Pearls from TWiV: Where We are for the moment

Listening to the last episode of This Week in Virology (#622) with a Dutch lady who does her virology at the NIH's Rocky Mountain Laboratory (RML), which is a level 3 facility where they don space suits to work with dangerous viruses, I realized how the information keeps changing but these scientists are fine with this.

TWiV remains, by far, the best source of information--I do not say "news"--about COVID19.  News organizations want to give you news, which is exactly what you do not want-- because news is only the first witness's testimony. You want to hear the whole story and you want to hear the witnesses cross examined-- and that's what TWiV gives you. 

Cast of Characters

As Rich Condit, a virologist living in Austin notes, "We don't learn as much from being right as we do when we are wrong. I've been wrong about so many things since January, but I've learned a ton."

Basic questions like whether or not the virus lives and circulates in the blood stream have been an ongoing question, and depending on which week you listen, and depending on the guest expert, you get a different answer: Daniel Griffin continues to say there is no significant viremia; today's guest,the virologist from RML, says there is no significant viremia for most respiratory viruses including influenza, but given the finding of virus in the liver of influenza patients, even viruses without much viremia, may have some. SARS COV-2 may be such a virus, with a brief but important viremic phase.  Other guests--one from NIH on episode 620, John Yewdell, have noted the renal disease and coagulopathies as suggestive of a viremia of significant magnitude. 

What is emerging consistently over time is the idea the virus enters the body through respiratory mucosa, nose, pharynx, lung and during the first week the virus enters the cells, replicates, multiplies and sheds and during this time the patient often feels pretty well, although may have symptoms of fever, fatigue, cough but it's during the second week you have "cytokine storm" when the innate immune system which is sort of the carpet bombing immune system, destroying whatever gets in its path, predominates. These are the hypoxic patients who wind up in the ICU's sometimes on respirators. 

During these first 2 weeks PCR testing for viruses is accurate and positive. Testing can be done by saliva with a Robert Wood Johnson test kit or by the "brain biopsy" deep nasal/pharynx swab but a simple nose swab or saliva tests are likely just as accurate, if you can find a place which does one but these tests do not tell you about infectivity and may be seeing only the detritus of battle, fragments of non infective virus and may be found 3-4 weeks after the infection has subsided. In stool PCR + fragments persists for over a month, again, not clearly infectious.

Obadiah Youngblood "Occohee"

A secondary wave of symptoms,recrudescent fever, cough, prostration can occur a month or 6 weeks after the first presentation. This may be a new infection with the same virus in the patient who has already had it once but is not immune or simply the virus re flaring, like a smoldering fire which suddenly explodes after the firemen have left. 

In children a widespread vasculitis involving coagulation defects with widespread organ damage from clotting occurs, rarely, but at Columbia's Children's hospital, they had 300 cases in a short few weeks. Three of 300 died, or something of that order.

Spread of the virus does not occur uniformly from all patients. There are "super spreaders" who are responsible for 80% of all cases although they are fewer than 10% of patients. This is a tricky number to pin down, but if true, what would that say about all our quarantine-ing? 

Other tidbits dropped off in discussion, but not supported with studies, are:
1/ The number of patients below age 50 who die is vanishingly low. All this quarantine-ing and shut down really is to save the elderly.

2/ The chance of getting COVID diminishes exponentially once you open the windows in a room or go outside, and yet transmission among people attending open air events like political rallies was well documented in the 1918 flu epidemic, although it's not clear if the virus was spread at the rallies or in bars and pubs afterward.

3/ Aerosolized virus particles on micron sized particles likely penetrate deep inside the bronchial tree whereas big droplets tend to get trapped by nose hair, in the anterior nose (tip) and sinuses. 

4/ Antibody testing, overall is accurate only 50% of the time, which means it's a flip of the coin whether your positive antibodies really do mean you had the disease.  
And then there's the question of whether having the antibodies means they will protect you against re infection. With other COVID viruses (the common cold viruses) the antibodies do not protect against reinfection with same virus, if if they do, only for a few months. On the other hand, measuring antibodies may miss the real protective cells--the T cells--which may protect you despite the low antibody levels. With re exposure, your T cells may protect you (as happens with some vaccines) and while they hold down the fort, the B cells ramp up antibody production to really whap the virus later. So simply measure "antibodies' may not tell us much, even if we could trust the accuracy of the antibody tests.

5/ Other Covid viruses stimulate antibodies, B cells which are reserve banks for production of antibodies on re exposure and T cells which are important memory cells. But B cell antibodies do not "sterilize" the virus, i.e. remove it, they simply "neutralize" the virus and keep it from reproducing. 

6/ Measles can "wipe the slate clean" when you get the real disease, rendering you susceptible to viruses you had developed previous antibody immunity to and oral (inactivated) polio vaccine can do just the opposite, stimulate an immune response to almost all new viral attacks, at least transiently, perhaps for a year.
Vaccines against measles do not wipe clean the slate, which is important to the discussion of anti vaxers claims that it's better to get the natural disease to be really immune to future infections. Actually, with measles, you'd far rather get the vaccine, so the rest of the cells protecting you against other viruses do not get wiped clean.