonia initially causes a form of oxygen deprivation we call “silent hypoxia” — “silent” because of its insidious, hard-to-detect nature.

Pneumonia is an infection of the lungs in which the air sacs fill with fluid or pus. Normally, patients develop chest discomfort, pain with breathing and other breathing problems. But when Covid pneumonia first strikes, patients don’t feel short of breath, even as their oxygen levels fall. And by the time they do, they have alarmingly low oxygen levels and moderate-to-severe pneumonia (as seen on chest X-rays). Normal oxygen saturation for most persons at sea level is 94 percent to 100 percent; Covid pneumonia patients I saw had oxygen saturations as low as 50 percent.

[…]

A vast majority of Covid pneumonia patients I met had remarkably low oxygen saturations at triage — seemingly incompatible with life — but they were using their cellphones as we put them on monitors. Although breathing fast, they had relatively minimal apparent distress, despite dangerously low oxygen levels and terrible pneumonia on chest X-rays.

We are only just beginning to understand why this is so. The coronavirus attacks lung cells that make surfactant. This substance helps keep the air sacs in the lungs stay open between breaths and is critical to normal lung function. As the inflammation from Covid pneumonia starts, it causes the air sacs to collapse, and oxygen levels fall. Yet the lungs initially remain “compliant,” not yet stiff or heavy with fluid. This means patients can still expel carbon dioxide — and without a buildup of carbon dioxide, patients do not feel short of breath.

Patients compensate for the low oxygen in their blood by breathing faster and deeper — and this happens without their realizing it. This silent hypoxia, and the patient’s physiological response to it, causes even more inflammation and more air sacs to collapse, and the pneumonia worsens until their oxygen levels plummet. In effect, the patient is injuring their own lungs by breathing harder and harder. Twenty percent of Covid pneumonia patients then go on to a second and deadlier phase of lung injury. Fluid builds up and the lungs become stiff, carbon dioxide rises, and patients develop acute respiratory failure.

By the time patients have noticeable trouble breathing and present to the hospital with dangerously low oxygen levels, many will ultimately require a ventilator.

Silent hypoxia progressing rapidly to respiratory failure explains cases of Covid-19 patients dying suddenly after not feeling short of breath. (It appears that most Covid-19 patients experience relatively mild symptoms and get over the illness in a week or two without treatment.)

And then the best part!

There is a way we could identify more patients who have Covid pneumonia sooner and treat them more effectively — and it would not require waiting for a coronavirus test at a hospital or doctor’s office. It requires detecting silent hypoxia early through a common medical device that can be purchased without a prescription at most pharmacies: a pulse oximeter.

Pulse oximetry is no more complicated than using a thermometer. These small devices turn on with one button and are placed on a fingertip. In a few seconds, two numbers are displayed: oxygen saturation and pulse rate. Pulse oximeters are extremely reliable in detecting oxygenation problems and elevated heart rates.

Pulse oximeters helped save the lives of two emergency physicians I know, alerting them early on to the need for treatment. When they noticed their oxygen levels declining, both went to the hospital and recovered (though one waited longer and required more treatment). Detection of hypoxia, early treatment and close monitoring apparently also worked for Boris Johnson, the British prime minister.

Widespread pulse oximetry screening for Covid pneumonia — whether people check themselves on home devices or go to clinics or doctors’ offices — could provide an early warning system for the kinds of breathing problems associated with Covid pneumonia.

Read the whole thing.

(3) (via Instapundit) KTLA reports on a new community antibody study in Los Angeles County https://ktla.com/news/local-news/l-a-county-officials-to-provide-latest-update-on-coronavirus-crisis/?fbclid=IwAR3ItNdY_00D6FkDjQRn-x5rK71A2XqLg-xgvPQFSN0YfI9batMXXNA6-s0  which corroborates various earlier reports that the USA, at least, may have a very significant Dunkelziffer/“stealth infection rate”.

While Los Angeles County has reported a total of 13,816 coronavirus cases, early results from an antibody study conducted with the University of Southern California shows that hundreds of thousands more could have had COVID-19 in the past, officials announced Monday.

So far, 863 L.A. County residents have been tested between April 10 and 14 as part of the study.

The study estimates a prevalence of COVID-19 antibodies in the county to be 4.1%, with a range that could be as low as 2.8% and as high as 5.6%, when you factor in the reliability of the tests.

An estimated 221,000 adults to 442,000 adults at the high end may have been infected at some point before April 9 with COVID-19, suggesting that the number of total people in the county with a past or current infection is 28 to 55 times higher than the number of reported positive cases, Dr. Barbara Ferrer, L.A. County’s public health director said Monday.

[…]

Although the sample size was relatively small, Ferrer shared some early estimates about who was most likely to be infected:

Men were more likely than women to be infected. The estimated prevalence is 6% among men and 2% among women

7% of African Americans, 6% of whites, 4.2% of Asians and 2.5% of people who were Latinx who were tested were found to be positive for COVID-19

2.4% of people who were between the ages of 18-34 were positive

5.6% were between 35 and 54

4.3% who were 55 and older tested positive

(4) And in what is rather distressing reading, Die Welt (in German) wonders why neighboring Belgium (!) has the highest pro capita COVID19 mortality in the world — actually, the absolute numbers are larger than Germany’s, which has seven times the population of Belgium! Summarizing a few of their points:

(a) Belgium counts deaths “with” COVID19 as COVID19 deaths, in the name of “transparency”, even if the cause of death is different. Germany uses a  more restrictive definition.

(b) 50-70% of all deaths in Belgium are in homes for the elderly [about 20% of care home residents over 85 test positive in facilities where everybody was tested]. Die Welt cites a report in Belgium’s largest French-language daily, LE SOIR  Wie die Tageszeitung „Le Soir“ berichtet]  Staff went around without even face masks for weeks because of (c)

(c) there is an acute shortage of PPE, particularly masks. The emergency stockpile (from SARS days) had been destroyed pre-epidemic as it had passed the expiration date — and had not been replenished even though that could then easily have been done. (Now Belgium was forced to startup domestic production. [Becoming dependent on China is a recipe for disaster across the world.])

(d) Nevertheless, it’s not all doom and gloom. Spread in the general population has been contained, the number of cases grows more slowly, and the number of deaths has peaked and is now holding at about 300/day. But this is cold comfort, or as you say in both Dutch and German, “meager comfort”…

(e) Finally, as things are again picking up at my day job, I am grateful to the people who have started sending me article tips!