Kiki’s Comments

            TWiV 606: Evidence-based science and medicine for COVID-19

General points:

*Proning has a large anecdotal evidence-base for increasing blood oxygen

*Thromboembolic complications are increasingly common and require monitoring, usually appearing 2-3 weeks post-infection; personalized and monitored dosing of anticoagulants are important therapeutics, but require clinical testing

*Speak to your doctors through telemedical calls to help determine whether you should come into the hospital, do not wait to communicate virtually with your physician

*antibody (serological) test positive means that you have been exposed, not necessarily infected

*Legislature has been passed that allows the FDA to consider challenging individuals with CoV-2

*Do NOT take disinfectants internally (intravenously, orally, nebulized) or expose your system to UV-C—this is harmful and will not help kill the virus in the human body

*Paper: Chinese vaccine trial using an inactivated virus has been promising in non-human primates

*Paper: Saliva is more sensitive for SARS-CoV-2 detection than nasopharyngeal swabs (Yale)

*Evidence that saliva may be more effective for detecting the virus than nasopharyngeal swabs

*Oxford University vaccine trial: Adenovirus that expresses the CoV-2 spike as antigen. Phase I/II; other vaccine trials are also ongoing

*It is unlikely that CoV-2 would become a dormant or persistent latent infection, although we do not yet know

*WHO has an updated list of all therapeutics being looked into

*It is possible that some vaccines, e.g. MMR and OPV, are protective, but this remains to be investigated further

*Both ACE2 and TMPRSS2 are important for the entry and infection of human tissues by SARS-CoV-2

*Things are getting getter, but we need more evidence-based medicine to return

*White House has released a four-phase roadmap for the future with regards to COVID-19

Summary of Daniel:

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*Switch away from evidence-based medicine: Normally we don’t give things to people until we really have an idea, but word from the trenches is a lot of physicians wanted something to try for therapeutics. We are moving now towards Careful observation and experience based medicine: we try something and we see whether or not it worked, e.g. proning, anticoagulation.

We are anxious to get back to evidence-based medicine and to get away from experience-based medicine, to avoid the Marik protocol incident that caused increase in Vitamin C, despite further clinical studies that invalidated the protective results. 

*The outpatient experience and current records: current disease progression has first week milder, second week is the critical week of decompensation, and the end of second week into third week of thromboembolic complications, even in outpatients who have not been treated in hospital. This is usually manifests as venous clotting (big clot in lower or upper veins of the leg, can sometimes be felt as a warm red coloration and warmth on the skin, although a lot of deep venous clotting goes unnoticed), but there are people with pulmonary emboli, strokes (evidenced by increase in oxygen need and breathing, but also a lot of peripheral clotting called subsegmental clotting), arterial clots are also developing. Clinical symptoms: D-dimer rising, platelets abnormal, breathing abnormal. Many patients that were never sick enough to go to the hospital are developing coagulation issues.

*Do not hesitate to be evaluated by doctors tele-medically and go to the hospital in emergency situations: Many patients are showing up with their appendix already burst. In New York, the hospitals may have been slow to keep up at first, but now telemedicine has been properly set up. Much rather have patients talking to their doctors by phone or video, so that the patients don’t show up at the Emergency Room unnecessarily or very late on. 

*Clinical findings and therapeutics: Interventions are not a one size fits all treatment

HCQ: Most major hospitals have stopped using HCQ during the second week, although some clinical trials, including the Patch Study in England, are ongoing on that indicate it may be helpful in the first week.

AZT: Reduction in the treatment with AZT (Azythromycin), which is great because people have stopped trying to treat a virus with an antibiotic

Remdesivir: still not seeing anything compelling, but studies ongoing

Plasma: anecdotally not seeing much of an impact, studies ongoing and some hospitals have widespread use

Steroids: only a minority of patients with COVID would benefit; these come with risks because you are suppressing patient immune systems while infected and if they end up on the ventilator they are at high risk for other infections

Tocilizimab: an IL6-receptor inhibitor, hamstringing the immune system with this medicine and at high expensive (around $5K a dose); we do not have the quality of data we would like to support this yet

Prone positioning: not evidence-based, but this works very well. Take people laying on their back who are not getting the oxygen levels that you want and shift to left side, right side, or stomach down, and there is a pretty quick positive oxygen feedback

Oxygen Levels: People tend to be tolerating lower levels of oxygen than what was previously accepted and recommended; there are not many signs that this is having any permanent psychological damage or effect

Neurological symptoms:  Neurological complications are very common, fair number of cases with a GBS-like (Guillain-Barré Syndrome) manifestation with patients that become flaccid with no reflexes, treated with IViG (intravenous immunoglobulin) and they are responding well and returned quickly to normal function. No evidence yet that this is due to viral neurotropism

Charting: Charting is critical. If a person is on nasal-canula oxygen, always document every litre, when they go to Venturi mask, when they go to a full breather, when consumption goes to the 80s, know they have to keep a closer eye on the patient.

Hypercoagulability: When we put people on anticoagulation, instead of just giving general dose, doctors are routinely monitoring efficacy e.g. low-molecular weight heparin, and have started individualized dosing through drips and inhibitors; when this is done, O2 requirements decrease, thromboembolisms decrease. This remains to be fine-tuned, but is recommended for most patients.

*When is it time to contact your physician or go to a hospital? It is really the second week that we worry the most about, the more issues you have earlier in that second week to more likely you should contact medical personnel. We really want phone conversations (telemedicine) during that second week and are looking to see if the patients sound like they are on a treadmill, doctors will count respiratory rate (10s versus 20s in respiratory rate). 

Serology: Large-scale testing with good and bad results. NYC over 20% of “randomly” sampled, 17% Long Island, 14% NY State. These results were published on Gov. Andrew Cuomo’s Twitter, so the results and methods will require further investigation when released. These are tube and blood quantitative virology IgG tests.

*The Summary of Good News:

Daily new case counts are stable or down in NYC

Daily deaths could be on their way down in NYC

Hospital admissions down in the area; census levels are down

Staff have become COVID experts

We need to make sure we are still treating non-COVID maladies, such as aspiration pneumonia, HIV, TB, influenza. Reminder that as COVID counts go down, there are other diseases out there.

Questions from listeners:

There are two kinds of disease, there are people who die from viral infections and there are people who die from ARDS and cytokine storm, is this correct? It appears that people are dying from just the latter, people aren’t dying from the virus. During the first week of viral replication kinetic, folks are not that sick until you see this inflammatory cascade, which is when you see people in the virus.

Does the more serious disease correlate to virus going down into the lungs? We don’t know. We would like more qPCR data to be able to understand this more. No evidence of prolonged viral shedding into the second week, but that it’s rather the prolonged cytokine storm.

When one does a protocol first time around, the results are not great, but a year later my production is much better because you learn to change a bunch of little stuff, is that whats happening? That’s what I worry about, I think we are doing much better, we have a lot more people being discharged and it looks like we are going in the right direction. We are doing a bit less than we were, as we have learned a lot of things not to do. The paradigm of stand there and see what to do rather than try to do everything.

How do you protect yourself from infection within your household from spreading? Ideally isolate yourself off from the other members, including not sharing a bathroom if this is an option. There should be a lot of disinfecting and hand-washing. Isolate either the person who is sick or person who is at highest risk. 

Is there a reason for the higher incidence of severe COVID-19 in black and minority communities? Higher incidence of various co-morbidities in various minority populations, as well as decreased testing and treatment, so the reasons for increased likelihood of severe COVID-19 are due to multiple factors, including societal and socioeconomic. This question will be elucidated in future papers. 

Is it possible that SARS-CoV-2 could lie dormant and resurface? Persistent and dormant infections are unlikely as they have not been noted previously in coronaviruses, but we do not know for sure. Best to not assume this until evidence to the contrary appears.

Final Note from Daniel: Please do NOT have patients inject or intake nebulized bleach. Don’t swallow any UV lights, don’t open up veins or arteries for sunlight. Please do not bleed people and replace with “good blood.”

Compiled by Kiki Warren