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Does tuberculosis vaccination hold clues to Covid-19’s spread?

Is the correlation between widespread use of BCG vaccination and low Covid-19 rates significant?

While deaths from Covid-19 continue to rise globally, tuberculosis, a bacterial infection, remains the most potent, highly-infectious killer in the world. The UK stopped general vaccination against TB in 2005. This cessation might prove to have been unfortunate because the latest research suggests that the TB vaccine we used until that date may confer protection against Covid-19.

There are very few cases of tuberculosis in the UK today. Infections are concentrated in minority communities with strong links to locations where TB is still an active threat. According to Public Health England, 2018 had the lowest number of cases ever recorded, at a little under 5,000. 72% of those infected were born outside the UK. Around 5% of those infected died; far fewer than are currently dying daily from Covid-19.

In the 1920s, a period of negligible immigration into the UK, there were 40,000 deaths each year in England from TB. The creation of a vaccine reduced the number considerably, but not for several decades. The Bacillus Calmette-Guérin (BCG) vaccine was first used in humans in 1921, but was only widely adopted after World War II.

Between 1953 and 2005, the BCG vaccine was administered by the NHS to all newborns in the UK as part of a routine vaccination schedule. However, today it is only given to children in high-risk communities, including recent immigrants and to adults under 35 who may come into contact with TB, including some healthcare workers. Effectiveness of BCG for those over 35 is not proven, and any protection it conferred upon anyone vaccinated in or before the year 2000 is unlikely now to be effective.

The decision to end general use of the BCG vaccine in 2005 made sense at the time. Many other western countries had already done so. In Italy, the BCG vaccine was introduced in 1970, but never mandated nationally and provincial health authorities ceased to use it in 2001. In Spain, the vaccine was used nationwide for newborns between 1965 and 1981, when it was discontinued. France was one of the few countries to mandate revaccinations, but the booster was discontinued in 2004, and the newborn vaccination in 2007. In the USA, the BCG vaccine has never been part of a regular vaccination schedule. Each country reached the same conclusion, that the small risks and considerable expense of administering the vaccine generally were no longer justified.

However, in recent years research has indicated that the BCG vaccine may offer protection against other infections caused by pathogens unrelated to the bacterium that causes TB, including viruses.

A paper published in the journal Clinical Microbiology and Infection last year, months before the novel coronavirus was identified, pointed up “important lines of evidence indicating that BCG offers protection against various DNA and RNA viruses.” SARS-CoV-2, the novel coronavirus that causes Covid-19, is an RNA virus.

Three very recent studies, all pre-published without peer review, come to the same conclusion: that the BCG vaccine may serve as a protective factor against Covid-19. The studies were undertaken independently by scholars at Johns Hopkins University, the University of Michigan and at Fujita Health University in Japan. How BCG may be effective is not known and is the subject of these studies, all of which are statistical rather than epidemiological in nature.

A follow-up study by scholars in Chandigarh, India, adds an additional crucial factor: whether countries have a revaccination policy, as France once did. BCG is believed to be effective for a maximum of twenty years, and most countries mandate its use only once with newborns. The Chandigarh paper concludes that “our data further supports the view that universal BCG vaccination has a protective effect on the course of Covid-19 probably preventing progression to severe disease and death. Clinical trials of BCG vaccine are urgently needed to establish its beneficial role in Covid-19 as suggested by the epidemiological data, especially in countries without a universal BCG vaccination policy.”

The effect of widespread BCG vaccination may be indicated in a graph produced by Our World in Data: “Total Confirmed Deaths from Covid-19 per million people vs. GDP per capita.”

If we discount San Marino and Sint Maarten, then (on 8 April) the top right quadrant of the graph (high GDP, high death rate) features Spain (295 deaths per million people/ $34,300 per capita), Italy (283/$35,200), Belgium (175/$42,700), France (158/$38,600), the Netherlands (123/$48,400), the UK (91/$39,000), and Sweden (59/$47,000). Somewhat lower, but still in the upper right quadrant of the graph, were the USA (39/$54,200), and Germany (22/$45,200).

The bottom right hand corner (high GDP, low death rate) features South Korea (3.9/$36,000), Qatar (2/$117,000), Singapore (1/$85,500), and Japan (0.9/$39,000).

there are currently no low-income countries  that have high death rates from coronavirus.

The bottom left quadrant of the graph features countries with very low GDP per capita and low rates of deaths. These include the African nations Liberia (0.59/$753), the Democratic Republic of Congo (0.2/$808), Malawi (0.1/$1100), and Ethiopia (0.02/1730). There are also very low-income nations in Asia, such as Afghanistan (0.3/$1800), and the Americas, Haiti (0.1/$1700).

The upper right quadrant of the graph is empty. In other words, there are currently no low-income countries (LICs) that have high death rates from novel coronavirus. However, great attention is being paid to these LICs, with many anticipating that their already stressed healthcare systems will be unable to cope and their governments will be unable to enforce effective NPIs.

It is worth noting that some countries in the lower half of the graph, both rich and poor, share an important trait: widespread vaccination with BCG. South Korea, Qatar, Singapore and Japan, as well as other countries clustered near them (Brunei, Kuwait, Oman), all mandate that babies be vaccinated against tuberculosis shortly after birth. So do the LICs listed, including Liberia, the DRC, Afghanistan and Haiti, as well as other clustered near them (Senegal, Togo, Zimbabwe).

These are all pre-published studies, and further peer review will challenge and may undermine their findings. Still, we may be tempted to regret the decision to end BCG vaccination. Meanwhile, other countries are acting. Clinical trials have just commenced in the Netherlands, Germany and Australia, where healthcare workers will receive the vaccine in lieu of one dedicated to Covid-19.

Is there a silver lining here? Will extensive BCG vaccination campaigns in poor nations make Covid-19 a far less effective killer? Since these countries tend to have far younger populations, the effectiveness of the TB vaccine may be quite widespread. This, combined with the well-reported tendency of the young who are infected with Covid-19 to be asymptomatic or have only mild symptoms, may lead to far lower death rates in some of the poorest countries.

However, we should also remember that TB infects up to 10 million people each year, and in 2017 claimed around 1.6 million lives, twenty times the current number of those reported to have died from Covid-19. If numbers are even roughly accurate, in the first months of 2020, TB may already have killed around four times as many people in LICs as Covid-19 has killed in high-income countries.

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