TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine, and Rick Lange, MD, president of the Texas Tech University Health Sciences Center in El Paso, look at the top medical stories of the week. A transcript of the podcast is below the summary.

This week’s topics include blood clots and COVID, neuropsychiatric sequelae of COVID, age at natural menopause in the U.S., and excess pandemic deaths.

Program notes:

0:40 Excess deaths in U.S. during pandemic

1:40 Think about the next pandemic

2:36 At highest risk for COVID complications

3:35 VTE following COVID

4:38 0.8% of those with a positive result

5:39 Don’t need prophylaxis in outpatients

6:20 Neuropsychiatric outcomes after COVID

7:21 If you were in the ICU

8:20 COVID and CNS

8:55 Age at natural menopause

9:55 Mean age increased

10:55 Improvements in health and nutrition?

11:20 Longer you delay menopause

12:22 End

Transcript:

Elizabeth Tracey: How often do blood clots form in people infected with SARS-CoV-2?

Rick Lange, MD: Excess deaths during the pandemic.

Elizabeth: How has age at menopause changed?

Rick: And a longer look at COVID-19 and neuropsychiatric outcomes.

Elizabeth: That’s what we’re talking about this week on TT HealthWatch, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I’m Elizabeth Tracey, a Baltimore-based medical journalist.

Rick: And I’m Rick Lange, president of Texas Tech University Health Sciences Center in El Paso, where I’m also dean of the Paul L. Foster School of Medicine.

Elizabeth: Rick, we’ve got three COVIDs and one not. Which of them would you like to start with?

Rick: Let’s start with mine, talking about excess deaths from COVID-19, and actually other causes, from March 2020 to January 2021.

Elizabeth: And that’s in JAMA.

Rick: You know, we had previously talked about early on it looked like there was an excess in related deaths during the pandemic. This is obviously a longer look at that. From March 1st, 2020 to January 2nd, 2021, the U.S. experienced 2.8 million deaths, 23% more than was expected. Many of these were related to COVID. In fact, COVID ended up being the third most leading cause of deaths, but there were other causes as well that increased — heart disease, Alzheimer’s, and diabetes as well. What that means is there were over 500,000 excess deaths during this particular time period. It’s estimated that this cost about $16 trillion to the economic output of the U.S.

We need to be thinking about future pandemics, because we were very poorly prepared for this particular one, and even though a couple of years ago we had predicted that a pandemic was likely to occur. This information ought to spur us to think about not the last pandemic, but what the future pandemic might look like, how it affects us, and how we can decrease excess mortality and the economic impact as well.

Elizabeth: Well, it also points to the fact that a lot of the official government tallies were really pretty far off and the officially reported deaths relative to COVID have been under-reported. The other thing, I think, it makes some sense relative to heart disease and stroke and that sort of thing, and even cancer, that COVID might have complicated care for those, but I guess I’d ask you to speculate on why you think Alzheimer’s disease deaths would have increased.

Rick: Elizabeth, I think there’s a couple of things. This has complicated care, not only care individually — chronic care for diabetes and heart disease, and cancer screening, we know that all of those have floundered because of the pandemic, but also care for individuals that have Alzheimer’s and dementia.

We also know, by the way, these are the individuals that are at highest risk not only of developing COVID, but also having COVID-related complications, especially if they’re in a nursing home or in a skilled nursing facility where people may not realize they have COVID, but nevertheless die as a result. COVID could either directly or indirectly affect mortality across these age groups.

The other thing I failed to mention is it actually makes the inequities in healthcare even more evident. For example, the African Americans had a particularly higher excess mortality than whites. This just exacerbates or highlights some of the inequities we’re already seeing.

Elizabeth: I think one of the other conclusions that I think is disturbing about this data is also the number of kids who have been left with one or both parents having died of COVID.

Rick: Your point is well-taken. Not only did they die, but they died in the circumstances we’ve talked about that are very traumatic, obviously, for the family, not being able to visit the individual, not being able to mourn or grieve or even to have funeral services, memorial services. It’s affected us in more ways than we care to recall.

Elizabeth: Let us remain in JAMA and let’s turn to a research letter. This one is taking a look at the issue of venous thromboembolism or blood clots — and now I’m going to just refer to it as VTE — in adults who tested for SARS-CoV-2. This is a gigantic database from Kaiser Permanente in Northern California.

As we’ve witnessed so many times, they retrospectively analyzed 220,588 adult members of their health plan who tested for SARS-CoV-2 by PCR. They also took a look at incidence and timing of 30-day VTE using diagnosis codes, new anticoagulant prescriptions, and VTE encounters with a management service. They ended up with 26,000-plus, about 12% with a positive result.

Then within 30 days of testing, VTE was diagnosed in 198 of the patients with a positive SARS-CoV-2 test result and 1,008 patients with a negative result. Interestingly — I think this is really interesting — that was 0.8% of the people with a positive infection and 0.5% of those without.

They also took a look at those who required hospitalization secondary to their positive test. Among those, it was 4.7 versus 1.6 cases per 1,000 individuals tested. Ultimately what they showed is that there is an increase in VTE among those who are hospitalized, but not those who are outpatients.

Rick: Bingo. We’ve talked before about how this COVID infection seems to increase the propensity to clot, and we focused primarily on the inpatient setting. We’ve not examined that in the outpatient setting, and the reason why it’s important is because if there is a higher incidence, then we need to put these people on appropriate medications to prevent that, that is prophylaxis.

The nice thing is in this large study, what they showed is that even though you test positive for COVID and you have an increased risk, it’s only among the inpatients. It doesn’t look like we need to give them any special therapy.

Now, we do need to address the inpatient population. There are studies going on about the best way to do that, whether it’s just antiplatelet agents like aspirin, whether they need to give an anticoagulant, and if so, which one and at what dose. But the nice thing is on the outpatient basis it doesn’t appear that they require any special therapy.

Elizabeth: Right. Then would you say that VTE is a proxy for more severe disease and what I’m going to call sort of the second phase of COVID infection?

Rick: Well, it could be more severe disease. The other explanation is in a hospital setting you’re less likely to be mobile as well, so the combination of those two things. The immobility, also, of having COVID may contribute, so I think there’s probably more than one component.

Elizabeth: OK. Let’s turn to the Lancet. This is a look at neuropsychiatric outcomes relative to COVID-19 infection.

Rick: You just talked about a large patient population dealing with VTE and examining that. This is an even larger population, looking at health records of over 81 million patients through electronic medical records. They identified almost 250,000 of those that had a diagnosis of COVID.

Then they looked at neurologic and psychiatric conditions, 14 different ones that occurred over a 6-month period after they developed COVID infection. We’re talking about things like intracranial hemorrhage, and stroke, and Parkinson’s, and Guillain-Barré, anxiety disorders, substance abuse disorders, and even insomnia. What they discovered is that individuals that had COVID infection, about a third of them over that 6-month period had one or more of these neurological or psychiatric diseases.

Furthermore, it seemed like there was a gradation. If you happened to be hospitalized — as about half of the individuals did, and half of those that was the first time they’d had that diagnosis, and even more so if you were in the intensive care unit — you were two to three times more likely to develop one or more of those, things like dementia — increased risk — mood disorders — increased risk as well — and increased risk of stroke and intracranial hemorrhage.

Elizabeth: OK. So what does this mean?

Rick: Well, the first thing you might ask is, “Is this just a manifestation of the fact they were in the hospital and you could develop these things?” Well, they compared it to people that had the flu, or people that had a respiratory illness — or even people that had other conditions like infection, or kidney stones, or a fracture or even PE — and it appears that this is in fact related to the COVID, not just being hospitalized.

What does this mean? First of all, we need to realize that a third of individuals are going to have neurologic or psychiatric disorders, address that, and to treat that. I think that’s really the major issue.

Elizabeth: I think I’m really curious about the presence of SARS-CoV-2 in the CNS [central nervous system]. I’m sure this is being studied. It’s just that that hasn’t come to the top, for me, anyway. Are you familiar with anything that addresses that?

Rick: Well, there are some. There is evidence that shows that it clearly caused encephalitis, and so it can infect brain tissue, but some of this may not actually be a true infection. Some of it may be due to immune responses. It may not be neurologic, but it’s psychologic because of the stress, the privation, and the isolation.

Elizabeth: And more to come, no doubt, as part of this whole long COVID syndrome and what that all might entail. Finally, let’s go back to JAMA. This is something that I’ve been watching with some interest. In this case, they’re taking a look at trends in age at natural menopause and the reproductive lifespan among U.S. women between 1959 and 2018.

What’s been happening that people have noted for quite a while is there is an increasing age at natural menopause that’s been reported worldwide. This study took a look at what turned out to be, initially, the precursor to NHANES, so the National Health Examination Survey and then the National Health and Nutrition Examination Surveys, and they took a look at these 60-year trends in age at natural menopause and reproductive lifespan.

All of the participants self-reported their ages at menarche and menopause. All women aged 40 to 74 years with natural menopause and no missing age data were included in this analysis. They ended up with a total of 7,773 women and overall they found that the mean age at natural menopause increased from 48.4 years to 49.9 years. Their mean reproductive lifespan increased from 35 years to 37.1 years, and also, the age at menarche decreased from 13.5 years of age to 12.7.

They speculate, the authors, that this might be due to positive things, better nutrition. I’m not sure that it’s really a positive that this has actually increased. One thing that we’ve noted in the past is that this younger age at menarche for young girls is related to BMI, and that the heavier girls are getting, the earlier they end up at that particular stage of life, and that also may be true at the end.

Rick: Elizabeth, I agree, and it is somewhat interesting. I wasn’t quite sure why you chose this till I gave it a little bit more thought. But as you’ve mentioned, the mean age of natural menopause has increased by about 1.5 years now and the mean reproductive span has increased by 2.1 years because menarche’s occurring earlier.

By the way, according to your hypothesis that it may have to do with some improvements in health and nutrition, it should note that in the adjusted models that being Black or Hispanic, being in poverty, being a smoker, or having hormone therapy use lowered your ages of menopause. Conversely, people that were better educated or on oral contraceptives had later menopause.

What does that have to do with health overall? Well, we know that the longer you delay menopause, the less heart disease and the less cardiovascular disease there are in women. Conversely, the more reproductive years you have, the more likely you are to develop breast cancer, endometrial cancer, or ovarian cancer. The follow-up will be, is there an overall benefit to women or not?

Elizabeth: Yeah. The other thing that I think is probably a factor that is not identified or even intimated in this particular letter is, what about the environmental exposure to endocrine disruptors and how that also might be impacting on this?

Rick: You’re right, so we’ve identified some of the factors. Nutrition some, access to healthcare is probably likely, and environmental factors as well, so a very interesting article. I’m glad you picked it.

Elizabeth: Could be a canary, one of the many that are out there. On that note, that’s a look at this week’s medical headlines from Texas Tech. I’m Elizabeth Tracey.

Rick: I’m Rick Lange. Y’all listen up and make healthy choices.

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