Miguel Hernán Profile picture
Sep 11, 2020 15 tweets 7 min read Read on X
1/
Look at the shape of these curves.

New York and Madrid had similar epidemics until they spectacularly diverged.

In March, both cities were caught by surprise and shut down because of #COVID19.

In September, the situation is under control in NY and alarming in Madrid.

Why? Image
2/
Let’s start with the similarities: two big, dense cities with a large network of public transit and lots of visitors.

An explosive outbreak of #SARSCOV2 overwhelmed their contact tracing system and their hospitals. A lockdown was required to reduce the public health disaster.
3/
By June, both places had succeeded in bringing down the number of new cases. That's precisely what lockdowns do.

In July, new cases started to increase in Madrid until reaching one of the highest incidences in Europe.

New York has not seen any increase in new cases yet.
4/
We could argue that number of new #COVID19 cases isn't the best metric for the severity of the #SARSCOV2 epidemic. Perhaps most cases are asymptomatic or mildly symptomatic?

Let's then look at hospital occupation. No problem in New York. Serious trouble brewing in Madrid.
👇 Image
5/
So what happened?

#NewYork and #Madrid had significantly different responses in terms of contact tracing, number of tests, and speed of reopening.

Let’s review each of these elements.

This comparison is a case study on epidemic management in hub cities around the world.
6/
CONTACT TRACING
New York state aimed at 30 contact tracers per 100,000 people before reopening. Minimum.

That translates into 6000 contract tracers in New York and 2000 in Madrid.

Madrid had about 200 contact tracers in July (maybe 700 now). An order of magnitude difference.
7/
TESTING
In April, >70% of PCRs were positive in both New York and Madrid.

New York aimed at achieving <5% positivity before reopening. It is now 1-2%.
www1.nyc.gov/site/doh/covid…

Positivity in Madrid is ~20% and increasing since July. That is, not nearly enough tests are done.
8/
SPEED OF REOPENING

Let's focus on indoor dining, a vital economic activity in both #NewYork and #Madrid, and arguably one of the main sources of transmission of the #coronavirus.
9/
Indoor dining in New York is CLOSED.

It'll open on September 30 at 25% capacity (50% on November 1) with

- NO bar service.
- Strict protocols
- Phone number to report violations
- Deployment of hundreds of enforcement personnel to ensure compliance
forward.ny.gov/nyc-indoor-din…
10/
Indoor dining in Madrid was OPEN at 60% capacity in June.

Bar service opened too.

Protocols weren't aggressively enforced.

Since June it has been easy to find crowded bars and tables. The contrast with NY was striking as anyone spending time in both places can tell you.
11/
Contact tracing, testing, and speed of reopening differed dramatically between #NewYork and #Madrid.

New York opened the economy without overwhelming the hospitals and confirmed its credentials as a serious place to do business.

By simply doing what experts say since March.
12/
A colleague asked whether New York may have reached "herd immunity" whereas Madrid has not. That'd explain the low number of cases in NY.

Unlikely. Based on the available seroprevalence studies, both places had a similar % of population who developed antibodies to #SARSCOV2.
13/
Of course, bad luck can never be ruled out in epidemics.
A spark at the right time may ignite a wildfire in one place but not another.

But bad luck seems a poor explanation for the NY-Madrid differences after comparing their testing, contact tracing, and reopening policies.
14/
Finally, some people have asked whether differences in number of international passengers may explain the different epidemic Summer in #NYC and #Madrid.

Unlikely.

NYC and Madrid had a very similar influx of international passengers, both before and after the lockdown. Image
15/
Maybe passenger screening was stricter in the U.S.?

Of 675,000 passengers screened in *all* U.S. airports, 15 were identified with #COVID19.

If Spain had implemented the U.S. screening procedures, Madrid would have found too few cases to explain the difference.

In fact... Image

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More from @_MiguelHernan

Jun 19, 2023
1/
One day everyone will recognize #selectionbias due to a #collider and the world will be a better place.

This time observational studies found a higher risk of omicron reinfection after a 3rd dose of #COVID19 vaccine. As usual, alarms went off.

Can you see the obvious bias? Image
2/
Those who receive a booster and get infected are, on average, more susceptible to infection than those who don't receive a booster and get infected.

So no surprise than those who receive a booster and get infected are more likely to get reinfected.

Led by @susanamcorella...
3/
... we described the bias @bmj_latest with simulations + real data.

We show that a vaccine booster will be associated with higher reinfection risk even if the booster has no harmful effect.

Now the good news: Preventing this #selectionbias is easy...
bmj.com/content/381/bm…
Read 6 tweets
Apr 13, 2022
1/
Our findings on a fourth dose (2nd booster) of the Pfizer-BioNTech #COVID19 vaccine are now published.

Compared with 3 doses only, a fourth dose had 68% effectiveness against COVID-19 hospitalization during the Omicron era in persons over 60 years of age.

Interestingly...
2/
... this is yet another example of the need for good #observational studies that emulate a #TargetTrial.

Would it be better to have a real randomized trial? Yes

Do we have a randomized trial? No

Will we have a randomized trial? Perhaps, but too late for a timely decision.
3/
Last year, observational evidence was also used to recommend a first vaccine booster.

Our and others' studies provided evidence on the booster's protection against hospitalization after infection with Delta:


Policy makers listened. Lives were saved...
Read 8 tweets
Dec 3, 2021
1/
We emulated a target trial of two #COVID19 mRNA vaccines in the largest healthcare system in the US.

Both vaccines were similarly effective, with Moderna slightly better than Pfizer-BioNTech.

But that isn't the most important conclusion of our study.

2/
Spring of 2020: #COVID19 vaccines are developed.

October 2020: Results from randomized trial are announced.
businesswire.com/news/home/2021…

~6 months from development to evaluation of effectiveness.

Utterly impressive. Unprecedented.

Kudos to the pharmaceutical industry.

Now...
3/
December 2020: Vaccines become available.

December 2021: Where are the big randomized trials for COMPARATIVE effectiveness?

1 year, still *crickets*

Billions of taxpayer dollars and we don’t get to know which vaccine is better and safer?

Not so impressive, pharma industry.
Read 6 tweets
Aug 25, 2021
1/
Vaccine safety: We compared excess adverse events after #COVID19 vaccination (Pfizer-BioNTech) and after documented #SARSCoV2 infection.

nejm.org/doi/full/10.10…

Take-home message: Low excess risk of adverse events after vaccination, higher after infection.

Some thoughts👇
2/
Preferring #SARSCoV2 infection over vaccination has become even harder. (Remember: infection also increases the risk of severe disease/death)

This is a good illustration of how #randomized trials and #observational studies complement each other for better #causalinference...
3/
The original #randomized trial estimated vaccine effectiveness to prevent symptomatic infection, but was too small to quantify vaccine safety.

That's what #observational studies do.

Now a different sort of question: Why could we do this study in the first place?

2 reasons.
Read 8 tweets
Mar 18, 2021
1/

Many countries are vaccinating their elderly. Can we relax control measures now?

No.

Even with 50% of elderly vaccinated, uncontrolled #SARSCOV2 transmission may overrun the healthcare system.

We explain @AMJPublicHealth today, led by @_gmales
ajph.aphapublications.org/doi/10.2105/AJ…
2/

Data from Madrid, Spring 2020:

Critical care requirements peaked at 5 times the usual capacity.

Hospitals managed to increase ICU capacity by 3-fold.

Heroic but, sadly, insufficient.

The healthcare system collapsed. Not everybody who needed critical care received it.
3/

If 50% of the elderly had been vaccinated, critical care requirements still would have peaked at almost 4 times the usual capacity.

Greater than the ICU capacity of any country in the world.

Only a prolonged lockdown could return ICU requirements to normal.

One last thing:
Read 4 tweets
Mar 12, 2021
@ProfMattFox 1/
The odds ratio from a case-control study is an unbiased estimator of the

a. odds ratio in the underlying cohort when we sample controls among non-cases

b. rate ratio in the underlying cohort when we use with incidence density sampling

No rare outcome assumption required.
@ProfMattFox 2/
Because the odds ratio is approximately equal to the risk ratio when the outcome is rare, the odds ratio from a case-control study approximates the risk ratio in the underlying cohort when we sample controls among non-cases and the outcome is rare.

But...
@ProfMattFox 3/
... for an unbiased estimator of the risk ratio (regardless of the outcome being rare), we need a case-base design, not a classical case-control design.

Of course, all of the above only applies to time-fixed treatments or exposures.

As for the causal interpretation...
Read 5 tweets

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