[BostonCard]

Columbia went ahead and screened all its pre-partum women for COVID-19 (215 in all).  They identified 29 asymptomatic women who were positive for SARS-CoV-2 (and 33 overall; 4 who had symptoms, plus maybe 3 of the asymptomatic women who developed symptoms).

https://www.nejm.org/doi/full/10.1056/NE...6?query=RP

Pregnant women are a different patient population than the population at large, but if the percentage of asymptomatic patients is anywhere nearly as large as it is in pregnant women, that dramatically changes the calculus around this infection.  Previously, the assumption was that somewhere between 1/4 and 3/4 of patients infected with SARS-CoV-2 were symptomatic.  However, this study would suggest that (at least in pregnant women) more like 80% of the women infected with the virus remain asymptomatic, and thus the infectious mortality rate would be much lower than previously measured (more along the lines of 0.1 to 0.4% than 1 - 4%).

BC

[BostonCard]

Columbia went ahead and screened all its pre-partum women for COVID-19 (215 in all).  They identified 29 asymptomatic women who were positive for SARS-CoV-2 (and 33 overall; 4 who had symptoms, plus maybe 3 of the asymptomatic women who developed symptoms).

https://www.nejm.org/doi/full/10.1056/NE...6?query=RP

Pregnant women are a different patient population than the population at large, but if the percentage of asymptomatic patients is anywhere nearly as large as it is in pregnant women, that dramatically changes the calculus around this infection.  Previously, the assumption was that somewhere between 1/4 and 3/4 of patients infected with SARS-CoV-2 were symptomatic.  However, this study would suggest that (at least in pregnant women) more like 80% of the women infected with the virus remain asymptomatic, and thus the infectious mortality rate would be much lower than previously measured (more along the lines of 0.1 to 0.4% than 1 - 4%).

BC

[2006alum]

Very interesting, and good news if true! There's a few caveats that make me a bit skeptical of being able to extrapolate to that extent:

Of the 29 women who had been asymptomatic but who were positive for SARS-CoV-2 on admission, fever developed in 3 (10%) before postpartum discharge (median length of stay, 2 days). Two of these patients received antibiotics for presumed endomyometritis (although 1 patient did not have localizing symptoms), and 1 patient was presumed to be febrile due to Covid-19 and received supportive care. One patient with a swab that was negative for SARS-CoV-2 on admission became symptomatic postpartum; repeat SARS-CoV-2 testing 3 days after the initial test was positive.

If I'm reading this correctly, of the 29 asymptomatic women, 3 developed symptoms within 2 days, so we're really only talking 26 of 33. At least one patient who tested negative actually had it (and became symptomatic), so then we're talking 26 of 34 (that's 75%, within the prior estimated range). And none of the patients were tracked after postpartum discharge (median length of stay 2 days), so in theory some could have (and probably did) develop symptoms later.

This is exactly the kind of data we need, but when the virus has a median pre-symptomatic infection window of 5 days and infected individuals can go as long as two weeks before showing symptoms, I feel like it's a bit tenuous to extrapolate so far from a testing and symptom presentation window of just 2-3 days?

[2006alum]

Very interesting, and good news if true! There's a few caveats that make me a bit skeptical of being able to extrapolate to that extent:

Of the 29 women who had been asymptomatic but who were positive for SARS-CoV-2 on admission, fever developed in 3 (10%) before postpartum discharge (median length of stay, 2 days). Two of these patients received antibiotics for presumed endomyometritis (although 1 patient did not have localizing symptoms), and 1 patient was presumed to be febrile due to Covid-19 and received supportive care. One patient with a swab that was negative for SARS-CoV-2 on admission became symptomatic postpartum; repeat SARS-CoV-2 testing 3 days after the initial test was positive.

If I'm reading this correctly, of the 29 asymptomatic women, 3 developed symptoms within 2 days, so we're really only talking 26 of 33. At least one patient who tested negative actually had it (and became symptomatic), so then we're talking 26 of 34 (that's 75%, within the prior estimated range). And none of the patients were tracked after postpartum discharge (median length of stay 2 days), so in theory some could have (and probably did) develop symptoms later.

This is exactly the kind of data we need, but when the virus has a median pre-symptomatic infection window of 5 days and infected individuals can go as long as two weeks before showing symptoms, I feel like it's a bit tenuous to extrapolate so far from a testing and symptom presentation window of just 2-3 days?

[dabigv13]

Very interesting. But only had median two days of follow up after the swab, would be more interesting to me if they continued to follow those patients after DC to see if they developed symptoms.

Perhaps pregnant women may be less likely to have severe disease because they are less likely to get a cytokine storm because their immune systems are attenuated to reduce risk of immune response to fetal tissue. This theory has no good evidence for it but could explain the data. The case of the immunocompromised cruise ship passenger who shed virus for weeks and weeks without symptoms comes to mind as well.

[dabigv13]

Very interesting. But only had median two days of follow up after the swab, would be more interesting to me if they continued to follow those patients after DC to see if they developed symptoms.

Perhaps pregnant women may be less likely to have severe disease because they are less likely to get a cytokine storm because their immune systems are attenuated to reduce risk of immune response to fetal tissue. This theory has no good evidence for it but could explain the data. The case of the immunocompromised cruise ship passenger who shed virus for weeks and weeks without symptoms comes to mind as well.

[BostonCard]

I agree with you; your caveats are well taken.

The biggest to me is that pregnant women are by definition pre-menopausal and consequently lower risk.  In addition, pregnancy has big effects on the immune system (it tends to somewhat depress the immune system, so it will make symptoms less prominent and in the context of COVID-19 that might be protective since there is some evidence that worse disease is due to an overeager immune system). The other major issue is that presumably the highly symptomatic group with moderate/severe disease is probably hospitalized before they show up in labor.

So, yeah, interpret with caution, and don't overly extrapolate.

Still, these data points are important.

BC

[BostonCard]

I agree with you; your caveats are well taken.

The biggest to me is that pregnant women are by definition pre-menopausal and consequently lower risk.  In addition, pregnancy has big effects on the immune system (it tends to somewhat depress the immune system, so it will make symptoms less prominent and in the context of COVID-19 that might be protective since there is some evidence that worse disease is due to an overeager immune system). The other major issue is that presumably the highly symptomatic group with moderate/severe disease is probably hospitalized before they show up in labor.

So, yeah, interpret with caution, and don't overly extrapolate.

Still, these data points are important.

BC

[burger]

Fun with math:

This study: 33/215 = 15.3% of pregnant women infected.

For all of New York City: 106,763 positive tests / 8.4 million residents= 1.3%

That implies that there are 12 times as many infections as reported positives (with lots of assumptions about susceptibility, behavior, etc.).  More than a couple of studies have produced estimates along those lines.  I was skeptical earlier, but now I'm starting to think that multiplying positive cases by ~10 gives you a decent estimate of the number infected.  In the US that would put the number at ~6 million.  That feels kind of high to me, but I've been assuming an infection mortality rate around 1-2%.  6 million cases in the US makes sense if the mortality rate is an order of magnitude lower.

Anyway, it'll be interesting to see what the multipliers end up being once we get serology tests.

[burger]

Fun with math:

This study: 33/215 = 15.3% of pregnant women infected.

For all of New York City: 106,763 positive tests / 8.4 million residents= 1.3%

That implies that there are 12 times as many infections as reported positives (with lots of assumptions about susceptibility, behavior, etc.).  More than a couple of studies have produced estimates along those lines.  I was skeptical earlier, but now I'm starting to think that multiplying positive cases by ~10 gives you a decent estimate of the number infected.  In the US that would put the number at ~6 million.  That feels kind of high to me, but I've been assuming an infection mortality rate around 1-2%.  6 million cases in the US makes sense if the mortality rate is an order of magnitude lower.

Anyway, it'll be interesting to see what the multipliers end up being once we get serology tests.

[BostonCard]

Agreed, it augurs for a higher prevalence and lower mortality rate with some caveats:
a) again, pregnant women are different than the population at large
b) there is a lot of heterogeneity in the infection rate across NYC.  Columbia is located in Washington heights, where the infection rate appears to be higher than the rest of NY City (but probably not 15%).

But there are a lot of datapoints out there that are starting to point towards a disease that is maybe more widespread and less lethal.  Serology testing can't come soon enough.

BC

[BostonCard]

Agreed, it augurs for a higher prevalence and lower mortality rate with some caveats:
a) again, pregnant women are different than the population at large
b) there is a lot of heterogeneity in the infection rate across NYC.  Columbia is located in Washington heights, where the infection rate appears to be higher than the rest of NY City (but probably not 15%).

But there are a lot of datapoints out there that are starting to point towards a disease that is maybe more widespread and less lethal.  Serology testing can't come soon enough.

BC

[oregontim]

In addition, pregnancy has big effects on the immune system (it tends to somewhat depress the immune system, so it will make symptoms less prominent and in the context of COVID-19 that might be protective since there is some evidence that worse disease is due to an overeager immune system). 


BC

Thanks BC for your thread here. I'm selfishly especially concerned for my youngest daughter, who is five months pregnant right now (also Stanford grad, FWIW) ... this looks like some reassurance, a touch of good news among all the bad, for the effects of pregnancy. Am I reading this right?

[oregontim]

In addition, pregnancy has big effects on the immune system (it tends to somewhat depress the immune system, so it will make symptoms less prominent and in the context of COVID-19 that might be protective since there is some evidence that worse disease is due to an overeager immune system). 


BC

Thanks BC for your thread here. I'm selfishly especially concerned for my youngest daughter, who is five months pregnant right now (also Stanford grad, FWIW) ... this looks like some reassurance, a touch of good news among all the bad, for the effects of pregnancy. Am I reading this right?

[BostonCard]

In addition, pregnancy has big effects on the immune system (it tends to somewhat depress the immune system, so it will make symptoms less prominent and in the context of COVID-19 that might be protective since there is some evidence that worse disease is due to an overeager immune system). 


BC

Thanks BC for your thread here. I'm selfishly especially concerned for my youngest daughter, who is five months pregnant right now (also Stanford grad, FWIW) ... this looks like some reassurance, a touch of good news among all the bad, for the effects of pregnancy. Am I reading this right?

There have been several studies showing the outcome of pregnant women with Covid-19.  So far, the data has been reassuring.  But of course every case is different.

BC

[BostonCard]

In addition, pregnancy has big effects on the immune system (it tends to somewhat depress the immune system, so it will make symptoms less prominent and in the context of COVID-19 that might be protective since there is some evidence that worse disease is due to an overeager immune system). 


BC

Thanks BC for your thread here. I'm selfishly especially concerned for my youngest daughter, who is five months pregnant right now (also Stanford grad, FWIW) ... this looks like some reassurance, a touch of good news among all the bad, for the effects of pregnancy. Am I reading this right?

There have been several studies showing the outcome of pregnant women with Covid-19.  So far, the data has been reassuring.  But of course every case is different.

BC

[akiddoc]

I would not be surprised at all if 6 - 10 million Americans have been infected. I think I have mentioned here several times (or maybe it was on CSR) that kids are well known to have a brobdingnagian number of symptom free viral infections. There is no reason to think this virus is so unique that we wouldn't see that. 

Pregnant women are unique in their response to infectious disease. They seem impervious to the illnesses that their older kids bring home, but they can get into a lot of trouble with bacterial sepsis. I'm not an Ob- Gyn or an ID specialist, but I've always thought that this is so because their inflammatory response is muted. They catch the viruses but do not show it. Which would certainly make sense in this instance. 

When schools are reopened this virus will be widely disseminated. No way around it. In every classroom in America there is a greater than 99% chance that some kid is shedding a virus everyday of the school year. Symptomatic or not. Kids are super spreaders. There is good and bad there. Herd immunity will improve. But many parents and grandparents will get seriously ill on a continuing basis.

[akiddoc]

I would not be surprised at all if 6 - 10 million Americans have been infected. I think I have mentioned here several times (or maybe it was on CSR) that kids are well known to have a brobdingnagian number of symptom free viral infections. There is no reason to think this virus is so unique that we wouldn't see that. 

Pregnant women are unique in their response to infectious disease. They seem impervious to the illnesses that their older kids bring home, but they can get into a lot of trouble with bacterial sepsis. I'm not an Ob- Gyn or an ID specialist, but I've always thought that this is so because their inflammatory response is muted. They catch the viruses but do not show it. Which would certainly make sense in this instance. 

When schools are reopened this virus will be widely disseminated. No way around it. In every classroom in America there is a greater than 99% chance that some kid is shedding a virus everyday of the school year. Symptomatic or not. Kids are super spreaders. There is good and bad there. Herd immunity will improve. But many parents and grandparents will get seriously ill on a continuing basis.

[OutsiderFan]

To add some anecdotal support to the 10x assumption...

Three supporting pieces of evidence:

1. Tweet thread from ER Doctor in NY saying only those who come to hospital are tested, and many with symptoms are told to stay home.

2. A fan on Cal Rivals board had all the symptoms - including 10 day fever and was told to stay home; never tested.

3. A friend of a friend had all the symptoms, tried going to see doctor and was told to stay home because she was not sick enough; never tested.

Basically, as long as you can still breathe you are told to stay home, which means you don't get tested. I'm operating on the 10x infected assumption, but that's still just 2% of the population. It just once again highlights how important testing and contact tracing is going to be.

[OutsiderFan]

To add some anecdotal support to the 10x assumption...

Three supporting pieces of evidence:

1. Tweet thread from ER Doctor in NY saying only those who come to hospital are tested, and many with symptoms are told to stay home.

2. A fan on Cal Rivals board had all the symptoms - including 10 day fever and was told to stay home; never tested.

3. A friend of a friend had all the symptoms, tried going to see doctor and was told to stay home because she was not sick enough; never tested.

Basically, as long as you can still breathe you are told to stay home, which means you don't get tested. I'm operating on the 10x infected assumption, but that's still just 2% of the population. It just once again highlights how important testing and contact tracing is going to be.

[BostonCard]

To add some anecdotal support to the 10x assumption...



Three supporting pieces of evidence:



1. Tweet thread from ER Doctor in NY saying only those who come to hospital are tested, and many with symptoms are told to stay home.



2. A fan on Cal Rivals board had all the symptoms - including 10 day fever and was told to stay home; never tested.



3. A friend of a friend had all the symptoms, tried going to see doctor and was told to stay home because she was not sick enough; never tested.



Basically, as long as you can still breathe you are told to stay home, which means you don't get tested. I'm operating on the 10x infected assumption, but that's still just 2% of the population. It just once again highlights how important testing and contact tracing is going to be.

No doubt there are a lot of patients out there who have COVID-19 and have never been tested.  We know that based on reported deaths the infected rate is higher than reported.  The question is how much higher.  Is it 10x higher?  NY has about 10,000 deaths (plus some that are unreported) and 200,000 reported cases.  If the ultimate CFR is 1 - 2% that implies that there are at least 500,000 to 1,000,000 symptomatic infected patients (at least because some infected patients haven't died yet).  If you presume that about half of patients who are infected are symptomatic, that means up to 2 million infected people in New York, out of a total population of <20 million, so 10% of the population.

I think it is somewhat unlikely that more than half of the population in New York has been infected silently (it would be great if it has been), but I can easily believe that 2 million infected with an ultimate CFR of 0.5% to 1%, and maybe lower.

BC

[BostonCard]

To add some anecdotal support to the 10x assumption...



Three supporting pieces of evidence:



1. Tweet thread from ER Doctor in NY saying only those who come to hospital are tested, and many with symptoms are told to stay home.



2. A fan on Cal Rivals board had all the symptoms - including 10 day fever and was told to stay home; never tested.



3. A friend of a friend had all the symptoms, tried going to see doctor and was told to stay home because she was not sick enough; never tested.



Basically, as long as you can still breathe you are told to stay home, which means you don't get tested. I'm operating on the 10x infected assumption, but that's still just 2% of the population. It just once again highlights how important testing and contact tracing is going to be.

No doubt there are a lot of patients out there who have COVID-19 and have never been tested.  We know that based on reported deaths the infected rate is higher than reported.  The question is how much higher.  Is it 10x higher?  NY has about 10,000 deaths (plus some that are unreported) and 200,000 reported cases.  If the ultimate CFR is 1 - 2% that implies that there are at least 500,000 to 1,000,000 symptomatic infected patients (at least because some infected patients haven't died yet).  If you presume that about half of patients who are infected are symptomatic, that means up to 2 million infected people in New York, out of a total population of <20 million, so 10% of the population.

I think it is somewhat unlikely that more than half of the population in New York has been infected silently (it would be great if it has been), but I can easily believe that 2 million infected with an ultimate CFR of 0.5% to 1%, and maybe lower.

BC

[Leftcoast]

Back to the original post, one of my original suite mates is works in neonatology at a local research hospital (I will leave this purposefully vague).  Our group does a once every two weeks check-in during the CV shutdown and our next call is coming up.  Any questions for him?

At our last check-in (early March) he said that there was limited research data available but early evidence showed no transmission from mother to child pre-birth (vertical transmission).  After birth a small number of babies showed evidence of anti-bodies but most others did not.  One early study showed possible transmission after birth (horizontal transmission) but also some anomalies - they needed more data.

[Leftcoast]

Back to the original post, one of my original suite mates is works in neonatology at a local research hospital (I will leave this purposefully vague).  Our group does a once every two weeks check-in during the CV shutdown and our next call is coming up.  Any questions for him?

At our last check-in (early March) he said that there was limited research data available but early evidence showed no transmission from mother to child pre-birth (vertical transmission).  After birth a small number of babies showed evidence of anti-bodies but most others did not.  One early study showed possible transmission after birth (horizontal transmission) but also some anomalies - they needed more data.