I thought that it might be useful to my patients and others to discuss some issues around the current Coronavirus pandemic. Although I’m not a Public Health classical epidemiologist, I have had training in Clinical Epidemiology, and have taught in the past what is now called Evidence Based Medicine and evaluates the validity and clinical use of diagnostic tests and treatments among other issues. I will suggest some articles and podcasts which I think are useful, but don’t plan on any formal referencing.
A little about the virus. There’s a great article in The Atlantic, I’m pretty sure available online without subscription. The official name of the virus is SARS-CoV2, because of the similarity with the first SARS virus, which was frequently deadly. Thankfully the first didn’t become a major pandemic because it wasn’t very good at transmitting from human to human. It, as with SARS CoV2, probably had been living in bats for 10,000 years. Bats harbor many viruses, although generally they don’t get sick from most. Rabies can make them sick, and blind so steer clear of any bat flying around in the daytime. MERS virus came up about a decade ago. It’s animal host is camels. It also wasn’t very good at human-to-human transmission, and it still is infecting humans who are up close and personal with camels. SARS CoV2 also probably came from bats, maybe first infecting another animal which then transmitted to a human. The thought is that this may have started with one human infection in China, probably in a “wet market” where live animals were sold for food. I don’t know a lot about this practice in China. In Africa animal viruses, like Ebola, can be transmitted from handling animals for “bush meat”. They aren’t transmitted by eating the cooked meat. In Africa I think this practice is largely driven by poverty, and not being able to afford to buy food. There are millions of very poor Chinese, so the driver may be poverty. Unfortunately there are Chinese practices which are cultural and actually promoted by the increase in Chinese middle and upper class. Yao Ming, the 7-1/2 foot basketball player after his retirement saved the lives of many sharks trying to educate his country about the ecological disaster of killing sharks for their fins. Wealthy Chinese men fuel the killing of endanger rhinos because they think the horn is a sex enhancer. Nevertheless this is not a “Chinese” virus, although education about the dangers of “wet markets” is crucial. Many experts, and pandemic novelists have predicted this source of infection. Portland Asian restaurants were harmed by the misplaced belief that they were any more dangerous than any other restaurants, which are all now largely closed. SARS CoV2 unfortunately is serendipitously very good at human-to-human transmission. The Atlantic article explains that totally coincidentally the virus developed the ability to utilize a mammalian enzyme present in most mammals, to perform a crucial step in infection, entering the human cells, which is necessary for the virus to replicate and spread in an individual and to then infect others. Everybody has seen the graphic picture (which is not an actual picture) of the beach ball with the little red spikes (they’re not really red). Those spikes have to separate into two halves in order to attach to the mammalian cell and be let in, like unlocking a key. The ubiquitous mammalian enzyme present in humans is used to make this splitting happen. I heard a journalist who has researched viral zoonotic infections, that SARS CoV2 “hit the evolutionary jackpot” by being able, coincidentally, to invade the dominant mammal on the earth.
One of my favorite podcasts on this subject, although there are only 2 episodes so far, is “Osterholm Update: Covid 19”. I have been familiar with Dr. Michael Osterholm since my time in Minnesota in the ‘80s, when he has the head of the Public health system there. Now he is at the University of Minnesota. Very informative podcast, in which he is interviewed by someone in his CIDRAP institute. He is critical of WHO, although generally is very supportive of that group, and of the US response. He feels that it is too late in the epidemic to use widespread testing and contact tracing, right now because of the lack of test kits, but points out that there are not enough public health professionals to carry out the work. He does think that this will be important to track new cases after quarantine and social distancing is relaxed, when new cases will start to rise. He disagreed with WHO and US professionals when they originally stated that the virus was spread by contact hand-to hand or on surfaces, and “droplet spread” but not “aerosols”. Droplets are relatively large globs of our mucous with tons of virus inside. They fall to the ground pretty rapidly, and don’t travel more than a few feet, and obviously on a downward trajectory. The droplets are created mainly by the infected person coughing, although as has been more recently acknowledged, and poetically described by Prime Minister Trudeau through “speaking moistly” Unfortunately he knew that they could also be spread by aerosols, which are smaller and can float in the air for hours. In his CIDRAP group he has a world renowned “aerobiologist” (who knew). Because of this widespread use of masks was not recommended initially, in large part to prevent hoarding of medical grade masks needed desperately by health care workers.
A little more about masks. N95 has become a new vocabulary word for all of us. The 95 is for 95% or particles less than 0.3 microns (which includes the SARS CoV2). My wife happened to buy a N99 mask in preparation for a trip including Beijing, for the notorious air pollution, although she didn’t use because there was rare clear blue skies. In my 30 plus years in medicine, including admitting my patients into the hospital, I had never heard of N95 masks. They are used widely in the construction trades to filter dust. There are also dangerous very small particles in building fires and wildfires, which can get all the way down into the lung air sacs, so are important for firefighters and probably would have been nice during the Gorge fire for residents nearby. Many N95 masks have a plastic valve, which gives them that distinctive look. Some N95 masks don’t have the valve. The masks with the valve work well to filter small particles and virus on inhalation, so protect the wearer, but the exhaled breath is unfiltered and so they probably don’t protect whoever is on the other side of the mask. The masks, because the fabric is so tight, makes it harder to breathe through them; the one-way valve makes it easier to at least exhale, so one can take the next breath in a little faster. There are N95 masks without the valve, but these need to be saved for first responder and direct patient care medical professionals. My wife found a pattern online for a cloth mask. She sewed some for us and a few friends, out of sewing materials she had on hand. The outer layer is a tightly woven (and quite attractive) cotton fabric on the outside, and 2 layers of tee shirt cotton forming a pocket which takes a piece of furnace filter fabric which can be replaced, and removed for washing; the furnace filter fabric would be damaged. Although a patient gave me an N95 industrial mask with a valve, I wear my wife’s DIY one, because I am mainly concerned about protecting the small number of patients that I am still seeing. The work of breathing is noticeably more difficult, so I would say that hers are N140 (get, it, blocks 140% of particles). Some of my patients wear different kinds of masks, and mostly use improper technique, which I am trying to train away. It’s a hard habit to not touch one’s face; I put up with a bit of misery with my mask and would love no more than to rip it off after a few hours, but I do not touch it other than doffing and donning, and wash hands before and after doing so. In a perfect world a new mask would be used for each patient, both in my practice, in hospitals and other settings. There was a heartbreaking OPB story of a Bend hospice nurse who’e company has given her 1 N95 mask and only gets another when it is obviously falling apart. Because of the limitation in mask availability and the need to reuse, it is important to use and handle appropriately. Do not touch the front of the mask unless there’s a sink in front of you to wash. If the front of the mask is contaminated, which for most of us it’s not going to be, but the only reason to wear it is that it could be at any one time, you don’t want to touch. I have seen people touch it with gloves, but then the glove is potentially contaminated. I have seen folks stick their hands under the mask, so if the glove is contaminated so are they. I launder my mask as I noted, as can other cloth masks, but some masks including N95 (remember these are for front line health care workers) can’t really be washed. The virus will become unable to infect after probably a number of hours but almost undoubtably in a few days. So don’t touch the front, hang it up somewhere with the front sticking out, to let it dry out, and if you need to use in less that a few days, put it on trying to avoid touching the front (sometimes not feasible if you need to adjust the nose metal piece to avoid blowby up to your eyes, wash your hands immediately and from then on don’t touch it unless you can wash again. One patient asked me about covering the eyes. The virus can infect by getting in the eyes. The nasolacrimal duct (the tear duct) starts in that little bump on our lower lids, and a small tube runs down into the nasal cavity to drain excess tears (that’s why our nose runs when we cry). It get’s in the nose and that’s where it enters our cells and replicates.
A bit about why some people get sick and die and some may not have any symptoms. As I sure most know, the main difference is the person (the “host”, although not like on Westworld, couldn‘t we use some of those now) can’t fight off the virus. Because this is a new virus for humans, we don’t have any preformed antibodies to get to work immediately. When we acquire an infection, not just viral, some of our white blood cells can “remember” the organism, and can ramp up production of antibodies which facilitate letting the rest of the immune system recognize and attack the invader. We do have some nonspecific defense as well, but these lessen with age, and so age alone can lead to more serious disease. Patients with immune deficiencies caused by disease, or by drugs that suppress the immune system, since many diseases are caused by imbalances in the immune system leading to attacking part of ourselves. (An aside, and I’m prone to asides, our immune system is a “matrix”. The way we recognize foreign invaders, and most of the time not attack parts of ourselves, is that the way we recognize “self” is to make antibodies targeting every protein in our body. If these were left unchecked and triggered an immune response, then we’d die in short order. In order to avoid this we form antibodies against the antibodies against our proteins, than then anti-anti and anti-anti-anti). These keep the original antibody at bay, but it is a delicate balance and no wonder sometimes there’s a crack and we have an autoimmune disease). Most deaths are caused by pneumonia directly caused by the virus getting in the lungs (Influenza, in contrast doesn’t itself cause pneumonia but can make us susceptible to Staph pneumonia, which otherwise is not a typical location for Staph infections).. People with damaged lungs from other disease will suffer disproportionately. There are case of young, healthy people dying of disease. Many of these are front line health care workers, like the 29-year old Chinese doctor, the “whistleblower”. On theory is that most of the time when the number of viral particles inhaled is relative small, most glom onto cells in our nose and throat. They may percolate there for a few days, allowing some antibody response to begin, so when the zillions of virus replicating in the cells, are released and we aspirate, or inhale the viruses from our nose, the immune system can help limit the extent of infection. If a health care worker is putting a breathing tube into the throat of a sick, writhing coughing patient, they inhale a huge dose of virus, particularly early on before it was known these patients had the infection now known as SARS Cov2. Enough get directly into the lung without this early immune response, leading to much more severe pneumonia.
A little bit about hydroxycloroquine, originally developed to treat malaria, although not used that much due to malarial resistance. Used, although there are newer more powerful drugs, for Lupus and other rheumatic autoimmune disorders. It inhibits the immune response, which how could that be useful in an infection when you want a good immune response . The notion is that much of the tissue damage is caused by our own immune response, with “collateral damage” killing our cells along with the pathogen. One term for this is “cytokine storm”, cytokines being the molecules that communicate among the different parts of the immune system. Not unprecedented, we pretreat some pneumonias with steroids before giving antibiotics to reduce the violence of the immune response. To make it clear, though, hydroxychloroquine doesn[t kill the virus, and the is only very weak, and mainly test tube evidence of any benefit so do not use.
A little about Covid19 symptoms. There seems to be less “coryza”, runny nose and sore throat than the typical cold virus or even the typical flu. Fever and cough seem to be the most common initial syndrome. Fever may be significant, 102 degrees or higher, including shaking chills.In China, and I think in the US as well, there were only 2 categories of severity, mild and severe, and severe meant you were in the ICU. I think Chris Cuomo’s was labelled mild despite his fever, shaking chills and hallucinations. Influenza can cause high fever, whereas the typical cold has no or low grade fever. With Covid 19 shortness of breath is the most important symptom to raise concern. Pneumonia of any kind fills the alveoli, the little air sacs, with fluid, so oxygen cannot pass through to the bloodstream. The more alveoli involved, the more short of breath. This can lead to low and even dangerously low blood oxygen levels and is why patients are intubated and placed on ventilators. Other syndromes seem to occur as well. One unusual one is loss of smell and because of the major role of smell in taste, taste is effected. This doesn’t seem to occur because of major mucous buildup which might cause loss of smell in colds or sinus infections. It’s unusual enough to see as a possible clue. There has been evolving understanding, recognition or reporting on the potential for asymptomatic persons. Initially it was recognized that “presymptomatic” persons can be contagious for a few days before symptoms occur. This can happen in the common cold, for a day or so which is why they can spread so much. I have suspected that some persons may not develop symptoms at all, but may be contagious. I would have assumed that the CDC, although advising against widespread testing due to the lack of supplies of tests available, would be doing population based samples in different areas to try to estimate the prevalence, or frequency of asymptomatic individuals, but I have not heard or read anything about this being done. I think this possibility was downplayed initially so as to not freak us all out more than everyone already is. Universal precautions, stay at home orders and social distancing should mitigate this transmission, but it may become more important as restrictions are lifted to prevent a “second wave” of infections. SARS CoV2 seems to be able to present in other ways and effect other organs. There seems to be some effect on the heart in some cases, I gather can cause a myocarditis or inflammation of the heart muscle. Some patients who have had sudden death, due to arrhythmia, who have tested positive. I have seen reports of deaths of 2 celebrities by pulmonary embolism, “blood clots to the lungs”. I don’t know any details, and don’t think that they were tested for SARS CoV2, but seems kind of weird and I wouldn’t be surprised to see a connection.
Never before has the average American known the difference between “respirator” and “ventilator”. The greatest threat for Covid 19 disease is typically going to the ICU and being put on a ventilator, leading to the ventilator shortages in the news. Being on a ventilator is never a good thing (unless it’s in the operating room for your hip replacement). Survival for patients with Covid 19 who need a ventilator seems to be pretty bad. I have seen estimates between 10-50% survival. Patients also seem to need the ventilator longer if they do survive, contributing to the shortages. Elizabeth Eckstrom MD, Chair of Geriatric Medicine at OHSU, who I know from my General Medicine fellowship and from windsurfing at the Fish Hatchery, had a very good interview on OPB. My wife was quite moved, and posted it to Facebook. A small part of the interview was her advice to her patients in their 80s and 90s. She feels that ICU and ventilators have dismal outcomes regardless of the disease at this age, and she recommends that they don’t go to the hospital. It is a miserable experience, and whether due to the underlying disease or the medications needed to prevent agitation, the patient is basically in a coma. Compounding the pain is that in this pandemic loved ones cannot even visit the hospital. She recommends hospice care, providing oxygen, morphine which is very effective to relieve the misery of shortness of breath. Depending on the setting, loved ones may be present. I did read one story in which a ninety year old was felt to require a ventilator for possible recovery, who declined, but nevertheless survived, so some good news.
Some thoughts on the logistics of the worldwide response to the emerging and now ongoing pandemic: “mistakes were made”. My (limited) understanding is that there were delays in China in getting out information. My understanding is that the local governments were afraid to notify the central party apparatus, but when the central government realized this, in part thanks to the "whistleblowing” physician, that they acted “strongly”, as they say. Massive and enforced quarantine seems to have worked to the degree that the US has overtaken China with the number of cases, and since our “curve” is delayed, probably more deaths. The huge manufacturing base has allowed China to resume exports of N95 masks, as an example.
In the US, mistakes were also made. Although very much not a fan of David Frum during his time in the Bush II administration, his Atlantic article from yesterday details the timeline of response and the obstruction of progress since the current administration learned of the China cases. Trigger warning, despite Frum being a republican, it is very and directly critical of Trump. I don’t remember if he mentioned the “dismantlement” of the Security Council office of pandemic management which was formed in the Obama years after the H1N1 influenza scare. The National Stockpile was also boosted. There was a disturbing interview of an American business owner whose company manufactured N95 masks, and because of government orders hired new workers, opened a new factory. After it turned out this would not become a major pandemic, the government stopped ordering, and he almost went out of business. He is now inundated by orders, from hospitals mainly and has “zero” government orders who are ordering from cheaper Mexican manufacturers (Made in America?). Some of the N95 masks in the stockpile did expire during the Obama administration (as well as the first three years of the current administration.. I don’t know how real the expiration dates are, even drug expiration dates have been criticized as a ploy for drug companies to sell more drugs when the bottle on the pharmacy shelf are expired and has to be thrown away. On the other hand I have heard reports of deliver N95 masks with the elastic crumbling. John Bolton defends the security council shakeup saying that there was redundancy with the pandemic office elsewhere. Another issue, I can’t recall if Frum mentioned, was the lack of reauthorization of the PREDICT program at the CDC, last October. PREDICT was created as a response to the H1N! influenza in 2009. It was intended to “predict” the next viral pandemic (get the acronym?), by working with virologists around the would, including “on the ground” virologists from the CDC, including in China. Part of the project was doing surveillance for novel viruses in wild animals. In 2009 PROJECT was funded for 5 years, reauthorized in 2014 but not last year. It was allowed to continue with “zero funding” for 6 months to write up reports, but all field work was halted.
I can’t think of anything else right now…..Check out Dr. Osterholm.