photo courtesy of pixabay.com
A report in STATnews (statnews.com): Just when you thought Ebola virus was only a memory, two more cases were discovered. By the time they were ascertained (found) they had already died. These cases brought a stop to the hoped-for announcement of the end of the latest Ebola outbreak. This outbreak, which was in the Democratic Republic of the Congo in the provinces of North Kivu and Ituri, has killed at least 2,274 people out of 3,454 known to have been infected. It was the second-largest outbreak on record, and it is still not quite over.
The World Health Organization (WHO), the Congolese government, and its partners (unspecified), are still monitoring the situation in Congo. There is no excuse for the administration’s threat to end US funding for the WHO when things like this are still going on. The fickle and sociopathic, narcissistic insistence on fealty continues.
photo courtesy of PublicDomainPictures and pixabay.com
This letter published in the New England Journal of Medicine (NEJM) reinforces the previous reports that I have found in stating that the majority of people who are positive for SARS-CoV-2 are asymptomatic.
Here’s the nut of the story:
From March 22 to April 4, some 215 women delivered babies at a New York City health system. Of these, four had symptoms at admission and tested positive for SARS-CoV-2. Of the remaining 211 asymptomatic women, 210 had nasopharyngeal swabs taken, and 14% (29 women) were positive for SARS-CoV-2. Therefore, nearly 90% of women who were positive at admission were asymptomatic.
These reports are very reassuring. Most people who are infected have no symptoms. It is only people at high risk who develop symptoms and get really sick. A few will die. It is these patients who are of concern, and it is for them that we have to isolate. Despite being reassured about personal risk, I am convinced that it is necessary to keep people isolated until we find effective treatments and even then, to maintain precautions until everyone can be either vaccinated or proven to be immune by blood antibody testing.
(image courtesy of pixabay.com and Gerd Altmann)
A report on the blog “FiveThirtyEight” from April 4, written by Nate Silver (already famous for his political polling expertise), explains why the case counts for COVID-19, the disease caused by SARS-COV-2, vary so dramatically from country to country. More importantly, they explain why all case counts deeply underestimate the actual number of infections– by a rate of anywhere from double to a hundred times less.
The blog post is long and complex, but those of you with a statistical bent or who are comfortable with numbers will find it fascinating. It explains what goes into a case count and why those numbers lag behind actual cases anywhere from a few days to two weeks. There are many reasons, from lack of testing materials to political propaganda (in some cases), for this undercount.
Attempts to determine the final case fatality rate (CFR, the number of patients with infection who eventually die) will not be successful until the peak of the pandemic has long passed. It takes, usually, about five days (anywhere from two days to more than two weeks) from exposure to the time symptoms appear (if they appear) or an infection is established. Nasopharyngeal swab testing for the presence of viral RNA (the actual genome of the virus) is most likely to show positive results by day eight of infection, and may precede symptoms by up to 48 hours– that is, if symptoms ever appear. Tests at this time show about 75% of actual cases. Once the infection is established, it may take anywhere from 48 hours to three weeks before a patient succumbs (dies) from the virus. Not all deaths are recorded as being due to the virus: for example, in New York in late March, there were over five thousand excess deaths, but only half of these deaths were recorded as being due to the novel coronavirus. Many, if not most, sudden deaths at that time were assumed to be due to stroke or heart attack; if they occurred at home before medical care was sought, there may be a mystery as to what symptoms preceded the demise (death).
A single excess death, viewed alone, cannot not be ascribed to the virus unless testing is done. Evaluation of people already dead seemed like a waste of resources in light of the shortage of tests, but it impaired our ability to see the excess deaths as due to the virus. People have been found dead at home, in the subway, lying on the sidewalk under a pile of newspapers, and in other unlikely places. Handling people recently deceased from the virus could be hazardous to the health of first responders who are needed for many other things during this emergency.
Another issue which is never mentioned (except in Nate Silver’s blog post) is the false positive rate (the rate of positive tests when the patient does not actually have the disease). This rate is trivial for the RT-PCR test except when the total positive rate is very small. In cases of very rare disease, the false positive rate, even if very low, may overwhelm the true positive rate to such an extent that confirmatory tests are needed to establish actual disease. In such cases, with very rare diseases, a positive test must be considered a “suspected” case and lead to further investigation. False positives may overestimate disease prevalence (the rate of disease at any point in time) by as much as two hundred to one in cases of rare diseases such as acromegaly (abnormal bone enlargement due to high levels of growth hormone) and autoimmune disorders.
All these factors (excluding false positive rates, which are trivial in such a common disease) have led to an underestimation of the case counts and deaths related to SARS-COV-2. Despite these obvious factors, the conservative media has been pushing the conspiracy theory that deaths due to the virus have been grossly overestimated. This is obviously false, but it feeds into the conservative mind-set that believes that the whole pandemic is a Democratic hoax. Nothing could be further from the truth or more dangerous at this dangerous time.
Coronavirus by Engin Akyurt via pixabay.com (open access)
NIH announced on Friday that they are starting a clinical study and recruiting patients to determine the prevalence (overall number of people positive now) of blood antibodies to SARS-COV-2, the virus that causes COVID-19. They plan to recruit 10,000 people to participate in the study. They will conduct virtual (over the phone or Skype) clinic visits and send participants an at-home blood collection kit with a questionnaire. The micro-collection kit has been well studied, and NIH is confident that it will allow them to obtain blood samples from a finger-stick. These will be adequate to obtain both IgG (chronic) and IgM (acute) antibodies (blood proteins that fight infections).
I am excited about this study, in part because an email address was provided for people who want to participate. As I mentioned in a previous post, I have an hypothesis that I may have had an inapparent infection with the virus, contracted from my wife, who is still practicing as a PA. She works in a community clinic in a rural town outside of Fresno. In mid- to late-February, one of the MAs at the clinic came down with a cough. It turns out that her husband works “out of town” in the Bay Area, one of the local epicenters of infection. The whole clinic staff came down with similar, mild upper respiratory infections (colds or mild flu) and were mostly recovered by mid-March. This was before the state was locked down and before the virus was anything but a gleam in my eye.
image courtesy of Safa Tuncel (TuncelSafa06) thru pixabay.com
photo by Andrew Martin courtesy of pixabay.com
This article by NBC discusses the administration’s response to the novel coronavirus in all its gory details. It seems that the first son-in-law has been making personal contacts, reaching out to large companies with sources overseas, ignoring smaller companies that do all their manufacturing in the US, failing to show any transparency at all, un-necessarily contracting with private companies for airplane transportation of essential supplies when the Air Force could do the job just as well, and on and on. The article is quite long and attempts to be more informative rather than accusatory, but you’ll get the point that the response is late and confused, while relying on personal contacts instead of long-established government expertise.
Read it and weep.
photo courtesy of engin akyurt and pixabay.com
These tidbits have come from a wide search of recent literature on COVID-19 (coronavirus disease 2019) and its causative agent, SARS-COV-2 (severe acute respiratory syndrome-coronavirus 2).
First, you should have blood type O positive. Not easy to do, but if you can arrange to be born this way, that would be nice. There is an association in multiple surveys between type O blood and less COVID (sorry, no reference at hand but there are several available).
Second, any diseases that you may have, such as asthma, high blood pressure, diabetes, kidney insufficiency, coronary heart disease, in fact any disease at all, even if it’s only a genetic tendency about which you are completely unaware, you should not have. If you do have it, keep it under rigid control. Now is the time to lose that weight, get your blood sugar down, lower your blood pressure, and take long-term asthma control medications like topical corticosteroids (inhaled cortisone and/or cortisone nasal spray)– but don’t take oral cortisone or other potent anti-inflammatories, unless your doctor tells you to do so. This is common sense, and many studies show an association between chronic diseases and high mortality in COVID.
Third, if you have a vitamin D deficiency, or even think you might, you should take replacement doses of vitamin D3. This is available over-the-counter– unfortunately, the research on all-cause mortality (death for any reason) is not conclusive (yet) but it is clear that even large doses of vitamin D3 are not bad for you (I’m gonna get dissed for saying that, but so be it). Many people are low in D and don’t know it because it is still not routinely evaluated with the widely available blood test. I won’t recommend a specific dose of D3, but you can ask your nutritionist.
On the other hand, vitamin A is potentially toxic and has not been seen to have any benefit in severe COVID-19 (see the above-referenced study again). Multivitamins are fine, but they haven’t been shown to lengthen your life in general, so they’re optional unless you have a terrible diet already.
Fourth, you should be young at heart. Try singing, the song that is. You don’t have to be chronologically young (again, see the above-referenced study). A positive mental attitude will help you no matter what else is happening. You can still get sick, but having a good attitude and not being a pain in the neck will help others around you to rally to your side.
Finally, if you should have the misfortune to be exposed to a patient with COVID, try to make sure it’s a very light exposure. I’m speculating here, but the experience with many other infectious diseases (like smallpox) is that small exposures can lead to mildly symptomatic disease, while massive exposures can be overwhelming. This aspect of the new coronavirus has not yet been studied, which is not surprising given that the disease is only four months old.
Until a vaccine is widely available or we have a positive blood antibody test, it is incumbent upon us (we are obligated to) be careful and try to stay healthy in case we are exposed despite physically distancing ourselves from other susceptible people.
Coronavirus by Engin Akyurt via pixabay.com (open access)
(Nota bene: This is an enlargement of my last post, with a title altered to be more specific and a few new sentences at the beginning about the initial stages of the outbreak. My statement about the size of the outbreak in China is merely speculation, but it is informed speculation.)
When COVID-19 was first detected in Hubei, China in late November or early December of 2019, it presented as an unusual outbreak of atypical viral pneumonia. Patients with this disease presented with fever, dyspnea, cough, and chest pain. They had negative tests for influenza, respiratory syncytial virus, and bacterial pneumonia, but their blood showed signs of raging infection: elevated C-reactive protein, abnormal white blood cell counts, and dropping oxygen saturation (blood oxygen levels). Their chest CAT scans (computer-assisted tomography) showed a characteristic pattern of hazy, “ground-glass” opacities (areas of increased density) in the lungs, usually bilaterally (on both sides). Some of these patients inexorably went downhill, stayed on the ventilator (a machine which pumps oxygenated air into the lungs through a tube inserted into the windpipe, while the patient is heavily sedated) for long periods of days and weeks, and developed multiple organ failure. Their kidneys, livers, brains, muscles, and finally hearts, broke down. Some of them died.
This was the picture of COVID-19 as it was presented to the world. No-one seemed to realize that the infection was in most cases completely asymptomatic (without any symptoms of illness) or trivially symptomatic (with a runny nose or fatigue). It was really looking at the tip of the iceberg to see the new virus as pneumonia. Within three months, the virus spread around the world, leaping country borders and side-stepping quarantines. It spread so fast that even our president was unprepared (although he later said that he had known it all along and was just making happy talk to keep people from panicking). /s
The Chinese government, once they realized (unwillingly) that they had a potential pandemic on their hands, reacted with draconian severity. Quarantines on patients were enforced by the police, who were used to keeping dissidents under close observation and applying all sorts of pressure to keep people under control. Contacts of known cases were separated from their families and put into rudimentary holding cells repurposed from hotels and inns. Eventually, the doctor who had sounded the warning about a new form of atypical pneumonia was vindicated– posthumously.
He received an official apology for being called in to a police station and being told to shut his face– unofficially arrested for making a case report– and the officials who oversaw his silencing were dismissed. His relatives appreciated the gesture, but he had already died of COVID-19. We can assume that he faced massive exposure to the virus in the course of his work and succumbed to an overwhelming infection.
Even now, the true scale of the epidemic in China is unknown. Estimates of the actual number of patients involved have not been publicized, in part for fear of sounding alarmist. The government still reports only clinical cases of the viral illness that require significant intervention as “positive for viral RNA” although it has reflexively quarantined anyone who comes in contact with known cases. They do have a count of people known to be exposed and known to have tested positive, but they have not revealed these numbers.
While it is unfair to the rest of the world not to reveal the true figures for known infections, the Chinese have done the only thing that could have been effective against an infectious agent of this degree of “sneakiness”. The Chinese system routinely violates civil liberties, but it is effective against an agent that “flies under the radar” in about 90% of cases. I, personally, based on developments described below and in my last few posts, roughly estimate that the true case count in China is five to ten times as high as what has been officially reported.
A study published in BioRxiv on April 6 analyzes the reports from Iceland, where a community-wide voluntary random sampling program is underway. These studies are based on two sample sets, as the abstract explains:
The criteria for testing within the Icelandic medical system, processed by the National University Hospital of Iceland (NUHI), have also been targeted at high-risk individuals, but additionally most Icelanders qualify for voluntary testing through the biopharmaceutical company deCODE genetics.
Based on these samples, the authors of the BioRxiv study analyzed the data and found that:
Our primary estimates for the fraction of infections that are undetected range from 88.7% to 93.6%.
This report and the reports from California described in my previous posts reinforce my impression that we are massively underestimating the rate of SARS-COV-2 spread through the community. My own personal experience suggests that a wave of infections passed through our rural area in mid- to late-February, hitting medical staff at a community clinic through exposure to one or a few symptomatic patients before anyone realized what was happening. Now the infection is reaching shut-ins and chronically ill people who are relatively isolated from the rest of the community. These patients are the most susceptible to severe and overwhelming disease, and they will represent the largest percentage of deaths due to COVID-19.
Robust patients with inapparent disease who travel widely have spread the virus throughout the community; less than 10% of them have been detected. Now the isolated patients will begin to fall ill, and they will be detected with much greater frequency. More than 10% of them will die.
We need a massive rollout of blood antibody tests for everyone so those who have been infected and are now immune can go back to work. We need a smartphone app, like so many other countries already have, so that susceptible people can avoid known cases, self-isolation can be monitored, and immune people can advertise that fact. That is the way to get from behind the eight-ball.
Data from Iceland suggest that roughly 89 to 94% of infections have gone undetected: BioRxiv
Coronavirus by Engin Akyurt via pixabay.com (open access)
A study published in BioRxiv on April 6 analyzes the reports from Iceland, where a community-wide voluntary random sampling program is underway. These studies are based on two sample sets, as the abstract explains:
The criteria for testing within the Icelandic medical system, processed by the National University Hospital of Iceland (NUHI), have also been targeted at high-risk individuals, but additionally most Icelanders qualify for voluntary testing through the biopharmaceutical company deCODE genetics.
Based on these samples, the authors of the BioRxiv study analyzed the data and found that:
Our primary estimates for the fraction of infections that are undetected range from 88.7% to 93.6%.
This report reinforces my impression that we are massively underestimating the rate of SARS-COV-2 spread through the community. My own personal experience suggests that a wave of infections passed through our rural area in mid- to late-February, hitting medical staff at a community clinic through exposure to symptomatic patients before anyone realized what was happening. Now the infection is reaching shut-ins and chronically ill people who are relatively isolated from the rest of the community. These patients are the most susceptible to severe and overwhelming disease, and they will represent the largest percentage of deaths due to COVID.
Patients with one foot in the grave will shuffle off the mortal coil and jump into their coffins when they are confronted with SARS-COV-2. I couldn’t resist using those stereotyped metaphors and similes to make a point: the most delicate patients will suffer the most from this virus. Robust patients with inapparent disease have spread the virus throughout the community; only 6 to 11% of them have been detected. Now the isolated patients will begin to fall ill, and they will be detected with much greater frequency. More than 10% of them will die.
Coronavirus by Engin Akyurt via pixabay.com (open access)
A study reported in BioRxiv on April 7 looked at using a combination of symptoms to predict infection with SARS-COV-2 and COVID in a UK (United Kingdom) community survey of 1,573,103 individuals, roughly 26% of whom said they had at least one symptom. They found that reports of multiple symptoms predicted infection with a greater likelihood than individual symptoms. Anosmia (loss of sense of smell and taste) was present in 59% of patients with confirmed infection; this symptom is a more recently recognized one. The group of symptoms that best predicted presence of the virus was the following:
… a combination of loss of smell and taste, fever, persistent cough, fatigue, diarrhoea, abdominal pain and loss of appetite is predictive of COVID-19 positive test with sensitivity 0.54[(range) 0.44; 0.63], specificity 0.86[(range) 0.80; 0.90] …
This specific combination of symptoms had not previously been reported to predict infection, but this large community survey confirms that there is a set of symptoms that together makes the diagnosis much more likely. Given that detection of the virus by nasopharyngeal swabs is not as sensitive as we would like (roughly 74% of victims have positive swabs on day eight after exposure) and depends on exactly when the test is done, we need a set of symptoms to guide us in presumptive identification of cases for isolation in the absence of universal testing.
Other symptoms, such as body aches (myalgia), headache, confusion, shortness of breath (dyspnea), chest pain, and productive cough, are also associated with COVID-19. They may relate to other manifestations such as pneumonia (possibly related to immune reaction) and brain infection (a feared but rare complication). The main symptoms of abdominal pain and diarrhea point to the presence of gastrointestinal (GI) (stomach and guts) infection as a primary factor in addition to the nasopharyngeal (nose and throat) route. GI infection has been suspected since fecal (stool) specimens have shown virus to be present in acutely ill patients.
This report suggests that patients with this combination of symptoms are the most likely to have the virus, although sensitivity is still poor at about 54%. RT-PCR testing of nasopharyngeal swab specimens to detect acute cases and blood antibody tests (a combination of IgG (chronic) and IgM (acute) antibodies) are needed to accurately outline the incidence and prevalence (new cases at any moment and overall number of cases) of COVID due to SARS-COV-2.
Other reports from early in the pandemic of wide community spread suggest that trivial or asymptomatic (no apparent illness) cases represent a major proportion of people with this virus, possibly as many as half. SARS-COV-2 may have been spreading widely on the West and East Coasts long before we realized that it was even present at all. Infected people without symptoms may have introduced the virus to the US early in January at the latest.
We were already far behind this virus when the first federal action was taken, a partial ban on travel from China, in late January. Warnings from the intelligence community in late December and early January were ignored. We have been playing “catch-up” ever since, a losing battle given the disorganized and tardy federal response. Even now, the administration is co-ordinating the sourcing of equipment through favored large companies and personal connections at great public cost. This is a subject for another post.
Conrad Theodore Seitz 