Saturday, March 14, 2020

COVID-19 (Coronavirus) - Complete Guide (Evidence based medicine with references)


COVID-19 Guide - by Oliver Zolman MD

Disclaimer: This document is not intended to replace medical advice. It is merely a compilation of research performed by Oliver Zolman MD

New separate companion doc: Covid-19 Treatment Strategy + Evidence & Drug Prescribing Management Summary To Take To Your Doctors

Use LitCovid database https://www.ncbi.nlm.nih.gov/research/coronavirus/ to keep up with the latest open-access studies each day!

Table of contents


1 Page Summary

Prevention & Preparation
  • Never touch 1) above your neck or 2) food, without washing hands first 
  • Hand washing technique: (Soap + water → 30 sec, 7 step technique) + moisturise 
  • Disinfect phone, tablet, keyboard, mouse, surfaces 2x/d; use gloves, soap & water to do this
  • Set daily alarms on your phone with popup text to remind you to wash hands, not touch above neck, to disinfect aforementioned objects → set this on your phone now
  • High grade mask/scarf/respirator if in high risk zone, or if have symptoms to limit spreading
  • Gloves/mask dispose at end of day or wash with soap & water + never touch outside of mask
  • Never be in same room as people with infection symptoms (fever, cough, sneezing)
  • Prep immune system (strep & and flu vaccine + Greg Fahy GH/DHEA-S protocol if high risk, vitamin D3 2000 IU/d, garlic 5-10g or 180 mg allicin supplement, Longevity Level 1 diet, 6hrs moderate exercise/wk, solve/optimise all other medical conditions, optimise sleep
  • Prepare access to testing & targeted therapies (access to sample kits and labs with RT-PCR turn around time under 24 hours ideally, thermometer (e.g. thermoscan), Drugs, e.g. chloroquine, ribivarin, remdesivir, lopinavir/ritonavir, alpha interferon, fetal stem cells & culturing protocol, arbidol; Prep emergency and ITU equip/services (e.g. ECMO) + cryonics if high risk)
  • Note testing and treatment may not be necessary if low risk e.g. under age 60/70 & healthy

Diagnosis
  • Can regularly test in ear temperature e.g. using a ThermoScan thermometer (buy from Amazon or Ebay or elsewhere); fever + new onset dry cough + no sneeze is more specific
  • In ear temperature above 38 = fever; in ear temperature of 37.5 - 37.9 has 20% chance of having a feverous core temperature → can buy rectal thermometer to see if rectal temp is above 38 dC, when ear temp in this range (if very keen to pick up fevers at earliest stage)
  • Viral swab RT-PCR tests at least from nose+throat+sputum (if have sputum), follow public health england & lab specific guidance to take and package samples
  • Stool and serum viral RT-PCR may be highly sensitive at day 5 - 10 after symptoms start so could add these tests to previous tests (based on old SARS/MERS data)
  • If test negative doesn’t mean you don’t have virus, have to test negative 10 days after symptoms started (based on old SARS/MERS data)
  • Sometimes can only diagnose through tracheal/bronchial/alveolar fluid aspirates

Treatment after diagnosis, or presumed diagnosis (as can often be hard to diagnose)
  • Moderate or High risk on NEWS2 score calculator or high risk symptoms → seek medical care
  • Carry on relevant “prepare the immune system interventions” from the prevent/prep stage
  • Chloroquine phosphate 500 mg twice daily for 5 to 10 days maximum has over 100 case reports improving outcomes from China (raw data not available) with no serious adverse events, or other drugs listed in prep section → these drugs may be extremely dangerous in some people, and in doses needed, follow the expert therapies doc for managing these drugs 
  • Optimise standard HDU/ITU outcomes (e.g. ECMO, ventilator pressure management, hospital infection prevention, sleep optimisation, complication prevention, medical error prevention)
  • Consider cultured fetal stem cells intravenous injection protocol as a novel potentially curative anti-inflammatory for severe acute respiratory distress syndrome (SARS)
  • Consider cryonics (www.alcor.org) in all people with mortality risk greater than X% 
      

Treatment Summary (With/Without Formal Diagnosis)


Without Formal Diagnosis (suggestive symptoms only)
Monitor NEWS2 
Blood pressure, heart rate, ear temperature, resp rate, SpO2, confusion
Quarantine
Keep away from high risk people, disinfect rooms air air, use PPE




With Formal Diagnosis (RT-PCR / IgM / meta-genomic sequencing positive)
(this section is a summary for your doctor)
Monitor NEWS2 
Blood pressure, heart rate, ear temperature, resp rate, SpO2, confusion
Quarantine
Keep away from high risk people, disinfect rooms air air, use PPE
Consider VTEP
E.g. LMWH + daily D-Dimer (Li et al 2020)
Consider chloroquine phosphate
Check inclusion, exclusion criteria, contraindications and drug interactions first.Check ongoing drug interactions. Before starting do ECG QT interval; before the second dose do ECG. Every other day do RT-PCR throat+nasal covid-19, liver panel, Na, K, chlorine, glucose, urea, creatinine, FBC, platelets, troponin or CPK. Every 5 days after starting, do ECG. CXR/CT/MRI/VBG/ABG depending on need. NEWS2 + CURB65 tailored frequency. Dose 500 mg BID 5 days minimum, 10 days max. Half daily dose if intolerable or high risk. Can stop at 5 or 10 days or if 3 days of negative RT-PCR. Every day check for tinnitus, hearing loss, loss of vision, cerebellar signs, dystonia, dyskinesia, tongue extension, torticollis, diarrhoea, nausea, vomiting, palpitations, dizziness, bleeding, depression, dermatitis, rash, headache. (source)

Evidence in covid19: improved outcomes in 100+ case reports, no severe adverse effects (source)
Consider hydroxychloroquine sulfate if chloroquine phosphate not available
Copy management for chloroquine phosphate

Dose 400 mg BID day 1, 200 mg BID Day 2 - 10 (source), minimum 5 day course. Half daily dose if intolerable or high risk.Can stop at 5 or 10 days or if 3 days of negative RT-PCR 

Evidence in covid19: less case reports than chloroquine phosphate




Treatment before formal diagnosis

A lot of people will be unable to get access to RT-PCR tests for the virus as they don't meet high priority and will be unaware of when to seek medical treatment with suspective symptoms 

so I'm adding in a summary of one way to manage it at home 

See below for 

-

First I'd say take vitamin D3 2000 IU per day with a meal if not already doing, and 5-10 g garlic a day if not contraindicated, zinc and vitamin C supplements (maybe max 500 mg a day) are fine too, but not as much evidence as garlic or vitamin D - these are all relatively super low risk

Also eat a good amount of probiotic foods each day, 30g+ of fibre, ideally 10 a day of fruit and veg, lots of teas, (although unclear evidence if these particular things helps much)

Making sure optimize good sleep is important too and has a lot of evidence 

RE when to seek medical help these are good rules to follow, in UK we often use the National Early Warning Score 2 (NEWS2 score to classify an acute patient as low, medium or high risk)


You could consider completing the NEWS2 score at home and at a frequency suggested in the results of your previous score (if you do not have all the equipment yoh could buy it or you can just leave thst part out)

If you are medium or high risk on the score, depending on your risk tolerance, you could seek medical care at this point - and you could communicate the news score and vital signs over the phone

 (this is what nurses and doctors do in hospitals) 

Additionally these things could trigger seeking medical care
- coughing up blood
- green sputum (suggests bacterial infection in lungs and may need antibiotics)
- ongoing shortness of breath at rest
- ongoing fever above 40 dC 
- respiratory rate above 25 breaths per min (not measured after exercise of course...)
- resting heart rate above 120 (if not anxious)  
- systolic blood pressure below 90 (if you have a cuff) (and assuming you dont normally have low blood pressure) 
- symptoms that are not improving after 7 days since the start of symptoms 

There's also the CURB65 score which is good to know about once/if you are diagnosed with pneumonia via chest imaging - https://www.mdcalc.com/curb-65-score-pneumonia-severity#use-cases  

Treatment after formal diagnosis

See 

Prevention & Preparation Summary 

Intervention
How to do it
Never touch face, mouth, tongue, eyes, ears, nose; if you have to then wash hands first
Set daily alarm 1 on your phone at least once per day e.g. saying “never touch neck upwards + wash hands with water/soap” to accelerate habit formation
Wash hands
Use the above phone alarm + 
Most effective: soap + water PLUS glycerin or aloe vera based moisturiser straight away afterwards
Next best: water alone plus above moisturiser strategy
Least best: alcohol gels
All of the above: 7 step hand washing technique and 30 seconds+
Hand moisturiser
Place moisturiser next to all handwashing stations
Buy containers of hand moisturiser and put in pocket or bag 
50 mL container size or less is most portable
Gloves
Wear e.g. on public transport then wash or dispose of at end of day, never touch outside of gloves
Masks/Scarves/Respirators
Wear in high risk areas e.g. public transport, any is better than none, but powered respirators may be best 
Clean phone/tablet, keyboards, mouse, non metallic frequently touched surfaces 2 x per day 
Set daily alarm 2 on your phone at least once per day e.g. saying “clean phone, tablet, keyboard, mouse & non-metallic highly touched surfaces” to accelerate habit formation
Avoid people with fever, cough, exposure to covid patients + rooms they’ve been since having symptoms
ANY symptoms = they are infectious, never be in same room as them 
Ventilate all rooms 
Can use hexito air purifier to sterilise air + deep clean surfaces for 4 wks
Don’t shake hands, avoid physical contact etc.
Prepare the immune system 
  1. Strep pneumonia and flu vaccine, especially if over age 60 or high risk ; flu vaccine at 11:15 am latest as much higher response
  2. Vitamin D3 2000 IU/day, Garlic 5 - 10 g / day or extract capsule with ~180 mg allicin, 
  3. Longevity Level 1 Diet, 6 hrs moderate exercise per week
  4. Growth hormone / DHEAS / Zinc / Vit D3 (metformin optional) via Greg Fehy protocol to rejuvenate immune system
  5. Solve or optimise all other medical conditions
  6. Do everything to optimise sleep as is huge anti-viral intervention
Prepare anti-covid drugs & testing strategy 
E.g. access to 24 hour multi-body-site RT-PCR testing services
ThermoScan ear thermometer / rectal thermometer (optional)
Drugs, e.g. chloroquine, ribivarin, remdesivir, lopinavir/ritonavir, alpha interferon, fetal stem cells & culturing protocol, arbidol
Prep emergency and ITU equip/services (e.g. ECMO) + cryonics if high risk 





  • Soap/detergent and water hand washing is likely superior to alcohol based handwashing for lipid enveloped viruses like flu and coronaviruses, can carry a small bottle of PUMP-delivered soap/detergent with you in pocket in case do not have access to soap/detergent elsewhere
  • Do not touch with fingers 1) door handles 2) toilet seats 3) toilet flushes 4) light switches 5) light switch cords (although top is cleaner than bottom) 6) taps to turn on tap 7) soap dispenser 8) taps to turn off tap - use clothing, or tissue paper, or arm, or wrist or back of hand (can use disposable gloves, making care never to touch the outside of the gloves); especially important in shared bathrooms as virus can likely be transferred by faeces 
  • Use the 7 step hand washing technique each time (see end of this section for graphic)
  • Once cases are confirmed in your city, washing hands 10 - 15 times per day for 30 SECONDS each time, (e.g. sing happy birthday) spread evenly throughout the day or after most prominent exposure risks might be more effective than washing less frequently per day 
  • Consider washing phone, mouse and keyboards 3 times a day for 30 seconds, with soap and water; water only or alcohol gel, as these are sources of viruses; don’t touch others’ phones
  • MERS and SARS coronaviruses can survive for up to 9 days at room temperature and pressure on plastic and cardboard surfaces; however coronaviruses may be inactivated on copper or steel surfaces within a few hours due to anti-viral nature of these materials (non-scientific reference)
  • Don’t touch coins, cash notes, public transport, door handles or door buttons with bare skin (can use disposable gloves, making care never to touch the outside of the gloves)
  • Don’t shake hands with anyone, if do don’t touch face and wash hands; hand on shoulder or fistbump is alternative, but ideal is nothing, or foot bump or elbow bump, or can use disposable gloves, making care never to touch the outside of the gloves
  • Large amounts of soap may damage hands, cause eczema and may make it easier for pathogens to inhabit the skin, or even enter bloodstream or tissues through skin; and importantly
  • Soap side effects may reduce your desire to washing your hands as frequently as may be optimal to prevent infection 
    • Using glycerin based moisturiser AFTER using water/soap/detergent may reduce side effects by restoring the lipid barrier to the skin → make sure to use moisturiser in a PUMP bottle rather than one you scoop out with fingers, as scoop out ones can harbour viruses
    • Using skin pH adjusted detergents (i.e. pH 4, acidic pH “fake soap” - as all soap is by definition, alkaline and pH >7) may reduce side effects of soap in some people (no evidence). But this may be a myth.
    • Using less / very small amount of soap may reduce skin dryness side effects (and may still be just as effective for removing viruses and bacteria)
  • “Anti-bacterial” marketed soaps don’t offer any benefits for bacteria or virus outcomes to my knowledge (and may cause excess harm if pregnant or allergic to these extra compounds)
  • Hot or cold water just as effective, just use what’s more comfy for your skin
  • Using water may be better than alcohol based hand wash, if highly intolerant to soap or no soap available
  • Using water for 30 seconds, followed by alcohol hand wash for 5 minutes may be better than water alone (no evidence of this, guess only)
  • Using 60%+ ethanol hand wash may still be effective if leave on hands for 5 minutes, if do not have access to water or soap
    • Wet mucus surrounded viruses are particularly resistant to ethanol handwash = ethanol may work better in this scenario if applied for 300 seconds (5 minutes) without being exposed to air: put on the alcohol gel then put on e.g. a pair of medical nitrile gloves (which don’t let ethanol evaporate through them) to be worn for at least 5 minutes after applying the alcohol gel, to prevent the alcohol evaporating) (Oliver’s opinion on how to simulate the tube they used in the study to keep the ethanol from evaporating from wet mucus flu virus on hands)
  • Keep nails short and visibly clean, e.g. gentle nail scrubber
  • Consider removing jewelry; however some metal jewellery may naturally kill viruses e.g. brass
  • Cover your exposed skin when touching handles on doors, especially public or house bathrooms, e.g. with your sleeves, brass or copper doorknobs may be safer to touch than any other types as naturally kill viruses within a few minutes or hours, but best to not take the risk 
  • Do not touch the outside of your sleeves, given the above strategy, wash clothes regularly 
  • Wearing gloves on public transport. and then washing them, makes sense
  • Don’t touch the outside of your gloves as this is a contaminated zone
  • P3 / APF 20 / APF >20 / FFP3 / N99 / N100 grade masks, including www.bioscarf.com have better theoretical evidence for protecting against 80 - 160 nanometer diameter viruses like coronavirus; FFP2 or N95 masks or surgical masks have no evidence for protecting against FLU virus, which is a similarly sized, similarly lipid enveloped virus. 
  • FFP3, N99, N100 masks can likely be used up to 56 hours use time ( 8 hours a day 7 days a week), whilst maintaining high theoretical reduction of such nanometer sized enveloped viruses, as long as mask is not damaged or becomes particularly soiled with sweat, but ideally should be used for the specific manufacturers stated maximum time (which may be 12 - 24 hours)
  • Breathing slower through the mask may increase the filtering capacity of it
  • Know how to test for an air seal of the P3/FFP3 or greater strength mask: 
    • hold a bottle of 10 mL essential oil (can keep in pocket); if can smell it then mask is not creating a perfect seal
    • If mask does not inflate and deflate when breathing, or glasses fog, suggests poor seal
  • Consider purchasing a battery powered mask with equal or greater filtering capabilities to FFP3/N99
  • Do not touch the outside of the mask, as it has been proven to collect pathogens
  • Do not touch the inside of the mask with your fingers as can contaminate human or bacterial cells with viruses and make the viruses replicate, and then transfer to your mouth
  • Do not have a beard as breaks the seal of the mask
  • ANYONE with any respiratory infection symptoms is INFECTIOUS, it is a MYTH that people with symptoms are not infectious: take away message: AVOID anyone with coughs, fevers, rigors/chills, sneezing and put up your bioscarf/FFP3 mask over your face as soon as someone does 
  • Avoid kissing, hugging, hand shakes, sex etc with people with symptoms
  • Know that even ordinary tidal breathing from symptomatic people can likely infect you
  • Know symptomatic animals, and asymptomatic animals or people can likely infect you, but lower risk; picking up the virus from people or surfaces onto your skin then into your mouth, nose or eyes can cause you to be infected
  • Wear bioscarf all the time when have likelihood of being exposed to people with above symptoms as much more practical than FFP3
  • Wash bioscarf with soap and water, follow washing instructions on label/website, as have to hand wash, wash hands first and use rubber gloves, or disposable medical nitrile gloves, so don’t touch the outsides of the scarf which is contaminated with viruses
  • Wear FFP3 in places where you cannot avoid exposure to people with symptoms, e.g. necessary public transport, gatherings, or people 
  • Open windows, as airflow and UV light (which is blocked by windows) disinfect air and surfaces
  • A Hexito (www.hexito.net) air purifier may sterilise air, can in placed strategically in rooms or cars (could even take one or more to quarantine zone or hospital); if infected, may reduce the extent of reinfection by killing the viruses you have placed into the air. 
  • Build a habit of telling yourself to not touch face or nose or eyes or ears with hands 
  • Essential oil mouthwash twice a day for 30 - 60 second gargles, BEFORE brushing (or 30 minutes after brushing, or after kissing someone), e.g. listerine, or 1-3 drops of peppermint oil in 25 mL water has theoretical antiviral activity and has multiple RCT evidence for reducing gum inflammation, and gum inflammation likely predisposes to viral infections in the mouth. Can add potassium bicarbonate or baking soda or toothpaste to listerine to make it alkaline if don’t want the acid exposure to damage teeth and increase risk of caries and intra-tooth infections); can also use pH paper to measure pH of listerine before and after adding alkaline compounds; aim for a pH of 8 (nicely alkaline). 
  • Wash face once or twice a day with face cleanser and water 
  • Change and wash pillow cases regularly 
  • Consider experimental therapies to rejuvenate the immune system especially if age 70+ or if have any chronic medical condition that puts you at higher coronavirus mortality risk (such as angina, peripheral vascular disease, prior heart attacks, mini strokes, full strokes, diabetes, pre-diabetes, COPD, emphysema, chronic bronchitis, cystic fibrosis etc.), such as the Greg Fahy Growth Hormone, DHEAS, Vitamin D, Zinc, Metformin protocol - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826138/ (2019 non-randomised non-controlled trial case series), https://www.ncbi.nlm.nih.gov/pubmed/14987435 (2003 case report)
  • Aim for 6 hours moderate exercise per week to slow/partially reverse immune system aging (see below infographics)
  • Score >8/10 on the alternative healthy eating index 2010 every day (see below infographics)
  • Meet all Longevity Level 1 requirements (see below infographics) (alcohol option, but alcoholic drinks have some low risk of bias randomised controlled trials evidence showing it reduced common cold risk, as contains ethanol and polyphenols which are all anti-viral)
  • Vitamin D level management
    • Take 2000 IU vitamin D3 a day with GMP certification; vitamin D2 does not work: 
    • Measure vitamin D blood level 3 months after this, must aim for blood level of 80-85 nmol/L ideally; weak evidence (18 patient study) that levels above 95 nmol/L are better at preventing viral infections than below this level (but not clear if different from 80 - 85 nmol/L, as confounded by people with levels much lower than this)
    • Doses under 1600 IU per day 
    • Work out the conversion from micrograms to IU if need to, make sure its the right dose otherwise unlikely to work
    • Convert your blood level from American units (ng/mL) to standard international units (nmol/L) by multiplying the ng/mL value by 2.5. Make sure you are aiming for 80 - 85 nmol/L not ng/mL, as this is a lot higher and may be associated with increased all cause mortality risk (but is associated with decreased breast cancer risk at least)  
    • If blood level is still not at 80 - 85 nmol/L range: 
      • Taking vitamin D3 pill with the largest meal of the day may increase Vitamin D blood level without having to increase the dose, compared to taking it with smaller meals or without food
      • Increase dose by 1000 IU for 3 months then remeasure
      • Increase skin sunlight exposure (e.g. 15 min a day whole body)
      • Increase Vitamin D3 rich foods 
        • If blood levels still not at 80 - 85 nmol/L range after these new interventions, consider increasing dose to 4000 IU per day, and discuss with doctor as may have underlying condition that prevents reaching this blood level
    • Blood levels may take 3 months to change, so measure after 3 months 
    • I think fingerprick tests for vitamin D are accurate enough, but venous sample is preferable 
    • Mega dosing vitamin D may be bad and result in no benefit in preventing viral infections, even for people with vitamin D deficiency; take away message: even if have vitamin D deficiency currently, start with 2000 IU for 3 months then measure blood level 
    • No point measuring baseline level as the initial therapy is always 2000 IU vitamin D3 a day (for optimising for infection outcomes at least)
  • Worthwhile doing the appropriate Flu and Streptococcal Pneumonia vaccines for your demographic and geography, as may prevent secondary infections from coronavirus, and may reduce risk of coronavirus acquisition or severity during periods of suffering with flu or streptococcal pneumonia
    • Note PCV13 vaccine may not cover the majority of strep pneumonia cases anymore in countries where PCV13 vaccine has been around for 5+ years, hence the PPV23 pneumonia vaccine may give better coverage due to the majority of cases of pneumonia being non-PCV13 subspecies
    • Note PPV23 may stop providing immunity within 2.5 years, whereas PCV13 may provide longer term immunity through B memory cell generation 
    • Note PCV20 vaccine from Pfizer is coming up (in 2021?) which may have both the advantages of wide coverage and long term immunity generation 
    • Note, vitamin D status, doing 12 weeks of 3+ hours moderate intensity cardiovascular exercise per week, multiple doses and vaccinating by 11:15 am latest may provide stronger immune responses to vaccines and increase the chance of developing sufficient and higher immunity response levels to the vaccine 









Alternative healthy eating index 2010 score to boost immunity

Coronavirus prevention shopping list - 27 items


  1. Pump delivered soap or pH neutral hand detergent (i.e. acidic soap (fake soap)), small enough bottles to carry around conveniently for you e.g. in pockets or bag, to help increase adherence if necessary
  2. Pump delivered hand moisturiser e.g. glycerin based to prevent side effects from after using water, soap and alcohol gel on hands; in small enough bottles to carry around conveniently for you e.g. in pockets or bag, to help increase adherence if necessary
  3. Disposable medical/nitrile gloves to keep ethanol exposure on hands high for 5 mins after using ethanol gel / or for using on public transport; don’t touch outside of gloves, dispose after use 
  4. General purpose reusable gloves to wear on public transport are an alternative option to disposable medical nitrile gloves (must be machine washable so don’t have to hand wash, if have to hand wash, wash hands first and use rubber gloves, or disposable medical nitrile gloves, so don’t touch the outsides of the gloves)
  5. 10 mL bottle of essential oil to test mask seals (£3 typically)
  6. Nail scissors/cutters
  7. Bioscarves (www.bioscarf.com) ~£35 each, reusable, washable, as have to hand wash, wash hands first and use rubber gloves, or disposable medical nitrile gloves, so don’t touch the outsides of the scarf
  8. P3 / APF 20 / APF >20 / FFP3 / N99 / N100 masks (if impossible to find, N95 or FFP2 is better than nothing… but bioscarf may be better than FFP2 and N95 as is as strong as FFP3)
  9. Vitamin D3 tablets 2000 IU (£10 for 1 years supply)
  10. Vitamin D blood test to measure after 3 months of taking vitamin D (£20 typically, venous may be more accurate than fingerprick)
  11. Hexito air purifier (£120) (www.hexito.net)
  12. Listerine mouthwash 
  13. Sodium or potassium bicarbonate (e.g. baking soda from stores) to alkalinise listerine to pH 8
  14. pH paper to test listerine mouthwash before and after alkalinising 
  15. Alternative to listerine mouthwash: 50 - 100 mL therapeutic/food grade peppermint oil (remember can’t take above 100 mL on a plane) WITH a dropper top to apply 1 drop (50 uL) into 25 mL water twice a day for mouth gargles → note the 10 mL bottles won’t be able to fit a dropper so they are almost impossible to use, must buy one that can fit a dropper top inside, e.g. 100 mL, unclear if 50 mL bottle size will work 
  16. Liquid dropper top for peppermint oil that fits your peppermint oil bottle, if does not come with one
  17. Multiple pillow cases
  18. Face cleanser to your preference
  19. Food to reach alternative healthy eating index 2010 score of 8/10 or more a day
  20. Wine e.g. 1 bottle per week with a meal 
  21. Smoking cessation products and services   
  22. Exercise equipment and memberships or budget to reach 6+ hours moderate exercise a week
  23. Growth hormone, DHEAS, Zinc, Vitamin D, Metformin, + safety tests and MRI imaging of thymus ideally + a doctor, if doing immune system rejuvenation protocol 
  24. Print out copies of the 7 step handwashing technique and bluetack (or other method) in bathroom/kitchen at home/office
  25. Print out copies of the alternative healthy eating index score and bluetack (or other method) on/inside fridge in house/office
  26. Print out copies of the exercise planner and bluetack (or other method) in house/office
  27. Consider battery powered mask with filtering capacity equal to FFP3/N99 or greater


Some quite good advice from Boris Johnson, although adding a small amount of soap has more evidence than just water alone + moisturising after to prevent dry skin.. And hot water isn’t necessary but may be more comfortable, so may make you more likely to do it: 



Diagnosis and when/how to test summary



How to diagnose covid-19
The most common symptoms at onset of illness were fever (136 [98.6%]), fatigue (96 [69.6%]), dry cough (82 [59.4%]), myalgia (48 [34.8%]), and dyspnea (43 [31.2%]

Fever is likely most predictive single symptom marker 
Fever + new onset dry cough without sneezing is likely most predictive double symptom marker
Step 1 - Measure ear temperature e.g. using Thermoscan thermometer
Step 2 
- If ear temperature is 38 dC or greater = fever → go to step 4
- If ear temperature is 37.5 - 37.9 dC = 20% chance of false negative and could have rectal temp of 38 dC or > (a true fever) → Consider measuring rectal temp in step 3 
- If ear temp is 37.4 dC or less, unlikely to have fever

Note that ear and rectal temps increase after exercise or saunas etc., so shouldn’t be measured soon after → learn more about temperature measurement interpretation in the bottom “know other things about fever” section of this table
Step 3 
  • Consider measuring rectal temp with probe, probe cover and lubricating jelly 
  • If dont have probe covers, you can use soap, water and 70% alcohol to clean 
  • Lubricating jelly can be used 
  • Rectal temp of 38 dC or more = fever 
Step 4 - Classify fever and decide follow on steps
  • 37.5 - 38 - Mild fever or no fever (38 is used as the cut off for fever)
  • 38 - 40 - moderate fever 
  • 40 - 41 high fever, 
  • 41 + severe fever 
  • 42-43 - likely tissue damaging
  • 43+ - life threatening

→ Write down the day your fever started (helps guide when to do stool test for virus, and when to use anti-virals)

→ For fever above 40 / high fever, consider contacting urgent health services

→ For any fever, potentially consider getting Flu and Covid-19 RT-PCR tests from ideally nasal and throat (and sputum if available) areas … (use this public health england guide)

→ For any fever if you have had symptoms for 5 days or more consider nasal, throat, sputum (if possible) / AND stool swabs for covid-19, as may show up in the stool a lot more commonly after day 5 of symptoms (public health england does not advise this yet, but it is based on previous SARS/MERS infection data (see detailed diagnosis section))

You want to use a test that has results in / within 24 hours so you can start potential antiviral therapy sooner 

If test negative go to step 5

If test positive go to step 6
Step 5 
if test negative and still have same or worsening symptoms 

→ repeat RT-PCR tests including stool test after day 4 of symptoms starting (use this public health england guide)
Step 6

If test positive consider taking targeted and general therapies and follow isolation for 2 weeks → read though the therapies sections of these doucments
Know other things about fever

Read this great guide on fevers! https://www.ncbi.nlm.nih.gov/books/NBK324/

Chills are the subjective reports of shivering or shaking associated with rapid changes in body temperature. They result from involuntary muscle contractions that occur in response to a sudden lowering of body temperature below the prevailing set point.
Night sweats are subjective reports of nocturnal sweating that results from an exaggeration of the normal circadian temperature rhythm.Night sweats may occur with any condition causing fever. Although suggestive of tuberculosis or lymphoma, they also occur in brucellosis, lung abscess, bacterial endocarditis, diabetic autonomic neuropathy, nocturnal hypoglycemia, nocturnal angina, and diabetes insipidus.
Moderate fever is safe for most
Except in patients with underlying heart disease, moderate fever has no deleterious effects on the patient.
Antipyretic (e.g. paracetamol/acetominophen/tylenol) may make worse
 Antipyretics, in addition to clouding the issue, make the patient uncomfortable because of periods of sweating when the antipyretic is given and chills when the effect of the agent is wearing off. If antipyretics are used, they should be given around the clock (e.g., every 3 to 4 hr) rather than as needed in response to symptoms, to avoid this rollercoaster effect.
  • Discussion of immune response to fevers below
Fever exerts an overall adverse effect on the growth of bacteria and on replication of viruses[15,16]. It also enhances immunological processes, including activity of interleukin-1 (IL-1), T-helper cells, cytolytic T-cells, B-cell and immunoglobulin synthesis[17]. The mobility, phagocytosis and killing of bacteria by polymorphonuclear leukocytes are significantly greater at temperatures above 40 °C. Elevated temperatures of 38 °C and 39 °C have a direct positive effect on lymphocyte transformation, the generation of cytolytic cells, B-cell activity, and immunoglobulin synthesis[18]. IL-1 is more active at febrile temperature than at an afebrile temperature. Interferon (INF), a potent antiviral agent, has enhanced antiviral activity above 40 °C[19].
Human studies are also in support that fever may be beneficial. Fever was the principal form of treatment for syphilis and gonorrhoea about a century ago. A study from Japan[20] found that the frequent administration of antipyretics to children with bacterial diseases led to a worsening of their illness. A study of 102 children with salmonella gastroenteritis from Finland[21] demonstrated a significant negative correlation between the degree of fever and the duration of excretion of organisms. In a series of children presenting with severe infection, such as pneumonia or septicaemia, it was found that the lower the body temperature, the higher the mortality[22]. Insufflations of humidified air at 43 °C (three 30-min sessions at 2-3 h intervals) into the nasal passages of patients suffering from coryza resulted in the suppression of symptoms in 78 per cent of patients[23]. In human volunteers infected with rhinovirus, the use of antipyretics was associated with suppression of serum antibody response, increased symptoms and signs and a trend towards longer duration of viral shedding[24]. In a study of children with chickenpox, half of whom received paracetamol four times a day, and half received a placebo, the time to total scabbing was slightly shorter in the placebo group (5.6 d) than in the paracetamol group (6.7 d)[25]. (ref)

Other non-infectious causes of fever




  • It can be very hard to diagnose, may need to test throat, nose, trachea, stool and blood, or even a tracheal/bronchial aspirate multiple times via RT-PCR or meta-genomic next generation sequencing (MG-NGS) to identify the virus
  • Requires 24 hour turnaround time, so can start anti-coronavirus therapies as early as possible, as starting them 5 or 10 days after symptoms may be a lot less effective as virus will have replicated by this time and most of these drugs work to prevent viral replication
  • Public health testing may be limited to moderate or severe cases only, or limited to a certain number of tests
  • RT-PCR is the main testing method used to diagnose
  • ELISA absolute level IgM and IgG tests are used to test if you are responding to the virus and have developed sufficient immunity
  • The most common symptom is fever (around 90% of people, sample size 50k+ cases from WHO data)
  • So one could regularly test to see if you have a fever using an in ear thermometer which is the most acute peripheral way of measuring temperature compared to internal body temperature measurements 
  • Core and peripheral body temperature can rise from exercise from as low as 35.8 degrees up to 40 dC after 45 minutes continuous exercise in hot humid environments (pubmed source) - so you should not try to measure temperature in the few hours after exercising (I haven’t checked how long it takes to cool down completely from exercise)
  • In-ear tympanic membrane measurement using a multi-point temperature measurement infra red thermometer with pre-heated tips, and using the correct technique, has the most accuracy versus directly measuring core temperature such as rectal temperature
  • This should be done be a CE/FDA 510k marked classified medical device which has mulitple pubmed papers on the exact device
  • An common one used in hospitals is the Braun Thermoscan Pro 4000 ear thermometer (which meets the above description)
  • the ear thermometer Braun Thermoscan Pro 4000®, released in 2006, where a heating element in the sensor warms the probe tip to just under normal body temperature to avoid cooling the ear canal, which has shown good correlation with the core temperature [3, 6]” 2018 study in adults

  • This thermometer is most easily and cheaply bought off eBay
  • The newer version the thermoscan 6000 is just as good and can be bought off ebay or elsewhere too, there is no disadvantage of having the 4000 version (both are accurate to +/-0.2dC) the 6000 version has a feature to help measure respiratory rate and heart rate too 


Thermoscan 4000
Thermoscan 6000
Measurement time 
3 - 7 sec
2 - 3 sec
Calibration accuracy
+/- 0.2 dC
same
PerfecTemp algorithm
No
Yes
“PerfecTemp supports accuracy by detecting direction and depth of probe placement in ear and adjusts temperature calculation”
ExacTemp algorithm
Yes
Yes
“ExacTemp helps support reliability and accuracy by detecting the stability of probe placement during measurement”
Pre warmed sensors 
Yes
Yes
Widely available disposable tip covers
Yes
Yes
Studies showing 6000 is more accurate than 4000 due to PerfectTemp algorithm
n/a
none


  • Versus core temperature, the sensitivity of other devices drops off dramatically (see below image from an ITU study). Also, due to the still low sensitivity of even the best in ear thermometers, a lower temperature cut off than normal can be used to increase sensitivity without loss of specificity, and trigger e.g. rectal measurement if the patient is willing 


  • So using normal cut offs of 38 dC for fever with ear temp measurement will miss around 20% of fevers, oral around 40%, whilst forehead or armpit measurements can miss up to 50% of fevers
  • One study actually used this approach to increase sensitivity and used an ear temperature of 37.5 dC - 37.9 dC to trigger a rectal temperature measurement; whilst 38 dC on the ear temperature measurement is sufficient to diagnose fever 

A strategy of using the TM thermometer as a screening tool and continue with rectal measurements for all patient with ear temperature of ≥37.5 °C would identify 95% of all patients with true rectal fever of ≥38.0 °C, and reduce the number of patients who needed a rectal measurement to 22%.” (2018 study of 600 emergency department patients)

Rectal temp measurement tips

Rectal temp can be measured in around 10 seconds e.g. with an Omron flex temp smart thermometer (which has been used in this 2018 emergency department study)

How to take rectal temperature - Omron flex temp smart thermometer




Video on how to take a rectal temperature 



Implants may diagnose flu and corona better in near future



4 Page Summary - Treatment


  • REINSTATING THIS IS NOT MEDICAL ADVICE: DO NOT BUY OR USE THESE DRUGS WITHOUT PRESCRIPTION AND GUIDANCE FROM YOUR DOCTOR AS THEY CAN BE VERY DANGEROUS
  • Note mortality rate is likely overestimated as skewed by Wuhan data (rest of China is 0.7% mortality) BUT the more likely thing (and hence more concerning) is permanent organ damage due to coronavirus infection → So should still be taken seriously at this point, and more seriously than a bad flu season
  • Note case reports of umbilical cord mesenchymal stem cell injections given IV (so travel straight to the lungs) can save patients that would have died from the high inflammation in the lungs caused by the virus 
    • Note case reports of umbilical cord mesenchymal stem cell injections given IV (so travel straight to the lungs) can save patients that would have died from the high inflammation in the lungs caused by the virus - https://regenexx.com/blog/stem-cells-and-coronavirus 
    • Case of an elderly woman in the ICU in China. She had been there for two weeks and her organs were clearly failing, so the Chinese doctors got approval to use stem cells that had been culture expanded in the lab. After the first two treatments and within days she was able to get out of bed and then after the third injection, she was able to leave the ICU and was found to be COVID-19 negative. [Big thanks to a reader who has since found the published study which is here].
    • Another study is underway in Hunan province using similar stem cells and the doctor there was quoted as observing similar results. 
    • "What often kills people with the flu is the massive inflammatory reaction in the lungs. This causes swelling and reduces the ability of the lungs to oxygenate tissues. Real stem cells are very good at the short-term reduction of inflammation. In addition, stem cells have been shown to be antibacterial and anti-viral (2,3)."
  • Anti-malaria drugs at much higher dose than normal, so carries increased risk of dangerous side effects - see the separate document on therapeutics 
    • “Thus far, results from more than 100 patients have demonstrated that chloroquine phosphate is superior to the control treatment in inhibiting the exacerbation of pneumonia, improving lung imaging findings, promoting a virusnegative conversion, and shortening the disease course according to the news briefing. Severe adverse reactions to chloroquine phosphate were not noted in the aforementioned patients. Given these findings, a conference was held on February 15, 2020; participants including experts from government and regulatory authorities and organizers of clinical trials reached an agreement that chloroquine phosphate has potent activity against COVID-19. The drug is recommended for inclusion in the next version of the Guidelines for the Prevention, Diagnosis, and Treatment of Pneumonia Caused by COVID-19 issued by the National Health Commission of the People's Republic of China. “ (source)
    • 500 mg twice a day for 10 days chloroquine phosphate (available without a prescription, contraindicated in certain medical conditions) 
    • Hydroxychloroquine may be better
    • Day 1 400 mg 2 x , 800 mg total 
    • Day 2 - 5, 200 mg 2 x, 400 mg total per day (4 days x 400 mg = 1.6 g) 
    • May work preventatively too (theoretically), but side effects risk increases proportionally 
    • Can get a prescription from a GP 
  • Do everything you can to not go on to infect people who are the most likely to die from it (Oliver)
    • People age 60+
    • People with diabetes
    • People with any heart or artery disease or stroke 
    • People with any chronic condition 
    • People with any respiratory condition 
    • People with cancer etc.
  • Make sure you are living in a place which has a very good ITU (intensive treatment/care unit) that you would be admitted to if needs be (Oliver)
  • Check that the ITU you would be admitted to has ECMO (extra-corporeal membrane oxygenation) services and check how many ECMO patients they can accommodate, and weigh this up against other ECMO enabled ITU options, taking into account population density and coronavirus case density (Oliver)
  • Check the ranking of the hospital you would be admitted to based on various quality scores, such as CQC or google reviews in UK, consider alternate options (Oliver)
  • Continue with the vitamin D optimisation protocol as with the prevention strategies, may improve outcomes (no direct evidence to date), no risk or significant cost to doing it - don’t megadose or weekly dose or monthly dose, just daily dosing (Oliver)
  • Optimise management of all underlying medical conditions (Oliver)
  • Use hexito UV air purifiers in the room that you are in (Oliver)
  • Do everything you can to ensure optimal sleep as sleep is major determinant of immune system strength e.g. by using CBT-for-Insomnia (CBT-I), blue and green light blocking glasses, low dose melatonin pills, earplugs, eye masks, black out blinds, temperature control, mindfulness apps etc - take these to hospital if being admitted, or order them in from Amazon or get someone to bring them in ASAP (Oliver)
    • Establish individual therapy regimens and to evaluate, monitor and adjust dynamically (Li et al 2020)
    • Monitor haemodynamics and for different types of shock, be sure to distinguish between different types of shock (Li et al 2020)
    • Assess risk of venous thromboembolism (VTE) and give appropriate preventive treatment in high risk groups (Li et al 2020)
    • Monitor D-dimer, in context of medical history and consider pulmonary embolism (Li et al 2020)
    • Nutritional support is basis of treatment (Li et al 2020)
    • Have instructions for your carers to continue vitamin D supplements at minimum 2000 IU per day, ideally with largest meal if you are unable to take it (Oliver’s opinion)
    • Convalescent blood products (as used in SARS and Ebola) (Li et al 2020)
      • Note that, theoretically, young healthy donor plasma or young blood products should have better outcomes than plasma from older donors or younger unhealthy donors (Oliver’s opinion, based on discussion with Jesse MD from Ambrosia LLC)
    • ECMO (Oliver)
    • General ITU admission multi-organ support, with 1:1 Nursin(Oliver)g or 1:2 Nursing (likely better than lower ratio of nurses to patients) 
    • High dependency unit (HDU) admission for single organ support (e.g. respiratory) with high patient to nursing ratio (likely better than lower ratio of nurses to patients) (Oliver)
  • Immune based treatment options summary
    • Intravenous remdesivir (Pang et. al Feb 26 2020)
    • Vitamin D3 2000 IU daily, with largest meal ideally (Oliver)
    • Full nutritional support and monitoring (Li et al 2020)
    • Optimal sleep length and quality (as aforementioned) (Oliver)
    • Pulsed methylprednisolone → “but Most importantly, the current guidelines emphasise that systematic corticosteroids should not be given routinely for the treatment of COVID-19, which was also the recommendation in a a Comment in The Lancet.14 - https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30141-9/fulltext
    • Intravenous immunoglobulin (IVIG) (Li et al 2020)
    • Convalescent blood products (as used in SARS and Ebola) (Li et al 2020)
      • Convalescent blood products (CBP), obtained by collecting whole blood or plasma from a patient who has survived a previous infection and developed humoral immunity against the pathogen responsible for the disease in question, are a possible source of specific antibodies of human origin4. The transfusion of CBP is able to neutralise the pathogen and eventually leads to its eradication from the blood circulation. Different CBP have been used to achieve artificially acquired passive immunity14: (i) convalescent whole blood (CWB), convalescent plasma (CP) or convalescent serum (CS); (ii) pooled human immunoglobulin (Ig) for intravenous or intramuscular administration; (iii) high-titre human Ig; and (iv) polyclonal or monoclonal antibodies - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4781783/
      • Evidence summary: A multicentre, prospective, double-blind, randomised controlled trial by Hung and colleagues showed that using convalescent plasma from patients who recovered from the influenza A H1N1pdm09 virus infection to treat patients with severe influenza A H1N1 infection was associated with a lower viral load and reduced mortality within 5 days of symptom onset.8 A meta-analysis by Mair-Jenkins and colleagues showed that the mortality was reduced after receiving various doses of convalescent plasma in patients with severe acute respiratory infections, with no adverse events or complications after treatment.9 Another meta-analysis by Luke and colleagues identified eight studies involving 1703 patients with 1918 influenzapneumonia from 1918 to 1925 who received an infusion of influenza-convalescent human blood products, which showed a pooled absolute reduction of 21% (95% CI 15–27; p<0·001) in the overall crude case-fatality rate at low risk of bias.10 - https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30141-9/fulltext
      • Note that, theoretically, young healthy donor plasma or young blood products should have better outcomes than plasma from older donors or younger unhealthy donors (Oliver’s opinion, based on discussion with Jesse MD from Ambrosia LLC)
    • Hydroxychloroquine (5 trials recruiting) (Pang et. al Feb 26 2020)
    • Loponavir plus ritonavir plus interferon alpha 2b (1 trial recruiting) (Pang et. al Feb 26 2020)
    • Loponavir plus ritonavir plus arbidol (Pang et. al Feb 26 2020)
    • Abidol hydrochloride or oseltamavir or loponavir+ritonavir (Pang et. al Feb 26 2020
    • Ritonavir + ASC09 (2 HIV protease inhibitors) (Pang et. al Feb 26 2020)
    • Molecules that inhibit 2 SARS coronavirus enzymes (Pang et. al Feb 26 2020)
    • 50k - 100k IV mesenchymal stem cells per kgbw every 2 days for 3 doses (1 trial recruiting) (Pang et. al Feb 26 2020)
    • Traditional chinese medicine xue bi jing (1 trial recruiting) (Pang et. al Feb 26 2020)
    • Oral liquid traditional Chinese medicine,Shuanghuanglian (Pang et. al Feb 26 2020)
    • Chloroquine phosphate (Pang et. al Feb 26 2020)
    • Monoclonal antibodies against Covid 19 or MERS/SARS (Pang et. al Feb 26 2020)
      • There is only one ongoing randomized controlled trial targeted at MERS therapeutics [99]. It investigates the usage of Lopinavir/Ritonavir and Interferon Beta 1B. Likewise, many prospective and retrospective cohort studies conducted during the epidemic centered on usage of ribavirin with lopinavir/ritonavir/ribavirin, interferon, and convalescent plasma usage. To date, only one trial has been completed. One phase 1 clinical trial investigating the safety and tolerability of a fully human polyclonal IgG immunoglobulin (SAB-301) was found in available literature [46]. The trial conducted in the United States in 2017 demonstrated SAB-301 to be safe and well-tolerated at single doses. Another trial on MERS therapeutics was found on ClinicalTrials.gov—a phase 2/3 trial in the United States evaluating the safety, tolerability, pharmacokinetics (PK), and immunogenicity on coadministered MERS-CoV antibodies REGN3048 & REGN3051 [100].
    • Steroid gluococorticoids (1 trial recruiting) (Pang et. al Feb 26 2020)
    • Other antivirals (not yet recruiting as of 26/2/20) (Pang et. al Feb 26 2020)
    • Abidol hydrochloride with atomized interferon (not yet recruiting as of 26/2/20) (Pang et. al Feb 26 2020)
    • Darunavir + cobicistat (not yet recruiting as of 26/2/20) (Pang et. al Feb 26 2020)
    • Remdesivir (not yet recruiting as of 26/2/20) (Pang et. al Feb 26 2020)
    • Niclosamide (in vitro evidence only) (Pang et. al Feb 26 2020)
    • Glycyrrhizin (from liquorice) (Pang et. al Feb 26 2020)
    • Baicalin (in vitro evidence only) (Pang et. al Feb 26 2020)
  • Note the need for the adaptive immune response to cure SARS - innate immune response may not work: Innate immune mechanisms are the earliest host defenses that control viral replication and, in the case of many respiratory viruses, do so within the first few days of illness, even before the specific adaptive immune responses have been activated. This response does not appear to occur with SARS, and viral load in the respiratory tract (4) begins to fall only when the antibody response appears, i.e., at approximately day 10 after onset of illness (4,5). This finding may suggest that SARS-CoV is able to evade the host innate response and requires the adaptive immune response to bring the infection under control. - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3322905/
    • Prepare for the psychological risks of quarantine - Most reviewed studies reported negative psychological effects including post-traumatic stress symptoms, confusion, and anger. Stressors included longer quarantine duration, infection fears, frustration, boredom, inadequate supplies, inadequate information, financial loss, and stigma. Some researchers have suggested long-lasting effects. In situations where quarantine is deemed necessary, officials should quarantine individuals for no longer than required, provide clear rationale for quarantine and information about protocols, and ensure sufficient supplies are provided. Appeals to altruism by reminding the public about the benefits of quarantine to wider society can be favourable.” - https://www.ncbi.nlm.nih.gov/pubmed/32112714

Also
‘According to Thailand’s health ministry, the 70 year old Chinese woman “tested negative” for the virus within 48 hours after being treated with anti-HIV drugs lopinavir + ritonavir + large doses of the anti-flu drug oselamavir’


1 Page Summary - Coronavirus vaccine as a prevention strategy in 2020/2021



“With the emergence of 2019-nCoV, there are about 15 potential vaccine candidates in the pipeline
globally (Table 3), in which a wide range of technology (such as messenger RNA, DNA-based,
nanoparticle, synthetic and modified virus-like particle) was applied. It will likely take about a year
for most candidates to start phase 1 clinical trials except for those funded by Coalition for Epidemic Preparedness Innovations (CEPI). However, the kit developed by the BGI have passed emergency approval procedure of the National Medical Products Administration, and are currently used in clinical and surveillance centers of China [40].

Of the total of 570 unique studies on 2019-nCoV, SARS CoV or MERS-CoV vaccines screened,
only four were eventually included in the review. Most studies on SARS and MERS vaccines were
excluded as they were performed in cell or animal models (Figure 1). The four studies included in
this review were Phase I clinical trials on SARS or MERS vaccines (Table 4) [44–47]. There were no
studies of any population type (cell, animal, human) on the 2019-nCoV at the point of screening. The
published clinical trials were mostly done in United States except for one on the SARS vaccine done
in China [44]. All vaccine candidates for SARS and MERS were reported to be safe, well-tolerated and able to trigger the relevant and appropriate immune responses in the participants. In addition, we
highlight six ongoing Phase I clinical trials identified in the ClinicalTrials.gov register ([48,49]); Table
S4) [50–52]. These trials are all testing the safety and immunogenicity of their respective MERS-CoV
vaccine candidates but were excluded as there are no results published yet. The trials are projected
to complete in December 2020 (two studies in Russia [50,51]) and December 2021 (in Germany [52]).”

Note on flu and pneumonia vaccine

See prevention summary section on this

The majority of pneumonia cases now seem to be from non PCV13 covered vaccine strains in the UK, so makes sense to do the PPV23 vaccine as recommended by NHS


Note having the PPV23 vaccine previously doesnt seem to reduce IgG response levels by a clinically significant level to subsequent PCV13 vaccination 1 year later in people age 65+ 

Note also the Flu + PPV23 or PCV13 vaccine can be given simultaneously to save time






Phase 2 Research

What is the best hand sanitizer to use consistently and how




In 2018 it was discovered for the first time that enveloped viruses may also cluster together in larger lipid envelopes called stealth spheres / stealth vesicles 



Influenza is also a lipid enveloped virus (source https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2794490/), and is well studied and diagnosed, so methods used to disinfect against influenza successfully can likely be applied to coronaviruses 

-

Sept 2019 study on alcohol vs non alcohol hand washing to remove enveloped flu virus
Variables
  • Type of washing media 
  • Length of exposure of washing media to the hands
  • Frequency of rewashing after reexposure 
“A new study from Japanese researchers challenges the idea that ethanol-based disinfectants are effective at completely destroying influenza A viruses quickly in all situations. The study was published yesterday in mSphere.
In a series of tests, the researchers from the Kyoto Profectural University of Medicine found that ethanol-based disinfectants, or hand sanitizers, would have be in contact for at least 4 minutes with the influenza A virus before killing it, a much longer duration than typical use. After 2 minutes of use, the virus was still active.” - 
The finding could be a game-changer for healthcare settings, where nurses and doctors often rely on quick uses of hand sanitizers between patients. Currently, the US Centers for Disease Control and Prevention (CDC) and the World Health Organization recommend hand hygiene practices that include using ethanol-based disinfectants for 15 to 30 seconds.”
“When mucus is dry, influenza is inactivated within 30 seconds. When the virus was contained in saline, ethanol-based sanitizers also worked in 30 seconds.”


A concentration of 31% ethanol for 30 seconds was required to kill all the Influenza A viruses in this study, so 40% should be aimed for as a minimum to allow for some leeway 
How did they apply the ethanol for such a long time without it evaporating?

A tube containing 95 μl of EBD was placed on the contaminated area and incubated for 30, 60, 120, or 240 s prior to neutralization and elution with 500 μl MEM; IAV was then titrated.

Take away message
  • Dry mucus = ethanol works after 30 seconds
  • Salty water = ethanol works after 30 seconds
  • Wet mucus = ethanol works well after 300 seconds (5 minutes) (but this requires e.g. medical nitrile gloves (which don’t let ethanol evaporate through them) to be worn for at least 5 minutes after applying the alcohol gel, to prevent the alcohol evaporating) (Oliver’s opinion on how to simulate the tube they used in the study to keep the ethanol from evaporating from the hands)
  • Wet mucus = washing with water alone works after 30 seconds 
  • Wet mucus = washing with water and soap works after 30 seconds (likely more effective than water alone)

A 2009 non randomised controlled trial found similar superiority (p<0,001) for soap and water over 3 different types of alcohol based handwashes  - https://www.ncbi.nlm.nih.gov/pubmed/19115974

Additional CDC advice



  • 7 step handwashing technique which covers a high % of the hands versus unstructured washing


Can someone who got infected once and didn’t die get reinfected and die?


Yes theoretically, but no evidence of this so far 1/3/20
“More likely, the “reinfected” patients still harbored low levels of the virus when they were discharged from the hospital, and testing failed to pick it up.
Even the mildest of infections should leave at least short-term immunity against the virus in the recovering patient, he said.
Even if there were occasional cases of reinfection, they do not seem to be occurring in numbers large enough to be a priority at this point in the outbreak.”




Post getting infected what are the best steps and treatments



Summary
  • Do everything you can to not go on to infect people who are the most likely to die from it (Oliver)
    • People age 60+
    • People with diabetes
    • People with any heart or artery disease or stroke 
    • People with any chronic condition 
    • People with any respiratory condition 
    • People with cancer etc.
  • Make sure you are living in a place which has a very good ITU (intensive treatment/care unit) that you would be admitted to if needs be (Oliver)
  • Check that the ITU you would be admitted to has ECMO (extra-corporeal membrane oxygenation) services and check how many ECMO patients they can accommodate, and weigh this up against other ECMO enabled ITU options, taking into account population density and coronavirus case density (Oliver)
  • Check the ranking of the hospital you would be admitted to based on various quality scores, such as CQC or google reviews in UK, consider alternate options (Oliver)
  • Continue with the vitamin D optimisation protocol as with the prevention strategies, may improve outcomes (no direct evidence to date), no risk or significant cost to doing it - don’t megadose or weekly dose or monthly dose, just daily dosing (Oliver)
  • Optimise management of all underlying medical conditions (Oliver)
  • Use hexito UV air purifiers in the room that you are in (Oliver)
  • Do everything you can to ensure optimal sleep as sleep is major determinant of immune system strength e.g. by using CBT-for-Insomnia (CBT-I), blue and green light blocking glasses, low dose melatonin pills, earplugs, eye masks, black out blinds, temperature control, mindfulness apps etc - take these to hospital if being admitted, or order them in from Amazon or get someone to bring them in ASAP (Oliver)
  • If critically ill 
    • Arrange cryonics if not already done (head only or full body) and contact local cryonics service to warn them of critical condition (www.alcor.org is preferred provider for storage), ensure your cryonics strategy is legally watertight, review all legal risks and create a legal risk mitigation framework and get reviewed by alcor lawyers etc., have copies of post-legal death cryonics drug protocol for doctors in the ITU and copies of relevant legal documents (on iPad, laptop, or printed out etc.), make sure all staff AND FAMILY MEMBERS and friends know about cryonics plans and procedure in case of legal-death; have it put into your medical records and ask for an alert that flashes up on your medical records that you have cryonics membership and want cryonics procedures in case of legal-death; make sure to organise cryonics drugs and ice bags / dry ice to have available at the hospital to mitigate risks of slow response from cryonics outreach standby/rapid response team (Oliver)
    • establish individual therapy regimens and to evaluate, monitor and adjust dynamically (Li et al 2020)
    • Monitor haemodynamics and for different types of shock, be sure to distinguish between different types of shock (Li et al 2020)
    • Assess risk of venous thromboembolism (VTE) and give appropriate preventive treatment in high risk groups (Li et al 2020)
    • Monitor D-dimer, in context of medical history and consider pulmonary embolism (Li et al 2020)
    • Nutritional support is basis of treatment (Li et al 2020)
    • Have instructions for your carers to continue vitamin D supplements at minimum 2000 IU per day, ideally with largest meal if you are unable to take it (Oliver’s opinion)
    • Convalescent blood products (as used in SARS and Ebola) (Li et al 2020)
      • Note that, theoretically, young healthy donor plasma or young blood products should have better outcomes than plasma from older donors or younger unhealthy donors (Oliver’s opinion, based on discussion with Jesse MD from Ambrosia LLC)
    • ECMO (Oliver)
    • General ITU admission multi-organ support, with 1:1 Nursin(Oliver)g or 1:2 Nursing (likely better than lower ratio of nurses to patients) 
    • High dependency unit (HDU) admission for single organ support (e.g. respiratory) with high patient to nursing ratio (likely better than lower ratio of nurses to patients) (Oliver)
  • Immune based treatment options summary
    • Intravenous remdesivir (Pang et. al Feb 26 2020)
    • Vitamin D3 2000 IU daily, with largest meal ideally (Oliver)
    • Full nutritional support and monitoring (Li et al 2020)
    • Optimal sleep length and quality (as aforementioned) (Oliver)
    • Pulsed methylprednisolone → “but Most importantly, the current guidelines emphasise that systematic corticosteroids should not be given routinely for the treatment of COVID-19, which was also the recommendation in a a Comment in The Lancet.14 - https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30141-9/fulltext
    • Intravenous immunoglobulin (IVIG) (Li et al 2020)
    • Convalescent blood products (as used in SARS and Ebola) (Li et al 2020)
      • Convalescent blood products (CBP), obtained by collecting whole blood or plasma from a patient who has survived a previous infection and developed humoral immunity against the pathogen responsible for the disease in question, are a possible source of specific antibodies of human origin4. The transfusion of CBP is able to neutralise the pathogen and eventually leads to its eradication from the blood circulation. Different CBP have been used to achieve artificially acquired passive immunity14: (i) convalescent whole blood (CWB), convalescent plasma (CP) or convalescent serum (CS); (ii) pooled human immunoglobulin (Ig) for intravenous or intramuscular administration; (iii) high-titre human Ig; and (iv) polyclonal or monoclonal antibodies - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4781783/
      • Evidence summary: A multicentre, prospective, double-blind, randomised controlled trial by Hung and colleagues showed that using convalescent plasma from patients who recovered from the influenza A H1N1pdm09 virus infection to treat patients with severe influenza A H1N1 infection was associated with a lower viral load and reduced mortality within 5 days of symptom onset.8 A meta-analysis by Mair-Jenkins and colleagues showed that the mortality was reduced after receiving various doses of convalescent plasma in patients with severe acute respiratory infections, with no adverse events or complications after treatment.9 Another meta-analysis by Luke and colleagues identified eight studies involving 1703 patients with 1918 influenzapneumonia from 1918 to 1925 who received an infusion of influenza-convalescent human blood products, which showed a pooled absolute reduction of 21% (95% CI 15–27; p<0·001) in the overall crude case-fatality rate at low risk of bias.10 - https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30141-9/fulltext
      • Note that, theoretically, young healthy donor plasma or young blood products should have better outcomes than plasma from older donors or younger unhealthy donors (Oliver’s opinion, based on discussion with Jesse MD from Ambrosia LLC)
    • Hydroxychloroquine (5 trials recruiting) (Pang et. al Feb 26 2020)
    • Loponavir plus ritonavir plus interferon alpha 2b (1 trial recruiting) (Pang et. al Feb 26 2020)
    • Loponavir plus ritonavir plus arbidol (Pang et. al Feb 26 2020)
    • Abidol hydrochloride or oseltamavir or loponavir+ritonavir (Pang et. al Feb 26 2020
    • Ritonavir + ASC09 (2 HIV protease inhibitors) (Pang et. al Feb 26 2020)
    • Molecules that inhibit 2 SARS coronavirus enzymes (Pang et. al Feb 26 2020)
    • 50k - 100k IV mesenchymal stem cells per kgbw every 2 days for 3 doses (1 trial recruiting) (Pang et. al Feb 26 2020)
    • Traditional chinese medicine xue bi jing (1 trial recruiting) (Pang et. al Feb 26 2020)
    • Oral liquid traditional Chinese medicine,Shuanghuanglian (Pang et. al Feb 26 2020)
    • Chloroquine phosphate (Pang et. al Feb 26 2020)
    • Monoclonal antibodies against Covid 19 or MERS/SARS (Pang et. al Feb 26 2020)
      • There is only one ongoing randomized controlled trial targeted at MERS therapeutics [99]. It investigates the usage of Lopinavir/Ritonavir and Interferon Beta 1B. Likewise, many prospective and retrospective cohort studies conducted during the epidemic centered on usage of ribavirin with lopinavir/ritonavir/ribavirin, interferon, and convalescent plasma usage. To date, only one trial has been completed. One phase 1 clinical trial investigating the safety and tolerability of a fully human polyclonal IgG immunoglobulin (SAB-301) was found in available literature [46]. The trial conducted in the United States in 2017 demonstrated SAB-301 to be safe and well-tolerated at single doses. Another trial on MERS therapeutics was found on ClinicalTrials.gov—a phase 2/3 trial in the United States evaluating the safety, tolerability, pharmacokinetics (PK), and immunogenicity on coadministered MERS-CoV antibodies REGN3048 & REGN3051 [100].
    • Steroid gluococorticoids (1 trial recruiting) (Pang et. al Feb 26 2020)
    • Other antivirals (not yet recruiting as of 26/2/20) (Pang et. al Feb 26 2020)
    • Abidol hydrochloride with atomized interferon (not yet recruiting as of 26/2/20) (Pang et. al Feb 26 2020)
    • Darunavir + cobicistat (not yet recruiting as of 26/2/20) (Pang et. al Feb 26 2020)
    • Remdesivir (not yet recruiting as of 26/2/20) (Pang et. al Feb 26 2020)
    • Niclosamide (in vitro evidence only) (Pang et. al Feb 26 2020)
    • Glycyrrhizin (from liquorice) (Pang et. al Feb 26 2020)
    • Baicalin (in vitro evidence only) (Pang et. al Feb 26 2020)
  • Note the need for the adaptive immune response to cure SARS - innate immune response may not work: Innate immune mechanisms are the earliest host defenses that control viral replication and, in the case of many respiratory viruses, do so within the first few days of illness, even before the specific adaptive immune responses have been activated. This response does not appear to occur with SARS, and viral load in the respiratory tract (4) begins to fall only when the antibody response appears, i.e., at approximately day 10 after onset of illness (4,5). This finding may suggest that SARS-CoV is able to evade the host innate response and requires the adaptive immune response to bring the infection under control. - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3322905/
    • Prepare for the psychological risks of quarantine - Most reviewed studies reported negative psychological effects including post-traumatic stress symptoms, confusion, and anger. Stressors included longer quarantine duration, infection fears, frustration, boredom, inadequate supplies, inadequate information, financial loss, and stigma. Some researchers have suggested long-lasting effects. In situations where quarantine is deemed necessary, officials should quarantine individuals for no longer than required, provide clear rationale for quarantine and information about protocols, and ensure sufficient supplies are provided. Appeals to altruism by reminding the public about the benefits of quarantine to wider society can be favourable.” - https://www.ncbi.nlm.nih.gov/pubmed/32112714

Also
‘According to Thailand’s health ministry, the 70 year old Chinese woman “tested negative” for the virus within 48 hours after being treated with anti-HIV drugs lopinavir + ritonavir + large doses of the anti-flu drug oselamavir’


How far are we from developing a vaccine? will it be a one time permanent effect vaccine or one that needs to be taken continuously



See previous section on Coronavirus vaccine option for details on how far we are from developing a vaccine.

Given how viruses mutate, it may need to be a new vaccine annually, or a combination of vaccines that protect against all mutants, or predicted mutants, like with the triple and quadruple flu vaccine used currently.

Likewise, vaccines may be useless if your Covid 19 IgG (long term immunity protein) level doesn’t rise above the estimated threshold level to provide immunity (as based on the levels of young healthy people that naturally develop immunity), so you may need booster doses of the vaccine, or immune system restoration or rejuvenation strategies to boost your vaccine response (as discussed in the prevention options), and in other studies on how to boost vaccine response in non-responders, such as morning vaccination versus afternoon.

Mask Research phase 2


Non-powered options

www.bioscarf.com (can tie it around your face, above the nose, may need to upgrade the tie so it fits more comfortably)

Regards P3 / AFP 20 / AFP > 30 / FFP3 / N99 / N100 masks, it is a case of trying as many different types of masks as you can, as each person will have a different shaped face/nose and will find specific ones more comfortable

One can search on amazon or eBay for them - however prices have increased 10x recently! 

Note searchign for P3 masks may yield better results

P3 masks can be much more reusable than FFP3


Highest rated (volume x average rating and low incidence of 1 star reviews) P3 mask on amazon 

Watch the video on the left hand side for instructions 

But when changing the filters make sure to wear disposable gloves and to dispose of those gloves and wash your hands after so you dont contaminate yourself with virus

“Also, I might have to buy my 10 year old son one because it looks like the mask they use in Fortnite and he keep pinching mine.” 😂



You can check the video on the left hand side

“Advanced exhalation valve provides low breathing resistance, low heat, moisture and CO2 build up also performs well at very low temperatures"

"Lightweight, flexible and durable thermoplastic rubber mask for superior fit to most face shapes, adjustable 4-point cradle ensures an effective facial fit"



Problems with non-powered options



Powered options
An alternative option is to use PAPR = powered air purifying respirator 

Advantages versus non-powered masks: - https://www.ncbi.nlm.nih.gov/books/NBK294225/
  •  A PAPR system uses a blower instead of lung power to draw air through the filter.  This allows the user to breathe comfortably with less resistance, as the airflow is delivered directly into the headgear from the blower. - https://ohsonline.com/Articles/2019/05/01/Why-Pick-a-PAPR.aspx 
  • “Everybody wants to be part of the PAPR program because then they don't have to do the N95 fit test, which takes 20 minutes every year,” said Garrison. From a manager's perspective, the advantage to using PAPRs is that employees do not have to be taken away from work and patient care in order to complete N95 respirator training.
  • less restricting and more user-friendly, 
  • they accommodate facial hair. 
  • Furthermore, patients can see the worker's face more easily when the worker is wearing a PAPR than when the person is wearing an N95 respirator, so patients are not as frightened.
  • Reusable so may be cheaper in long run
  • Provide eye and sometimes ear protection
Disadvantages versus non powered masks - https://www.ncbi.nlm.nih.gov/books/NBK294225/
  • The biggest challenge to using PAPRs is financial. Each PAPR costs about $1,800, which comes out of departmental equipment budgets.
  • May be noisy
  • May be heavy to wear
  • Parts may wear out and require replacing with specific parts
  • May misplace parts
  • Few people use them routinely, so remembering how to use the PAPR effectively is a challenge. 
  • Batteries may not be charged
  • Batteries may need replacing due to wear
  • May misplace charger
  • Batteries may run out 
  • May not have replacement batteries
  • May be a source of infection
  • May be difficult to disinfect
  • May not work if used correctly
  • May have to modify exhaust airflow for use in sterile environments
  • Half the PAPRs in their user instructions just say yes, they can be cleaned and disinfected. I called to talk to the reps at the manufacturers. They had to get back to me because they did not know exactly what type of disinfectant I should be using
  • workers need to know when the PAPR headpiece can be reused and when it has to be discarded due to exposure to certain infections
  • Must remember to return to charger after use
  • decontamination process can be arduous and requires a fair amount of time both to train the workers and for workers to complete the process.


Want a PAPR with a rating of at least an FFP3 mask; i.e. AFP UK rating of at least 20, 40 might be ideal - discuss with the supplier about viral protection specifically 

-


Celios’ PAPRs which are under development are likely the most user friendly and quietest

The Celios P300 is due for release in the second half of 2020

Other options

The atmos mask provides at least 5 times better filtration at 300 nanometers than an N95 mask and (results below) costs $350 and is available for pre-order

As a result it may be better than a N95 mask, but slightly worse than a FFP3 mask , given that FFP3 filters out sub 100 nanometer particles around 20x better than N95






1000 hours use, 2 hour battery life per charge, for the active ventilator


The Cambridge Mask is N99 rated, filters 99%+ virus particles, shipping latest batch in May 2020



Other options

Examples


Mortality rates

  • Please add mortality rates by age and other factors here so that there is a ready reference

Retrieved 1st March 2020 

Different ways of contracting Covid

  • Sub question - i understand it can stay alive on surfaces and hence touching an infected surface could result in contracting it

Likely routes of transmission:
  • Via the air
  • Via “mucous membrane smear” transmission - i.e. from surfaces or other peoples skin, to your hands or skin, to your mouth and eyes
  • Via kissing
  • Via saliva
  • Via hugging
  • Via hand shakes
  • Via ordinary tidal breathing - just breathing 
  • Via hi fives
  • Via fist bumps
  • Likely via sexual fluids (virus enters urine and faeces by day 5 after symptoms, so likely in most organs at some point)
  • Likely via faeces and urine 
  • Likely via asymptomatic people, but may be less common and tidal breathing less of an issue (theoretically)
    • The fact that the paper got it wrong doesn’t mean transmission from asymptomatic people doesn’t occur.  Fauci, for one, still believes it does. "This evening I telephoned one of my colleagues in China who is a highly respected infectious diseases scientist and health official," he says. "He said that he is convinced that there is asymptomatic infection and that some asymptomatic people are transmitting infection." But even if they do, asymptomatic transmission likely plays a minor role in the epidemic overall, WHO says. People who cough or sneeze are more likely to spread the virus, the agency wrote in a situation report on Saturday. “More data may come out soon. We will just have to wait,” Lipsitch says. - https://www.sciencemag.org/news/2020/02/paper-non-symptomatic-patient-transmitting-coronavirus-wrong 
  • Very likely by symptomatic people (cough, fever, sneeze, chills etc.) (even normal tidal breathing may spread it) (keep a far distance and wear mask if must be around these people)
  • Via pets/animals to humans
    • People should also avoid direct, unprotected contact with live animals and surfaces in contact with animals when visiting live markets in affected areas. 
  • Likely from infected dogs or animals to humans (as dogs have been diagnosed with it now)
  • Unknown if via ears
  • Unknown if via food
    • If want to err on side of caution “People should also avoid eating raw or undercooked animal products and exercise care when handling raw meat, milk or animal organs to avoid cross-contamination with uncooked foods. “

“It’s a social virus,” Oxford said. “I think we have to galvanise ourselves in our social actions – how we interact with people.
"And I think that is extremely important; more so than wearing a mask. I think that’s a total diversion. 
“What we need to do is less of the handshaking, hugging, kissing, that sort of thing, because this virus looks like its spread by ordinary tidal breathing, not necessarily colds and coughing.”
Oxford added that coronavirus “hates” the UK because Britons are naturally “standoffish”.


Phase 1 Research

Live map showing infection status

Masks I have purchased

Details on the virus


Names
SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2
COVID-19 = coronavirus disease 2019
nCov = novel coronavirus

In humans, the viruses cause respiratory infections, including the common cold, which are typically mild, though rarer forms such as SARS, MERS and COVID-19 can be lethal

It is an RNA virus, like HIV (viruses can be RNA viruses or DNA viruses - different antiviral drugs may work better against each type. That’s why HIV drugs may help against treating coronavirus.)

Seven strains of human coronaviruses are known:
  1. Human coronavirus NL63 (HCoV-NL63, New Haven coronavirus)
  2. Middle East respiratory syndrome-related coronavirus (MERS-CoV), previously known as novel coronavirus 2012 and HCoV-EMC.
  3. 2019 novel coronavirus (2019-nCoV),[27][28] also known as Wuhan coronavirus.[29] ('Novel' in this case means newly discovered, or newly originated, and is a placeholder name.)[28]


The Wuhan strain has been identified as a new strain of Betacoronavirus from group 2B with an ~70% genetic similarity to the SARS-CoV.[54] The virus has a 96% similarity to a bat coronavirus, so an origin in bats is widely suspected.[50][55]

There are 4 types of coronaviruses
  • Alpha
  • Beta --> 2019 virus is this type
  • Delta
  • gamma

How it spreads


Infection rate, symptom development rate, mortality risks



80% fever, cough, fatigue, shortness of breath etc. only
14% get pneumonia
5% have critical disease and should be admitted to intensive care
2.5% die overall
If have pneumonia and hospitalised, 4% - 15% die 


The infection rate of those exposed is unknown, but may rise to 100% if kept if in quarantine with people that are infected and airborne and touch transfer routes are not stopped.

Symptom development rate: it is not known how many people that are infected develop symptoms

In those that develop symptoms the following process occurs 

  1. Infected with virus 
  2. No symptoms for 2 - 14 days, some people may not develop any symptoms and only test positive
  3. Symptoms start: Fever, cough, shortness of breath most common (Frequently reported signs and symptoms include fever (83–98%), cough (46%–82%), myalgia (muscle pain) or fatigue (11–44%), and shortness of breath (31%) at illness onset. [24]_
  4. The most common consequence of the virus is pneumonia (a lower respiratory tract infection (LRTI) (to diagnose pneumonia there must be signs of lung damage on x ray, CT or MRI scan)
    1. Other reported complications include acute cardiac injury, arrhythmia, shock, and acute kidney injury
  5. If hospitalised
    1. In around 8 days after hospitalisation Acute respiratory distress syndrome (ARDS) developed in around 25% of hospitalized patients, and secondary infection developed in 10%. [2,4]
    2. Around 25% of hospitalized patients with 2019-nCoV infection AND pneumonia have required intensive care for respiratory support 
    3. Around 8% death rate if you have pneumonia AND are hospitalised 



Overall Mortality risk: 
  • 18th Feb: 1,874 confirmed deaths and more than 73,336
  • = 2.5% chance of dying overall (4 % - 15% (8% on average) if have pneumonia and hospitalised and test positive for virus

Prevention especially for frequent travellers (what masks to buy, what other precautions)



CDC and WHO DO NOT recommend masks for asymptomatic people
  • But if you are at risk of exposure to someone with the virus then mask is good
  • Likewise, masks work to protect against all airborne viruses, bacteria and pollution (e.g. flu, colds etc.) so generally it is a good rule to wear a mask if you are around any SYMPTOMATIC people, sneezing, coughing etc. 

What mask works for coronavirus?



Coronavirus may be as small as 80 nm diameter so masks must filter out 99.9%+ ideally at 80nm or lower

Masks filtering capacity at a given diameter are based on near perfect use of the mask, and often a limited numbers hours use of the mask - so ideally you want some leeway in the filtering capacity to allow for mistakes or degradation if using for a long period of time e.g. >12/24 hours seems reasonable


First.. How long can you use a single mask for, how to clean it and how to test if still safe to use after cleaning?


First read CDC guidance on extended use of masks - https://www.cdc.gov/niosh/topics/hcwcontrols/recommendedguidanceextuse.html 


8 hours a day x 7 days = 56 hours 
But outside of mask is contaminated so may want to wash it with soap and water and with gloves on and then wash hands with soap and water afterwards before rewear, and let it dry before using; do an essential oil test to see if it has the same filtering capacity as before (hold a 10 mL bottle of essential oil and see if you can smell it after washing it each time to test seal; also do breath test seal to see if mask inflates and deflates)


But


N95 masks not good enough?

N95 masks had up to a 27% failure rate IN JUST 20 MINUTES in protecting against live attenuated influenza virus tested in a real world setting low bias 2018 RCT - https://www.ncbi.nlm.nih.gov/pubmed/30558691 (flu virus is diameter 80 - 120 nm - https://www.sciencedirect.com/science/article/pii/S002196731631133, which is the same diameter range as coronaviruses) 
  • They stated “A 10% failure rate compared to the complete protection provided by a Pioneer 300 powered air filtering mask raises the question of acceptable limits for virus exposure especially to resistant or novel pathogens”

N95 masks were found in a 2016 systematic review and meta analysis of real world RCTs and cohort studies to be no better than surgical masks for preventing respiratory infections in healthcare workers in a real world setting. “Although N95 respirators appeared to have a protective advantage over surgical masks in laboratory settings, our meta-analysis showed that there were insufficient data to determine definitively whether N95 respirators are superior to surgical masks in protecting health care workers against transmissible acute respiratory infections in clinical settings.” - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4868605/ 

Similarly in a 2017 individual patient data meta analysis of 2 Chinese real world RCTs of N95 masks, found no statistically significant reduction in influenza virus (but it did for bacterial infection, which are larger diameter pathogens) - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705692/

Failure of N95s and FFP2 to protect against similar nanometer diameter viruses as coronavirus and influenza virus in a simulation study
  • Monodisperse aerosol penetration levels showed that the most penetrating particle size (MPPS) was in the 30–60 nm range for all models of FFRs tested in the study. Percentage penetrations at the MPPS were <4.28, <2.22, <0.009 and <0.164 for the N95, FFP2, P100 and FFP3 respirator models, respectively
  • Mask efficacy hierarchy: P100 > FFP3 > FFP2 > N95 for coronavirus protection
N95 could allow 4% of coronaviruses to pass the mask; FFP2 2%
FFP3 could allow 0.2% (1 in 500) of coronaviruses to pass the mask
P100 could allow 0.01% (1 in 10,000) coronaviruses to pass the mask
Note this test was done with average 45 nm particle size, whereas coronaviruses are 80 - 160 nm

Another study found N95 masks to fail for 10 - 80nm virions, letting in over 5% of viruses

This study found N95 masks to protect against 98% of virions but the nanometer diameter range could not be identified as the study could not be retrieved - https://www.ncbi.nlm.nih.gov/pubmed/24011377 

  • This study found higher flow rates through the mask allowed more 20 - 90 nanometer viruses to get through; N95 masks let through 50% more on these diameter viruses compared (1% of viruses) to N99 masks (1.5% of viruses) (~equivalent to FFP3). 
  • Respiratory minute volume is the volume of gas inhaled (inhaled minute volume) or exhaled ... A normal minute volume while resting is about 5–8 liters per minute in humans. Minute volume generally ... Minute ventilation during moderate exercise may be between 40 and 60 litres per minute” - https://en.wikipedia.org/wiki/Respiratory_minute_volume  
  • This suggests, if breathing through the N95 and N99 masks at regular breath rates, such as 10 L/min, then the superiority of the N99 over N95 mask would be even greater - 


Powered Masks Better than non-powered FFP3/N100?

https://celios.com/personal-respirator-development/  - the Pioneer 300 specifically: this is also potentially even better than FFP3/N100 masks, but its still under development

This mask was used in this study and outperformed N95 (unclear if outperforms FFP3/N100) - https://www.ncbi.nlm.nih.gov/pubmed/30558691  - ZERO of 30 people got influenza virus (80 - 120 nm) infections 

I think these "powered masks" may be easier to breathe through as they create pressure for you; it can be a bit annoying to breath through FFP3/N100 masks for hours on end, but I guess its quite a good lung work out and may improve lung function!

Although if you already have bad symptoms, e.g. shortness of breath, it might be too exhausting to breathe through FFP3/N100 masks for extended period of time. Which is annoying, as you are then exposed to new viruses, on top of the existing infection. This could be another advantage of powered masks in an acute care situation.




Note that the outside of facemasks is contaminated with viruses and bacteria so don’t touch it - proven by this study “hese results also support previous studies that suggest that virus trapped on the outside of facemasks and respirators may pose an indirect contact transmission risk as the HCW doffs these PPE after seeing a patient or continues to wear their PPE for an extended period of time, and testing of contaminated PPE can help advise emergency preparedness plans to decontaminate and re-use respiratory PPE in a pandemic (Fisher et al., 2014; Fisher and Shaffer, 2014).” - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6482848/ 





IF DO NOT HAVE A FFP OR N/P RESPIRATOR MASK THEN CAN USE MULTIPLE SURGICAL MASKS 
… But it's likely 10x less effective 

Surgical masks may actually work QUITE WELL to prevent 10 - 80 nm range viruses (up to 80% protection), but its a lottery depending on the brand “The 2 surgical masks, which originated from the same manufacturer, showed tremendously different penetration levels of the MS2 virions (The virions were detected in the particle size range of 10 to 80 nm): 20.5% and 84.5%, respectively, at an inhalation flow rate of 85 L/min.” - https://www.ncbi.nlm.nih.gov/pubmed/16490606 

So this could be used in a scenario where respirators are not available

Wearing multiple surgical masks that provide 80% protection will likely increase the protective level more against 10 - 100 nm viruses;. (see below image and reference)

Wearing 2 - 5 masks reduces the transmission rate through the surgical mask even further 


Takeaway message: There is no good evidence N95 or FFP2 masks work for preventing small diameter viruses, only FFP3, N100 or better. Make sure to look for these numbers whenever buying masks. 

For example, healthcare professionals get viruses because they use N95 or FFP2 or surgical masks rather than FFP3 or N100. For example, gynaecological surgeons that are treating cervical cancer via laser ablation are exposed to aerosolised HPV virus, leading to HPV inhalation, causing oral cancer... as men are not vaccinated against HPV as the NHS can't afford it until recently and cause they didn't wear an FFP3 or N100 mask. - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3843579/

Bioscarf is still good   It does 99.75% filter rate at 100 nanometers. This is essentially the same as FFP3, assuming the filter rate doesn't dramatically drop off below 100nm. But that does not make physical sense as the material used to make bioscarf and  FFP3 masks is similar (cotton I believe)


But bioscarf is harder to use for long periods. 

The best is bioscarf for short risk periods, FFP3 or N100 for long risk periods.

I mean there is zero evidence that they improve small viral clinical outcomes... As shown by the 5 RCTs in the 2 meta analyses! Doesn't seem to work to prevent flu. Whereas higher filtration grade might... Which is likely given that FFP2/N95 worked to reduce total viral illnesses and bacterial illnesses. Which suggests it's not entirely a problem of not using the mask right or non-air based transmission... It could just be an issue that it's letting in too many small particle viruses to prevent influenza. 

Here's another 2019 RCT to back up this evidence - https://www.ncbi.nlm.nih.gov/m/pubmed/31479137/?i=1&from=(Therapy/Narrow[filter])%20AND%20((Mask%20Or%20respirator)%20AND%20influenza)

'Among outpatient health care personnel, N95 respirators vs medical masks as worn by participants in this trial resulted in no significant difference in the incidence of laboratory-confirmed influenza.'

The booth trial earlier mentioned is lower evidence than real world trials of practicing clinicians which focused on clinical outcomes in a fully real setting 

The problem is there are no RCTs I can find on FFP3 or N100 masks against clinical outcomes... Don't think they've been done. Which is interesting.

All we know with Grade A certainty evidence (6RCTs) is that N95 don't work for (small particle virus) influenza even when good technique is adhered to.

But yeah, totally agree with Jian, as he was saying,  coronavirus isnt really important by itself in most countries right now... But finding techniques to reduce small particle viruses or Nanoparticle pollution I think is an important general longevity concept for immunocomprimised peopls, given the death rate from influenza in the elderly and potential accelerated lung aging from sub 100 nm diameter pollution. 

But then again all these studies are in Healthcare provider setting... should people age 75+ wear FFP3 masks in hospital if surrounded by people with fever and chills / coughs etc? Or on public transport in flu season? Would this reduce flu or small diameter virus related hospitalization and death? 

This would be an interesting population to run the FFP3/N100 mask... Or powered respirator and or UV air purification in hospitals... RCT on, beyond Healthcare providers.

Oh yeah, there are studies showing comparison against non mask wearing groups: They found no added benefit of surgical mask or N95 mask versus no mask group for preventing flu in this study within the meta analysis I referenced.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941587/?report=reader

-

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2662657/#!po=0.925926

Same with this trial of no mask versus P2 mask versus surgical mask... No difference in influenza versus no mask unfortunately 

'the low rate of confirmed influenza A or B infection (18.4%) in the study could mean that our findings are not directly applicable to a scenario in which influenza predominates. If influenza is more likely than the other viruses in our study to be transmitted by the respiratory route, the prevalence of mixed infections would tend to bias our results toward the null'

-

So in summary:

There are only high bias observational studies that suggest N95 or Ffp2 masks prevent influenza (grade C evidence), the small RCTs all failed to show benefit.

So there is no good evidence FFP2/N95 or surgical mask have any difference compared to using no mask at all to prevent flu.

And yeah correction: there is no 'good evidence' in terms of RCTs specifically that FFP3/N100 masks are better than no mask, FFP2/N95 or surgical mask - the only evidence they are better is that FFP3 filter out 30-60nm Nanoparticles (a smaller size than flu and coronavirus) 30 times better than N95 masks and N100 filter out these size Nanoparticles 400 times better than N95 masks, in non-human lab studies.

These masks are just filtering out nanoparticles so much better in the lab studies, and given the failure of surgical masks and N95s for reducing flu infections, and the similar costs between N95s and FFP3, there doesn't seem to be any reason to go for N95s or surgical masks if you want to prevent flu or potentially airborne coronaviruses.

Also note that these masks will on estimate from the company 3M lose 50% of their efficacy after 7 days of use. So an N95 mask could let in 10% of 30-60nm viruses after a week of use, whilst an FFP3 might let in 0.4%; Having a much larger absolute increase in % of particles let through day by day. So maybe you could use FFP3/N100 longer if you cared for the elastic and inside of mask cleanliness well and actually could make it cheaper compared to FFP2 or N95.
^ also fun picture of viruses, Ebola is huge! This is useful to know as different masks work best for filtering out different viral sizes... Although a group of these are not airborne (e.g. Are transmitted only via blood etc). Rhinovirus is 30 nm diameter apparently, and this is the most common common cold virus. So it appears N100/FFP3 would have huge theoretical efficacy against the common cold virus versus FFP2 and N95 masks as based on the non-human lab test where they tested to see how many 30-60nm viral particles got through different types of masks.

Yeah but statistically insignificant, the study was underpowered... Check the P values. 

And second study it's not influenza but influenza like illness... Again statistically insignificant for influenza, as it's confounded by other viruses like they said in disucussion. 

These common colds aren't going to kill you, so I don't really care about them as much. 

Personally I'm only wearing a mask if I'm high risk of at least moderate illness, in which case I'd use FFP3/N99/100 otherwise for common cold I'd use bioscarf.









Expected progress around the world


The possibility of unreported cases is particularly concerning in countries with weaker health-care systems, such as those in southeast Asia and Africa,




Seems to be contained in China well








Definitive tests


Laboratory diagnosis can be performed by: (a) detecting the genetic material of the virus, (b)
detecting the antibodies that neutralize the viral particles of interest, (c) detecting the viral epitopes
of interest with antibodies (serological testing), or (d) culture and isolation of viable virus particles.
The key limitations of genetic material detection are the lack of knowledge of the presence of viable
virus, the potential cross-reactivity with non-specific genetic regions and the short timeframe for
accurate detection during the acute infection phase. The key limitations of serological testing is the
need to collect paired serum samples (in the acute and convalescent phases) from cases under
investigation for confirmation to eliminate potential cross-reactivity from non-specific antibodies
from past exposure and/or infection by other coronaviruses. The limitation of virus culture and
isolation is the long duration and the highly specialized skills required of the technicians to process
the samples. (Pang et al 26 Feb 2020)


What sample site is best?

The relative virus detection rates from different specimens during the illness suggests that respiratory specimens (nasopharyngeal aspirate, throat swab) are more useful in the first 4 days of the illness, while fecal samples are better later in the illness. Urine samples, on the other hand, are not useful at any stage of the illness. A productive cough is not common in the early stage of illness, but in patients who do produce sputum, this specimen provides a high diagnostic yield. Thus, nasopharyngeal aspirates, throat swabs, and sputum, if available, are the best specimens in the first 5 days of the illness. - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3322905/

RT-PCR from respiratory fluid (NPAs (nasopharyngeal aspirates), throat swabs or sputum if available/coughing is ideal in early stages - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3322905/


Covid-19 Diagnosis and Immunity Monitoring Strategy
Highest sensitivity+specificity testing panel in first 3 days of symptoms
RT-PCR for NPA (nasopharyngeal aspirate) + Nasal Swab + Throat Swab + Sputum if available (+ Covid-19 IgM/IgG absolute level at all sites and serum)
Highest sensitivity+specificity testing panel on day 4 to day 60 or later of symptoms
RT-PCR for Stool + NPA + Nasal Swab + Throat Swab + Sputum if available + Urine (+ Covid-19 IgM/IgG absolute level at all sites and serum)
Long term immunity status
Covid-19 IgG absolute level in serum, may not appear until 21 days after symptoms first appear 
First 2 days of symptoms, highest accuracy single tests
  • RT-PCR NPA (nasopharyngeal aspirate)
Day 3 - 4 of of symptoms, highest accuracy single tests
  • RT-PCR NPA (nasopharyngeal aspirate)
  • Or RT-PCR Nasal Swab AND Throat Swab
  • Ideally all 3 of the above...
Day 5 onwards of symptoms
  • RT-PCR stool swab, especially if concurrent diarrhoea  
  • Ideally NPA + Nasal + Throat + Urine too 


2004 paper on SARS coronavirus epidemic - shows you can't diagnose coronavirus 100% accurately until 21 days after symptoms start, and then its with a blood test to see if you have produced coronavirus specific IgG antibodies; also accuracy of the test you have before that time depends on the site, day after symptoms started, and exact type of RT-PCR test

take away message: 2019 coronavirus testing strategy may be more accurate taking into account days after symptoms, sites tested, and specific RT-PCR test used *, as based on past coronavirus epidemic data + the accurate number of cases may not be known until 21 days after symptoms, so the actual case number in any country may be 2x higher, and the case to death ratio potentially lower or higher (unknown until at least 1 month later)

“It was found that the respiratory specimens were positive for the virus while serum was negative in the early period. It has also suggested that in the early days of illness, patients have high levels of virus despite the mild symptoms” (Pang et al 26 Feb 2020) referencing  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3322905/

Respiratory fluid versus urine or stool samples?
  • Sensitivities for qRT-PCR (80% for fecal samples and 25% for urine samples) were higher than those of the polyclonal (50% and 5%) and monoclonal (35% and 8%) antibody-based nucleocapsid antigen capture enzyme-linked immunosorbent assays.

RT-PCR vs ELISA?
  • Comparison between the molecular test (i.e RT-PCR) and serological test (i.e., ELISA) showed that the molecular test has better sensitivity and specificity. (Pang et al 26 Feb 2020)

Alternatives to RT-PCR that have same sensitivity and specificity
  • RT-LAMP
  • RT-iiPCR
  • rRT-PCR with TaqMan probes

Problems with RT-PCR?
  • Although real time RT-PCR is a primary method for diagnosing MERS-CoV, high levels of PCR inhibition may hinder PCR sensitivity (Pang et al 26 Feb 2020) referencing this study http://www.annlabmed.org/journal/view.html?uid=2731&vmd=Full
  • PCR inhibitors:  Inhibitors can also interact directly with a DNA polymerase to block enzyme activity. DNA polymerases have cofactor requirements that can be the target of inhibition. Magnesium is a critical cofactor, and agents that reduce Mg2+ availability or interfere with binding of Mg2+ to the DNA polymerase can inhibit PCR. The presence of inhibitors in samples has been the focus of much of the published literature. Common sample types known to contain inhibitors include blood, fabrics, tissues and soil (Table 1). Other important sources of inhibitors are the materials and reagents that come into contact with samples during processing or DNA purification. These include excess KCl, NaCl and other salts, ionic detergents such as sodium deoxycholate, sarkosyl and SDS (1), ethanol and isopropanol (2), phenol (3) and others - https://www.promega.es/-/media/files/resources/profiles-in-dna/1001/an-introduction-to-pcr-inhibitors.pdf?la=es-es 
  • In the case of RNA PCR, it is RNA polymerase rather than DNA polymerase so the above may not apply identically to RNA polymerase

How to get around RT-PCR inhibitors?



Background info from CDC about RT-PCR for coronavirus

2019-Novel Coronavirus (2019-nCoV) Real-Time Reverse Transcriptase (RT)-PCR Diagnostic Panel

It is intended for use with the Applied Biosystems 7500 Fast DX Real-Time PCR Instrument with SDS 1.4 software. 

This test is intended for use with upper and lower respiratory specimens collected from persons who meet CDC criteria for COVID-19 testing. 

CDC’s test kit is intended for use by laboratories designated by CDC as qualified, and in the United States, certified under the Clinical Laboratory Improvement Amendments (CLIA) to perform high complexity tests. 

The test kits also will be shipped to qualified international laboratories, such as World Health Organization (WHO) Global Influenza Surveillance Response System (GISRS) laboratories. 

The test will not be available in U.S. hospitals or other primary care settings. The kits will be distributed through the International Reagent Resource
 (IRR)


Types of samples for RT PCR acceptable
  • Respiratory specimens including: nasopharyngeal or oropharyngeal aspirates or washes, nasopharyngeal or oropharyngeal swabs, broncheoalveolar lavage, tracheal aspirates, and sputum.
    • Swab specimens should be collected only on swabs with a synthetic tip (such as polyester or Dacron®) with aluminum or plastic shafts. Swabs with calcium alginate or cotton tips with wooden shafts are not acceptable.
  • Serum

Must be stored at cold temperature or processed immediately 

RT PCR should be done according to these guidelines

-

How to decide who to test with RT-PCR?


  1. A history of travel to Wuhan or potential exposure to someone with coronavirus

  1. AND 1 or more of the following: fever, imaging features of pneumonia, normal or reduced white blood cell count, or reduced lymphocyte count.[38]

The most common laboratory abnormalities reported among hospitalized patients with pneumonia on admission included 

  • low white blood cells (9–25%)
  • High white blood cells leukocytosis (24–30%)
  • Low lymphocytes (63%)
  • High ALT and or AST (37%)

Flu kils up to 50k people per month - will be interesting to see if corona reaches this range - https://www.who.int/news-room/fact-sheets/detail/influenza-(seasonal)