A Problem With COVID-19 Virus Antibody Testing

While going through each state's COVID-19 virus reports, I have noted that, among those states that report antibody testing, the antibody positive rates are generally substantially lower than the confirmatory test rates. 

Why is this significant? Three possibilities come to mind. 1) Antibody testing is of a substantially different population than is the test for the presence of virus. 2) There is little community immunity or little community exposure. 3) The antibody tests are flawed. I will discuss these possibilities further below. 

Background. 

There are two general ways to test for COVID-19 virus/exposure. The PCR test (sometimes called the molecular test) is the gold standard and says that someone is currently infected. It should only show a positive result if a person is secreting the virus. Typically this is performed from an oral or nasal swab. 

The antibody test (sometimes called the serology test) says whether the person has been exposed to COVID-19 to the extent that he or she produces antibodies. This can be due to a full-fledged infection or due to a silent, asymptomatic infection. The person may have recovered and may no longer be infectious--or else not. This person may be immune to future infection--or else not. Antibodies take a period of time to generate in a body and will not appear immediately after infection, so this test does not account for the very recently infected.

Now to the Data. 

Although several additional states report the total number of antibody tests, seven states report both test numbers and how many are positive. This latter group is, in alphabetical order, Arizona, Georgia, Iowa, Maine, Missouri, North Dakota, and South Carolina.

Arizona, which is undergoing a massive increase in the number of confirmed (PCR) infections, has been providing antibody positivity data since May 7. Unfortunately, they provide only a percent positive figure, not the actual number. Here is a brief table with some of their antibody results.

Arizona	Ab tests	positive	PCR tests	positive
May 7	14652	3.7%	96434	10.31%
June 1	93586	3.0%	228070	8.82%
June 17	136117	3.0%	365846	11.19%

   

The above numbers are cumulative. For example, a total of 14652 antibody tests were performed up to May 7, the day they were first reported, and 3.7% (Arizona calculations, meaning 3.65 to 3.749%, they do not provide an exact count) of those were positive at that time. 

Six weeks is a long time in the history of this pandemic. Rather than cumulative, let's break these down in two time periods. 

Arizona	Ab tests	Ab pos min	Ab pos max	Ab %	PCR tests	pos.%
May 7 to June 1	78934	2215	2319	2.81 - 2.94	131636	7.73
June 1 to June 17	42531	1162	1390	2.73 - 3.27	137776	15.1
May 7 to June 17	121465	3470	3616	2.86 - 2.98	269412	11.5

Even during the month of June, when the PCR tests passed 15% positive, the antibody tests remained around 3%.

The other states provide numbers rather than vague percentages, so their data are more straightforward without the need for ranges. They have, however, been reporting their antibody positivity rates for a briefer period.

Georgia	Ab total	Ab pos	Ab %	PCR tests	PCR pos	PCR %
June 2	91325	5395	5.91	474287	48207	10.16
June 17	118426	6912	5.84	644723	60030	9.31
June 2 to 17	27101	1517	5.60	170436	11823	6.94

Since Georgia began reporting recently, I included cumulative and time period data in one table. Again, the PCR rate is higher than the antibody rate.

Iowa places their antibody testing data on an inner page of their report. There is not an archival record of these data, so to access the data you have to visit on a particular day. They began reporting antibody tests results on June 9.

Iowa	Ab total	Ab pos	Ab %	PCR tests	PCR pos	PCR %
June 9	24290	2046	8.42	198123	22238	11.22
June 18	27575	2157	7.82	240657	24805	10.31
June 9 to 18	3285	111	3.38	42534	2567	6.04

Again, the first two rows are cumulative data to that date, the last row is over the past nine days since Iowa began testing.

Maine began reporting antibody results on May 27. It has a low new infection rate, 45th out of 51 in the nation (including DC) in new weekly cases per million population. When the PCR rates are very low, it seems that the antibody rates can be slightly higher.

Maine	Ab total	Ab pos	Ab %	PCR tests	PCR pos	PCR %
May 27	3661	198	5.41	46043	2137	4.64
June 17	6137	294	4.79	74648	2836	3.80
May 27 to June 17	2476	96	3.88	28605	699	2.44

Missouri also has a report on antibody testing on an internal page. Along with daily data, they provide a chart of daily tests with numbers positive and negative. When the negatives are more than a thousand in a day, they present the number as "k," for example, 1705 becomes 1.7 k. In spite of this inexactness, the daily information is useful.

Missouri	Ab total	Ab pos	Ab %	PCR tests	PCR pos	PCR %
May 24	18868	692	3.67	151619	11988	7.91
June 20	37210	1387	3.73	311115	17590	5.65
May 24 to June 20	18342	695	3.79	159496	5602	3.51

Like with Maine, low PCR numbers coincide with low antibody positivity rate.

North Dakota began reporting antibody testing on May 29. The PCR positivity rate is low, the antibody testing rate, lower.

North Dakota	Ab total	Ab pos	Ab %	PCR tests	PCR pos	PCR %
May 29	2546	86	3.38	69453	2520	3.63
June 17	4125	128	3.10	89674	3166	3.53
May 29 to June 17	1579	42	2.66	20221	646	3.19

Like Arizona, South Carolina is undergoing a surge in confirmed COVID-19 cases. Like Arizona, the antibodies have barely register an uptick.

South Carolina	Ab total	Ab pos	Ab %	PCR tests	PCR pos	PCR %
June 11	27609	1337	4.84	236456	16441	6.95
June 17	31376	1538	4.90	272749	20556	7.54
June 11 - June 17	3767	201	5.34	36293	4115	11.34

These seven states, since the beginning of the pandemic, have performed a total of 360,966 antibody tests with a positivity rate of 4.40 to 4.44%. These states have performed a total of 1,979412 PCR tests with a positivity rate of 7.53%. They have a combined population of 34.4 million.

Over the course of the time in which they reported their data, the states performed 192,667 antibody tests with a positivity rate of 3.47 to 3.54%. Over that same period, the states performed 726,997 PCR tests with a positivity rate of 7.76%. These are the better figures for comparison: the cumulative data includes a higher positivity rate period near the beginning to the pandemic, when antibody tests were not in common use.

So, we have roughly 7.8% by PCR and 3.5% by antibody. In theory, the antibody tests should find a larger group and include those who had mild disease. Something is off here.

High and Low Antibody Testing Rates.

In a highly publicized study conducted by Stanford, approximately 50 times the number of people in the community of Santa Clara, California tested positive for COVID-19 virus antibodies than did for PCR testing. If accurate, this study could have far-reaching implications. It suggests widespread immunity, many people having minor or no symptoms, and a far lower death rate for those who do have infections.

That study, which did have glaring faults, went on to be criticized, perhaps even demonized. In a more recent study, Stanford found an antibody positivity rate of 0.3% among 11,000 asymptomatic  university employees.

Spain was an epicenter of the infection from March to May, for a time leading Europe in cases. A study of 70,000 individuals in mid-May found that only 5 percent of Spaniards possessed antibodies to the virus with one region as high as 14.2%.

Spain: On May 15, had a cumulative 274,367 cases (population 46.94 million) for a nationwide positivity rate of 0.58%. In this same time period, the antibody positivity rate was 5.0%. This suggests the total case number is underestimated by about 8.6 fold.

What's Going On?

One piece of the puzzle is that different groups are being tested. The PCR, confirmatory, test for infection is more likely to be used for those who show symptoms and those who are directly exposed to the infected individuals. The antibody studies are more likely to survey others, for example, the entire workforce of health care facilities.

Still, I find this explanation unsatisfactory, or, at least incomplete. In Spain's broad survey, the positivity rate for antibodies was several-fold higher when trying to select a representation of the total population. Why would the American antibody surveys choose a population with such a lower fraction of those positive?

Another possibility is that there is simply very little community exposure. This explains the low numbers in the antibody test, but not why it is even lower than confirmatory tests or why it is not in line with other studies.

A final possibility is that the antibody tests are flawed. The positivity rate per test continues to linger around 3% in Arizona even as the PCR rate doubled.

Of course, the answer may be due in part to combinations of the three possibilities.

Martin Hill Ortiz is a Professor of Pharmacology at Ponce Health Sciences University and has researched HIV for over thirty years.

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Discrepancies in Florida COVID-19 Data Reporting

One measure of COVID-19 virus infections is the positivity rate. This is the percent of tested samples reported positive for infection.

In one of almost a dozen tweets, Florida governor Ron DeSantis has crowed about his state's day-to-day positivity rate.

In one example, DeSantis wrote:"Yesterday yielded 187 new cases in Phase 1 counties with a positivity rate of 1.43%. The positivity rate has ranged between 1.43% and 4.2% over the past 2 weeks for our Phase 1 counties and has noticeably declined in the past week." Ron DeSantis, May 11, 2020.

This tweet was accompanied by the graph:

Concurrent with this "noticeable" decline, on May 5th, Rebekah Jones, the manager of the Florida State Department of Health COVID-19 database was removed from her position, saying it was for not complying with orders to delete data. A quote from the Tampa Bay Times:

In her [Jones] Friday email to subscribers of a COVID data listserv, Jones said she was reassigned on May 5 "[f]or reasons beyond my division’s control" and warned that whoever took over may be less straightforward.

The above graph can be compared to others that DeSantis tweeted. This graph represents the last days of Jones.

Ibid, 5/2/2020

Notably, the overlapping data points between the above two graphs (5/6 to 5/10) do not match.

Overlapping	Tweet 5/5	Tweet 5/11
Apr. 27	5.98	4.04
Apr. 28	4.57	3.46
Apr. 29	5.00	3.83
Apr. 30	5.11	3.91
May. 1	4.09	3.03
May. 2	4.81	4.20
May. 3	4.68	2.41
May. 4	2.61	1.67

The rates for each overlapping date was revised downward post-Jones.

DeSantis last tweeted a positivity graph on May 26.

So, what is going on? What I suspect.

The numbers changing in the positivity reports is too great for the normal adjustments that usually take place. It is likely that Florida is mixing antibody positives with COVID-19 confirmatory tests (PCR). Antibody positives run about half the rate of PCR rates. One explanation for the numbers dropping between reports is that the tests were added to old data, retroactively.

On May 5th, 2020, Governor De Santis declared:

"Antibody testing is finally here."

He said that 200,000 antibody tests were already in Florida and more were on their way.

Combining antibody tests with PCR tests is a form of data manipulation. According to the prestigious COVID Tracking Project:

"As antibody tests become more widely available across the United States, we call on all states and territories to preserve the integrity and usefulness of their COVID-19 testing data by maintaining separate viral testing and antibody testing counts."

Furthermore, Florida counts multiple negative results from the same individual, rather than reporting the number of individuals who tested negative. "People tested on multiple days will be included for each day a new result was received." as quoted by The COVID Tracking Project.

Florida does not support data integrity.

Ten nurses and ten National Guard members for 500 tests a day?

On May 6, the Florida Department of Health announced a mobile testing lab testing up to 500 individuals a day. The mobile testing unit will be staffed by 10 members of the National Guard and 10 nurses, DeSantis said.

Breaking news: (6/18) Florida reports record-breaking 3207 new cases.

Martin Hill Ortiz is a Professor of Pharmacology at Ponce Health Sciences University and has researched HIV for over thirty years.

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Undercounting the COVID-19 Deaths

The excess number of deaths that are not explicitly being attributed to SARS-CoV-2 (coronavirus) has become mainstream news recently. The New York Times recently put out a series of graphs that look at localities that provide their COVID-19 death statistics in comparison to the average number of deaths in the same time period over the previous five years. Those five years include the late winter-early spring of 2018, when a particularly lethal flu virus dominated.

The U.S. deaths for flu for the 2017-18 season was initially calculated at 79,400 and then reduced to 61,000. The former number would have made it the worst flu season since modern tracking techniques in the mid-1970s and even the adjusted numbers made it one of the worst. Due to the 2017-18 bad flu season, in the initial parts of 2020 the number of deaths showed a slight decline when averaged out over previous years.

The United Kingdom provides mortality statistics, including those deaths due to coronavirus weekly, with about a two week delay. These numbers are gathered separately for England and Wales (combined), Scotland, and Northern Ireland. I present these below as a peek into both the number of increased deaths attributed to COVID-19 and the number not attributed.

I updated these tables using the figures most recently available as of 4/29/2020.

England and Wales.

First, England and Wales which have a combined population of 59,115,800 (2018). The raw numbers came from the UK Office of National Statistics, England and Wales .

*The initial period of deaths are presented as average deaths per week. The determination of excess deaths not classified as COV-19 (1 - (column 2/(column 4 - column 3)) as percentage) is performed the two most recent weeks when total deaths rise above noise. An excess death figure of 100% means that the increased deaths over the week were twice what was attributed to COVID-19.

England and Wales are having a considerable degree worse time with COVID-19 than Scotland or Northern Ireland, below.

Scotland

Here are the numbers for Scotland which has a population of 5,438,100 (2018). Here the raw numbers are from the UK official site for Scotland. Note: Scotland does their counting using Week Beginning rather than Week Ending and start on a different weekday.

Northern Ireland.

Northern Ireland has a population of 1,881,600 (2018). The raw numbers came from the UK official site for Northern Ireland.

The Scotland and the Northern Ireland figures are not included in the New York Times article cited above. I used the figures for only the most recent weeks in estimating the undercounting of COV-19 deaths. In each instance, the undercounting occurred to a much lesser degree over subsequent weeks and, in the most recent weeks, there was even overcounting.

Previously:
SARS-CoV-2 Infection and Mortality Rates
The Coronavirus: Potential Treatments and Drugs to Potentially Avoid

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SARS-CoV-2 Infection and Mortality Rates

COVID-19 is the name given to the disease caused by the SARS-CoV-2 virus (commonly called coronavirus). SARS-CoV-2 is listed in a recent article by LiveScience.com on the viruses most deadly to humans, not because it has the highest rate of mortality, but because it rapidly becomes widespread. The mortality rate given in the article is 2.3%, but open to conjecture.

Worldwide numbers for infections by SARS-CoV-2 have topped 2 million but are likely to be a gross underestimation. The politics of 200 different countries, the rates in which test for infections take place, how countries they define their positive cases, and how they define deaths by COVID-19 are not only variable, they are confounding. For example, Chile counts those who have died due to SARS-CoV-2 virus as being recovered. They are no longer infectious.

This leads to two important issues are: how many people have SARS-CoV-2 but are either untested or asymptomatic; and, how many people die of SARS-CoV-2 but are not listed among the total deaths.

How Many Total Infections?

In regards to the first question, an interesting observation was reported in the New England Journal of Medicine. One New York City hospital tested all of the women (215) admitted for childbirth and found an infection rate of 15.4%. Of these, 87.9% were asymptomatic. Several factors suggest that late-term pregnant women may not be representative of infection rate in the population as a whole, but nevertheless, this is an intriguing number comparing infections to those asymptomatic.

This report states the United States is detecting only 9% of the coronavirus infections.

Such reports are political fodder and it is difficult to be sure if the input is unbiased. One model generated by Chicago economists says that 1.5 to 14% of the infections have been detected depending on lag time involved in detecting the infections.

Why political fodder? If the risk from SARS-CoV-2 is much smaller than reported, then the number infected (and perhaps immunity) is much higher. In such a case the risk of opening the economy is lessened. Some are gung-ho to lift safety measures in place.

The ultimate risk of SARS-CoV-2 is both from its morbidity and mortality rates and its degree of infection. A virus that causes a 0.5% death rate (low end) and saturates at 70% of people infected (high end estimates), would kill 25 million worldwide along with a million Americans. A similar number would come from a 1.5% mortality rate and 23% infection rate.

What We Can Learn from the Diamond Princess Cruise.

The Diamond Princess cruise ship is instructional when trying to determine unknowns regarding SARS-CoV-2 infection rates. I agree with this quote in the scientific journal, Nature. “Cruise ships are like an ideal experiment of a closed population. You know exactly who is there and at risk and you can measure everyone.” John Ioannidis, an epidemiologist at Stanford University in California.

According to the CDC's March 27, 2020 report, the ship set sail on January 20th from Yokohama with 3711 passengers and crew. When stopping in Hong Kong on January 25th, one passenger disembarked due to being symptomatic. This passenger was later confirmed to have SARS-CoV-2.

The crew averaged 36 years of age and the passengers 69 for a combined average age of 59.6. Due to concerns regarding SARS-CoV-2, those on the ship were not allowed to disembark when it docked in Japan on February 3rd. On February 5th passengers were quarantined in their cabins.

According to the Nature report, over 3,000 tests were run on those aboard the Diamond Princess, with some tested more than once. This says that the testing was not comprehensive. A total of 712 tested positive. Back to the CDC report: Of those testing positive, 46.5% had no symptoms at the time of testing. Furthermore, and more revealing, it was estimated that 17.9% never developed symptoms.

At the time of the CDC and Nature reports, 9 of those aboard the Diamond Princess had died. I have found more recent figures place the number of deaths at 12, these from Sydney Morning Herald and Wikipedia. A higher figure makes sense: the previously mentioned articles spoke of some of those from the Diamond Princess as being in critical condition. Using the figure of 712 testing positive this has a mortality rate of 1.3 to 1.7%. On the one hand, the cruise ship did skew toward elderly passengers. On the other hand, the attendant publicity likely ensured top quality care for those who were aboard.

There are other cases of cruise ship outbreaks with some continuing to be in quarantine.

Excess Deaths in Nembro, Italy (citation) The red line is the number of deaths in the time period in 2020. The green line is the number of official COVID-19 deaths (all 2020). The blue line is the average number of deaths in the same time period but from 2015-19.

Undercounting Mortality

To what degree are deaths due to COVID-19 undercounted? One way in which this can be addressed is by looking at the excess number of deaths taking place in a location where SARS-CoV-19 has become prominent in comparison to previous years. A number of studies have been made.

One is a look at the mortality statistics collected in England and Wales. This is not a small population sampling: together they have a population of 60 million. The following table lists the number of deaths attributed to COVID-19 and compares those to the increased number of deaths. England began its lockdown on March 23rd. The table below is my creation taken from the aforementioned dataset.

Weekly deaths in England and Wales

 The small decrease in the early part of 2020 may be due to a particular virulent strain of flu virus dominant in 2017-2018.

 For the week ending April 3rd, those deaths officially deemed to be due to COVID-19 accounted for only 57% of the increase in deaths (that is a total of 33.6% of the 59% increase).

Because the report notes that the final week's cause of death may be incomplete, it is worth noting that for the week ending March 27th, the official COVID-19 deaths account for only 53% of the increase (5.3% of the 10%). It might also be noted that a 59% increase in death does not correspond to a virus that was as lethal as the annual flu. The annual flu had been around in previous years.

Two factors may contribute to the total deaths figure. One is an increase in deaths due to other causes due to, for example, an overwhelmed health care system. The other could be an underestimation due to the decrease in certain deaths such as traffic fatalities due to the lockdown conditions.

 According to the UK Office for National Statistics, these data will be updated on April 21st. Considering the rapid rise in the number of weekly deaths, that update will be crucial to providing an even better picture.

This phenomenon is hardly limited to England and Wales. This report from Netherlands analyzes increases in deaths compared to previous years and find that the official COVID-19 numbers only account for half of the deaths.

Similarly, from Spain, a study described in El Pais, says that while the official number of COVID-19 deaths was 3439 during the time period of March 14th through March 31st, there was an increase in total deaths of 6613 when compared to the same time period in the previous year.

This news report describes several U.S. cities as having significant undercounting.

What's the takeaway from this? First of all, although there are a variety of models that come to different conclusions, there is some hard evidence out there about the undercounting of infections and deaths. The very fact of the spikes in deaths exist indicates that SARS-CoV-2 has a much higher lethality rate than a typical influenza virus. Deaths are probably double the official figures in places where deaths are meticulously counted. In other parts of the world, where the government either wishes to lowball the pandemic or else just doesn't count, the statistics on death are meaningless.

Previously: The Coronavirus: Potential Treatments and Drugs to Potentially Avoid
Next: Undercounting COVID-19 Deaths.

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The Coronavirus: Potential Treatments and Drugs to Potentially Avoid

Pharmacology and SARS-CoV-2

I have taught pharmacology, the science of drugs, going on thirty years. Several matters related to pharmacology have appeared regarding SARS-CoV-2. I will address two broad questions. First: do some drugs work against the virus? Second: do some drugs make the infection worse?



Let's start off with some perspective. All of this is new. Even a quick study rushed to publication takes months: and we are not many months into this infection. There is no definitive statement regarding any of these matters, just a handful of very recent publications along with too many anecdotal reports. In the early days of AIDS (of which I have some familiarity), a lot of the original information about treatment candidates proved to be born out of desperation rather than usefulness.

Coronaviruses, along with rhinoviruses and adenoviruses, are among those that cause the common cold. That's the bad news: common colds are common. They are readily transmissible and, as we all know, there is no cure for the common cold. Beyond that, SARS-CoV-2 is much more dangerous than a typical cold or flu.

On the other hand, treating the SARS-CoV-2 virus is not the same as curing the common cold. We are not targeting all of the potential "cold" viruses here: just one. That provides hope for vaccines, and perhaps, pharmaceutical agents. (Strictly speaking, vaccines are pharmaceutical agents, but for the sake of this piece, I'll only be talking about non-vaccine drugs.) Some of the drugs mentioned here were tested during previous SARS outbreak.

Potential Drugs to Treat Coronavirus

These are some of the drugs that have been put forward as to helping with COV-19 infection.

Oseltamivir (Tamiflu). This drug is taken orally to help curtail influenza disease course. It is useful only if the drug is taken within the first two days of symptoms. Even then, it will only briefly shorten the recovery time. Oseltamivir helps prevent newly-formed viral particles from escaping an infected cell and therefore infecting new cells. It does this by inhibiting the neuraminidase enzyme. It is available orally and that's probably why it is prescribed a lot: convenience. In contrast, zanamivir (Relenza) is an inhalant that also inhibits neuraminidase used for flu. It has less side effects than oseltamivir because it is an inhalant: less gets to the blood, more hangs around the lungs where it is needed. Perhaps the best thing about oseltamivir is that it can be used for prophylaxis of the flu, which is especially helpful in high intensity infection settings such as nursing homes.

I've never been a big fan of oseltamivir. Its window of use is brief, its maximum effect is limited, and its side effects are potentially problematic. When I was hospitalized for bacterial pneumonia I was started on oseltamivir -- six days after arrival. That made no sense to me unless there was a concern I was coming down with a secondary infection. I experienced hallucinations. I can't be sure it was the oseltamivir, but delirium is one of its side effects.

Oseltamivir has not been shown to be effective in the previous SARS outbreak, nor did it change long-term outcomes of previously infected SARS patients. It is unlikely that it will work for the current coronavirus.

Favipiravir (Avigan) is fascinating. It has been shown to have efficacy for a variety of RNA-viruses. It has been approved for use in China, Japan, and Italy and has made it through a pair of Phase 3 studies in the US for the treatment of influenza. (China and Italy approved it just this past week.) Its mechanism of action is similar to that of ribavirin and remdesivir (below): they all inhibit RNA virus RNA polymerase.

On March 17, China announced that they had completed clinical studies for favipiravir and that it was helpful in recovery from the disease. To quote:

"The Third People's Hospital of Shenzhen in Guangdong province conducted a clinical trial on 80 patients, with 35 receiving the drug. The results have shown patients treated with favipiravir took four days before being tested negative, whereas the control group took 11 days."

That's a pretty dramatic difference. It is said to not be helpful in severe disease. As I discussed in my pharmacology class, with severe viral diseases such as influenza, all the cells that are going to be infected are infected.

I am surprised by their description of "no obvious adverse effects," same source as above, however, Phase 2 trials in the US showed a low degree of side effects.

Phase 3 studies against influenza virus were finished in 2015. No results have been presented. That suggests the results were not good, at least against the flu virus. Good results get published and the drug is put in for approval.

Remdesivir is much like favipiravir, only earlier in being studied. It has the same mechanism of action. Studies are beginning now.

Lopinavir/ritonavir (Kaletra in combination). These are anti-HIV protease inhibitors. There is no reason to believe they should work on coronavirus and an initial study indicates that they don't.

Chloroquine (Araclen) and hydroxychloroquine are classical antimalarial drugs. For decades chloroquine was the drug of choice against malaria due to being effective while being safer than the others. Now chloroquine-resistant malaria dominates the world and, we have some newer choices that are more powerful, the artemisinins. Hydroxychloroquine is also an antiinflammatory and is used for rheumatoid arthritis.

When I said these are safer than other antimalarials, I didn't mean that they don't have any toxicities. Like quinine, chloroquine and hydroxychloroquine can affect blood sugar. It can cause headaches, diarrhea, and hemolytic anemia in patients with G-6-PD deficiency.

There has been one smallish study that found that azithromycin (an antibacterial protein synthesis inhibitor, Zithromax) and hydroxychloroquine helped to dramatically reduce the length the patient carried the virus and the amount of the virus. The drop out rate was high (6 out of 26) among those initially treated with three of those going to the ICU and one dying. All in all, the study is open for interpretation as either hopeful or problematic. As is usually the case, more studies are needed.

Another study from China found efficacy from chloroquine and remdesivir, in vitro. 

So how does chloroquine or hydroxychloroquine help? That's unknown. Perhaps it is the anti-inflammatory effect. The azithromycin might be preventing secondary bacterial pneumonia infection or it might be due antiviral properties that azithromycin is claimed to have. Furthermore, azithromycin is also an antiinflammatory. On the other hand, since chloroquine has been shown to be effective in vitro, that suggests its effect is more than the antiinflammatory actions.

Concerns about what drugs not to use.

ACE inhibitors / Angiotensin Receptor Blockers (ARBs)

These drugs are standard care for high blood pressure and are used as adjuncts in congestive heart failure. Do they make coronavirus symptoms worse? There are three reasons why this is suspected.

1) SARS-CoV-2 uses the angiotensin coverting enzyme type-2 as a cell receptor for infection.
2) ACE inhibitors, in particular, have been shown to upregulate angiotensin converting enzyme. 
3) Among the co-morbidities for death in Italy in one study, 74% of patients had high blood pressure. This might simply be because high blood pressure and age have a strong association. Age also presents a strong association with SARS-CoV-2 lethality.

In a recent commentary, it was strongly suggested that patients do not stop using these popular blood pressure medicines: the evidence for bad outcome with SARS-CoV-2 infection is not clear. The authors disclosed pharmaceutical ties. Nevertheless, the advice is generally sound.

Ibuprofen / NSAIDs / Acetaminophen.

Ibuprofen in particular was mentioned as something that might be avoided. The director of the National Institute of Allergy and Infectious Diseases, Anthony Fauci, suggests that this is an alarmist extrapolation from aspirin in viral infections causing Reyes' syndrome in children. Others have suggested that fever has a place in the body's fight against infections, and that NSAIDs and acetaminophen lower fever.

Let's take these one by one. The Reyes' concerns should not carry over to other NSAIDs and should not affect decisions in adults. For children, for pain and fever, it is generally recommended to avoid aspirin. Some physicians recommend acetaminophen. Acetaminophen overdose is so common, I would go with a non-aspirin NSAID.

Is lowering the fever in the case of a viral infection a bad strategy? Is the body fighting the infection with fever? In the case of bacterial infections this makes more sense to me. When culturing human pathogenic bacteria, the classic temperature of the heating device is 98.6 F (37 C). This concept to  doesn't pass over to viruses. Viruses in the blood are not going to affected by a fever. Viruses perform their main functions, including replication inside of cells, which I suspect are less susceptible to overall body temperature changes. That said, there is an argument that the induction of heat-shock proteins is protective. In the cited study, the temperature was raised to 40 C (104 F), which is a fairly heavy duty fever, the upper range below emergency.

Asthmatics are advised to avoid NSAIDs. This is because NSAIDs block the production of prostaglandins and the action of blocking the production of prostaglandins shunts the precursors over to leukotrienes, some of which mediate inflammation, and, in particular, mediate inflammation in asthma. If those leukotrienes are exacerbating symptoms in coronavirus patients with compromised respiration, this may be a concern. Of course, some asthma patients will have coronavirus. Perhaps using a leukotriene synthesis blocker such as zileuton could be helpful to overcome this.

The FDA is stating that there is not enough evidence to exclude the use of NSAIDS in coronavirus.

So, what's the bottom line? This is my take. If you have mild symptoms of fever and aches and you don't know if you have coronavirus, and you are over 12 years of age and don't have asthma, take an aspirin or other NSAID. The most significant exception to that rule is if you are allergic to aspirin. In the same situation if you're under 12, then try acetaminophen or ibuprofen. If you have coronavirus and you are not actively have problems breathing, then the NSAIDs are okay. For asthma, acetaminophen will not cause the problems with peripheral leukotrienes.

NSAIDs may be contraindicated if the infection is severe and with active respiratory problems. Even then, the evidence is out.

My primary sources in putting this together were (a) Anthony Fauci's March 18 podcast with the editor of the Journal of the American Medical Association, and (b) Derek Lowe's In the Pipeline blog as part of Science Translational Medicine, his March 6th and (c) March 19th entries.

(a) https://youtu.be/EXY76TKNy2Y
(b) https://blogs.sciencemag.org/pipeline/archives/2020/03/06/covid-19-small-molecule-therapies-reviewed
(c) https://blogs.sciencemag.org/pipeline/archives/2020/03/19/coronavirus-some-clinical-trial-data

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Who Topped the New York Times Adult Best-Selling Ficiton List, 2010-19, Men or Women?

I have made a number of posts regarding the nature of the books and authors that have made it to the top of the New York Times Best-Selling Adult Fiction List. These include the age of the authors, the length of stay on top, the length of the books, and the sex of the authors.


In the past, men have dominated that list. For example, in the years 1958 to 1961, and as recently as 1993, no woman author made the top spot on the list for even one week.


Things started to changed in the late nineties. The reason was J.K. Rowling. Her Harry Potter series started dominating the list. The New York Times would not allow this. Kids fluff? Beginning with the fourth Harry Potter book, Harry Potter and the Goblet of Fire, July 2000, they banished her works from the Best-Selling Fiction List and created the Best-Selling Children's Fiction List.

The exclusion of Rowling was one of the two main reasons why, during the period between 2000-2009, women faired poorly. The other reason was The DaVinci Code, which topped the list for 59 weeks spread out over four years, 4 of those weeks in 2006, 7 in 2005, 28 in 2004, and 20 in 2003.

So, was it really a blockbuster to beat all blockbusters? J.K. Rowling, sold more books in 2003 than did the Da Vinci Code, with Harry Potter and the Order of the Phoenix, and again won in 2005 with Harry Potter and the Half-Blood Prince.

Yes, Dan Brown has been seen laughing all the way to the bank.

So, let's look at the just-finished period of 2010-2019. Who topped the New York Times Adult Best-Selling List for the decade?

The contest was close. From the period of 2010 to 2018, men were leading, by one week.

In 2019, Delia Owens began a remarkable run with the book, Where the Crawdads Sing, 25 weeks at number one in 2019 and still dominating the list in 2020.

With that bolus, the women won the decade, 268.5 weeks to 253.5 for men. (Books with male and female co-authors, i.e., James Patterson and Maxine Pietro received one half point.)

With so close of totals, I went over the figures of the period 2010 to 2019, raking them to find errors. I did find some, but now am satisfied my tabulations are correct.

Congratulations women!

Female authors were atop the list 268.5 compared to 253.5 for male authors.

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Francis Valencia Ortiz

My grandfather is the subject of a piece of flash fiction that I wrote and which now appears in the October edition of Rendez-Vous Magazine. My mother also makes a guest appearance.

Our family called my grandfather Gee-Gee (hard Gs). We tended to adopt pet names for extended family members.

As it says in the story, Frank spent his life in a war with the willows. His ranch located a few miles from up into the cold mountains Santa Fe.

He bought Rancho Pancho in the 1930s when he had a steady job in spite of the depression and the landowner was desperate to sell.

Since he was my grandfather, I only knew him later in his life. He lived to 96, fighting with the willows into his nineties. In his seventies he had more vigor than me or my visiting college friends.

Frank Ortiz showing off an oversized pine-cone. The piñones inside were the size of a thumb. Unfortunately, they didn't taste good.

Frank Ortiz and my sister, Claire at the ranch.

Frank was very influential in my youth. His energy, positive spirit, and hard work inspired me.

I wrote this cowboy poem about him a time back which first appeared in Rope and Wire. It's in my cranky cowboy voice which possesses me from time to time.

The Nod

I know this might just start a fight but I never liked John Wayne.
It wasn't war or politics, if you'll just let me explain:
Now movie stars always are larger than life and taller than time,
With a dimpled smile in Panavision, they trip the light sublime.
They cast shadows out of sunset that stand grander than any man.
But you don't measure a real cowboy by the life he's larger than
Or how he towers above the Alamo like Widmark with his knife.
You see a cowboy, a true cowboy, is the exact same size as life.

Life fits him well, it's a riding glove he's mostly broken in.
Its favors and tangled pains are a tongue he's always spoken in.
And taller than time? Well, sir, the minute-hand lost its fingers
While roping calves. It oughta know, a minute's too long to linger.
He's not so phony as to hawk colog-ne or ever stoop to rave
Undying zeal for some lame smell: he's more "during grizzle" than after-shave.
He's a side of beef left on the grill well after the cookout's done.
A walking wrinkle, all-caked with clay, and baked by too mean a sun.

In Hollywood what they call "Rodeo" is one long bastardly boutique.
A drive you can't rightly drive, a place where oily leather squeaks.
In LA-LA land you can measure a man by the kind of truck he keeps
Out there a broncobuster is an SOB who broke into their Jeeps.
And when they cruise down Sunset their pickups are anything but Chevies.
(I hear they send their stuntmen in when the kissing gets too heavy.)
It’s all those Hollywood lies that have set their souls off-balance.
They all get told "You're beautiful, babe." (Well, maybe not Jack Palance.)

Which brings me to my grandfather (I'm sorry for the delay).
More a rancher than a wrangler, with less cattle than he had hay.
His sunbaked days meant yanking stumps and ditches to be dredged.
He paid his dues, he lost his teeth from a wild recoiling sledge.
He told me, "We're only visiting here as we toil this rocky land.
We're all just migrant workers, and never more than hired hands.
When laborers do their chores, they don't look for people to applaud."
And when I'd done a good day's work, he gave me a gentlemanly nod.

Death will tarry for the stubborn but still eventually it arrives.
When I last saw my grandfather he had just turned ninety-five.
We spoke of football and then he asked as he took me in his eyes
"Will I see you again?" I wished right then, I had a Hollywood lie.
I voiced some words at his service that really weren't inspired
Then I helped carry out the casket of the man I most admired.
So now I tell my tales before the crowds and bow when they applaud
And yet I'd trade their praise for just one more gentlemanly nod.


Here is a photo of my mother at 16 in a classic Latina dress. (In the story she is referred to as "Sister.")

Finally, here is a photo of my mother, later in life. She died in 2014.

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The Best Jane Marple / The Best Hercule Poirot

Poirot and Hastings. I definitely need to start a finger puppet collection.

The Best Miss Jane Marple.

Miss Jane Marple, Dame Agatha Christie's matronly detective, sleuthed her way through twelve novels and twenty short stories.  A new series is in the works, set to premiere in 2020.

Back in April of 2019, the website Britishperioddramas conducted a readers poll asking which actress did the best job of portraying Marple.

I am personally fond of Margaret Rutherford who appeared in four movies in the 1960s and solidified my vision of the character when I was young. I love Angela Lansbury in whatever she's in. I remember an episode of Murder She Wrote where a man about 30 years younger than Jessica Fletcher had a crush on her. I thought the episode was about me.

A Miss Marple car decal. Only 37 Norwegian krone.

So, here are the top five vote-getters for the best Miss Marple.

5. Angela Lansbury
4. Julia McKenzie
3. Geraldine McEwan
2. Margaret Rutherford
1. Joan Hickson

I have to confess that I haven't seen Joan Hickson's Marple. I suspect that it is very good. This was the period when the BBC was making the definitive Jeremy Brett Sherlock Holmes. I have a fondness for Helen Hayes, who did not make the list.

The Best Hercule Poirot.

A year earlier the same website ran a poll for the best Hercule Poirot. I am glad their commentary mentioned the too-much fidgeting and too-much foppishness of some portrayals. In my opinion, with all of his ticks and quirks, and with an improbable accent, the Poirot character is a minefield where many great actors have exploded. They leaned into his mustache and never escaped. I've seldom seen a sad side of Poirot, and yet this is an impression I get from reading the books.

Their top five list.

5. Alfred Molina
4. Albert Finney
3. Kenneth Branagh
2. Peter Ustinov.
1. David Suchet.

The top vote-getter had to be David Suchet. He is seared into my mind as Poirot. 

In 2015, Vulture magazine produced a list of the top Poirots as determined by critic Kyle Turner.

9. Andrew Sachs
8. Tony Randall
7. Satomi Kotaro
6. Peter Ustinov
5. Alfred Molina
4. Ian Holm (Poirot argues with Agatha Christie for the right to live)
3. Kenneth Branagh
2. Albert Finney.
1. David Suchet.

The Best Christie Film Adaptation.

As a bonus, here is a list from Taste of Cinema curated by film critic Ryan Anderson as to the best Agatha Christie adaptations: my comments added.

9. Ten Little Indians (1965)
How did this get on the list? I remember stiff acting and no tension. Starring, among others, Fabian.

8.  The Mirror Crack'd (1980)
Full of crackling wit. Probably my favorite color film adaptation of Christie.

7. Murder at the Gallop (1962)
Another great Margaret Rutherford/Marple film. I kind of like the idea that they took a Poirot novel and fitted it for Marple. I think Marple would be a great choice in The ABC Murders. 

6. Evil Under the Sun (1982)
I've seen it. But I can't remember it.

5. And Then There Were None. (1945)
Great wit, great acting, great directing. Should be in the number two spot.

4. Death on the Nile (1978)
I remember knowing whodunnit the moment the murder happened. This movie jaded me as to Christie's plots, at least for a while.

3. Murder, She Said (1960)
Why I love Margaret Rutherford.

2. Murder on the Orient Express (1974)
Very good. I wasn't that crazy about Ingrid Bergman's performance though.

1. Witness for the Prosecution (1957)
All of Billy Wilder's films from this period were perfect.

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