Kiki’s Comments                                                                                                        May 2020

                                                TWiV 611: Corona and crowns

            Key Points:

*remember that all of the numbers are people

*new manifestations with COVID-19, including skin manifestations and a late hyperinflammatory phase, which is also affecting children, that occurs four weeks or more post exposure

*plasma is potential useful early in the disease course and harmful later on

*antivirals will be most effective earlier, particularly pre-symptomatically, and may be less effective in ICU use

*continue to take prescribed ARBs, anti-hypertensives, anti-steroidals

*sneezing is not a symptom of COVID-19

*Serology tests DO NOT confirm that you are immune—continue to follow healthcare and hygiene guidelines (wash hands, wear protective equipment)

*be in contact with your doctor if you are on medications that have an impact on clotting (e.g. contraceptive pill) and have questions or concerns—this is something to be aware of

*dentistry is a very high risk category for the transmission of SARS-CoV-2 because of the aerosols caused by the tools

*There is one strain and many patient isolates of SARS-CoV-2—the difference in disease course is likely due to comorbidities and factors not to do with difference in the viral genome itself between infections

*Broad UV-C lamps are dangerous to humans and should not be used or confused wit Far UV-C

            Clinical Report:

*Do no harm and be careful with experimental therapies

*Stages of the illness: very difficult to control pre-symptomatic viral phase, symptomatic viral phase (large range of symptoms, including skin manifestations like COVID-toes, vesicular eruptions, urticaria (hives), maculopapular patches (small patches and bumps), livedo reticularis (serpiginous edges to rashes on arms), necrotic tissues (dead black pieces of skin, more common in children)), a coagulation stage, and then a late hyperinflammatory stage

*Late hyperinflammatory phase: noticed a cluster of children with vasculitis (Kowasaki’s-like manifestation, not just swollen lymph nodes or vasculitis, this is being seen in children above 10 as well)—many of these children were PCR-negative, but post-exposure. Revision of previous thoughts of children: you may now not have to worry about children in the first week, second week, third week, but we are seeing children afterwards (four weeks on) with this late hyperinflammatory stage and abrupt onset of quadriplegia (possibly immunoglobulin related; the Guillain-Barré-like symptomology)

*more control trials—people are remembering the ‘Do no harm’ core of medicine, as many of the varied attempts at therapeutics and interventions can often cause more harm than help.

*Antivirals: the antivirals work earlier—you want to get the antivirals to patients earlier on in the clinical progression rather than the ICU stage. You do not want to wait to use Remdesivir until the deathbed. We are moving away from off-the-shelf and moving towards specific engineered therapies

*Plasma: this is packed full of clotting factors—if you give this in the first week of the virus this may be helpful, but it you give this later during the coagulation phase (patients with thromboembolic issues) it may have antagonistic or detrimental effects

*Patient immune response: the patients with the most robust immune responses and the higher immunoglobulin productions are doing the worst. If you can get rid of the virus early on, during the first 10 days, you can try to prevent the antigenic stimulation of the immune system and possibly keep people from ending up in the hospital or even late stage complications.

*Humanized antibody cocktails: low-risk therapy in phase I trials, given with a butterfly IV, that should be given early on or pre-infection

*Testing: looks like the virus was already in New York in late January. We are at a stage where we need to do testing to figure out who is sick as people head back to work. Encouraging more testing.

*Telehealth: this has been ramped up, communicate with doctors about questions and symptoms

*General patient advice: even patients not sick enough to end up in the hospital have questions; do not stop taking ARBs, anti-hypertensives, anti-steroidals (i.e. keep taking prescribed medications)

*sneezing: NOT a symptom of COVID-19

*serology: the tests that we have available have varying sensitivity and specificity, particularly not FDA reviewed (e.g. Quest Diagnostic’s test is not FDA reviewed), so most of the results should been taken as a “probably.” We have had patients with documented PCR-positive and negative serology (antibodies) and visa versa. Serology tests DO NOT confirm that you are immune—continue to follow healthcare and hygiene guidelines (wash hands, wear protective equipment)


*Elena: are people taking hormonal birth control or who are pregnant at higher risk for developing a blood clot because they both get higher estrogen? We have seen a fair amount of clotting issues with pregnant women and people on hormonal therapy; in general we would say we haven’t seen the signal in pregnant women that we have in other diseases, but the clotting issue is definitely a problem and should be monitored.

            Michael & Dentistry:

*when you can use a tool that has a lot of kinetic energy in contact with a liquid, the particulates or the liquid are more likely to be aerosolized, which has an impact for spread of CoV-2—this is what many dental tools do

*dentistry is a very high risk category for the transmission of SARS-CoV-2 because of the aerosols caused by the tools

*Teaching: classrooms have air-change requirements or social distancing requirements

*Protection: face shields in concert with N95 masks are the best protective levels 

*How routine physicians should care for people: we need to change our routine a little bit. Check patient’s temperature when patients arrive. Have patients swish with 50:50 hydrogen peroxide to water solution for one minute before looking into the patient mouth to try to reduce the viral load in the saliva. This should be repeated periodically if the check or procedure is extended. This should also be repeated post-care to limit spread as the patient is going home.

*Peroxide alternatives: some examples of solutions that can decrease viral load in the mouth other than peroxide are bioflavinoids (e.g. citrox) that might interfere with chymotrypsin protease as a protease inhibitor and amphiphilic cyclodextrin (safer for silver or gold that is already in the oral cavity)

*Rubber dams: minimize anything that can generate an aerosol—this is where rubber dams come into play that helps to create a dry field on which to work. Rubber dams minimize aerosol production.

*Bite wing X-rays: traditionally generate a bunch of saliva; it might be better to use a different type of X-ray (cone beam, panoramic x-ray)

*Clean the operatory: decontamination of the operatory will require specific chemicals

*Dentist hygiene: personal protective equipment will need to be doffed between patients

n.b. we do not know whether having IgG makes individuals resistant to future infection by SARS-CoV-2, but we have started testing more frequently

            General Questions:

*Nicholas: could CoV-2 be a man-made or lab-cultured virus? No, for multiple reasons. First, the technology to create a virus like this is far beyond current understanding and technology, which would present a huge intellectual leap. Second, looking at synonymous mutations (changes that do not make an amino acid difference), there are a lot of synonymous mutations included in the genome that would make the work harder and not provide any benefit. There are also mutation that reduce fitness that are within the genome. Finally, the last common ancestor with other coronaviruses was many years ago (the pangolin virus branched off from this current virus around 30 years ago). Given that it would take 30 years to acquire all of the mutations between this coronavirus and its closest known relative, it is unlikely that this could be man-made or lab-created because at the time (30 years ago) they were not aware of the existence of coronaviruses. 

*Anthony: Contaminated water is a potential vehicle for SARS-CoV-2—could the clouds carry CoV-2 around?Unlikely due to dissipation and movement. If the virus was evaporated into an infectious form in the clouds, most likely the virus outside of water would then be destroyed by UV rays.

*Margaret: Are multiple strains of SARS-CoV-2 causing dramatically different clinical symptoms? It is not different strains, it is different situations, comorbidities, levels of testing. It is really easy to not think hard and blame the genome, but these are apples and oranges. There is one strain and many patient isolates of SARS-CoV-2.

*Greg: can you comment on far UV-C light, which has been noted as safe for humans and inactivates the virus in a study by a Columbia lab? UV-C lights are spooky. UV-C light is toxic to humans and can cause a burn, in most cases. UV-C lamps will nuke your skin and damage plastic near it, possibly even blinding you if you look into it. Far UV-C is using 205-230nm wavelength (very short) is being proposed as a safe option, although it is $500-1,000 per lamp. This might be subject to shadowing and this is not a panacea. This is a totally different tool than a commercially available UV-C lamp—do NOT buy or use any commercially available UV-C lamps or go to the tanning salon.

*Ben: can you explain seroconversion and the effects in asymptomatic individuals? We cannot conclude that there is no immune response in asymptomatic carriers. If asymptomatic carriers do not seroconvert, this would add to the many reasons to not use ‘immunity passports,’ Serological testing has shown seroconversion in ‘asymptomatic’ people, but we have to remember that asymptomatic may mean a range of body responses that may or may not have been noticed.

*Steven: what is the evidence that COVID-19 has been identified? First, the virus is called SARS-CoV-2. Second, the entire virus sequence is available online.

*David: what is the relationship of ACE2 and the African American community and does this account for the disease course disparity? There are many factors associated with race and healthcare disparities, so it may be difficult to parse out whether there is a difference in ACE2 expression that causes differences in disease severity. It may be epistatic mutations (where the body begins to change its genome in a non-uniform way that is non-heritable). The genetic difference between racial groups is much smaller than the genetic difference within most racial groups—what we see in skin color effects social categorization, but does not differ as much genetically.

*Victor: what is the role of throwing antivirals at CoV-2? If you go around prophylactically giving antiviral drugs to everyone then resistances can occur. We need general purpose platforms for viral testing. We are returning to evidence-based administration of antivirals.

*Brigitte: how will we be able to interpret the number of positive cases per day if testing capabilities are expanding at a slower rate than case rate—will testing be based on hospital admission rather than population-wide antibody testing? Population-wide, reliable antibody testing will be globally very important to be able to optimize and balance medical and societal needs in the future and to figure out more about the dynamics of the disease. These are tough questions and the only way to answer these questions is through better, more thorough testing. Until then, epidemiologists and statisticians will try to model as best as they can. Something to pay attention to is the number of positives being received—if half of the tests come back positive then either you are testing the wrong groups or you are not testing enough. Good antibody testing will be a key component in figuring out who was already infected. It will be a three stage process of returning to work, and testing will be incredibly important for this. A phased reopening is sound, although this will have to be moderated and parameters reset depending on the place and circumstances.

n.b. the immunity passport idea is dangerous and will likely cause a spike in cases

            General Topics:

*Judy Mikovits: XMRV (retrovirus) was suggested to play a role in the disease chronic fatigue syndrome (ME/CFS). At some point in the investigation, they found the virus was a contaminant that was made by passaging cells in mice. The lab produced papers that were then rescinded for being fraudulent. There may be a virus that can be useful in the treatment of ME/CFS, but this virus was a lab-created virus that was not helpful. Mikovits has been the source of many conspiracy theories about man-made CoV-2, which have been debunked by virologists. 

n.b. TWiV episode 136 discusses this issue

*Sweden: this is a multifaceted issue. Sweden has a robust health system that has some capacity to take care of more ill patients. While legislature has not forced businesses to shut down, most people who can are working from home and social distancing without regulation—in other words, the Swedish people are also changing their behaviors, social interactions, and educational and occupational habits in a way that has helped to mitigate spread. There is a difference of capacity, capability, and public education in different countries. The Swedish healthcare system might be useful for lessons on how to rebuild and remodel other healthcare systems. Infrastructures of countries and their health systems are largely affecting how COVID-19 interferes with the populace. At the same time, it is important to note that the number of fatalities in Sweden I relatively much higher than surrounding countries and there are many issues that will likely be elucidated with their response in the months to come.

n.b. Sweden’s policy would definitely not work in the current U.S.