Role of Vitamin D in the prevention of Coronavirus 2019 infection and mortality

https://www.researchsquare.com/article/rs-21211/v1

by pseudolus • 6 years ago

162 109 6 years ago

Can these studies lead to a recommendation for how much vitamin D supplements for adults to take to reduce likelihood of severe infection?

abendy• 6 years ago

"It is often difficult to determine how much vitamin D supplementation is needed to obtain the “sweet spot.” For these reasons, you should routinely get your vitamin D levels tested and rely on dietary sources or supplementation to boost your levels when necessary."

http://blog.wellnessfx.com/2013/08/14/the-vitamin-d-sweet-sp...

yasp• 6 years ago

From what I can tell, it's still not clear that vitamin D isn't a just biomarker.

open-source-ux• 6 years ago

In the UK, the NHS (National Health Service) recommends a daily vitamin D supplement of 10 micrograms (400 IU). In a previous discussion on Hacker News a few days ago, some posters mentioned this was a low and outdate dosage.

However, the NHS site also warns against taking more than 100 micrograms (4000 IU) of vitamin D. In the previously mentioned HN discussion, some posters stated they take more than this (some have been told to by their doctors).

What the NHS website says:

Taking too many vitamin D supplements over a long period of time can cause too much calcium to build up in the body (hypercalcaemia). This can weaken the bones and damage the kidneys and the heart.

If you choose to take vitamin D supplements, 10 micrograms a day will be enough for most people.

Do not take more than 100 micrograms of vitamin D a day as it could be harmful.

[1] https://news.ycombinator.com/item?id=23119949 [2] https://www.nhs.uk/conditions/vitamins-and-minerals/vitamin-...

bluecalm• 6 years ago

The calcium build up of the reason they often add vitamin K2 to vitamin D supplements. I am not qualified to say if it works at preventing the build up but it's often the stated rationale.

hanniabu2• 6 years ago

In the US the only dosage I see available in the stores is 4000IU so what I usually do is take 1 every 2-3 days.

kerkeslager10• 6 years ago

I don't know what you mean by "these studies" as the link is to only one study.

This study does a pretty questionable job of establishing that any amount of vitamin D levels reduces likelihood of severe infection. It doesn't even attempt to say what level of supplementation would lead to what vitamin D levels. So I think the answer to your question is a firm, "No."

BurningFrog• 6 years ago

There are general vitamin D recommendations available a google search away.

I take a 2000 IU pill every day since a few years. I think that's both safe and sufficient for normal people.

Nit pick: Vitamin D reduces the likelihood of dying if you get infected, not the likelihood getting it in the first place.

dna_polymerase• 6 years ago

I know of at least one study in COVID-19 cases that suggested a correlation between mortality and Vitamin D levels [0], tested in patients rather than comparing national averages. That said, I'd like to see more tests in confirmed cases and even more than just mortality correlation, I'd like to see if it helps with long term lung damage.

[0] https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3585561

atourgates2• 6 years ago

That's really interesting, and has an even stronger conclusion:

"When controlling for age, sex, and comorbidity, Vitamin D status is strongly associated with COVID-19 mortality outcome of cases."

elliekelly2• 6 years ago

The vitamin D deficiency is particularly interesting to me with respect to pregnant women and smokers. There have been cases of pregnant women who were unknowingly infected with Covid-19[1] and it seems there’s some evidence the smokers are less likely to be admitted to the hospital with a severe case.

I would expect both groups to have higher than average vitamin D regardless of their age, background, health issues. Pregnant women consistently take prenatal vitamins for months and (most) smokers consistently get daily sun exposure because they go outside to smoke. And from what little we know it seems both groups fare better when they are infected.

[1]https://www.nejm.org/doi/full/10.1056/NEJMc2009316

DanBC• 6 years ago

There's this, which didn't find much: https://www.cebm.net/covid-19/vitamin-d-a-rapid-review-of-th...

We found no clinical evidence on vitamin D in COVID-19. There was no evidence related to vitamin D deficiency predisposing to COVID-19, nor were there studies of supplementation for preventing or treating COVID-19.
There is some evidence that daily vitamin D3 supplementation over weeks to months may prevent other acute respiratory infections, particularly in people with low or very low vitamin D status. This evidence has limitations, including heterogeneity in study populations, interventions, and definitions of respiratory infections that include upper and lower respiratory tract involvement.

klmadfejno• 6 years ago

I haven't dug into this, and, for the record, I do think vitamin D is likely an important factor here. But I find the two charts to be very worrisome.

Their claim of a very high p value and significant effect is VERY strongly influenced by a single outlier. It's not even close. On this unlabeled graph, I think x axis is vitamin D levels and y axis is deaths per million. They've got ~16 data points in the range of 0-10 deaths, one point at ~20, and one at 65. If you removed the 65 point the line would get a hell of a lot less convincing.

zebrafish• 6 years ago

This study is not exactly rigorous. There doesn't appear to be any controls for age or health risks or anything else. Their methods are literally to take worldometers data and vitamin D concentration data per country from the European Calcified Tissue Society and plug those values into a t-test calculator.

When HN was in a tizzy over p-values a year or so ago, this is what people were concerned about. It's below .05, so what?

Not saying there is or isn't an affect on covid by vit D, but this isn't the study to prove it.

namdnay• 6 years ago

Wait a sec... they're taking their data at country level? How on earth is that supposed to mean anything for anywhere apart from Belgium and the like?

marcosdumay• 6 years ago

Their methods are literally to take worldometers data ... and plug those values into a t-test calculator.

I have seen more papers like this recently. It seems to have become a popular format in hypothesis discovery, usually followed up by others with better methodologies.

They become a problem if the popular press takes the results to publish out of context, or if they enter meta studies.

mikece• 6 years ago

Most of us (computer people) are Vitamin D deficient and taking a supplement to get us up to the healthier levels is a good thing, but focusing on just one nutrient without taking all of nutrition into account is like focusing on fixing only one nasty anti-pattern while letting dozens of other anti-patterns continue unchecked.

new2628• 6 years ago

How do you know it is a good thing? Maybe vit-D is just a marker for sunlight-exposure, and you are gaming the marker with the supplements.

briantakita4• 6 years ago

Which is why the beaches & parks should be open to the public...

Edit: The down votes only supports what I have suspected, many on HN are authoritarian & should not be in positions of power. This is why many in the public don't trust you or your "Science", which are mainly buggy software models built on a tower of assumptions, enforced (ahem peer reviewed) by a priesthood of like-minded fools.

People do support empiricism & the humility of knowing there are unknown unknowns in any model

jshevek• 6 years ago

In your edit, you jump to unsubstantiated speculation about the motivation of others. There are many possible explanations.

briantakita4• 6 years ago

Think in terms of perception, possibility, & risk management. Here's one possibility. The usage of buggy, non stoichiometric, & non empirical models & questionable data collection led to the unstantiated fear mongering leading to the application of public policy which resulted in social & economic disruption. The politically connected benefited from policy while independent businesses were harmed.

kerkeslager10• 6 years ago

There are some good reasons that beaches and parks should be open to the public. There are also good reasons that beaches and parks should not be open to the public.

This study is not one of those reasons. The conclusion of this study is not one of those reasons.

briantakita4• 6 years ago

The study recommends supplementation, which could come from sunlight & being outdoors, as sunlight increases vitamin d in the body. Getting out of the house by going to public parks or the beach is one way of getting sunlight & vitamin d...

cpncrunch2• 6 years ago

Pretty poor study. Look at figure 1...

cpncrunch2• 6 years ago

For a proper review, see:

https://www.cebm.net/covid-19/vitamin-d-a-rapid-review-of-th...

tinus_hn2• 6 years ago

This review found nothing, so they found ‘no clinical evidence on vitamin D in COVID-19.’ No evidence for and no evidence against.

‘We found no trials of vitamin D in COVID-19 that have reported results.’

‘As our searches returned no relevant results, [...]’

Hitton• 6 years ago

The study from which they took average vitamin D levels per country is rather flimsy source to make reliable conclusions from. If you look it up, you'll see that the data is gathered from multiple studies with different methodologies.

And it seems they didn't control for various factors which could influence spread and mortality of the virus either.

hocuspocus2• 6 years ago

You don't even need to look this far.

Number of Covid cases and deaths reported across Europe mean wildly different things. Especially in early April.

Even if I look at today's numbers in my country, there's been only 30k cases officially. We know we could be off by a factor of 6, even though Switzerland did quite a bit of testing:

https://www.swissinfo.ch/eng/serological-test_antibody-test-...

CyanLite2• 6 years ago

Classic case of causation versus correlation.

Is COVID-19 more severe because of a Vitamin D deficiency or does severe COVID-19 cause vitamin D deficiency? Or perhaps people with Vitamin D deficiencies also not get outside for enough sunlight or eat healthy enough, and poor diet/nutrition results in more severe symptoms of COVID-19?

hirundo• 6 years ago

It could be that Vitamin D levels are correlated with sun exposure, which improves health via a hormesis response to oxidative stress on the blood in the skin and eyes.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122858/

SketchySeaBeast3• 6 years ago

Vitamin D levels are severely low in the aging population especially in Spain, Italy and Switzerland. This is also the most vulnerable group of population for COVID-19.

It could also be that age is the important factor here and that Vitamin D actually isn't relevant at all - as they said Vitamin D is low in all those populations already.

firethief3• 6 years ago

Sun also improves health by killing viruses that can cause illness, and by reducing time people spend enclosed in unventilated spaces, where they are prone to respiratory pathogens.

GloriousKoji• 6 years ago

My hypothesis is that COVID-19 is more severe because of a Vitamin D deficiency and old people are more likely to be deficient.

The discussion section references a study from 2017 which shows Vitamin D's helps protect against acute respiratory infections, especially those who are D deficient.

It mentions the countries with lower levels of vitamin D and higher mortality rates (Spain, Italy, Switzerland) also have an older population.

On a different topic: Vitamin D has been touted as this miracle vitamin but studies and trials have shown that it's not effective for improving cardiovascular health or bone density.

hellofunk4• 6 years ago

I’ve been thinking about reports like these for a while, and suppose you had a study that said 100% of all COVID-19 cases in the world are in people who live in areas with less than healthy air pollution. Does that mean the air pollution causes the disease? Because nearly everyone in the world lives in such an area.

KerryJones2• 6 years ago

This is a good point to bring up -- but it was actually proven not to cause Vitamin D deficiency: http://agingbiotech.info/vitamindcovid19/

Of note, the hospitals tested D levels repeatedly and also had pre-admission levels. The author performed an analysis to determine whether the levels changed much within a patient and found that they did not for 95% of the overall cases examined, which then made up the 212 cases kept for analysis. The vitamin D levels used were pre-admission. Thus, though the data are associative, the reverse causality that the infection caused dropping D levels can be ruled out.

caseysoftware• 6 years ago

I've been pondering this one too.

If there's just correlation, then it makes sense. Odds are older people - especially those in nursing homes - don't get much sunshine and therefore would have lower vitamin D.

Alternatively, if there is causation where lower vitamin D levels make you higher risk of infection or a more severe infection, then forcing everyone inside (aka reduced sunshine) via lockdowns is the exactly wrong policy.

And if sunshine kills the virus in the first place, then the lockdowns are worse on another front. We should encourage people to hang out in the sun before going inside anywhere. It would be a form of decontamination.

Regardless, this is further encouragement to stay away from the NYC subway system!

interestica• 6 years ago

It's so strange to me that these studies seem to generalize findings (eg results by country) when one of the key biological factors for how we get vitamin D is skin colour. And at its most basic relationship, the whiter ones' skin, the better one is at generating Vitamin D from sunlight. Perhaps it points to another way in which this disease could disproportionately affect persons of colour?

If anyone has any literature that explores it more I'd love some direction.

atourgates2• 6 years ago

I did see that mentioned as a theory a few weeks ago. My best guess is that in the United States especially, it's a combination economic/socitial factors and vitamin D deficiency that's making the virus have higher mortality in populations of racial minorities with darker skin.

Here's a study that looked at vitamin D levels and found that they're significantly lower in both people with darker skin, and (independently of skin color) those who are overweight. https://www.jabfm.org/content/29/2/226

oneiftwo• 6 years ago

My best guess is that in the United States especially, it's a combination economic/socitial factors and vitamin D deficiency that's making the virus have higher mortality in populations of racial minorities with darker skin

African American communities are hardest hit because of genetic and especially cultural practices which predispose them toward obesity, high blood pressure, heart disease, etc. Further, let's not pretend that African American communities have the same level of respect for authority (i.e. following recommendations/orders) as other groups (though to some degree that disdain may be justified, but that's another discussion).

wnmurphy• 6 years ago

And the elderly...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3782116/

This is a contributing factor to fractures from falls.

vmception2• 6 years ago

so active people of color in environments with sunlight wouldn't have this effect?

like countries closer to the equator

WaterSponge• 6 years ago

accept Ecuador is being particularly ravished by Covid-19 so dont know what that says.

kerkeslager10• 6 years ago

It's so strange to me that these studies seem to generalize findings (eg results by country) when one of the key biological factors for how we get vitamin D is skin colour.

They bypass skin color by just measuring levels of Vitamin D directly. This study doesn't care how you got the Vitamin D, it just cares how much you have.

There are tons of problems with this study, but failure to look at skin color isn't one of them.

JumpCrisscross3• 6 years ago

They bypass skin color by just measuring levels of Vitamin D directly

People with darker skin will, ceteris paribus, have lower vitamin D levels. And all else is not equal.

osazuwa• 6 years ago

I'm actually pleased it was a study on white folks because since we know that this disease disproportionately kills blacks in the US, and blacks tend to have higher rates of vitamin D deficiency (because of the sunlight/skin pigment issue you mentioned) that we were merely seeing a reflection of the racial imbalance. This study suggests otherwise.

That said, there could be other confounding factors. COVID-19 could in fact "drain" vitamin D in some way. We know elderly people are disproportionately killed by the disease, perhaps vitamin D deficiency is more common amongst the elderly. Causal inference from observational data is tricky indeed.

That said, vitamin D supplements are cheap (for now). And most people don't get enough anyway. So people should take it.

ltbarcly3• 6 years ago

Vitamin D supplementation is relatively harmless at reasonable levels, so advising it makes sense.

However, taking country wide averages is begging for confounding factors, right? I bet you could find a higher correlation with lots of things than Vitamin D, for example amount of per capita olive oil usage (Spain and Italy are #2 and #3), time that dinner is eaten (Spain and Italy both tend towards 9pm, vs 6:30 for Germany), etc etc etc. It doesn't prove anything and there isn't a proposed mechanism of action, so it's just correlation bingo at this point.

econcon• 6 years ago

Isn't it that when someone is sick or their health is detriorating, the first thing that happens is that their body stops producing Vitamin D? And since they are not able to go out from that point it further reduces vitamin D?

zamfi2• 6 years ago

This is looking at population-wide measures of Vitamin D deficiency from before COVID-19, so...maybe the argument you're making is that these populations with lower Vitamin D were already sick and thus more prone to COVID-19?

Because they're not measuring post-COVID-exposure Vitamin D levels.

hanniabu2• 6 years ago

maybe the argument you're making is that these populations with lower Vitamin D were already sick and thus more prone to COVID-19?

No, he's making an observation unrelated to covid. At any time you're sick your vitamin D production stops so you're deficient and then on top of that you don't feel good enough to go outside so your further deprived of vitamin D.

ellyagg• 6 years ago

There are a ton of RCTs showing that vitamin D supplementation prevents respiratory infections: https://www.google.com/search?q=vitamin+d+respiratory+infect...

AuryGlenz2• 6 years ago

It takes a while for Vitamin D levels to raise or lower as it’s stored in fat.

lultimouomo• 6 years ago

Old people lack vitamin D. Old people get symptomatic Covid-19. Thus lack of vitamin D causes exposes to Covid-19. NOT.

meiraleal2• 6 years ago

Sick people lack vitamin D. Most people grow sick when they get old. Sickness and autoimmune diseases exposes to Covid-19.

backtracking3• 6 years ago

It is not merely that people are old that makes them susceptible to Covid-19. It is other factors that correlate with age that make them more susceptible. One of those factors could very well be lack of vitamin d.

rustybelt• 6 years ago

I'm guessing wrinkles and gray hair make covid worse, too. Hair dye and facelifts for everyone!

tinus_hn2• 6 years ago

Lol so funny! Better dismiss this out of hand and keep doing nothing!

vmception2• 6 years ago

okay and now explain Italy

kasperni2• 6 years ago

Vitamin D deficiency in Northern Italy is prevalent.

meiraleal2• 6 years ago

Healthy people have healthy levels of Vitamin D. Sick people that ingest VitD will still get sick, vitamin D is a signal of healthiness, not something you can ingest to get healthier. Lose weight, eat meat, sunbath.

alexbanks• 6 years ago

I'd prob delete this.

SketchySeaBeast3• 6 years ago

Vitamin D levels are severely low in the aging population especially in Spain, Italy and Switzerland.

So.... all old people are unhealthy? Across the board?

And are you saying that sunbathing makes you healthy? That would be the closest link to Vitamin D, but I'd suggest sitting around outside doesn't actually mean you're healthy.

yters2• 6 years ago

If you graph covid-19 death rate by latitude, all the warmer latitudes (tropics and southern hemisphere) have significantly lower death rate.

I'd say vitamin D is a proxy for sunnier latitudes.

hellofunk4• 6 years ago

I have been particularly amazed by the reported deaths in Singapore, which has been struggling with multiple outbreaks. To date, only 21 people have died from the virus there, supposedly, despite over 25K infections. That is a remarkable contrast to many other countries. Malaysia, Singapore's only land border neighbor, has nearly the same rate.

backtracking3• 6 years ago

Vietnam has zero reported deaths.

hocuspocus2• 6 years ago

Trivial counter-example: Iceland.

Very few countries can give you an accurate death rate at this point.

If you look at mortality among demographics that were thoroughly tested, you can tell that the age distribution was definitely higher on the Diamond Princess than on the French aircraft carrier. That's about it.

yters2• 6 years ago

That's the other interesting point about graphing by latitude: the very cold countries such as Iceland also have remarkably low death rates.

It is the temperate, winter latitudes that have extremely high death rates.

Here's the graph, you can see for yourself. A very clear trend based on latitude.

https://github.com/yters/covid-19-latitude/blob/master/coron...

I'm not sure why this trend isn't discussed more in the popular media. Seems quite significant, and is very easy to reproduce. Just scrape Google's covid-19 stats and join with a geographic coordinate source. A journalist could do this by hand with an Excel spreadsheet in about half an hour.

If this trend holds up, then as the Northern hemisphere hits summer, the death rates should plummet. On the other hand, in the Southern hemisphere as winter approaches the death rates will go up.

kasperni2• 6 years ago

Trivial counter-example: Iceland.

Iceland actually has Vitamin D deficiency levels comparable to a country such as Greece [1][2]. Supplements such as fish oil liver are in widespread use.

[1] https://www.careacross.com/blog/are-you-getting-enough-vitam...

[2] https://academic.oup.com/ajcn/article/103/4/1033/4662891

ginko• 6 years ago

If that were the case you'd see significantly different infection and mortality numbers for the Nordic countries than for the rest of Europe since many people supplement vitamin D there. Norway, Denmark and Finland seem to be doing relatively well, but Sweden's rates are pretty similar to France's.

KerryJones2• 6 years ago

For those that missed it, this came up recently in another place that links to many more studies relating to it: http://agingbiotech.info/vitamindcovid19/

HN Link: https://news.ycombinator.com/item?id=23119949

fattire• 6 years ago

Posted this previously when the subject came up, but John Campbell, an nurse and educator in Northern England who's been doing daily Youtube updates on global Covid news since January I believe, has put out a few videos from time to time related to vitamin D:

https://www.youtube.com/watch?v=W5yVGmfivAk - 2 months ago

https://www.youtube.com/watch?v=GCSXNGc7pfs - 4 weeks ago

https://www.youtube.com/watch?v=K-mHCn74E5o - 1 week ago

https://www.youtube.com/watch?v=Bga_qG30JyY - 4 days ago

https://www.youtube.com/watch?v=1fxw3nTZYlA - today

He offers published studies as evidence to suggest vitamin D deficiency may play a partial role in explaining higher mortality rates among people with darker skin (other important social disparities notwithstanding).

Eric_WVGG• 6 years ago

There was an article here just the other week suggesting that vitamin D could very well be not a supplement to, but rather a marker of, good health.

If it is true that Vitamin D is a marker of good health, and people with high levels of Vitamin D do well against the virus, this study suddenly turns out to be a lot less interesting.

https://news.ycombinator.com/item?id=23086211

dwheeler• 6 years ago

This is a quick study, and there are lots of flaws in it.

That said, vitamin D deficiency is a real thing, and is especially common in as you get older. Vitamin D supplements are also pretty cheap.

It's not unusual to have to make quick decisions with little information. This study is enough to justify making sure that you have enough vitamin D, and probably to take reasonable dosages of supplements. You have to be careful, you can kill yourself with overdosages of vitamin D... it is a hormone and not technically a vitamin.

Vitamin D supplemenation is an easy and cheap thing to do, not harmful as long as you don't overdose, and there is some evidence here that could be helpful. So it is reasonable for the moment to take Vitamin D supplements, at least until we've had time to do more detailed studies.

ColanR2• 6 years ago

There have been other studies into the use of Vitamin D to prevent the flu, where it has been shown to be very effective. I think there's a decent connection between contracting the flu and contracting Covid?

dukha• 6 years ago

I don't know about other countries, but in Russia blood test for vitamin deficiency costs about $40 and can be D done in any lab, which are very common in cities. Simple thing to do is to go and test for do you really have deficiency or not and then proceed with supplements program. That's how I identified my deficiency and successfully fixed it by taking oral supplements.

ColanR2• 6 years ago

Prior discussions that seem similar enough to be relevant:

https://news.ycombinator.com/item?id=23023703

https://news.ycombinator.com/item?id=22463713

https://news.ycombinator.com/item?id=23119949

https://news.ycombinator.com/item?id=22582387

https://news.ycombinator.com/item?id=23167802

https://news.ycombinator.com/item?id=22600685

https://news.ycombinator.com/item?id=23083619

https://news.ycombinator.com/item?id=23069001

https://news.ycombinator.com/item?id=22632542

https://news.ycombinator.com/item?id=23118830

https://news.ycombinator.com/item?id=22621191

https://news.ycombinator.com/item?id=23040868

https://news.ycombinator.com/item?id=23129529

https://news.ycombinator.com/item?id=23137546

https://news.ycombinator.com/item?id=23102020

https://news.ycombinator.com/item?id=22594740

https://news.ycombinator.com/item?id=22529035

https://news.ycombinator.com/item?id=20014940

https://news.ycombinator.com/item?id=23155437

https://news.ycombinator.com/item?id=23123222

https://news.ycombinator.com/item?id=22600709

https://news.ycombinator.com/item?id=20776603

https://news.ycombinator.com/item?id=20020134

https://news.ycombinator.com/item?id=22675466

https://news.ycombinator.com/item?id=22104904

https://news.ycombinator.com/item?id=23150839

zapf• 6 years ago

Urgh...

https://en.wikipedia.org/wiki/Correlation_does_not_imply_cau...

https://www.goodreads.com/book/show/195024.A_Mathematician_R...

cameldrv• 6 years ago

It may be that people with low Vitamin D are low because of a combination of their skin tone and the amount of sunlight they get. This causes them to also be low on Nitric Oxide. You see the low Vitamin D as a marker, but it might not be the true cause.

The shelter in place is causing people to get less sunlight, so until we know more, I'd focus on getting more sun.

m463• 6 years ago

I think people should be aware of sunlight and vitamin D.

Lots of old people never go out in the sun, and that could be a huge contributing factor.

From wikipedia[1]

Adequate amounts of vitamin D can be produced with moderate sun exposure to the face, arms and legs, averaging 5–30 minutes twice per week, or approximately 25% of the time for minimal sunburn.

[1] https://en.wikipedia.org/wiki/Vitamin_D#Synthesis_in_the_ski...

cameronh90• 6 years ago

For what it’s worth, I had an extremely severe vitamin D deficiency (8 nmol/L - not a mistake!) measured in mid summer, despite going outside 5hrs a week on my commute by bicycle. I’m pale and Scottish.

I now take a supplement every few days and my level is up to around 150. I feel much better now.

Point is, if anyone’s reading this and thinking they can’t be deficient because they are outside a lot, that is not a always the case.

stx• 6 years ago

Adequate sleep is very important to immune function. I should sleep more at night but its my most productive time. I started taking some vitamin D when all this started because a doctor recommended it. Granted I think if I just go outside into the sun a little bit I should have enough.

Role of Vitamin D in the prevention of Coronavirus 2019 infection and mortality

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