Vol. 232 May 1, 2020 SARS-CoV-2 is not only NOVEL; It Is WEIRD

May 1, 2020

A few not-so fun facts about the strange behavior of COVID-19 (the disease) caused by SARS-CoV-2 (the virus).

COVID-19 is proving to be so unpredictable with so many variations that it really is weird. Most other coronaviruses merely cause a mild cold. This one can be lethal.

It’s deadliness is presumed to be from a “cytokine storm”, an explosive immune response to the virus within the infected person. This “hyper immune response” causes massive vascular damage in the lungs (and now kidneys and brain and toes.), BUT the people most vulnerable to the virus are those with suppression of their immune system (the elderly, people on chemotherapy, people taking high doses of steroids). You would expect that if your immune system was suppressed you would be less likely to have a “cytokine storm”.

SARS-CoV-2 causes major damage to essential organs, but it can also cause isolated loss of smell and taste, gastro-intestinal upset, headache, aches and pains, and, most mysteriously, just purple bruises on the toes of young adult males.

It is more likely to  kill the elderly and those with chronic diseases like diabetes, high blood pressure, and autoimmune diseases, but it can kill healthy 21 year olds with no other disease. There is some evidence that the amount or “dose” of the virus one receives is the cause of this variability. Young, healthy health care workers caring for Covid-19 patients in ICUs have higher rates of serious illness presumably due to the large amount of virus shed by their patients to which the workers are exposed.

It is highly contagious because one infected person can infect 2 or 3 other people before they have any symptoms. The SARS and MERS epidemics, the two previous lethal coronaviruses we experienced, were not so contagious. Both were spread by people who already knew they were sick, so it was possible to identify infected people, isolate them, and take containment steps. Also SARS and MERS  killed their hosts (patients) so quickly that the spread of the infection to others was much less. In truth, why SARS and MERS disappeared before becoming a wider spread epidemic is not really known. (Maybe that’s where Trump got the idea of “a miracle” saving all of us from economic ruin.)

The higher death rate of infection in blacks and Hispanics has been explained by 1) assumed ethnic/racial differences, 2) the close living of tightly packed urban areas, and now 3) the greater exposure to air pollution from increased tiny particles (PM 2.5 – 2.5 millimeters in size) more prevalent in city air. Maybe all three?

Men are much more likely to die from the virus than women. Studies are now under way  to test whether female hormone administration might protect infected males. We know that women are hardier than men in many diseases, and that it may be genetic rather than hormonal, but who knows?

Originally it was thought to skip children, but recent data from China shows that it can infect and cause serious illness in children, including infants. The virus apparently does not cause infant infection in utereo,  but it is unclear whether infant infection occurs during the birth process or later by contact with the infected mother.

Rational, specific recommendations to meet a pandemic in the U.S. were developed in detail by a 2005 Pandemic Task Force  started by President George Bush after he read an account of the 1918 influenza epidemic while on vacation. It was disbanded by Trump in a cost cutting move, and its report was ignored.

Pharmaceutical companies don’t like to invest in developing vaccines. It is very expensive, and they make little or no profit. Vaccines are administered once or maybe twice in a lifetime. Big Pharma makes more money out of treating chronic diseases like diabetes, heart disease, and cancer because those patients are on medications for a long time (like the rest of their lives). Even the development of antibiotics is low profit because patients only take them for 7-10 days, and they’re cured. 

We know that three medications in combination suppresses HIV (the “AIDS cocktail”) . That treatment changed AIDS from an acute, lethal disease to a chronic, livable condition. Likewise, it may take several different medications in combination to suppress this virus.

Very rich capitalists (Bill and Melinda Gates) in the absence of  governmental funding have given millions of dollars to support vaccine and medication development for the use of the world-wide population. (“Taking money from the rich to benefit the poor” sounds like Socialism doesn’t it?) Bill Gates sounded a pandemic warning as long ago as 2015, and as recently as this week.(1)

SARS-CoV-2 infection may or may not provide protection from reinfection. Most viruses, like measles, can infect you only once because the infection causes you to produce protective antibodies that persist for years. Unfortunately other coronaviruses studied have shown that their antibodies persist only for a few months, certainly not for over a year. This obviously has implications for administration frequency of any soon-to-be-developed vaccine. 

We don’t know if SARS-CoV-2 will mutate like the flu virus does. If it does, then vaccination frequency will be like that for the flu: every year to protect against our the best guess of the strain that will appear that year.

Scientists are suspicious that this virus may become “seasonal” like influenza, despite it’s appearance world-wide in very different climates. It flourished in our winter and Australia’s summer, in our cold, wet  Northeast and in sunny, dry California.

With the current state of knowledge about this virus it seems to me that we all are enrolled in a giant clinical study while  awaiting the development of a vaccine and effective treatment. We are even dividing ourselves into “experimental groups” like Oklahoma, Iowa, and Florida that are lifting social restrictions and “control groups” like New York and Massachusetts that are not. Unlike the usual clinical study no one asked for our consent. It is just happening.

Clinical studies are very expensive for a variety of good reasons.  It is very clear that this one, though unintentional, is costing all of us a great deal. Let’s hope that some results come soon.

References:
1. New England Journal of Medicine 382;18 April 30, 2020


Vol. 231 April 15, 2020 After The Pandemic – Back To The Future??

April 15, 2020

 

“The transmission of SARS-CoV-2 could resemble
that of pandemic influenza by circulating seasonally
after causing an initial global wave of infection.”

 

 

A recent mathematical simulation study from the Harvard Chan School of Public Health suggests that our current pandemic could follow the path of the 1918 flu pandemic, i.e. recurrent surges of infections after quarantine measures are relaxed.

FACT: SARS-CoV-2 was, and is, NOT containable. Each infected person transmits the virus to 3 other people on average. Most people infected with this virus will have mild cold-like or flu-like symptoms. In fact, two other known coronaviruses are the second most frequent cause of colds. Unfortunately this coronavirus of SARS-CoV-2 can cause severe illness and even death in some per cent of the infected.

FACT: “Flattening the curve” through social distancing and isolation does not decrease the number of infected people. It’s sole purpose is to change the timeline of illness to reduce the peak demand for services for the severely ill (estimated 3% hospitalized). It is hoped that spreading that demand over time for ICU services (estimated about 1%) will reduce the number of deaths due to “lack of available resources”.

FACT: There are really only two ways to stop an pandemic, a vaccine or herd immunity. Immunity develops when individuals get infected, respond by making antibodies, get better, and end up protected from getting the illness again. Herd immunity exists when so many people have developed antibody protection that the few people who don’t have such immunity are surrounded by others who cannot have the disease again, and so can not transmit it to them. (There is a third way an epidemic stops, of course, where most people die before they can pass it on, like Ebola, but this virus is not like that.)

You have heard about herd immunity for children unvaccinated against measles (another very highly contagious virus) when they are surrounded by children who have been vaccinated against measles. Herd immunity works by lowering the risk of anyone being exposed to a person with the infection. I can remember the “last of the chicken pox parties”, another method to expedite herd immunity in a timely fashion, in my old neighborhood in the 80’s.(The chicken pox vaccine became available in 1984). An epidemiological term for herd immunity may be more intuitive, though it sounds a whole lot colder; “depletion of susceptible individuals.” The estimated herd immunity threshold for measles is 95% of the population vaccinated. The ideal is often stated as 98% vaccinated against measles.

SPECULATION: A team of scientists from Harvard using mathematical model simulations have diagramed how herd immunity might develop for SARS-CoV-2 depending on different durations of social distancing while we wait the 12-18 months necessary for vaccine development and testing. Their study of other coronaviruses (the common cold ones) indicates that a herd immunity threshold of 60% would reverse the epidemic,  BUT that different durations of social distancing could result in a HIGHER number of total cases.

I, as a pediatrician, don’t do math very well, so I’ll let the conclusions of their mathematical model simulations speak for themselves. These estimates assume rigorous social distancing and that about 80% of us will eventually be infected. 

No social distancing – 60% herd immunity reached in October, no peak delay, no “flattening of the curve”.

4 weeks of social distancing (to mid May) – peak is delayed, 60% herd immunity threshold is reached in October, total number of cases are 10% higher than “no social distancing”.

8 weeks of social distancing (to mid June) – peak is delayed, 60% herd immunity is reached in November with 15% higher number of total cases than “no social distancing”.

12 weeks of social isolation (to mid July) – markedly reduced new cases during the summer, 60% herd immunity in January,  and 20% higher number of total cases than “no social distancing”.

20 weeks of social isolation (to late August) – markedly reduced new cases through November, 60% herd immunity in February, and 20% higher number total of cases than “no social distancing.” (1)

The mathematical model predictions represent infections only, not amount of severe illness or death rates.

I know just enough mathematics to appreciate that there are lots of assumptions incorporated into mathematical modeling, just like CFO reports to Boards of Trustees, you know , as in “smoke and mirrors”, but these predictions are sobering.  The researchers suggest that periodic, intermittent relaxation of social distancing might give the best results in the long run, i.e. allow and deal with recurrent surges of infections from relaxation of restrictions until most of the population becomes immune.

“Intermittent social distancing might maintain critical care demand within current thresholds, but widespread surveillance will be required to time the distancing measures correctly and avoid overshooting critical care capacity.”

Thankfully for us mathematically impaired the study stated some conclusions in English :

SARS-CoV-2 can proliferate at any time of year.

The duration of immunity to SARS-CoV-2 is not known. If immunity to SARS-CoV-2 is not permanent, it will likely enter into regular circulation.

High seasonal variation in transmission leads to smaller peak incidence during the initial pandemic wave but larger recurrent wintertime outbreaks.

New therapeutics, vaccines, or other interventions such as aggressive contact tracing and quarantine – impractical now in many places but more practical once case numbers have been reduced and testing scaled up – could alleviate the need for stringent social distancing to maintain control of the epidemic.

Then they blur that bit of hopeful glance into the future with, of course, “virus mutation might give us a new SARS-COV every winter season just like the flu . . . until 2024”!

Enough of these not-so-fun medical facts. Let’s finish with some good news.
The recovery rates from this virus as of today are 78% in the  U.S.
For even more good news (on a variety of subjects) tune into SGN – SOME GOOD NEWS , a brand new weekly YouTube news program by John Krasinski.

References:
1. Boston Globe, April 12, 2020, Ideas Section K; includes excellent graphs of the different social distancing duration scenarios.


Vol. 229 March 15, 2020 Beware the Ides of March

March 14, 2020

In Shakespeare’s play Julius Caesar, a soothsayer attracts Caesar’s attention and tells him:
            “Beware the ides of March.”
Caesar demands:

            “What man is that? Set him before me, let me see his face.”
When the soothsayer repeats his warning, Caesar dismisses him, saying:

            “He is a dreamer; let us leave him. Pass.”

When I started writing this blog a couple of days ago I was going to call it “A Politically Incorrect View of the Coronavirus” because I wanted to say that the virus will not be contained, that it will very shortly be community-wide,  and that we should marshall our efforts at monitoring, protecting, and treating the high risk people. But today, that is no longer “politically incorrect.” Many of our civic leaders and our leading medical scientists (Anthony Fauci, MD is my most famous medical school classmate, Class of ’66 Cornell Medical College) are now labeling COVID-19 as “community spread” , i.e. not containable through contact tracing since the sources are so numerous that we can not pinpoint a source, like the common cold and the flu.  We are now “mitigating” COVID-19, not “containing” it; just trying to “blunt the peak” on the graph of numbers of infected people.

The stakes are higher for COVID-19 (the name of the disease) then for the seasonal flu because it is more deadly to certain segments of our population. The name of the actual virus that causes COVID-19 is SARS-cov-2, and that is a real clue as to the nature of this virus given our experience with previous coronaviruses.

The good news is that the death rate is not expected to be as high as the past two coronavirus epidemics SARS (10% death rate) and MERS (35% death rate). SARS originated in Southeast Asia bats and civets (small, cat-like mammals) . MERS originated in Middle Eastern camels. SARS-cov 2 has been attributed at various times to be transmitted from bats, snakes, and now, pangolins (anteater-like reptiles with scales); all animals available in Southeast Asian “wet markets” of live animals. There is no evidence that implicates domestic dogs and cats as vectors for the virus. There is also no confirmed evidence that a mother can transmit it to her newborn during delivery.

As the number of identified cases increases (the denominator) we were hoping that the calculated death rate would decrease since the actual calculation =  #of deaths/#of cases. It appears now that the death rate could be between 1.6% (University of Bern, Switzerland estimate based on China’s CDC data) to 3.4% (WHO’s estimate from selected outbreaks), clearly at least 10 times the death rate for seasonal flu (0.1%). However, South Korea has the largest number of tested cases with cold symptoms (140,000) and their death rate is 0.6%. Of even more interest, of those 140,000 South Koreans with cold symptoms who were tested, only 4% were positive for SARS-cov-2, i.e. 96% of those with symptoms were infected with the flu virus or some other non-coronavirus.

The bad news is that about half of those in high risk populations who develop significant symptoms will require hospitalization.  80% of those hospitalized will be so sick that they will require ICU care for a number of days. The people at highest risk of requiring hospital-based medical care are those with underlying chronic diseases, called co-morbidities, like congestive heart failure, hypertension, diabetes, chronic obstructive pulmonary disease (COPD), chronic kidney disease, and those over 80 years old (a stage of life, NOT a co-morbidity thank you!).

Nearly 90% of COVID-19 cases have been in people between 30-79 years old. Less than 1% were in children under 9 years. Despite this fact that children are not the primary vector for this virus (unlike influenza), we are closing many elementary schools. In the swine flu epidemic of 2009 we closed 1300 schools for 7-14 days because of evidence that children were primary vectors for its spread. Despite the run on toilet paper resulting in empty market shelves, diarrhea is not a common symptom of the disease.

If COVID-19 is going to be as common as a cold or the flu, but has a lethal potential for select groups of people, how do we triage the people who think they have it while we wait for the coronavirus nasal swab test to become widely available?
The simplest triage diagram has just three branches in the decision tree:

  1.  If you have cold symptoms (but remember a runny nose is not a common symptom of COVID-19) — treat it like a cold with rest, fluids, and decongestants and try not to spread it to other people. (YOU wear the mask, not everybody else)
  2. If you have a fever over 101 and a cough — go see your primary care provider.
  3. If you have the above and feel weak or tired and are short of breath — the PCP may send you to the hospital.

How do people with COVID-19 die?  In the severe stage of the disease (called ARDS- Adult Respiratory Distress Syndrome) respirator machine support (a ventilator) in an ICU is usually needed. Another cause can be an overwhelming secondary bacterial pneumonia and sepsis later in the disease (similar to deaths caused by the flu) and, unexpectedly, some deaths have occurred without pneumonia or severe lung inflammation, particularly in patients with very high blood pressure or those on kidney dialysis.

Watch out for advertisements of fraudulent cures or “protections” from COVID-19. The FDA has formally warned 7 companies, including the Jim Baker Show, that their advertisements for “silver solutions” to kill the virus must stop. There is no evidence that solutions of colloidal silver can kill the virus. Vitamin C is no help either. If Purell with alcohol can kill the virus some people think that alcohol by mouth could kill it. Unfortunately alcohol does not kill the virus. Soap and water or bleach does. Do NOT gargle bleach.

The AMA has responded quickly to the epidemic and filed a request for a rush approval of a CPT code for COVID-19 testing (necessary for insurance reimbursement, hence maybe the urgency of the request). AMA President Patrice A. Harris, M.D., M.A. has said,  “By streamlining the flow of information on novel coronavirus testing, a new CPT code facilitates the reporting, measuring, analyzing, researching, and benchmarking that is necessary to help guide the nation’s response to the public health emergency.” Also as I said, health insurance companies will be asked to pay for the test.

Two surveys released this week show that the Corona beer brand is suffering from a negative buzz. A 5W Public Relations poll of 737 beer drinkers in the U.S. showed that 38% of them wouldn’t buy Corona “under any circumstances”, and another 14% said they wouldn’t order a Corona in public.  However, Corona beer and seltzer sales actually increased in February.

 


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