Short thread:

Cases are starting to plummet quickly.

This isn’t from vaccines (yet).

Possible we may be starting see a combination of seasonality on our side and likely seeing herd effects kick in.

1/x
On seasonality:

We knew in the summer that this virus was going to roar back in the fall. It did!

While coronaviruses collectively have a broad window each year, We can see that each individual coronavirus in the graph 👆has only a few months when it peaks. And then drops

2/x
This virus started really hitting us hard a second time in November. Oct-Jan may well be this viruses peak transmission window. We could be entering a reprieve from its grasp, at least for a while. If so, could help us get vaccines out and control spread quickly.

3/x
On herd effects:

At least in the US, we have RECORDED 27 million cases.

I’ve long held there is a very good chance we are undercounting my massive margins. In first wave there is no way we caught near 1 in 10 cases. Possible on average we’ve caught fewer than 1:10 since..

4/x
Catching 1 in 10 would put US at 250 million cases occurred. This doesn’t agree with the serologies. But serologies for a first infection are limited. We’ve calibrated assays around sick people since they serve as positive controls... may miss many w low grade infections.

5/x
This is all speculative. The data and history is limited. But the quickly diminishing cases should be viewed firstly as a good thing and secondly in light of natural effects. I don’t think this is owing to vaccines (it’s just not...yet) nor any massive behavioral change.

6/x
Possible this is some combo of herd effects from many mild/ asymptomatic infections that went untested (obviously vast majority were not tested) and some benefits of seasonality

For the moment, we need to keep taking this as seriously as possible and see cases approach zero

7/7
I want to clarify that these are some of my thoughts. Not owing to a rigorous analysis.

I do think we need to look to the past (other viruses) to gain insight into this one.

Also, the extra transmission owing to the variants may breakthrough the seasonality.

8/x
We know from many countries now just how devastatingly fast the new variants have swept through and replaced the original.

This could spell a lot of trouble for us in the near term. We can’t let our guard down now. But rather should have it as high as possible at moment.

9/x
It’s possible these variants will have unique characteristics that don’t follow seasonal “rules” or could breakthrough pre-existing immunity (from infection or vaccines)

So need to remain vigilant and keep doing what we can to roll out effective mitigation strategies

10/x

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More from @michaelmina_lab

1 Feb
NOTE:

If you see papers/media that show very low sensitivity for rapid Ag tests (i.e. 30%-60% sensitivity) the report is most likely making a common mistake:

Comparing a test meant to detect viable virus to a test that can detect minuscule amounts of RNA is a mistake.

1/x
PCR RNA stays around long after live virus is cleared

So if you see a paper that shows very low sensitivity, ask:

"Are they comparing rapid antigen tests to "anytime" PCR RNA positivity? (Especially studies asking about sensitivity among asymptomatics)

2/x
To interpret this, you should know that only 25%-40% of the time someone is PCR positive are they infectious w live virus.

So... even a test that is 100% sensitive for live virus should only show a 25%-40% sensitivity against PCR among asymptomatic people.

3/x
Read 9 tweets
28 Jan
Important: on the resurgence of SARS-CoV-2 in a place where herd immunity was already attained.

The authors lay out 4 reasons:

1) didn’t actually attain herd immunity
2) waning immunity
3) new strains evading immunity
4) much more transmissible strains

thelancet.com/journals/lance…
Waning immunity is likely as a component. The immune system memory is just like real memory. I needs to be exercised w repetition - like studying for a test. A single event will not likely offer life long immunity.

2/x
My real concern is mutation that will evade, even If partial our immune responses to earlier versions of the virus or to vaccines being made (which are directed specifically towards mimicking earlier versions)

We have to act now on slowing spread in this case w/out immunity

3/x
Read 4 tweets
24 Jan
Short🧵 On mutant strains emerging:

It’s a new virus - not in an optimal state upon “birth” as it leaped into humans.

Has so much room to grow and ‘learn’

Increases in transmission rates and evasion of immunity should be expected.

We can anticipate and act accordingly.

1/x
We can start now to think through new vaccine designs that are not all narrow number of epitopes (in this case single [important] protein) and essentially identical to each other.

We can start “future proofing” our vaccine design choices to reduce immense risk of escape.

2/x
We can also immediately start building an Arsenal of contingency plans.

Tools that will not be susceptible to the same risk of mutants escaping immunity that arise from the ecological pressures from vaccines and infections....

3/x
Read 6 tweets
19 Jan
Rapid Antigen tests for #COVID19 in UK are working!

Purpose is to rapidly identify infectious people - that is exactly what they are doing!

And doing it very well!

With an R=1.4, those 37000 would have otherwise become >100,000 in weeks.

1/x

thisislocallondon.co.uk/news/national/…
In the article, Jon Deeks, derides the tests saying the tests:

"missed 60% of the cases which would have been picked up by PCR" - Jon Deeks

YES! This is a good thing!

MOST time someone is PCR+, they are No Longer Infectious! Rapid tests are catching the infectious only!

2/x
This issue is mentioned above continues to plague people's understanding of rapid tests

The tests are different

Rapid Antigen Tests are BETTER than PCR at being specific for infectious virus

A public health test should not pick up people after they are infectious

3/x
Read 7 tweets
15 Jan
Apparently I cannot say this loudly enough

The recent @bmj_latest articles by @deeksj et al deriding Rapid Ag Innova Tests are simply WRONG

They simply do NOT appropriately interpret Ct values & do NOT consider massive importance of how long PCR remains + post-infectiousness
Inspection of Ct values among the Asymptomatics & correlation to RNA copies / ml shows Ct values in Liverpool are ~8 lower than often seen in literature. The failure to recognize this means the estimates of Ag test sensitivity for "high virus" are totally off.

2/x
The sensitivity for "moderately high" or "high" viral loads in the Liverpool data are ~90% and ~100%.

But to know this you cannot just assume a Ct of 25 elsewhere (often described as entering "high viral load") means same thing as a Ct value in other labs.

3/x
Read 9 tweets
14 Jan
Will delaying #COVID19 vaccine doses cause vaccine immune escape?

This nice article misses an extremely important part - that unvaccinated ppl too have so called “partial immunity” while infected.

Escape from immunity isn’t same as from antibiotics

1/x

sciencemag.org/news/2021/01/c…
Unlike antibiotics where resistance happens w partial doses, to be a risk you also must be taking them in first place.

When considering escape from spike protein derived immunity - must consider everyone w/out sterilizing immunity at risk to induce a mutant upon infection.

2/x
Whether no vaccine or a single dose (or two) people create antibodies against the same part of the protein.

If discussing “partial immunity” or low affinity antibodies, must consider that a fully naive person might pose greater risk for escape than a single dose person

3/x
Read 11 tweets

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