Covid 19 – Volume 2 – Part 2 – Coronavirus Background

See our detailed report for more background info.

In early January 2020, a novel coronavirus (2019-nCoV) was identified as the infectious agent causing an outbreak of viral pneumonia in Wuhan, China, where the first cases had their symptoms onset in December 2019. Coronaviruses are enveloped RNA viruses that are distributed broadly among humans, other mammals, and birds and that cause respiratory, gastrointestinal/liver, and neurological diseases.

How many Viruses are there?

Six coronavirus species are known to cause human disease. Four viruses- 229E, OC43, NL63, and HKU1- are prevalent and typically cause common cold symptoms in immunocompetent individuals. The two other strains- severe acute respiratory syndrome coronavirus (SARSCOV) and Middle East respiratory syndrome coronavirus (MERS-COV)- are zoonotic in origin and have been linked to sometimes fatal illness. Coronaviruses are zoonotic, meaning they are transmitted between animals and people.

Wake Up Call: Why is the 60+ Age Group Particularly Vulnerable to This Virus?

Dr. Peter Attia’s comments from a recent interview:

Different populations are susceptible to different viruses. In the case of the SARS-CoV-2 virus (the coronavirus responsible for COVID-19) it’s been clearly observed that the risk of death rises sharply for people older than 60, and especially for people over the age of 75. This does not mean people younger than 50 are safe, but their risk is much lower.

There are probably a few reasons for this observation. First, age is a strong proxy for other conditions that increase risk — most notably high blood pressure, heart disease, type 2 diabetes, and lung disease. Second, as people age, their immune responses change, and there is typically a diminished adaptive response. Finally, as people age their “physiologic reserve” (how much physiological stress they can tolerate) goes down, so they have less buffer to combat severe illness.

I would add as well, a few other important points:

1. Suboptimal micronutrients- What the legendary scientist Professor Bruce Ames called the micro-deficiency of nutrients of the aging process. See below for more details about micro or bio protective nutrients and their role in the immune system.
2. Insulin resistance, poor glucose control and faulty metabolism as a unifying factor in most of these comorbidities such as diabetes, heart disease, and hypertension or high blood pressure as outlined by many. I’m concerned this is one of the reasons why the British Prime Minister is now being hospitalized after a slow response to COVID-19 treatment. Although I don’t know his health history I’m confident, based on his body habitus, that he suffers from the diseases of Western civilization including insulin resistance and its many varied forms.
3. The high risk age group that most define older than 60 is not completely accurate. In my experience, we should be on alert for the many patients in their 50s and even younger as being vulnerable. For example based on current data we now know, for those 50-59 the morbidity from COVID-19 vs the flu is 20x greater, and for those 18-49 at least 10-20x greater; 1.3% and 0.4% may be generally low numbers for mortality but are way too high for the average person. In the U.S. nearly 40% of hospitalized people involve those less than 55 years of age.
4. Of course, these general numbers don’t take into account the greater number of morbidity in men as compared to women which may also reflect a weaker general immune system by the former. Men need to step up and take more responsibility for their health.
5. Finally, as scientist and prominent lifestyle expert P.D. Mangan states, and as all military fans and current and former members (such as my twin brother Tom) would appreciate:
   1. Generals are always preparing to fight “the last war.”
   2. In the last war, acute medicine was going to save you, and is still undoubtedly necessary.
   3. But the enemy has learned to attack our weak underbelly, which is chronic metabolic disease.

Vaping An Increased Risk to COVID-19?

Important potential risks about the vaping and COVID-19 are being reviewed. With the very high incidence of vaping in high school and college students, we must be on high alert and review this troubling trend with our families. In New York City it has been estimated that 54% of hospitalized patients for COVID-19 are between the ages of 18 and 49. This article from San Francisco shares similar concerns.

Doctors say COVID-19 directly attacks the lungs. Vaping has skyrocketed particularly in young people. The CDC reports that young adults from ages 20 to 44 make up a big part of COVID-19 hospitalizations in the United States. There’s been little to no research but Glantz questions whether the virus is tied to vaping. “A couple of colleagues here who are actually taking care of patients have noticed younger people who came in noticed that they were vaping,” Glantz said.

COVID-19 vs COMMON COLD VS FLU vs ALLERGIES

SYMPTOMS ARE CHANGING – ABOVE CHART IS NO LONGER FULLY ACCURATE

LOSS OF SMELL and TASTE- “ANOSMIA”– Emerging as a common early symptom (30% in the Korean data)

GI SYMPTOMS NOT RARE– 20% of patients in recent study had diarrhea, vomiting, abdominal pain (these patients may have a worse outcome based on some of the studies in China)

Shortness of Breath (S.O.B.)– may be an early indicator of rapid deterioration

Many are currently experiencing their normal ALLERGIES which has many distinct but some common features as COVID-19. Sneezing, runny nose, lack of sore throat or loss of smell, and lack of GI symptoms are important distinctions.

Viral Shedding Begins When Asymptomatic

• No difference in viral loads in nasal swabs between symptomatic and asymptomatic
  • Lot of viral shedding occurs in patients without symptoms

Data from Italy’s first 5000 COVID-19 confirmed patients demonstrated -47% of positive cases required hospitalization and 18% required intensive care. U.S. – nearly 40% of those hospitalized involve adults < 55 years old.

Potential early good news: Per population our COVID-19 cases are less than Spain + Italy from Dr. Gottlieb.

Please also see What Coronavirus does to the body, an informative and easily digestible article from USA today.

I found the illustrations on the following page, from Professor Siddharth Sridhar, Depart. of Microbiology, Hong Kong Univ., to be helpful and informative, as well.

Self-Care and Prevention: Nonpharmaceutical Interventions (NPIs)

The importance of viral dose is being overlooked in discussions of the coronavirus. As with any other poison, viruses are usually more dangerous in larger amounts. Small initial exposures tend to lead to mild or asymptomatic infections, while larger doses can be lethal.

From a policy perspective, we need to consider that not all exposures to the coronavirus may be the same. Stepping into an office building that once had someone with the coronavirus in it is not as dangerous as sitting next to that infected person for an hourlong train commute. This may seem obvious, but many people are not making this distinction. We need to focus more on preventing high-dose infection.

Virus experts know that viral dose affects illness severity. In the lab, mice receiving a low dose of virus clear it and recover, while the same virus at a higher dose kills them. Dose sensitivity has been observed for every common acute viral infection that has been studied in lab animals, including coronaviruses.

Despite the evidence for the importance of viral dose, many of the epidemiological models being used to inform policy during this pandemic ignore it. This is a mistake.

People should take particular care against high-dose exposures, which are most likely to occur in close in-person interactions — such as coffee meetings, crowded bars and quiet time in a room with Grandma — and from touching our faces after getting substantial amounts of virus on our hands. In-person interactions are more dangerous in enclosed spaces and at short distances, with dose escalating with exposure time. For transient interactions that violate the rule of maintaining six feet between you and others, such as paying a cashier at the grocery store, keep them brief — aim for “within six feet, only six seconds.”

While preventing viral spread is a societal good, avoiding high-dose infections is a personal imperative, even for young healthy people. At the same time, we need to avoid a panicked overreaction to low-dose exposures. Clothing and food packaging that have been exposed to someone with the virus seem to present a low risk. Healthy people who are together in the grocery store or workplace experience a tolerable risk — so long as they take precautions like wearing surgical masks and spacing themselves out.

When society eventually reopens, risk-reduction measures like maintaining personal space and practicing proper hand-washing will be essential to reducing high-dose infections. High-risk sites for high-dose exposure, like stadiums and convention venues, should remain shuttered. Risky but essential services like public transportation should be allowed to operate — but people must follow safety measures such as wearing masks, maintaining physical spacing and never commuting with a fever. Now is the time to stay home. But hopefully this time will be brief. When we do begin to leave our homes again, let’s do it wisely, in light of the importance of viral dose.

Face Masks and You

We have been recommending wearing masks in areas of close personal contacts outside the home, such as supermarkets, since we received first confirmation of a positive case in our area.

It’s been frustrating to see how slow this has taken to be adopted. Here is a picture of my oldest son and I at a local supermarket from a few weeks ago (he’s enjoying letting his hair grow out). I have the N95 mask– which should be reserved for those of us medical personnel. My son has a simple surgical mask, but almost any mask or covering will work well as indicated below.

As an aside, unfortunately, the only other people to be wearing masks in the market were a few Asian couples. Their cultural and shared experience in dealing with infectious pandemics, as I referenced above, should be copied by all of us. The lack of masks for the dedicated employees of supermarkets, who are at a particularly high risk, is terrible to see and should be rectified by their leaders ASAP.

Face mask facts per economic researcher and futurist Chris Martenson, PhD:

1. Face masks stop the spread of the virus from infected people- both symptomatic and asymptomatic.
2. Reminds you not to touch your face.
3. Low inoculum or low dose of virus gives you a much better chance of “starting small” for a much better disease outcome. (see the NY Times article above about viral dose)
4. Countries that have used masks aggressively have had better outcomes. (see below)

Face masks have been discouraged because of lack of enough supply for health care workers but are critical for the population, as outlined above. WHO and CDC say use only when sick. It seems as though the CDC is changing their policy.

See this compelling table on the importance of masks:

DIY home face masks

Many of these are made from material easy to get and most of them do a reasonably decent job- they can be at least 50% effective in capturing particles. See the following links for more information:

Smart Air’s Clean Air Blog

Business Insider

Sterilize masks in home ovens?

Commercial ovens can be used to resterilize N95 masks worn to protect against COVID-19 according to researchers at Michigan State University, which has been hit particularly hard.

Chris Martenson recommends using a home oven set at 200℉ and placing a paper bag with a mask inside for 30 minutes. Tamara, our Jack of All Trades, has confirmed its effectiveness when used with caution.

DO NOT USE A MICROWAVE OVEN.

Hand Washing

This is an excellent video done by an infection prevention nurse demonstrating proper technique and the importance of thorough hand washing to include the nails and back of the hands.

South Korea, Japan, Singapore, and Hong Kong used masks and other Nonpharmaceutical Interventions (NPIs) as outlined above to slow the spread of the virus.

Tips for cleaning home, phones, and devices

Business Insider’s tips on thorough cleaning.

TechRadar’s walkthrough on effectively cleaning your smartphone.

Here is a “handy” home hand sanitizer recipe which can help in this time of national shortage:

An Excerpt From KevinMD Post Covering Mitigation Measures For COVID-19

• Support your schools’ decisions to close: Proactive school closings save more lives than reactive school closings. Your schools should close now … before infections are present. Closed schools do not mean playdates for children – this counteracts the social distancing the school closures are meant to create in the first place.
• 6 feet: The COVID-19 virus spreads through droplets. They can move 6 feet before gravity brings them to earth. Stay 6 feet away from people if you need to go outside.
• Meticulous hand washing: Wash thoroughly and wash often. Alcohol-based hand sanitizer works well if your hands are otherwise clean.
• Do not touch your face. This is hard. This is a learned skill: Practice often.
• Clean doorknobs, toilets, cellphones, countertops, refrigerator handles, and so on many times each day. The virus could live on certain surfaces for 4-72 hours.
• If you can work from home, work from home.
• No tournaments, no sports events, no soccer, baseball, dance, volleyball, softball, gymnastics, concerts, martial arts, etc. We don’t care how much they claim they will clean the equipment.
• Cancel vacation travel. We know you planned this for a long time. You will be saving many lives by doing so … perhaps someone you know.
• Cancel weddings/ bar/bat mitzvahs, birthday parties, and so on. Help other people live so they can celebrate future events too.
• If you are over 60 years old, you should stay home. You should only go out if there is a critical need.
• If you have parents/grandparents in a nursing home, you should consider moving them home for now.
• Do not congregate in a restaurant, bar, etc. Again, you will save the lives of people you will never meet.
• If you feel sick, stay home. It doesn’t matter if you don’t feel too sick. Going to work will put countless other people at risk of suffering or dying.
• Cancel all business travel. Your life and the lives of others are more important.
• Expect supply chain issues: Work with your doctor to try to get a three month supply of medication.
• Many grocery stores offer order-ahead options with either pick-up or delivery. Online grocery delivery services are available in many areas. Wash your hands thoroughly after unpacking groceries.

Contributors: Howard J Luks, M.D. (@hjluks), Joel Topf, MD FACP (@Kidney_Boy), Ethan J. Weiss, M.D. (@ethanjweiss), Carrie Diulus, M.D. (@Cadiulus)

TESTING

I know this has been a frustrating topic for all of us. We are all in agreement about the importance of greater testing and the unacceptable delay in getting enough tests available for broad use.

Please note that we are NOT able to perform testing at our office– no outpatient doctor’s office has the capability due to the lack of specialized rooms and appropriate protective equipment for health care workers. Unfortunately, at the moment testing criteria remains limited to only those with symptoms- fever, cough, and shortness of breath. This will be problematic, for we believe based on the data that only half of the positive COVID-19 patients have any symptoms.

Here’s what we know for our local area:

Arlington County (as of 4.5.20)

A drive through testing center has been established in Arlington through collaboration with Virginia Hospital Center and Arlington County.

How do I get tested at the Virginia Hospital Location?

• The Virginia Hospital Center has mobilized a sample collection site, in partnership with Arlington County, to provide Arlington residents and employees a safe and convenient opportunity to have their samples collected for COVID-19 testing.
• ONLY patients who are displaying symptoms of COVID-19 and have a written order from their doctor will receive a scheduled appointment at the VHC sample collection site.
• This site is for drive-up only.
• Learn more about this.

Arlington County Public Health, along with other public health agencies in the region, is not testing for COVID-19. You must contact your doctor to be evaluated.

Fairfax County (as of 4.5.20)

From the county government website:

We recognize there has been much confusion and frustration on the topic of COVID-19 testing. Up until recently, COVID-19 testing was only available through the Centers for Disease Control and Prevention and state laboratories, with local health departments like ours helping to coordinate and facilitate those tests based on very specific testing criteria. Now that we have commercial laboratories testing capability, physicians have wider latitude to order testing.

Still, several challenges have limited testing for Fairfax Health District residents:

1. With shortages of personal protective equipment across the nation, health care providers who lack recommended protective equipment may not test because of the risk to their health and ability to continue providing care in the community.
   
2. The materials needed for specimen collection before being sent to the lab are in limited supply nationwide.

INOVA health care system has urgent care respiratory illness clinics at 3 locations- Chantilly, Tysons Corner, and North Arlington. A doctor’s order is required and as of now they will only accept patients with the official COVID-19 symptoms of fever, cough, and shortness of breath. ARLINGTON residents thus have 2 options for testing through VHC or INOVA locations. We also recommend Loudon County residents use INOVA in Fairfax as needed.

OF NOTE: We have begun utilizing community testing as of last week (3.30.20) and have confirmed positive cases. They are middle-aged, healthy, and doing well on the Pappas Plan without any need for hospitalization. However, there is currently a longer than expected delay in results-taking our patients about 10 days to get results back.

Loudon County (4.5.20)

From the county government website:

Where can I get tested for COVID-19? (Posted 3/17/20) Contact your doctor if you believe that you may be infected with COVID-19 and would like to get tested. Unless you are having a medical emergency, residents are discouraged from going to the emergency department for evaluation or testing.  Currently, testing capacity is limited so testing is limited to doctors’ offices and emergency departments.  As availability of specimen collection kits improve, information on additional testing location will be provided.

Note: The Loudoun County Health Department does not provide testing or evaluate ill individuals. 

Types of Testing

A swab and a wait- Currently, testing done analyzes the DNA genetic material of the virus from a nasal or throat swab. This looks for the presence of an active infection through Polymerase Chain Reaction (PCR) technology but samples need to be sent out from facilities as these tests are done by labs that constantly batch many samples. At this time, there is a backlog and delay of pending tests, again often delaying results for up to 10 days.

This article from Live Science looks at the various new tests coming out that result quickly at the Point of Care- to be done at the time of service with immediate results as quick as 5 minutes- similar to rapid flu testing done commonly. Of note in the article, tests manufactured by Illinois-based medical technology company Abbott will be a DNA test of a single sample and diagnose an acute infection but can’t be massed produced so they won’t be able to handle the large number of tests of a population to get a broad picture of the pandemic. This will be helpful for clinics, urgent care centers, and hospitals that are in dire need, but will not be as helpful for immediate widespread use.

From this Vox article on immunity testing:

Testing to see who has [COVID-19] has become one of the most crucial elements of slowing the global pandemic. And it may also hold the key to a return to normal. “Everyone staying home is just a very blunt measure. That’s what you say when you’ve got really nothing else,” Emily Gurley, an associate scientist at the Johns Hopkins Bloomberg School of Public Health, told NPR. “Being able to test folks is really the linchpin in getting beyond what we’re doing now.”

In particular, serological tests, also known as “immunity tests,” for antibodies to the virus could reveal the true extent of the pandemic and help scientists answer basic questions about COVID-19 and the virus that causes it, SARS-CoV-2: How many people have been infected with the virus? Who may have spread it without knowing it? Why do some people have mild illness while others become gravely ill? How deadly is the disease? What tactics are actually working to slow its spread?

Serological tests could also potentially allow people who have immunity to return to work. That could be a huge boost to front-line health workers who may have been exposed to the virus but are desperately needed back in action.

Countries are now racing to acquire more of these tests. The United Kingdom ordered 3.5 million serological tests. Germany is considering using these tests to issue immunity certificates to people who have survived COVID-19.

These are examples of the premier antibody tests soon to be available. It is unclear if the point of care finger prick test will be more accurate than the blood or serum test more widely done in China. Undoubtedly all companies will eventually have rapid pinprick testing to complement blood testing.

What the Antibody Tests Measure

We believe the key to getting our patients and the workforce in general back on the job is to utilize Antibody or serological immunity tests. Like Germany, which is considering using these tests to issue immunity certificates, we believe this could be a huge lever in our tool book of combatting the coronavirus pandemic by getting healthy and immune patients out of quarantine.

These antibody tests have several important caveats:

Firstly, because they measure molecules from our delayed or adaptive immune system, it takes a few days after an exposure to the virus for them to show up positive- perhaps 5 to 7 days- so they are not useful for an active infection.

Secondly, the antibodies can linger long after the infection has faded. This makes them ideal for identifying past cases of the virus.

Thirdly, to quote from the article, “to safely return to work, a patient would have to ensure that they have immunity and that they are no longer spreading the virus. Since a serological test can only confirm the former, a patient may still need an additional RT-PCR test to establish the latter. That is, they need to test positive for immunity and negative for the virus itself.”

Lastly, since there are usually two types of antibodies measured, IgG (past exposure) and IgM (ongoing infection), one could conceivably proceed forward with a positive IgG and negative IgM but would need a DNA PCR test if they have a positive IgM.

We certainly think this can be a gamechanger for our patients and community, not least which because according to Dr.Fauci, immunity could be quite lengthy, “You’re going to have some degree of durable immunity,” Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, told the Doctor Mike YouTube show. “It may not be 50 years, but it’s certainly going to be a matter of a few years.”

For this reason, we eagerly await the ability to broadly test our patients/clients; as you all know we highly value the importance of drawing lab tests and measuring key markers that can demonstrate where “one’s biochemistry is taking you”. Furthermore, we are actively brainstorming how to partner with our patients/client’s businesses and organizations to help them create a plan to get back to work and help them break free from our current restrictions.

The employer will test you now

Matters such as cost, insurance coverage, liability, and FDA disclaimers will need to be worked out.

However, we look forward to continuing this dialogue and will surely let you know when we are able to get this type of testing kit.

Population Density for Our Region

Keep in mind the importance of population density for your region as discussed above. Northern Fairfax and eastern Loudoun counties are actually much more dense (see colored map below). Thus, as below Northern Virginia is the most dense part of the state and like most of the DMV very dense overall.

Rank	County/Region	State	Population Density/sq.mile	Land Area-sq.miles	2018 pop
1.	Alexandria and Co.	VA	10,399	15	156,505
2.	Arlington County	VA	8,918	26	231,803
3.	Falls Church and Co.	VA	6,860	2.1	14,067
4.	Manassas Park + Co.	VA	6,468	2.5	16,423
7.	Manassas and Co.	VA	4,195	9.9	41,457
8.	Fairfax and Co.	VA	3,824	6.2	23,865
12.	Fairfax County	VA	2,926	390	1,143,530
39.	Loudoun County	VA	650	521	338,916

Virginia population density (measured in people/square mile) is projected to increase primarily in Northern Virginia, Richmond, and Hampton Roads by 2035.

Source: Virginia Department of Transportation Population Forecast

Density around the Beltway. There is a lot of Yellow and Orange in our regions that we live in.

Compare this to how our region’s density stacks up nationally as it is of further importance to understand as we discuss policy, population densities, and getting back to work:

The Power of Exponential Growth

Virginia cases as of 3.22.20:

People tested 3337

Positive cases 219 (in our area: Fairfax- 31, Arlington- 26, Loudoun- 15)

Hospitalized 32

Deaths 3

Virginia cases as of 4.4.20:

Telemedicine and the Health Care system

The above article proposes the long-term effects of COVID-19 on the system as we know it. As most of you are aware we have been using Doxy, a secure, HIPAA-compliant telemed application, for 4 years and are excited to be ahead of the curve and be using it more broadly these days.

RESOURCES FOR DOCTORS AND HEALTH CARE WORKERS (and for those intellectually curious non-clinicians and citizen scientists)

• Coronavirus Tech Handbook
• Treatment Roundup
• An ER doc’s detailed notes about how to evaluate COVID-19 patients

Comprehensive COVID-19 Summary

Thomas Pueyo an engineer and MBA who has extensive experience with viruses has written arguably the most thorough and widely read articles about COVID-19. They are very detailed but worthy of some attention.

• Coronavirus: Why You Must Act Now
• Coronavirus: The Hammer and the Dance

Where we are currently and the road ahead by Dr. Scott Gottlieb

From a lengthy twitter discussion, Dr. Gottlieb discusses where we stand currently and what the immediate future holds.

• You can read the entire thread here
• See also: Dr.Scott Gottlieb’s road map to reopening

From Dr.Gottlieb:

Staying at home is what we need to be doing now. But as we get through April, and chains of epidemic transmission are hopefully broken through our current mitigation steps, we can start to transition to different approaches that gradually rely more on case-based interventions. April will be a hard month but we’ll get through it. This will end. We need to stick with current strategies. We can look toward May as a month when we carefully transition to a new posture. For now focus must be on supporting healthcare systems, preserving life, ending epidemic spread.

Powerful and optimistic words. I hope he is correct, especially as the timeline for Virginia’s peak seems to be in mid May per most experts.

MEDICATIONS

No time in history has all of the world, especially scientists, been simultaneously focused on fighting one medical problem and curing one disease. Countless trials are under way to find medicines that can be proven in a formal trial to be effective against this novel virus. Nothing has caused as much hope and controversy as the talk about potential medicines to treat COVID-19. We know that there have been a number of medicines already being used for patients, mostly in the hospital setting but their lack of formal and typical studies have left some doctors, researchers, and policy makers skeptical to proceed.

• For example the Japanese antiviral medicine Avigan (or favipiravir) has been used in Japan and China, apparently with some success, though it may be limited in supply to only a few countries, including Turkey.
• Another agent that has received a lot of attention is Gilead Science’s Remdesivir. The early word has been promising and active trials are ongoing. Its cost and availability appear to be limiting steps in its widespread use.
• Other common and generic antibiotics Azithromycin and Doxycycline have the potential to treat or prevent COVID-19.
• Hydroxychloroquine and Azithromycin

The most attention and early promise has come from the old antimalarial drug Hydroxychloroquine (HCQ) which has shown growing evidence of helping those in the early stages of the illnesses, often in combination with the generic and long standing antibiotic Azithromycin, and zinc as well. Below, I highlight the research and articles pointing to its early success and growing interest by doctors.

Chloroquine, a closely related medicine to HCQ, which has been around for sometime and is also cheap, and was used early on as part of a South Korean protocol with zinc and in China. Both places showed with some success and raised questions about lower mortality rates in South Korea being the result of this medicine. HCQ was then used by a French virologist with the addition of Azithromycin, commonly known as a Z-Pack with purported promising results. Although there was much scrutiny as to the results and methods, this combination has been tried more frequently and with growing consensus of benefits. HCQ’s better safety profile and long track record of success in autoimmune diseases pointed to a potentially better option.

Dr. Paul Marik, a renowned intensive care doctor from Eastern Virginia Medical School in Norfolk shares many valuable insights below. His pragmatic wisdom and plans based on the available data and safety for both medications and supplements is an ideal template from which to give the best possible care to ill patients. He is also the famous author of a study that showed a 40% reduction in mortality in pneumonia and sepsis in a critical care setting using IV vitamin C. As I point out in the next section, vitamin C is showing great promise, as well.

New COVID-19 protocol by Paul Marik, MD Chief of Pulmonary and Critical Care Medicine Eastern Virginia Medical School, Norfolk

The World Health Organization has now launched the SOLIDARITY trial to investigate four potential treatments: Remdesivir, Chloroquine/Hydroxychloroquine; Lopinavir and Ritonavir; and Lopinavir and Ritonavir plus interferon-β. It will likely take many months before this study is completed and the results are available; many tens of thousands of patients will die from COVID-19 related complications in the intervening time.

Good medical practice and the best interests of the patient require that physicians use legally available drugs according to their best knowledge and judgement. If physicians use a product for an indication not currently approved, they have the responsibility to be well informed about the product, to base its use on firm scientific rationale and on sound medical evidence, and to maintain records of the product’s use and effects.

It is important to stress that there is no known drug/treatment that has been proven unequivocally to improve the outcome of COVID-19. This, however, does not mean we should adopt a nihilist approach and limit treatment to “supportive care”. Furthermore, it is likely that there will not be a single “magic bullet” to cure COVID-19. Rather, we should be using multiple drugs/interventions that have synergistic and overlapping biological effects that are safe, cheap and “readily” available. The impact of COVID-19 on middle- and low-income countries will be enormous; these countries will not be able to afford expensive designer molecules.

Preliminary data suggests that Chloroquine and Hydroxychloroquine decrease the duration of viral shedding. In addition, Chloroquine has favorable immunomodulating properties including inhibition of PAI-1 expression. These agents are now FDA approved for the treatment of COVID-19

Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro (from March 18, 2020 before favorable HCQ trials as below)

Malaria Drug Helps Virus Patients Improve, in Small Study

Doctors surveyed rated HCQ the most effective therapy

Governor Cuomo of New York touting HCQ effectiveness in a recent statement

ATS Publishes New Guidance on COVID-19 Management

This article details newly-released guidance for clinicians who are treating COVID-19 patients. Here are key excerpts I find most intriguing:

… to prescribe hydroxychloroquine (or chloroquine) to hospitalized patients with COVID-19 pneumonia if all of the following apply: a) shared decision-making is possible, b) data can be collected for interim comparisons of patients who received hydroxychloroquine (or chloroquine) versus those who did not, c) the illness is sufficiently severe to warrant investigational therapy, and d) the drug is not in short supply.

The evidence that exists around the use of hydroxychloroquine and chloroquine is contradictory. Acknowledging this, “we suggest that, if the drug is prescribed, that it be done in the context of data collection for research,” said Kevin C. Wilson, MD, chief of Guidelines and Documents at the American Thoracic Society. “We believe that in urgent situations like a pandemic, we can learn while treating by collecting real-world data.”

“There are in vitro studies that suggest that hydroxychloroquine and chloroquine have activity against SARS-CoV-2019, the virus that causes COVID-19,” added Dr. Wilson. “There are also several controlled trials from China and France, but they all have serious flaws and inconsistent findings. Even interim analyses of data from institutions that are using hydroxychloroquine and chloroquine are inconsistent. Thus, the bottom line is, whether hydroxychloroquine and chloroquine confer benefits to patients with COVID-19 are unanswered questions.”

The prestigious ATS organization has taken the bold and appropriate stand that, based on urgent times we find ourselves in and some good but not complete studies (the in vitro, as referenced above), we can learn by both treating and collecting data. In my opinion, this further opens up the possibility of using these safe medications not only in the inpatient setting but I believe also they would be helpful in the non-hospital setting for which they have a long and safe track record.

In closing, I echo Dr. Paul Marik’s wise sentiments, which bear repeating:

Good medical practice and the best interests of the patient require that physicians use legally available drugs according to their best knowledge and judgement. If physicians use a product for an indication not currently approved, they have the responsibility to be well informed about the product, to base its use on firm scientific rationale and on sound medical evidence, and to maintain records of the product’s use and effects.

It is important to stress that there is no known drug/treatment that has been proven unequivocally to improve the outcome of COVID-19. This, however, does not mean we should adopt a nihilist approach and limit treatment to “supportive care”. Furthermore, it is likely that there will not be a single “magic bullet” to cure COVID-19. Rather, we should be using multiple drugs/interventions that have synergistic and overlapping biological effects that are safe, cheap and “readily” available. The impact of COVID-19 on middle- and low-income countries will be enormous; these countries will not be able to afford expensive designer molecules.

I have personally prescribed both HCQ and Azithromycin for many years for a variety of ailments including both autoimmune disease and lyme disease. In fact, a common lyme disease protocol by the renowned specialist Dr.Richard Horowitz, calls for the combination of both HCQ and Azithromycin, in addition to some other medications, for an extended period of time- perhaps months. This is far more intense than the 5-day course being recommended for COVID-19. I have never seen a problem with these meds, although the potential for eye disease in chronic usage of HCQ needs monitoring and its combination with Azithromycin can theoretically be associated with heart arrhythmias.

Furthermore, HCQ use in the elderly with autoimmune disease is so safe that there has never been a need to monitor such patients for cardiac or blood testing. Its many years as a malarial medicine and safety record is quite impressive and it should be pointed out that members of our military use chloroquine weekly for malaria prophylaxis without any known incident. It may not be a cure-all or effective in patients severely ill with COVID-19 but the growing consensus among doctors coupled with an excellent safety record and finally more prevalent promising studies all lead to its burgeoning use. That fact that its early success is being minimized by those looking through a political lens is quite unfortunate for the many patients who may benefit from it.

A number of medicines look very promising on the near horizon and we all look forward to the growing list of COVID-19 treatments. Political biases and the undue caution of researchers and physicians awaiting detailed studies should not stop physicians in utilizing all of the tools at our disposal to provide the best possible care in this time of crisis and many unknowns. I would in closing make an additional point, based on my review of the data and knowledge of the science recommend the addition of zinc to the HCQ and azithromycin.

Prophetic Science Wisdom

I close this section with information from the New England Complex Systems Institute and showcase the important work done by its leadership team of Yaneer Bar-Yam and the great Nassim Nicholas Taleb who I referenced in my Part 1 writeup. This report from January 26 is reported to have been used by the administration of President Trump to institute his ban of travel from China to the U.S. (Joseph Norman, Yaneer Bar-Yam, and Nassim Nicholas Taleb, Systemic risk of pandemic via novel pathogens – Coronavirus: A note, New England Complex Systems Institute (January 26, 2020))