Thread on BCG vaccination and #COVIDー19.

There has been a flood of ecological studies & media reports claiming that BCG vaccination protects against COVID-19. See:

https://www.medrxiv.org/search/BCG%252Bcovid%252B

Some of the studies are thoughtful/cautious but most lack epidemiological awareness (to put it mildly). None are peer-reviewed.

They use the BCG data we put out in our World BCG Atlas: http://www.bcgatlas.org/ . I am happy our free database is being used!

As a TB researcher born in India, I would be thrilled if BCG does indeed turn out to be protective against COVID-19:
-It is a cheap, safe, widely used
-It does have non-specific immune-boosting properties
-It protects against leprosy
So, we must explore the BCG hypothesis

BUT, I am surprised to see how uncritical the media has been about these ecological studies.

I am also worried that policy makers in some countries have been quick to pounce on this and might not do what they could be doing (e.g. ramp up testing, contact tracing, PPE, hygiene).

I am aware that randomized trials on BCG and COVID are starting and welcome them.

Until then, we need to very cautious about getting too excited about ecological studies for several reasons:

Ecological studies are inherently limited since they take aggregate data and try to infer to the individual level. Sometimes, this can hold, while other times it can be seriously flawed (‘ecological fallacy’).

See this teaching case study for example: https://www.teachepi.org/wp-content/uploads/OldTE/documents/courses/bfiles/The%20B%20Files_File3_Durkheim_Final_Complete.pdf

Timing really matters. Some of these analyses were done a month ago. COVID numbers have shot up in many LMICs since then. See India’s trajectory on this @FT chart today. See the 2nd chart @MaxCRoser which shows that the growth rate of confirmed cases is now much faster in LMICs.

So, if these ecological analyses were to be repeated in a month, they might produce very different results.

Most LMICs are seriously under-testing. COVID cases & deaths under-reported. @MaxCRoser shows data for African countries. Confirmed cases=those with a lab confirmed infection. But even with little testing the # of confirmed cases in many African countries is increasing rapidly.

Confounding is a major issue. In this case, age structure of countries are vastly different. Europe and North America have ageing populations, while Asia and Africa have younger populations. Only a few of the ecological analyses have adjusted for age as a confounder.

Even if known confounders are adjusted for, it is impossible for ecological analyses to adjust for all confounders. That is why randomized trials are critical for vaccines and drugs - randomization is the surest way to reduce the risk of bias due to confounding.

There are inconsistencies in the ecological association. The epidemic began in China, and China routinely vaccines everyone at birth. Same with Iran & South Korea, where BCG is given at birth. The COVID epidemic is sharply taking off in other countries where BCG is given.

BCG offers little protection to adults, but has some protection against severe forms of childhood TB. So, even if BCG offers some protection against COVID, it is hard to extrapolate that it will protect older people from COVID-related mortality.

A detailed critique of the first ecological study by @LenaFaust1 @emilylmaclean @svadzianita @SKHuddart epidemiology doctoral candidates @McGill_TB is available at: https://naturemicrobiologycommunity.nature.com/channels/2549-coronaviruses-past-present-and-future/posts/64892-universal-bcg-vaccination-and-protection-against-covid-19-critique-of-an-ecological-study

So, while we wait for trial results, we should repeat these ecological analyses by May & once countries have increased their testing rates. And we should adjust for confounding. That might provide insights on whether early trends still hold. I would love for BCG to be protective!

I am getting emails from people asking how they can get BCG shots!

My answer: no evidence to back such practices at present. Let’s wait for trial results!

I know the whole world is desperate for good news re #COVIDー19 & we are clutching at straws.

But we cannot extrapolate from weak, ecological studies and promote unproven interventions. It’s like chloroquine for COVID – we need better evidence! It is coming.

END