Why COVID-19 Is Dangerous and What's the Hope?

Figure 1.  Covid-19 compared to other common conditions

COVID-19 typically causes fever and a dry cough. One may have aches in the body—the muscles—and if it's severe enough, there would be shortness of breath.

Gastrointestinal symptoms can occur and are an indication of more severe disease. It's not very common to have a runny nose or the sniffles, and a sore throat is not common either.

COVID isn’t just a respiratory disease; it also affects other organ systems. It can make a weak heart beat erratically, turn a manageable case of diabetes into a severe one, or weaken a frail person to the point where they fall and break something.^[44]

The incubation period from exposure to onset of symptoms is between four and six days; and if you want to cover 95–98 percent of the cases it is between three and 10 days. It's pretty rare to have an incubation period outside of that range.

Figure 2. Covid-19 survivors report a wide range of long-term symptoms

Why COVID-19 is dangerous^[1,8]

On 08/26/2021, total COVID-19 worldwide deaths were 4.47M.  

With SARS-CoV-2 it was apparent early on that something was not working quite right—not only is the immune response delayed, enabling the virus to quickly replicate, unhindered, but once this response does occur, it's often so severe that instead of fighting the virus it causes damage to its human host.

SARS-CoV-2 induces an inflammatory state, evidenced by raised acute markers like interleukin-6 (IL-6), c-reactive protein (CRP), ferritin, d-dimer etc. and may lead to lung damage especially in the second week of illness owing to the cytokine storm.^[43]

One of the largest studies of Covid-19 “long haulers” has proved what many doctors suspected: Not only are many patients suffering a raft of health problems six months after infection, they’re also at significantly greater risk of dying.^[38] 

Furthermore, Covid-19 patients who survived hospitalization were found to have a 51% increased risk of dying compared with 13,997 influenza patients who also had been hospitalized.^[38] 

Figure 3.  Aerosols vs droplets (Sars-CoV-2 can be spread via aerosols)

Transmissibility and Stability of Virus

What is disturbing is that virus shedding, as detected in the mouth or nose, is very, very common and could be there prior to onset of symptoms. That's why transmission could occur from asymptomatic individuals. And virus shedding could continue for days up to three weeks after a person recovers. That is extremely worrisome for the spread of this virus.

Furthermore, the stability of this virus is worrisome as well. Based on a recent study, researchers at Australia’s national science agency, CSIRO found that ^[22] 

• At 68 ℉, COVID-19 can survive on banknotes, glass and stainless steel for up to 28 days, much longer than the flu virus which is 17 days
• However, the survival time declined as the temperature increased
• Proteins and fats in body fluids can also sharply increase virus survival times
• This helps to explain the apparent persistence and spread of SARS-CoV-2 in cool environments with high lipid or protein contamination, such as meat processing facilities

How the COVID-19 affects each individual could be different based on a person's genes,^[30,31,36]  pre-exiting health conditions, immunity profile history,^[29]  incomes, risk-taking behaviors and, also, local healthcare facilities.  Read the below articles for more details:

• Even Mild Covid-19 Infections Can Make People Sick for Months
• Covid-19 survivors report a wide range of long-term symptoms (Figure 2)
• As evidence builds that COVID-19 can damage the heart, doctors are racing to understand it
• A perspective on potential antibody-dependent enhancement of SARS-CoV-2
• COVID-19 survivors suffer long term heart conditions
• Your Risk of Getting Sick From Covid-19 May Lie in Your Genes
• Male coronavirus patients with low testosterone levels are MORE likely to die from COVID-19, German hospital finds
• Covid Doctors Find a Turning Point in Life-Threatening Cases
• Strokes and mental state changes hint at how COVID-19 harms the brain
• Death Rate of Covid-19 by Age / Prior Illness / Ethnic Group
• COVID's cognitive costs? Some patients' brains may age 10 years
• The major genetic risk factor for severe COVID-19 is inherited from Neanderthals
• Neuroinvasion of SARS-CoV-2 in human and mouse brain

Figure 4.  A review on mRNA vaccines at @NatRevDrugDisc (Source: [41])

What's the Exit Strategy

Local lockdowns and social distancing could be the emergency measure to prevent a catastrophic death toll. But no western democracy has yet been able to lay out a good plan for how normal life can resume. The Imperial College study that heavily influenced UK government policy envisions some form of social distancing until a vaccine or treatment is available. However, that could still be sometime down the road.^[3]

The Hope: Population Immunity

We are looking at a world with parameters bounded by pure imagination; 

where we go from here is anyone's guess.

—Will Thomson and Chip Russell

Covid-19 raced through the world much faster than previously thought, a U.S. research team said,^[5] suggesting that extremely widespread vaccination or immunity will be necessary to end the pandemic.

There are a few anecdotes from China about re-infection but, if you look at those reports carefully, they're not well-documented. It could be that folks just continued to shed virus from the initial infection. Only one study was formally done and it is not a human study. It's a macaque study. They infected macaques with this virus, then waited until the monkeys recovered and tried to re-infect them. They could not. That bodes well for human immunity.

We have now looked at a lot of serum from convalescent individuals and those serum samples have antibodies against the so-called spike protein of the virus. That's the protein that sits on the surface of the virus particle. By tightly binding, the antibody could neutralize the virus. Once an infected person develops antibodies, there should be protective immunity for quite some time. That's why we need to buy time for immunity to develop in the population.

What if Sars-CoV-2 mutate and quash the hope?

One aspect of Sars-CoV-2 is how it has evolved more slowly than some other viruses such as HIV or the flu. Just 40 differences have evolved so far between the most distantly related samples.^[10] Although surveillance has not shown any mutations that would affect its transmissibility or virulence, scientists are watching closely in case they appear.

How about the Next 10 years Down the Road?

Based on [28], for the next 10 years, John Mauldin has predicated that:

We are going to see major advances in healthcare. I mentioned a few weeks ago the invention of Far UVC which doesn’t penetrate the skin or eyes of human beings, but will kill viruses and bacteria. 

And while the pandemic has caused a major setback in worldwide poverty, I expect that to be short-lived. We will see the number living in poverty steadily decrease, as it has for the last 50 years.

References

1. The Tip of the Iceberg: Virologist David Ho (BS '74) Speaks About COVID-19
2. Even Mild Covid-19 Infections Can Make People Sick for Months
3. [WEBCAST REPLAY] COVID-19 Pandemic Update: Analysis From Neil Howe & Daryl Jones
4. Why U.S. hospitals see promise in plasma from new coronavirus patients
5. Virus May Spread Twice as Fast as Earlier Thought, Study Says
6. What Does Your Cough Say About Your Illness?
7. The COVID-19 vaccine development landscape
8. She spent 9 days in a coma and relearned how to walk. What this Covid-19 survivor wants protesters to know
9. If you’re hoping a vaccine is going to be a knight in shining armor saving the day, you may be in for a disappointment. SARSCOV2 is a highly contagious virus. A vaccine will need to induce durable high level immunity, but coronaviruses often don’t induce that kind of immunity (link)
10. Mutations map holds the key to bringing coronavirus under control
11. Virus Likely to Keep Coming Back Each Year, Say Top Chinese Scientists (Bloomberg)
• “The virus is heat sensitive, but that’s when it’s exposed to 56 degrees Celsius for 30 minutes and the weather is never going to get that hot,” said Wang Guiqiang, head of the infectious diseases department of Peking University First Hospital. “So globally, even during the summer, the chance of cases going down significantly is small.”
12. All the Covid-19 Symptoms You Didn’t Know About
13. Coronavirus: Can it affect eyesight?
14. What Troponin Tells Us About Myocardial Injury in COVID-19
• Clinicians then assess potential causes of troponin elevation, including hyperinflammation, which may respond to immunosuppressive therapy.
15. Strokes and mental state changes hint at how COVID-19 harms the brain
16. A family physician’s COVID story
17. A COVID-19 vaccine: 5 things that could go wrong
18. Studies detail conjunctivitis in kids, adults with COVID-19
19. A perspective on potential antibody-dependent enhancement of SARS-CoV-2
20. COVID-19 survivors suffer long term heart conditions
21. As evidence builds that COVID-19 can damage the heart, doctors are racing to understand it
22. Novel coronavirus survives 28 days on glass, currency, Australian researchers find
23. CDC Expands Covid Risk Warning to Include Overweight People
• Nearly 72% of American adults are overweight (25 < BMI < 30) or obese (BMI ≥ 30)
24. CDC Says Virus Can Spread Indoors in Air Beyond Six Feet
25. Covid may cause sudden, permanent hearing loss – UK study
26. 29-Year-Old Overcomes COVID-19, Cardiac Arrest While On Ventilator
27. Hospitalised COVID-19 patients can have ongoing symptoms for months -study
28. What Will Not Change
29. Common cold antibodies hold clues to COVID-19 behavior
30. Your Risk of Getting Sick From Covid-19 May Lie in Your Genes
31. The major genetic risk factor for severe COVID-19 is inherited from Neanderthals
32. 'Breakthrough finding' reveals why certain Covid-19 patients die
33. Diverse and functional autoantibodies revealed in COVID-19 patients
34. Diverse Functional Autoantibodies in Patients with COVID-19
35. Pandemic Appears to Fuel Rise in Stress Cardiomyopathy Rates
36. Genetic mechanisms of critical illness in Covid-19
37. Coronavirus Deranges the Immune System in Complex and Deadly Ways
38. ‘Long Hauler’ Study Shows Covid Can Kill Months After Infection
39. SARS-CoV-2 uses a multipronged strategy to impede host protein synthesis
40. Rapid induction of antigen-specific CD4+ T cells guides coordinated humoral and cellular immune responses to SARS-CoV-2 mRNA vaccination (good summary)
41. mRNA vaccines for infectious diseases: principles, delivery and clinical translation (accessed on 08/26/2021)
42. Antigenic drift: Understanding COVID-19
43. Liu F. Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19. J Clin Virol. 2020;127:104370.
44. COVID-Hospitalization Numbers Are as Bad as They Look

Why does soap work so well on most viruses?

Soap is better if you rub with it for 20 secs

Note that the below article is based on @PalliThordarson's tweets.

What Is Virus?

Building Blocks

Most viruses consist of three key building blocks:

• RNA
• The RNA is the viral genetic material -it is very similar to DNA.
• Proteins
• The proteins have several roles including breaking into the target cell, assist with virus replication and basically to be a key building block (like a brick in a house) in the whole virus structure.
• Lipids
• The lipids then form a coat around the virus, both for protection and to assist with its spread and cellular invasion.

The RNA, proteins and lipids self-assemble to form the virus. Critically, there are no strong “covalent” bonds holding these units together.  Instead the viral self-assembly is based on weak “non-covalent” interactions between the proteins, RNA and lipids. Together these act together like a Velcro so it is very hard to break up the self-assembled viral particle. Still, we can do it (e.g. with soap!).


Nanoparticles

Most viruses, including the coronavirus, are between 50-200 nanometers – so they are truly nanoparticles. Nanoparticles have complex interactions with surfaces they are on. Same with viruses. Skin, steel, timber, fabric, paint and porcelain are very different surfaces.


Multiplication within Host Cells

When a virus invades a cell, the RNA “hijacks” the cellular machinery like a computer virus (!) and forces the cell to start to makes a lot of fresh copies of its own RNA and the various proteins that make up the virus.

These new RNA and protein molecules, self-assemble with lipids (usually readily present in the cell) to form new copies of the virus. That is, the virus does not photocopy itself, it makes copies of the building blocks which then self-assemble into new viruses!

All those new viruses eventually overwhelm the cell and it dies/explodes releasing viruses which then go on to infect more cells. In the lungs, some of these viruses end up in the airways and the mucous membranes surrounding these.

Spreading to Surrounding Environments

When you cough, or especially when you sneeze, tiny droplets from the airways can fly up to 10 meters (30 ft)! The larger ones are thought to be main coronavirus carriers and they can go at least 2 m (7 ft). Thus we should always cover our coughs & sneezes!

These tiny droplets end on surfaces and often dry out quickly. But the viruses are still active! What happens next is all about supramolecular chemistry and how self-assembled nanoparticles (like the viruses) interact with their environment!

Now it is time to introduce a powerful supramolecular chemistry concept that effectively says:

Similar molecules appear to interact more strongly with each other than dissimilar ones. 

Wood, fabric and not to mention skin interact fairly strongly with viruses.  Contrast this with steel, porcelain and at least some plastics, e.g. teflon.

The surface structure also matter – the flatter the surface the less the virus will “stick” to the surface. Rougher surfaces can actually pull the virus apart.

So why are surfaces different?

The virus is held together by a combination of hydrogen bonds (like those in water) and what we call hydrophilic or “fat-like” interactions. The surface of fibers or wood for instance can form a lot of hydrogen bonds with the virus.

In contrast steel, porcelain or teflon do not form a lot of hydrogen bond with the virus. So the virus is not strongly bound to these surfaces. The virus is quite stable on these surface whereas it doesn’t stay active for as long on say fabric or wood.

For how long does the virus stay active? 

It depends. The SARS-CoV-2 coronavirus is thought to stay active on favourable surfaces for hours, possibly a day. Moisture (“dissolves”), sun light (UV light) and heat (molecular motions) all make the virus less stable.

The skin is an ideal surface for a virus! It is “organic” and the proteins and fatty acids in the dead cells on the surface interact with the virus through both hydrogen bonds and the “fat-like” hydrophilic interactions.

So when you touch say a steel surface with a virus particle on it, it will stick to your skin and hence get transferred onto your hands. But you are not (yet) infected. If you touch your face though, the virus can get transferred from your hands and on to your face.

And now the virus is dangerously close to the airways and the mucus type membranes in and around your mouth and eyes. So the virus can get in…and voila! You are infected (that is, unless your immune system kills the virus).

If the virus is on your hands you can pass it on by shaking someone’s else hand. Kisses, well, that's pretty obvious…It comes without saying that if someone sneezes right in your face you are kind of stuffed.

Figure.  The Structure of Virus

Why exactly is soap so good? 

Why does soap work so well on the SARS-CoV-2, the coronavirus and indeed most viruses? Because virus is a self-assembled nanoparticle in which the weakest link is the lipid (fatty) bilayer. This is how it works the magic against viruses:

• The soap dissolves the fat membrane and the virus falls apart like a house of cards and "dies", or rather, we should say it becomes inactive as viruses aren’t really alive. Viruses can be active outside the body for hours, even days.

Disinfectants, or liquids, wipes, gels and creams containing alcohol (and soap) have a similar effects but are not really quite as good as normal soap. Apart from the alcohol and soap, the “antibacterial agents” in these products don't affect the virus structure much at all.

Consequently, many antibacterial products are basically just an expensive version of soap in terms of how they act on viruses. Soap is the best but alcohol wipes are good when soap is not practical or handy (e.g. office receptions).

 See Also

1. The Tip of the Iceberg: Virologist David Ho (BS '74) Speaks About COVID-19

Precautions You Probably Should Take

The author of this coronavirus precautionary measures is James Robb, MD UC San Diego. It’s a really great read.

Subject: What I am doing for the upcoming COVID-19 (coronavirus) pandemic

Dear Colleagues, as some of you may recall, when I was a professor of pathology at the University of California San Diego, I was one of the first molecular virologists in the world to work on coronaviruses (the 1970s). I was the first to demonstrate the number of genes the virus contained. Since then, I have kept up with the coronavirus field and its multiple clinical transfers into the human population (e.g., SARS, MERS), from different animal sources.

The current projections for its expansion in the US are only probable, due to continued insufficient worldwide data, but it is most likely to be widespread in the US by mid to late March and April.

Here is what I have done and the precautions that I take and will take. These are the same precautions I currently use during our influenza seasons, except for the mask and gloves.:

1) NO HANDSHAKING! Use a fist bump, slight bow, elbow bump, etc.

2) Use ONLY your knuckle to touch light switches. elevator buttons, etc.. Lift the gasoline dispenser with a paper towel or use a disposable glove.

3) Open doors with your closed fist or hip - do not grasp the handle with your hand, unless there is no other way to open the door. Especially important on bathroom and post office/commercial doors.

4) Use disinfectant wipes at the stores when they are available, including wiping the handle and child seat in grocery carts.

5) Wash your hands with soap for 10-20 seconds and/or use a greater than 60% alcohol-based hand sanitizer whenever you return home from ANY activity that involves locations where other people have been.

6) Keep a bottle of sanitizer available at each of your home's entrances. AND in your car for use after getting gas or touching other contaminated objects when you can't immediately wash your hands.

7) If possible, cough or sneeze into a disposable tissue and discard. Use your elbow only if you have to. The clothing on your elbow will contain infectious virus that can be passed on for up to a week or more!

An restaurant at Amsterdam during COVID-19 pandemic

What I have stocked in preparation for the pandemic spread to the US:

1) Latex or nitrile latex disposable gloves for use when going shopping, using the gasoline pump, and all other outside activity when you come in contact with contaminated areas.

Note: This virus is spread in large droplets by coughing and sneezing. This means that the air will not infect you! BUT all the surfaces where these droplets land are infectious for about a week on average - everything that is associated with infected people will be contaminated and potentially infectious. The virus is on surfaces and you will not be infected unless your unprotected face is directly coughed or sneezed upon. This virus only has cell receptors for lung cells (it only infects your lungs) The only way for the virus to infect you is through your nose or mouth via your hands or an infected cough or sneeze onto or into your nose or mouth.

2) Stock up now with disposable surgical masks and use them to prevent you from touching your nose and/or mouth (We touch our nose/mouth 90X/day without knowing it!). This is the only way this virus can infect you - it is lung-specific. The mask will not prevent the virus in a direct sneeze from getting into your nose or mouth - it is only to keep you from touching your nose or mouth.

3) Stock up now with hand sanitizers and latex/nitrile gloves (get the appropriate sizes for your family). The hand sanitizers must be alcohol-based and greater than 60% alcohol to be effective.

4) Stock up now with zinc lozenges. These lozenges have been proven to be effective in blocking coronavirus (and most other viruses) from multiplying in your throat and nasopharynx. Use as directed several times each day when you begin to feel ANY "cold-like" symptoms beginning. It is best to lie down and let the lozenge dissolve in the back of your throat and nasopharynx. Cold-Eeze lozenges is one brand available, but there are other brands available.

I, as many others do, hope that this pandemic will be reasonably contained, BUT I personally do not think it will be. Humans have never seen this snake-associated virus before and have no internal defense against it. Tremendous worldwide efforts are being made to understand the molecular and clinical virology of this virus. Unbelievable molecular knowledge about the genomics, structure, and virulence of this virus has already been achieved. BUT, there will be NO drugs or vaccines available this year to protect us or limit the infection within us. Only symptomatic support is available.

I hope these personal thoughts will be helpful during this potentially catastrophic pandemic. You are welcome to share this email. Good luck to all of us! Jim

James Robb, MD FCAP

See Also

1. The Tip of the Iceberg: Virologist David Ho (BS '74) Speaks About COVID-19