Civil Defense Perspectives – January 2020 (vol. 35 #1) – posted June, 30, 2020
In January, there were many unknowns about the terrifying new demon that was raging in China, causing untold numbers of deaths. The official statistics were appalling enough, but there were rumors about crematoria working constantly, incinerating undiagnosed and uncounted corpses. Then horror stories started pouring in from Italy, which has a very large Chinese work force, especially in the fashion industry, with frequent travel to and from China. Ominous red dots on the Johns Hopkins Center for Systems Science and Engineering (CSSE) website spread to engulf most of the world, especially the U.S. and Europe (tinyurl.com/uwns6z5).
In late June, when this is being written, unknowns remain. The disease offers an opportunity to learn a tremendous amount about viral diseases and their treatment—which may be squandered because of political opportunism and financial conflicts. Your editor has been sorting through a tsunami of information—see bit.ly/coronavirusarticles and jpands.org/jpands2502.htm.
Disease Characteristics
Based on early clinical manifestations, COVID-19 may be indistinguishable from influenza or other “influenza-like illness” (ILI): fever, body aches, cough, prostration. Gastrointestinal symptoms may be prominent, and virus or viral fragments are frequently found in feces. One distinguishing feature, which may occur in around 40% of cases, is loss of the sense of smell and taste. A CT scan of the chest may show ominous-appearing “ground-glass” opacities on both sides, even in patients who do not appear severely ill. It is important to check oxygen saturation with a pulse oximeter even if the patient is not short of breath.
Striking features and devastating complications that may occur in COVID-19 patients (see p. 2) also occur in other viral illnesses that are generally believed to be benign.
It is possible that outbreaks of severe ILIs in the U.S. last winter might have been COVID-19, as testing for influenza is commonly not done. Research based on satellite images done at Harvard Medical School suggested that China may have been dealing with clusters of unusual pneumonia cases as early as August 2019 (https://tinyurl.com/yc54jqr3). Beijing called the study “ridiculous” (https://tinyurl.com/y8worzyz). The timeline is important; if disease was present months before it was recognized, containment was already impossible in January.
The SARS-CoV-2 virus, which causes COVID-19, is covered with “spike” proteins, which attach to cell receptors for angiotensin converting enzyme 2 (ACE2). These receptors are found in many tissues, including lung, kidney, heart, liver, blood vessels, fat, and gastrointestinal tract. Persons with hypertension, diabetes, obesity, or coronary heart disease may have more ACE2 receptors, possibly explaining their high risk for more severe disease, and children appear to have fewer in their airway, making it more difficult for the virus to infect them. Research in several countries has found that “children are weak carriers, poor transmitters, and when they are infected it is almost always adults in the family who have infected them” (tinyurl.com/ya2k39mu).
The illness has four stages, according to the Eastern Virginia Medical School (EVMS) group headed by Dr. Paul Marik (https://tinyurl.com/vytf3ye): incubation, symptomatic, early and late pulmonary. Initially rapid viral replication peaks during the early symptomatic stage and wanes during the pulmonary phase, when immune dysregulation (“cytokine storm”) is the main threat, and the virus is mostly cleared from the blood.
Testing
Testing was mostly unavailable in the U.S. in January because the Centers for Disease Control and Prevention (CDC) forbade testing by others but produced a faulty test itself. By late June there was a testing frenzy and a predictable surge of positive tests, each one called a “case,” even if no signs of illness ever occur, writes Dr. John Littell (tinyurl.com/ycmp4pgo).
A “test adoption curve” could be mistaken for a “disease spreading curve” (https://tinyurl.com/yanha48o).
There are two basic types of tests: the polymerase chain reaction (PCR) test, used to identify fragments of the viral genome in secretions, and antibody testing (see p 2). The CDC has evidently been conflating the two, compromising the metrics used by health departments (https://tinyurl.com/y92ea59f). IgM antibodies are produced first, and IgG antibodies after about a week.
Testing serves an important epidemiological function for identifying hot spots of infection and tracking the course of an epidemic. In the absence of specific antiviral therapy, it is of limited use for guiding patient treatment. Unlike bacteria, viruses are usually not grown in culture to determine drug sensitivities.
No test is perfect; all have false positives and false negatives. If a low-risk population is tested, the chance that a positive test will be a false positive may exceed the probability that it is a true positive, even if the sensitivity and specificity of a test are impressively high. This is why screening everybody for everything is not a good idea. Some have proposed widespread screening for HIV. Huge numbers of uninfected people could be stigmatized and sentenced to lifelong, expensive, toxic therapy.
As Dr. Wolfgang Wodarg pointed out, a test with a 1.4% false-positive rate could “find” about 3 positive persons in a church with 200 worshipers and send the entire congregation into quarantine to “fight” COVID-19. In his view, the red dots on the CSSE map “usually have less to do with disease than with the activity of…crowds of sensationalist reporters.” One cannot say there has been an increase in positive tests without a baseline for comparison (https://tinyurl.com/y9hh8oab).
Could a positive IgG test show that a person is immune and could travel and work without restriction—and not need the currently nonapproved vaccine? Some state that the natural antibodies might not be effective at neutralizing the virus—although donated plasma from recovered patients is being used with some success in treatment—or might not persist long enough. Vaccine effectiveness, however, is judged by antibody titers.
Antibody tests “should not be used to make decisions about returning persons to the workplace,” stated CDC. Antibody tests are wrong up to half the time. If just 5% of the population being tested has the virus, a test with more than 90% accuracy can still miss half the cases (tinyurl.com/y94mo3yy).
Perhaps a vaccination certificate would do?
Kawasaki Disease
A new scare concerning COVID-19 is Kawasaki disease, a form of vasculitis that affects many organs in children. Its cause is unknown despite several decades of investigation. It may be associated with a viral respiratory infection in the 30 days prior to the diagnosis. A number of viruses (including rhinovirus/enterovirus, parainfluenza, respiratory syncytial virus, influenza, and adenovirus) have been implicated, and recently some patients have tested positive for COVID-19 (tinyurl.com/y77vupgc).
There are about 5,000 hospitalizations each year for KD in the U.S., and fewer cases than expected are being seen this year. However, based largely on a dubious study of eight cases published in Lancet, the CDC rushed to create a new notifiable condition that amounts to Kawasaki in the presence of coronavirus: Multisystem Inflammatory Syndrome in Children Associated with Coronavirus Disease 2019, “asserting by way of definition an association not proven to exist” (tinyurl.com/ya2k39mu).
Some research suggests lockdowns may make KD more common by reducing immune system stimulation. But the more likely cause of recent severe cases in cities with hard lockdowns is that lockdowns discourage or prevent parents from seeking treatment earlier in the disease. Prompt treatment is needed to prevent heart complications (ibid.)
“COVID Toes”
“Frostbite-like” blue or red patches, primarily on the toes, have been reported in many patients who tested positive for COVID-19. Usually the rash disappears in 2–3 weeks. Most patients are children or young adults and have few other symptoms. The rash also occurs in patients who test negative.
In the case of a 23-year-old student in Belgium, researcher Curtis Thompson said a biopsy showed inflammation in the dermis that looked nearly identical to what he’s seen in patients with lupus (https://tinyurl.com/y86euykh).
Viral diseases frequently produce a rash. So many types of rashes have been described in COVID-19 patients—“it’s like reading a dermatology textbook”—that it is hard to tell whether they are associated with SARS-CoV-2 or are possibly a coincidence (https://tinyurl.com/y7rl3p85).
Vascular and Neurologic Complications
Occasional severe and horrifying complications in COVID-19 patients contribute to its popular reputation as a unique demon virus. Neurologic complications include encephalitis or inflammation of the brain, also caused by many other viruses. Strokes can occur in young persons, and other problems with microscopic or large clots. An extreme form of the cytokine release storm, called the systemic inflammatory release syndrome (SIRS), damages blood vessel linings, activating coagulation factors, and also impairing clot-dissolving factors (Science 6/5/20).
This is also not unique to SARS-CoV-2. A horrible case of infectious mononucleosis at Yale led to quadruple amputation. The classmates of this unfortunate young woman, who acquired the illness at the same party on spring break, experienced only a moderate illness. The coagulation problems also occurring in SARS-1 (acute respiratory distress syndrome) and MERS (Middle East respiratory syndrome)—caused by other coronaviruses) have furthered our understanding of SIRS.
Why Mothers Kiss Their Babies
All mothers kiss their babies, and barnyard mothers lick them. The immune system of newborns is not well developed; they can’t produce IgG antibodies until a few months after birth. Antibodies from the mother’s blood can pass the placenta and provide temporary passive immunity. During lactation, plasma B cells migrate to the breasts, which secrete IgA molecules into the milk. When the mother kisses the baby, she samples the pathogens that the baby is about to ingest. These travel to her lymphoid organs, where memory B cells are reactivated, so mother can feed the baby the exact antibodies it needs (Lauren Sompayrac, How the Immune System Works, 6th ed.)
Dr. Anthony Fauci says we might never be able to shake hands again. But does touching hands or surfaces serve the purpose of sampling pathogens in the environment to alert our adaptive immune system?
What the PCR Test Tests
The real time reverse transcription-polymerase chain reaction (RT-PCR) test detects fragments of RNA or DNA that match the nucleotide sequence in a primer. It finds a “needle in the haystack” and amplifies the signal many times. Developed as a powerful manufacturing technique, PCR was never meant to be used for clinical diagnostics. Its developer, the late Nobel laureate Kary Mullis, argued against PCR as diagnostic tool for AIDS (https://tinyurl.com/sftup2t).
A positive test doesn’t mean that you “have” COVID-19. Samples taken from recovered patients who re-tested positive in South Korea did not grow virus in culture. Presumably they were shedding non-infectious particles (tinyurl.com/y7juxzj3).
Dr. Wodarg suggested testing German or Italian cats, mice, or even bats. In Tanzania, President John Magufuli had security forces use CDC-supplied kits to test samples from a pawpaw, a goat, and a sheep. The pawpaw and the goat were reported as positive for COVID-19 (https://tinyurl.com/yaqunvjl).
PCR may be used to estimate “viral load,” which appears to correlate with severity of disease. Viral duration appears to correlate with duration of treatment with corticosteroids, but effects of steroid and other treatments on the virus have not been well studied. PCR “cannot distinguish between viable and non-viable virus and does not reflect the replication level of the virus in different tissue” [emphasis added] (tinyurl.com/y75tzx5t).
The accuracy of a test is tested by comparing its results with a reference standard. For sick persons, the reference standard is likely to be a clinical diagnosis. “Designing a reference standard for measuring the sensitivity of SARS-CoV-2 tests in asymptomatic people is an unsolved problem” (tinyurl.com/ycyvlngo).
What has not been done is to take tissue samples from sick and healthy volunteers, run PCR tests for various disease-causing viruses, do viral cultures, examine sections with electron microscopy, and correlate the results with clinical findings (https://tinyurl.com/y8d827z8).
The latest 59-page CDC guidance on PCR testing (www.fda.gov/media/134922/download) states the following: (1) Negative results do not preclude 2019-nCoV infection. (2) If the virus mutates in the rRT-PCR target region, 2019-nCoV may not be detected…. An interference study evaluating the effect of common cold medications was not performed. (3) Detection of viral RNA may not indicate the presence of infectious virus.