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    Covid-19

June 20, 2020

Covid19 Unhysterical Data Are Emerging

By Andrew Bostom, M.D. Professor of Family Medicine Brown University School of Medicine

“—CDC itself in its “COVIDView” as of 5/1/20 maintains covid19 hospitalization rates are directly comparable in those > 65 years old to “ recent high severity influenza seasons”, and for children (0-17 years old) “much lower than influenza hospitalization rates during recent influenza seasons””

“–Covid19 Infection Fatality Rate (IFR) summary estimate =0.28, derived from > 50 pooled SARS-Cov2
antigen/antibody studies, each hyperlink referenced https://bit.ly/3bcFi8R”

“–Updated Diamond Princess cruise ship outbreak analysis (5/6/20) reveals covid19 infection fatality ratio = 13/1304, or 1.0% given 1304 SARS-Cov2 infections and 13 deaths (deaths as of 4/14/20). All fatalities (like
13th) were elderly.”

“–Full Heinsberg Covid19 Study (“Germany’s Wuhan”) results published (~5/2/20): “the corrected higher infection rate reduced the Infection Fatality Ratio to an estimated 0.278% [0.228%; 0.351%]”. If applied to Germany with currently ~ 6,575 SARS-CoV-2 associated deaths (5/2/20), the estimated number of infected in Germany would be > 1.8million” crude IFR might be ~6575/1,800,000 =0.37%, or (likely) less. “Secondary household members may have acquired a level of immunity (e.g. T cell immunity) that is not detected as positive by our ELISA, but still could protect those household members from a manifest infection” (on T-cell immunity, see just below)”

“–Published evidence of the existence of specific cell-mediated immunity to covid19, not detected by antibody
testing: 34% of healthy German blood donors, seronegative for SARS-Cov2 Abs, had T-cell-mediated immune activity possibly due to past exposure to ubiquitous human coronaviruses responsible for common colds.”
““ We demonstrate the presence of S-reactive CD4+ T cells in 34% of SARS-CoV-2 seroneg ative healthy donors (HD)”… Healthy donor (HD) S-reactive CD4+ T cells reacted almost exclusively to the C-terminal epitopes that are a) characterized by higher homology with spike glycoprotein of human endemic “common cold” coronaviruses (hCoVs), and b) contains the S2 subunit of S with the cytoplasmic peptide (CP), the fusion peptide (FP), and the transmembrane domain (TM) but not the receptor-binding domain (RBD)… Our study demonstrates the presence of S-reactive CD4+ T cells in COVID-19 patients, and in a subset of SARS-CoV-2 seronegative HD. In light of the very recent emergence of SARS163 CoV-2, our data raise the intriguing possibility that pre-existing S-reactive T cells in a subset of SARS-CoV-2 seronegative HD represent cross-reactive clones raised against S-proteins, probably acquired as a result of previous exposure to HCoV. Endemic HCoV account for about 20% of“common cold” upper respiratory tract infections in humans. HCoV infections are ubiquitous, but they display a winter seasonality in temperate regions. Based on epidemiological data indicating an average of two episodes of common cold” per year in” “the adult population, it may be extrapolated that the average adult contracts a HCoV infection on average every two to three years. Protective antibodies may wane in the interim but cellular immunity could remain.””

“–Boise/Ada County Idaho (pop. 481,600) SARS-Cov2 IgG antibody seroprevalence 1.8% (sample 4,856) vs. 664 confirmed cases (~8670 by +Ab%, or ~13X confirmed); 17 covid19 deaths (as of ~5/2-3/20)/8670= CFR
of ~0.20%”

“–Lombardy region, Italy (hard hit by SARS-Cov2): 58-61% SARS-Cov2 antibody positive among 1500
persons (unknown sampling scheme) from Nembro and Alzano (published 4/30/20)”

“–Denmark (published 4/28/20): 0.08% Covid19 case-fatality ratio (CFR) for those <70 years old applying population-based prevalence of infections via SARS-Cov2 antibody testing in ~ 9500 blood donors 17 to 69
years old (overall antibody positivity 1.7%).” ““The death toll among all citizens below 70 years was used even though only 16 of 53 deaths appeared among individuals with no comorbidity. This was chosen because the denominator included all citizens in the age strata, thus, also individuals with comorbidity. The IFR (Infection Fatality Ratio=CFR) including only individuals with no comorbidity is thus likely several fold lower than the current estimate.””

“–Minnesota (reported 4/28/20): Mayo Clinic SARS-Cov2 antibody testing in n=12,000 convenience sample—patients and healthcare workers—yielded 20% positives, n~2400. The entire state had 3816 swab test positive for viral antigen.”

“–NYC SARS-Cov2 seroprevalence data updated (on 4/27/20) to almost 25% (24.7) meaning true covid19 case fatality ratio (CFR), even in overwhelmed NYC, ~ 11,460 confirmed deaths/8,399,000(.247)= 11460/2,074,553= 0.55%; For those <65, 2935 deaths, =0.14%; <65, without major morbidity, 59 deaths =
0.003%”

“–WORCESTER, MA (reported 4/26/20): SARS-Cov2 antibody testing (by University of Massachusetts Memorial Medical Center) of Worcester staff at the Beaumont Rehabilitation and Skilled Nursing Facility
revealed that 20% (16/80) tested positive, and were asymptomatic.”

“–Miami-Dade’s population, based on serological testing of a representative sample of n=1400, had a SARS- Cov2 antibody prevalence of 6%, ~165,000 infections, ~16-fold confirmed cases; 270 deaths/165,000= crude
CFR of 0.16%”

“–Italy: SARS-Cov2+ seroprevalence among blood donors in N. Italian “red zone”–30% of blood donors from all 10 municipalities, while 66% (40/60) of asymptomatic donors were positive in 1 of towns under lock-
down”

“–Italy: (Covid19 Herd Immunity in the northern Italian Dolomites resort of Ortisei? 49% serological positivity in a non-random, convenience sample of n=456 persons, aged 20-59, undergoing serological testing; 2/3 were asymptomatic”

“April 22, 2020: New York State-Preliminary (read: underestimated) SARS-Cov2 seroprevalence data =13.9%;
19.45 million state pop (https://www.statista.com/statistics/206267/resident-population-in-new-york/)=
2.7 million infections https://abcnews.go.com/Health/coronavirus-updates-american-red-cross-antibody- tests-id/story?id=70301746; For New York City the estimate was 21.2% positive (see image below from Gov. Cuomo presser, 4/22/20)”

“*Edit: The U.S. covid19 case-fatality ratio per viral antigen throat swab testing as of 4pm Saturday, April 18th, used an erroneous denominator of those tested vs. positive tests (722,182 at this archived tallying website, for example, as the Johns Hopkins site does not archive accessibly). The actual CFR at that time= 37, 938 deaths/722,182 cases= 5.25%, (an even more) heavily biased estimate, as the detailed discussion reveals.*”

“Updates (4/21/2020):”
“–Los Angeles County covid19 infections by antibody-testing were up to 55X higher than the 7,994 confirmed
cases, i.e., ~440,000. Renders case-fatality ratio (CFR)= 617 deaths (as of 4/20/20) /440,000= 0.14%”

“–Stockholm County crude covid19 CFR may be as low as 0.12%: “blood donor anti-body testing in Stockholm area reveals that at least 11% had developed [SARS-Cov2] antibodies. The actual figure is believed
to be higher (i.e., up to 33%)” [crude CFR=944 deaths/784,437 infections= 0.12%]”

“Multi-billionaire software savant, Bill Gates—hardly the infectious (or any other) disease expert he fancies himself—commented with acid hysteria, several weeks ago (3/24/20), on the mere prospect of lifting draconian “covid19”, Wuhan coronavirus-related shutdowns, to reduce the economic havoc they have wrought:” ““It’s very tough to say to people, ‘Hey, keep going to restaurants, go buy new houses, ignore that pile of bodies over in the corner. We want you to keep spending because there’s maybe a politician who thinks [gross domestic product] GDP growth is what really counts.”” “Mr. Gates’ self-righteous fulmination, notwithstanding, his morbid, grotesque exaggeration, captures a widely prevalent, critical ignorance of the actual SARS-Cov2 (Severe acute respiratory syndrome coronavirus 2 of the genus Betacoronavirus, which causes Covid19 disease) virus’ lethality embodied in what is known as” “the infection, or case-fatality ratio (CFR).”

“Simply and accurately defined, the CFR is the ratio of the number dying from a severe infectious illness, the “numerator,” to the total number infected, the “denominator.” Clear evidence of infection, no matter how severe or mild (even unnoticed by the infected person), is determined, typically, by “immunoassay”, a blood “seroprevalence” test that measures the presence of so-called “antibodies” to an infectious agent such as SARS-Cov2. It is understandable, during the early throes of an outbreak like covid19 disease, that rapid tests which detect (ostensibly) “live virus antigen” (i.e., specific fragments of its genetic code “RNA”), in readily accessible body fluids (eg., from the throat, or mouth), among the most ill, are prioritized, often to the exclusion of blood seroprevalence antibody testing. However, this viral antigen methodology, and testing scheme, over representing the severe cases, introduces profound biases which may vastly underestimate the “denominator” of total cases, especially the mildest, required for determining an actual CFR. Accordingly, as of 4:30pm, Saturday, 4/18/20, accepting at face value the gross over-counting of covid19 fatalities, absent appropriate validation by Centers For Disease Control (CDC), and individual state (glaringly, out of hospital deaths in New York, and Massachusetts) “guidelines”, the widely referenced Johns Hopkins Corona Virus Resource Center (JHCRC) tallied 37,938 deaths. Applying the concurrent JHCRC enumeration of covid19 cases relying solely on selective “live virus” testing, i.e., 4,690,482, yielded 37,938 deaths/ 4,690,482 cases, a CFR of 1.03%. (See correction at top of blog)”

“Contra these JHCRC tabulations, emerging covid19 case “denominator” findings from both an innovative, thoughtful analysis of U.S. CDC influenza-like illness (ILI) data for March 2020, and initial U.S. seroprevalence assessments (here; here; here), tell a different, less biased CFR story, one very consistent with the historical impact of pandemic influenza on the American population. The 1957-58 influenza A H2N2 virus pandemic, and its overall U.S. mortality, and CFR, provide useful benchmarks for comparison. Also originating (like SARS-Cov2) in China, the CDC estimated that just over 25% of the U.S. population then (census of ~ 170 million), some 45 million persons, were rapidly infected with the new virus between October, and November, 1957. Despite a vaccination program, there were ultimately 116,000 deaths, a resulting pandemic H2N2 influenza A CFR of 0.26% (116,000 deaths/45,000,000 infections).”
“Silverman and colleagues analyzed a decade of background non-influenza ILI, per CDC records, and identified a non-influenza ILI surge beginning the first week of March, 2020. They correlated this vast excess of ILI with established SARS-Cov2 proliferation patterns across U.S. states, indicating the surge was indeed due to the new virus, but orders of magnitude greater than the number of covid19 cases reported (i.e., as detected by viral antigen testing). After conservatively re-calibrating their estimates, these investigators calculated that some 8.7 million Americans were infected between March 8 and March 28, 2020. Moreover, when asked specifically about the current number (prevalence) of those infected in the U.S. (as of April 17-19, 2020), given covid19 cases dating back to January, 2020 (on 1/19/20, the first covid19 case was reported in WA state), lead investigator Silverman commented (14:48-15:05), “at least 10% of the U.S. population”—a minimum of ~33 million Americans infected (current U.S. population equaling 329.5 million). The CFR from these data, 37,938 deaths (per the JHCRC)/33,000,000 cases, or 0.11%—generates a current estimate for covid19 less than half the 0.26% CFR of the 1957-58 H2N2 influenza pandemic. As a final CFR comparison between the 1957-58 influenza, and current covid19 pandemics, we can use the latest (3/17/20) much ballyhooed Institute for Health Metrics and Evaluation (IHME) model estimate (the 6th iteration in under 3-weeks: 4/1; 4/5; 4/8; 4/10; 4/13; and 4/17) for covid19 deaths through August 4, 2020, and assume an equivalent number of infections, 45 million each. It is important to note the 4/17/20 IHME model no longer expects “full social distancing through May (2020).””
“Projecting 60,308 covid19 deaths/ 45,000,000 infections, yields a CFR of 0.13%, half the 1957-58 pandemic
influenza CFR.”
“Appropriately, Silverman and colleagues have insisted that their CDC non-influenza ILI surveillance analyses be confirmed by seroprevalence studies. Albeit rather piecemeal, seroprevalence validation of their estimates is accumulating, from both early representative U.S. community samples, and less rigorous “convenience” samples (here; here; here). Additional independent confirmation of Silverman et al’s assessment of the scope of U.S. covid19 infections can be gleaned from viral antigen screening reports of patients presenting with ILI to urgent care facilities, asymptomatic (overwhelmingly) pregnant women admitted for delivery, and homeless populations (here; here). A bulleted summary of this cumulative evidence is provided below:”

“–Stanford investigators conducting a population-based seroprevalence study (4/3 to 4/4/20) in Santa Clara County, CA among 3,330 residents, determined the prevalence of covid19 ranged from 2.49% to 4.16%, representing 48,000 to 81,000 infected by early April, some 50- to 85-fold greater tan the number of confirmed cases. Applying these infection rates to the county’s covid19 deaths yielded a CFR of 0.12 to 0.20%, or less.”

“–A convenience sample of Chelsea, MA residents—excluding any who were viral antigen positive by nasal swab testing—demonstrated that 64/200, 32%, tested positive for SARS-Cov2 antibodies. A crude CFR from these limited data, assuming 32% of Chelsea’s population was actually infected (0.32 X 35,177= 11,257)/ 39
time period relevant covid19 deaths, = 0.35%.”

“–A provocative, if entirely anecdotal report (4/9/20) from the South Chicago, IL community hospital, Roseland Community Hospital: : “A phlebotomist working at Roseland Community Hospital said Thursday that 30%- 50% of patients tested for the coronavirus have antibodies while only around 10% -20% of those
tested have the active virus.””

“–5% of patients presenting March 12-13, and March 15-16, 2020, with mild ILI to Los Angeles County and University of Southern California Medical Center urgent care/emergency room facilities tested positive for SARS-Cov2 by viral antigen nasal swabbing. (All had mild illness, and tested negative for influenza and
respiratory syncytial virus.)”

“–15.4% of 215 pregnant women who delivered infants at the New York–Presbyterian Allen Hospital and Columbia University Irving Medical Center between March 22 and April 4, 2020, tested positive for SARS-
Cov 2 by nasal swabbing. 29 of the 33 (87.9%) total woman positive for SARS-Cov 2 were asymptomatic.”

“–During late March, 2020 147/408 (36%) of Boston homeless shelter residents screened from a single large
facility, tested positive for SARS-Cov2 by nasal swabbing. Less than 10% were symptomatic.”

“–As reported April 17, 2020, 49/114 (43%) of homeless residents at a Worcester emergency shelter screened SARS-Cov2 positive (presumptively by viral antigen testing). Most were asymptomatic, or with minimal
symptoms.” “One of the most striking features of covid19 disease is its overwhelmingly disproportionate lethality in those
≥ 65 years old, vs. those < 65. Stanford University Prevention Research Center’s Dr. John Ioannides, and””colleagues, analyzed covid19 mortality data as of April 4, 2020 from European countries and U.S. states, or major cities, with at least 250 covid19 deaths (total deaths included=25,692). An analysis pooling data from New York City, Italy, and the Netherlands, for example, revealed that only 0.9% of all deaths occurred in those < 65, without known underlying co-morbidities. Given these findings and the more modest overall U.S. covid19 CFR based upon realistic population infection estimates (i.e., 0.13%), the CFR should be considerably lower still, in those < 65 years of age.””Ioannides et al proffered (on April 8, 2020) these increasingly evidence-validated, eminently rational recommendations for managing the covid19 pandemic going forward:”

““If larger scale studies further document that the infection is very common and infection fatality rate is modest across the general population, the finding of very low risk in the vast majority of the general population has major implications for strategic next steps in managing the COVID-19 pandemic. Tailored measures that maintain social life and the economy functional to avoid potentially even deaths from socioeconomic disruption plus effective protection of select high-risk individuals may be a sensible option.”” “Unaccompanied by mass economic lockdowns, the 1957-58 H2N2 influenza A pandemic—equal, at least, in virulence and lethality to the current covid19 pandemic—had only a negligible effect on the U.S. GDP, within the range of ordinary economic variability.” “February 28, 2020 (published online), the lead author editorialist of a New England Journal of Medicine oped entitled, “Covid-19—Navigating the Uncharted”, referencing the 1957-58 H2N2 influenza pandemic, observed:””“If one assumes that the number of asymptomatic or minimally symptomatic cases is several times as high as the number of reported cases, the case fatality rate may be considerably less than 1%. This suggests that the overall clinical consequences of Covid-19 may ultimately be more akin to those of a severe seasonal influenza (which has a case fatality rate of approximately 0.1%) or a pandemic influenza (similar to those in 1957 and 1968)…””

“That lead editorialist was Dr. Anthony Fauci.”

“Hope springs eternal Dr. Fauci will very soon short-circuit his own present cognitive dissonance. Let us pray Dr. Fauci openly acknowledges his concurrence with Dr. Ioannides both on the pandemic influenza-like CFR range of covid19, and its circumscribed lethality disproportionately targeting the elderly, and support accelerated easing of the economy-crushing lockdowns plaguing our country much more severely than the new virus.

March 28, 2020

Covid-19: Korean Quarantine Model

There has been criticism on the web about shutting down the entire State of California since community spread of the disease is only apparent in the San Francisco Bay area, Los Angeles county, San Diego county, Sacramento county, the Seattle environs, and New York city.

Community spread means the people who’ve gotten Covid-19 don’t have any idea who infected them. Tracing contacts of infected people and isolating those contacts is the first line of defense in stopping an epidemic, but does not work when the people to contact and isolate cannot be identified.  When contagion happens by community spread, a disease can take off throughout the population as happened in the infamous “Spanish Flu” of 1917 though 1918.

Some critics suggest we adopt the South Korean model of Covid-19 containment, which seems to be working well there. They are isolating seniors and the chronically ill while letting the rest of the population go about their business. Infection rates seem lower and their health care system is not being overrun.

The foregoing said, there are some important facts that make suggestions of following the South Korean model of isolating only seniors and the chronically ill from the rest of us now pre-mature in areas of the country where community spread has already taken hold, such as New York City, Seattle environs, Los Angeles, San Diego, and the San Francisco Bay area.

There is an important difference between the US and Korea. South Korea has a well-developed and well stocked traditional Asian medicine component to its health care system. Traditional Asian medicine works well at combating Covid-19 infections.  It is not 100% effective, no medical approach is, but it is far more effective than western medicine. There are multiple studies that support this. The Chinese government has utilized it in this latest pandemic with good results. Entire hospital teams are on government recommended herbal regimens as they fight the disease. Doctors dying on the front lines has dropped off since those regimes were implemented. More on how it works and why in another post. Koreans can use it at will throughout their country, many do. I suspect this has more to do with the low mortality and severity rate in Korea than is currently reported.

Medical masks, until our government put out the call for domestic manufacture in February, were not made in the US.  They were imported from China.  When the Chinese government realized what was happening in Wuhan, they bought up almost the entire stock of medical masks in the world’s commercial pipeline and all Chinese manufactured masks were diverted to domestic Chinese consumption.  New medical masks stopped being available for purchase by health care workers in the US in late February. I, a primary care health care provider, was told there would be no shipments of medical masks into the US from China till sometime in the fall or next winter when I tried to buy some masks for my clinic and family.

Whether one gets sick from a virus depends on the number of viral particles to which one is exposed and the state of one’s immune system.  Once the virus is in one’s lungs and tissues the term is “viral load”. The higher the viral load, the more stress on the immune system and normal functions of the host.  If one already has diabetes, any cardiovascular disease, asthma, other breathing disorder, or is exhausted, the immune system is compromised.  Covid-19 kills its host by infecting and damaging the lungs thus reducing oxygen supply to the body. Once the lung tissues have been damaged, viruses enter the blood stream and are seeded throughout the organs, resulting in multiple organ failure.  Like the general population, a very significant percentage of health care workers have these pre-existing conditions.

Medical staff in Wuhan were killed by Covid-19 because they were exposed to high viral load before the nature of the illness was apparent and were exhausted.  Medical staff treating a stream of patients all day, a small percentage of which actually have Covid-19 and a larger percentage have common flus, are exposed to tremendous viral loads.  If we were to follow the Korean model in areas where community spread already exists, the general population would quickly become majority infected and, even if told to stay home unless very ill, many would show up at their medical providers.  Even 10% of them showing up for treatment or diagnosis would quickly overwhelm the capacity of our medical services to treat them.  More importantly, there are not enough masks yet for all staff who come in contact with the patients (meaning everyone from the doctor to the janitor). Viral load would be so great for these workers that many who would otherwise shrug off a minor infection would come down with serious illness and need hospitalization.  But our hospital capacity is only able to bed 2% of our population at a time.  Thanks to the leadership of Mr. Trump and Mr. Pence and the rapid response of American manufacturers, we’ll have sufficient supply of masks to front line clinics and hospitals within several more weeks.  It looks like the same can be said of gowns, gloves, hand sanitizer, face shields and other personal protective equipment (PPE).

Lack of PPE is not the only problem. We cannot successfully identify, track infections and quarantine if we cannot test to determine who has Covid-19.  The automated testing that the South Koreans have been doing existed only in South Korea until our leaders cut through the regulatory morass and arranged with our medical manufacturers to get them manufactured here. We’ll have enough tests within the next several weeks.

So, yes, for USA areas where community spread is now occurring, mandatory school and business closure, social distancing, and self-isolation are the best defenses.  Where community spread has yet to occur, such actions are pre-mature and far too damaging to the economy.  Once we have sufficient PPE and medical capacity to identify and treat only those who actually need treatment for Covid-19, following the South Korean model of keeping Grandma, Grandpa and those vulnerable away from those who are not, will probably work; and will create far less damage to the economy and our children’s education.  In the meantime, we are staying put and not getting within 6 feet of anyone other than my patients.  I’m happy to hear from my patients that the roads are deserted.

Many people have expressed their desire to communicate their opinions to their representatives regarding handling of this pandemic. You can find your Congresspeople and State Legislators for free at USgeocoder.com. Enter your address and zip code, then the + at the top left corner of the column of data that appears. Scroll down and click on the name of your representatives, their contact information and role in their legislative bodies will pop up for you.  The email addresses and webform links you’ll find are the best means of communicating with your elected representatives.  I would appreciate it if you could mention getting PPE to traditional Asian medical practitioners (Licensed acupuncturists in the US are the ones practicing Asian medicine.) Without PPE we risk getting infected and then infecting our families and our patients as well as anyone who comes in with symptoms but just has an ordinary flu or brings a relative for care.  Although I have PPE sufficient to treat some patients, most of my colleagues and I do not have enough to treat more than a handful of patients.  Since we cannot obtain PPE at the moment, we are having to sit on the sidelines when we could be helping.

Full disclosure, my wife and I co-founded and own USgeocoder LLC.  We hope you find it useful in communicating with your elected representatives regardless of your opinions and ideologies.