JPMorgan Chase ventures into primary care clinics for employees

 JPMorgan Chase is jumping into primary care and is piloting office-based clinics for employees in the Columbus, Ohio area.

The financial institution is teaming up with healthcare startup Vera Whole Health and Central Ohio Primary Care to open three new on-site advanced primary care centers across the company’s Columbus offices (Polaris, Easton and Brooksedge).

More than 20,000 JPMorgan Chase employees will have access to a full suite of comprehensive in-person and virtual health and wellness services, according to the companies.

Vera Whole Health and COPC will provide the same advanced primary care services at two near-site care centers in Dublin and Westerville to serve employees and the more than 15,000 spouses/domestic partners and children enrolled in JPMorgan Chase’s benefit plan.

The new primary care service is part of a collaboration between the company’s benefits team and Morgan Health, the healthcare-focused arm of JPMorgan Chase. At the J.P. Morgan Healthcare Conference in January, the bank announced it was partnering with Vera to test the company's services for 38,000 employees. A year ago, in August 2021, Morgan Health invested $50 million into Vera Whole Health.

JPMorgan launched the new firm after the collapse of Haven, its joint venture with Amazon and Berkshire Hathaway.

“We know our employees and their families are looking to ease the anxiety, stress and inconvenience of managing their health. As we look at how to support and empower employees with their health choices, our goal is to make it as easy and straightforward as possible to receive the highest quality and most comprehensive care services available at any point,” Daniela Nese, head of U.S. Benefits for JPMorgan Chase, said in a statement.

As part of the collaboration, Vera, part of the larger apree health brand, and COPC will manage and staff the on-site and near-site care centers. Vera offers a holistic primary care model that incorporates coaching, behavioral health specialists, and wellness alongside a primary care physician to form an integrated care team.

COPC is one of the largest independent physician-owned primary groups in Ohio and the U.S. and currently serves many Columbus-based JPMorgan Chase employees and their families, according to the company.

All JPMorgan Chase employees will have access to a range of healthcare services across each of the three on-site care centers, including treatments for sore throat, ear aches, cough and colds as well as headaches, dizziness and other neurological concerns.

Services also will address chest pain, palpitations and other cardiovascular concerns, stomach aches, pains and upset stomach, urinary tract infections, muscle aches and pains, blood or other lab draws and allergy shots, travel immunizations and other vaccines.

Employees and their families enrolled in JPMorgan Chase’s health plan will get access to advanced primary care services at on-site and near-site care centers, such as comprehensive wellness exams, behavioral health screenings, virtual primary care consultation and support services and chronic disease management and treatment. 

The companies plan to add more digital tools and health services in the coming months.

“The partnership with Vera and COPC is deeply rooted in our vision and mission to provide a better health care experience for our employees, and in turn, to provide a realistic path forward for other employers to implement these same value-based programs,” Dan Mendelson, CEO of Morgan Health, said in a statement. “By establishing provider partnerships based on improving health outcomes for employees, we can make in-roads across communities and markets to provide higher quality, more affordable and equitable care to JPMorgan Chase employees and more than 150 million Americans who depend on employer-sponsored coverage.”

https://www.fiercehealthcare.com/providers/jpmorgan-chase-teams-vera-whole-health-open-primary-care-clinics-employees

Patient preference survey finds drop in telehealth use, ER visits compared to 2021

 Fewer Americans are using telehealth compared to earlier in the pandemic, a new survey has found.

Stericycle Communication Solutions, a patient engagement solutions vendor, released the results of its third annual survey, which reached more than 1,000 adults. It found that 45% of respondents had used telehealth in the last year, compared to 78% in 2021 and 71% in 2020. It also found 93% of respondents had their last primary care visit in person. That is likely due to consumer preference, not a lack of telehealth availability, Stericycle’s senior vice president Matt Dickson told Fierce Healthcare. 

“We’ve seen a precipitous decline in telehealth appointments,” Dickson noted. “Overall, the preference certainly has been to lean much more heavily to in-person care.” 

Among those that had used telehealth, younger adults were much more likely to have done so. These consumers (ages 18 to 34) were also more likely to seek care at nontraditional venues like retail health clinics and to display less provider loyalty than older generations (age 55 and up). 

The vast majority of those who sought care outside the typical clinic said they would again. However, nearly half said their experience felt disjointed from the rest of their medical care. 

Respondents of all ages prioritize location and convenience when seeking care, followed by insurance coverage and the quality of the provider. Additionally, online scheduling and positive reviews matter more to younger adults. 

Younger adults reported being more mentally impacted by the pandemic and more likely to seek behavioral health care, with telehealth remaining popular for therapy and primary care visits. 

“Consumers are very quickly figuring out what kinds of appointments can be done successfully virtually,” Dickson said. 

Home care remains an “untapped resource,” per the report, with most respondents not having used the service in the past year. Of those that did, most were very satisfied. As with telehealth, younger adults were more likely to seek the service. 

High costs were a deterrent to care, with a third of adults delaying some type of care in the past year for this reason. Half were 18- to 34-year-olds, compared to 16% of those 55 and older. Besides costs, a lack of appointments, not feeling safe to get in-person care and forgetting to schedule were other reasons for delayed care.

There was a notable drop—less than half—in the number of people receiving ER care compared to 2021. Those who did visit the ER most often were younger adults, with ambulances shrinking as the most popular method of arrival. Of those who needed follow-up care following their visit, a third didn’t get a referral.

The findings suggest that providers need to streamline appointment scheduling and have better patient outreach to ensure continuity of care and patient satisfaction, the report authors wrote.

https://www.fiercehealthcare.com/digital-health/stericycle-survey-patient-preferences-care

YouTube Health invites medical professionals to apply for health product features

 YouTube Health has unlocked a new door for health professionals to bring high quality health information into the homes of patients.

Medical professionals can now apply to make their videos eligible for the popular video-sharing app’s health product features, which were launched last year and were previously only available to educational institutions, public health departments, hospitals and government entities.

Licensed doctors, nurses, mental health professionals and healthcare information providers must show that their content follows best practices for health information sharing as determined by the Council of Medical Specialty Societies (CMSS), the National Academy of Medicine (NAM) and the World Health Organization (WHO) and have a channel in good standing on YouTube. Approved channels will receive a health source information panel to confirm their medical credibility, and their videos will appear in search results for health content.

“It’s important that information be not just credible but engaging at the same time,” Garth Graham, M.D., director and global head of healthcare and public health at YouTube, told Fierce Healthcare. “Healthcare is still at the point where we're distributing information to patients in flyers and pamphlets and even billboards. I would say those days are becoming more antiquated in terms of healthcare communication; people are looking for information as part of their daily journey. They're looking for it to show up on their phone at the time they have questions looking for answers. So it’s important for us to evolve that communication to where people are.”

Additional requirements from YouTube Health denote that the channel must be mostly comprised of medically informative videos, have more than 2,000 valid public watch hours in the last year and follow YouTube monetization policies. To follow best practices for health information sharing as defined by CMSS, NAM and the WHO, a channel must demonstrate alignment with NAM principles by its content being science-based, objective and transparent and accountable.

Health content creators in the U.S. can now apply for the distinction. Outside the U.S., medical professionals will be able to apply at a later date, aside from nurses, who must be licensed within the U.S. to apply.

“Many years ago, we clinicians may have been more apprehensive when patients came into the visit armed with their own set of information,” Graham said. “But I'm now starting to realize more and more that that's a good thing, because it's a part of the patient engaging in their own journey, acquiring information that then empowers them to make decisions. That clinician interaction, the time we have with the patient, is still a part of their journey.”

Video platforms like YouTube and TikTok are increasingly where new generations are looking for information. Google, YouTube’s parent company, has followed the trend and now includes images and videos, including TikTok videos, in its search engine results.

Many corners of the health industry have rejected traditional ads for direct-to-consumer videos featuring phallic vegetables inspired by emojis, conversations dominating the zeitgeist around health inequity promoting inclusive clinical trials and flashy marketing videos reflecting a new generation of outreach.  

Amid sluggish booster uptakes, the Department of Health and Human Services released an ad on television and YouTube nodding to a modern viral video style.

In mid-September, YouTube unveiled a collaborative program with the Kaiser Family Foundation called THE-IQ, or Tackling Health Equity through Information Quality. The partnership provides seed funding and video production expertise to organizations addressing health inequity.

“Trust comes in a variety of ways; it comes in trust in terms of trust of credentials, but also trust that you are a relatable source that understands where I am, where the user may be coming from, in general,” Graham said.

YouTube channels like Doctor Mike, with 10.3 million subscribers, and Osmosis, which has received hundreds of millions of views, have tapped into the public’s desire to access medical information in an engaging way.

Graham said the expansion of YouTube’s health product features has been in the works for some time as health misinformation ran rampant during the pandemic and mistrust of the medical establishment spread. By placing videos on credited health content shelves and higher in feeds, Graham hopes that trust can be rebuilt and well-informed medical knowledge can expand.

YouTube Health has reciprocated that trust with patients by creating a shelf for personal stories relevant to search topics. The section was built after YouTube’s data revealed that users were not searching for health information but what Graham calls “human questions.”

“People come to YouTube with questions that are not necessarily just about treatment, but just, 'how do I exist? How do I cope? How do I deal with kind of the challenges here?'” Graham said. “And so that's an important component of where video platforms like ours can allow people to get a lot of information in the context of their own lives but also don’t have to have all the medical jargon.”

COVID exposed the challenges and opportunities within healthcare overall, Graham said. As COVID becomes chronic, Graham sees it enter a collection of diseases that can be best addressed on a public health level.

Chronic diseases like diabetes, cancer and hypertension are being searched for more. Information also needs to increase around regular screenings, vaccinations and the upcoming flu season, according to Graham. Another area that Graham says has been a high search driver is women’s and maternal health.

“Whenever I see things like this, I always worried that the traditional ways of that information being distributed and circulated is not necessarily meeting the needs of the audience,” Graham said. “I don't necessarily think it's a marker of any disease process that is having more impact on morbidity and mortality than others, but I think it’s indicative of people looking for answers and then it not being ultimately clear where they can find answers.”

Graham thinks this announcement is only the beginning of getting credible health information to patients in an engaging way at scale. What is in journals and textbooks needs to reach dinner tables and college dorm rooms, Graham said. That gap must be closed so when a person can’t call their doctor at 4 a.m., they can go to YouTube and be well informed.

https://www.fiercehealthcare.com/health-tech/youtube-health-inviting-medical-professionals-apply-health-product-features-boosting

Inspector Genral urges CMS to do more to collect Medicare overpayments from hospitals

 The Centers for Medicare & Medicaid Services (CMS) hasn’t done enough to recoup Medicare overpayments to hospitals and wants the agency to follow key recommendations, a federal watchdog found. 

The Department of Health and Human Services’ Office of Inspector General (OIG) did an update on its previous 12 hospital compliance audits. The watchdog's report, released Thursday, couldn’t verify that the agency had fully recouped Medicare overpayments. 

“CMS has said that it does not have enough resources or staff available to centrally track every issue or error identified in our reports,” the report said. “If CMS used our provider-specific audit reports, it could improve Medicare program oversight by focusing on services at high risk for improper payment.”

The watchdog reviewed prior audits of 12 hospitals from 2016 through 2018 that identified 387 improperly paid Medicare claims totaling $82 million in overpayments. 

Of the 387 claims, 333 were related to inpatient services and 54 were outpatient claims. Hospitals disagreed with the findings, appealing 223 out of the 333 inpatient overpayment claims and 6 of the 54 outpatient ones. 

The most common type of overpayment was linked to incorrectly billed inpatient rehabilitation facilities, with 60% of errors. Hospitals also incorrectly billed Medicare Part A for 71 stays that didn’t meet Medicare’s criteria.

OIG recommended to CMS that the 12 hospitals repay the funds; however, since the last audit, CMS has “provided us with insufficient information; therefore, we could not identify the actions CMS had taken to ensure our recommendations were implemented,” the report said.

The agency, for instance, did not provide information on the status of appeals hospitals levied against OIG’s overpayment findings. CMS didn’t provide information on the reason for the appeal or status of the action. 

“CMS stated that, beyond checking the status in its system of record, further communication from CMS to an appellant during the appeals process would have been inappropriate,” OIG wrote. “CMS further indicated that any actions that take place after the appeals process has concluded would be handled as part of debt collection and oversight.”

OIG also recommended that the hospitals follow CMS’ 60-day rule, which requires facilities to repay any overpayments 60 days after they are identified.

CMS requested hospitals attest that no claims were submitted in error “or that they identified and were returning applicable overpayments to the [Medicare Administrative Contractor] and provide supporting documentation,” the report said. 

OIG called on the agency to improve its internal controls and require MACs to report more when hospital appeals are pending. 

If the agency doesn’t fully follow the recommendations, it risks “not capturing all overpayments identified by the hospitals in response to our 60-day rule recommendation,” the watchdog added.

Ten of the 12 hospitals agreed to strengthen their internal controls to avoid payment errors, and the remaining two have delayed responding to OIG’s recommendations until the appeals process is completed.

CMS concurred with some of OIG’s newest recommendations to improve tracking and responding to the status of overpayment claims but did not concur with a recommendation to consider the results of this audit in future risk assessment processes. The reason is the agency relies on a “larger picture of provider activity” when considering any policy changes.

https://www.fiercehealthcare.com/providers/oig-calls-cms-do-more-collect-medicare-overpayments-hospitals

Two-Twenty-Two

 BY DEREK LOWE

There's some interesting work being done on a disinfection technique that could have some good public health effects on the current coronavirus, on influenza spread, and on future outbreaks of both bacterial and viral diseases. As a small-molecule drug discovery guy, my thoughts naturally turn to fighting off these things through enzyme inhibitors and the like, but of course that's really hard to do. Effective compounds are not easy to come by in these areas, and the bacteria and viruses are of course constantly mutating (especially under the selection pressure of your new drugs!) So while those are valuable, an even better preventative is vaccination, when you can come up with an effective vaccine. But that's not always so easy, either - witness influenza, whose coat-protein-swapping ways keep it changing from season to season in ways that are very hard to keep up with. And of course witness the various infectious diseases for which no effective vaccine has ever been produced at all. An good vaccine is hard to beat, but good vaccines don't come easy.

What's even better than that are public health measures that are taken even more broadly and don't require individual actions. In the industrialized world, we took many of these a long time ago, things like providing clean water without pathogens floating around in it. It comes as a shock to us when that layer of defense breaks down, because we're so used to it that we take it as part of the natural order of things (which of course it's not - it takes money and effort and equipment to keep potable water coming out of the taps). Cleaner air is in the same category, and as someone who grew up in the 1960s and 1970s, I can tell you that the air in the US today is very noticeably better than what we were breathing back then, particularly in more heavily populated areas.

But air purification of viral and bacterial pathogens is not so easy. There are HEPA filters which will catch some of the pathogens, but getting the air turnover through them that's needed isn't so easy (and naturally, the filters have to be replaced at intervals), and there's ultraviolet light. The germicidal effects of short-wavelength UV have been known for a long time - it doesn't penetrate very far, but it's very effective. This technology is used for disinfection purposes in liquids (water purification and in pasteurization of things like milk and fruit juices), and for surface disinfection of fruits and vegetables, and there have been several studies of it for air purification in hospitals and other settings. These have been equivocal - those two links, for example, report significant results, but other studies have not, and fewer of the published articles have gone on to show actual reductions in infection, as opposed to reductions in the air counts of bacteria, fungi, and so on. You'd hope that that latter would connect with the former, but you have to prove these things, since a lot of seemingly straightforward ideas don't work out in practice.

The mechanism of all these disinfections is pretty straightforward: ultraviolet light is not good for living cells, and it's especially damaging to DNA and RNA as well as to unsaturated lipids (and thus ultimately to cell membranes). Some of that is direct photochemical damage, as in pyrimidine dimer formation with nucleic acids, and some of it (such as peroxidation of lipids) is downstream of the production of reactive oxygen species which do other kinds of damage as well if they overwhelm the cellular defenses against such things. All of these of course operate on pathogens, too, so the question has always been how to zap them without zapping ourselves. For air purification, there are are sorts of subtleties around the total light flux, the methods of exposing room air to it, and the various wavelengths of ultraviolet used, which can make things difficult to compare. All of those papers linked in the above paragraph use "UV-C", which is broadly defined as light of roughly 100 to 280 nm, but that's a lot of territory, and as anyone who's done photochemistry reactions can attest, different wavelength can give you different results. But it became apparent early on during our SARS-CoV-2 era that the current coronavirus was indeed inactivated by UV-C in general at several wavelengths and more work has gone into quantifying this effect.

This all leads to thoughts of large-scale disinfection of offices, meeting rooms, churches, restaurants and other public spaces, as described in this new article at The Atlantic. You'll note that it focuses on light at 222 nm, as do several of the links above. I was interested to see this described as a safe for human exposure, since as a bench scientist I've very much avoided exposure to such short wavelengths. But the reasoning makes sense: down in that range, the penetration of such light is only a few microns, and it doesn't even get past the dead cells on the surface of the skin and the cornea of the eye! Now if it did, it would certainly wreak all kinds of ultraviolet havoc, and that's what happens to bacteria and to viruses: they are small enough that they get thoroughly irradiated, and it does severe damage to them. Some of the papers above are from the Brenner group at Colombia, and they have been proposing for several years now that such far-UVC light (200-222 nm) could be deployed as an all-around germicidal method (down below 200 is impractical, because you get into the "vacuum UV" range where the light doesn't even get very far through the air before being absorbed by oxygen molecules themselves). In Japan, the Nakane group at Hirosaki University has been making the same case, and has demonstrated that indeed, 222 nm light does not induce DNA damage in mice, even at much higher flux than would be used for disinfection. That's very much as opposed to (say) 254 nm light, which starts doing damage immediately due to greater penetration into animal tissue.

The Brenner lab's experiments with other coronavirus strains in an UV-irradiated aerosol droplet chamber led them to conclude that at the current OSHA regulatory standard for continuous 222 nm light exposure that you would see 90% viral inactivation at 8 minutes and 99% inactivation in about 16 minutes. That seems promising, and I'm glad to report that there's a randomized trial underway in Nova Scotia in some long-term care facilities. They're running over two rounds of flu season using ordinary fluorescent lights along with the (invisible to the eye) UV ones as a control and looking to see if the number of respiratory infections goes down. We need more such studies, I'd say. The expectation would be that getting rid of the need to push the room air past a concealed hazardous UV fixture (as with those links in the third paragraph above) will improve things, but that has to be proven in the real world, too. We'll also need to collect more safety data, naturally, before we start bathing indoor spaces in invisible germicidal rays. But it's not at all a crazy idea, and it really deserves to be tried out thoroughly.

https://www.science.org/content/blog-post/two-twenty-two

Hold Up On Some of Those Antibiotic Combinations

BY DEREK LOWE

Here's a rather unnerving article on using combinations of antibiotics to treat disease. There have of course been a lot of studies in this area, but they have tended to look at easier-to-measure outcomes like effects on bacterial growth. Not that that doesn't make sense! You'd think that the combinations that have the strongest effects there would also be the ones that have the best effects overall, but that's what this new work is challenging. If you keep your eye on things and wait to see what the effects are on total bacterial clearance, the authors say, things change.

And to be fair, some of this shows up in the growth experiments, too. You can see additive effects with some combinations, positive synergy (once in a while), where the combination is better than you'd have expected versus the two ingredients, and (unfortunately) negative synergy as well, where the combination is actually less effective than you would have predicted. Now, if you listen to nothing but management seminars (not a lifestyle I'm recommending), you'd never believe that there is such a thing as negative synergy out in the real world, but yep, things really can end up as less than the sum of their parts. As the literature review at the beginning of this paper notes, the usual situation when this happens is that the activity of one of the combination drugs ends up being suppressed, while the other one goes along as usual - you don't usually see "reciprocal suppression". Here's one such earlier study and here's another, although there are many others.

This team has come up with a high-throughput cell viability assay system that can be taken out further than usual, with good enough signal/noise to get a reading on bacterial persistance at longer time points. They're using the same strain of Staphylococcus aureus engineered with two different fluorescent markers and co-cultured. This generated a gargantuan pile of microplate images as they tested 14 different antibiotic combinations - the starting measurements were the "early killing" effects of each drug individually at a 90 minute time point (which is certainly enough to show effects on fast-dividing critters like S. aureus), and then they looked at the combinations at that time point as well. They also looked at growth inhibition effects at that same time point.

These experiments showed some complex patterns. There were both synergistic and antagonistic combinations, but these didn't always match up between the growth-inhibition measurement and the "outright killing" ones. Many of these interactions are already well-known in the antibiotic and clinical literature - there's a general antagonism, for example, between "bactericidal" agents and "bacteriostatic" ones (the latter slow growth but don't kill outright). It's been terribly clear since the 1950s, for example, that combining penicillin-type antibiotics ("cidal" drugs that mess up the bacterial cell wall) with tetracycline-type antibiotics (bacteriostatic drugs that inhibit protein synthesis) is a really bad idea and leads to much higher levels of treatment failure and deaths due to infection. The problem is that the former only really kill multiplying bacteria, while the latter prevent bacteria from multiplying in the first place, wiping out the benefit of the penicillin component completely. Overall in the 90 minute experiments here, there was more of that non-reciprocal suppression mentioned above in the killing data - quite a bit of it, in fact, but no actual reciprocal suppression where each drug hurt the other one's activity. 

But that reciprocal suppression behavior was "pronounced and widespread" in the long-term clearance data at 8 hour time points, which is the surprise here. These turned out not to be related at all to the growth-inhibition data, but did show a pretty strong correlation to the early-killing data, which suggests that you might be able to use that (much easier) experiment as a proxy or at least as an early warning system. But you'll have to be careful if you try that, because (for example) some of the strong nonreciprocal suppression examples seen in that early-killing data basically disappeared by the 8 hour measurements. Examples of this are the interaction between tobramycin and the protein synthesis inhibitors, or between trimethoprim and ciprofloxacin. You'd have marked those down via the early-killing data, but the 8-hour clearance data showed that the effect wasn't there any more. That said, some of the classic interactions turn out to be even worse when you look at the longer time points, such as one mentioned earlier between the beta-lactams and the tetracyclines, which seems to slide over from suppression of the beta-lactams to suppression of both partners. The team tried various growth conditions, antibiotic concentrations, and various long time points, but these reciprocal interactions persisted under all sorts of conditions.

The authors went on to try 63 different multidrug combinations of clindamycin, tetracycline, fusidic acid, meropenem, ciprofloxacin, and oxacillin, and found that the situation doesn't get any better. It's known from past experiments that adding in more drugs almost always make the growth-inhibition effect stronger in bacterial assays (as opposed to early-killing measurements, which don't change that much). But in these new clearance measurements, the multidrug combinations were worse across the board. To be sure about that, they repeated the measurements with combinations of five more diverse antibiotics (cefoxitin, linezolid, cefazolin, minocycline, and pristinamycin) and saw the same effects. These experiments are covering a lot of antibiotic space, as folks who have worked with bacteria will appreciate from those lists, and it certainly looks like this clearance effect is (unfortunately) robust. The worst offenders were (as before) combinations of "cidal" and "static" agents, though, so we at least already should know to avoid those.

But there's some good news as well: adding in bacteriostatic drugs that don't depend as much on the rate of cell metabolism (daptomycin or mitomycin) actually potentiated things very strongly with all of the above mixtures (!) These drugs are presumably targeting the metabolically inactive bacteria that the other combinations are (disastrously) missing. And this paper uncovered another interaction that clinicians should be aware of: it turns out that adding a β-lactamase inhibitor can actually lower the clearance efficacy of various drug combinations against β-lactamase-resistant strains, which is not what you would have predicted from first principles. The authors note that combinations of macrolides or doxycycline with the commonly used amoxicillin/clavulanate pair (sold as Augmenin) are prescribed for the treatment of community-acquired pneumonia, and that their work indicates that this has a good chance of making the overall antibiotic efficacy worse, not better. We've clearly got a lot more to learn about these combinations, but this looks like it could be a really useful addition, and should set off a lot more research in this direction.

https://www.science.org/content/blog-post/hold-some-those-antibiotic-combinations

ApoE and the Coronavirus

 BY DEREK LOWE

Apolipoprotein E has generated many surprises over the years. I was working in the Alzheimer's field when it was discovered that a genetic variant of this one, APOE4, is a significant risk factor for Alzheimer's. There was a lot of speculation at the time for why this might be so, because it's not an obvious connection. ApoE carries cholesterol in the blood, and no one had really linked lipid handling to Alzheimer's at the time. Thirty years of work have gone into tracking the details down, and only recently it look like we might know the details: if this hypothesis is correct, the lipoprotein variant leads to unusual lipid profiles in glial cells in the brain, which impairs their function. (More recently, several disruptions in lipid pathways have been linked in one way or another to dementia - see the references in that linked paper).

And Alzheimer's isn't the only disease that is affected by the ApoE4 variant. Lipoprotein behavior is important in the immune system as well, which is one of the reasons that it's so hard to untangle mechanisms in this area. Atherosclerosis, for example, most certainly has a connection with cholesterol trafficking, but it also has a strong connection with inflammation and the immune response to the arterial plaques. These things can have large clinical and public health implications, because while most of the human population has the canonical form of the protein (ApoE3), about 40% of us have one copy of either the APOE2 or APOE4 gene to go along with it. And about 3% of the world population is homozygous for one of those two variant forms, which adds up to a lot of people.

It now looks like these have a connection to the coronavirus pandemic as well. This paper examines mouse models of coronavirus infection, using mice that have had the various human forms of the protein knocked in and exposing them to a mouse-adapted form of SARS-CoV-2. And it turns out that the results are quite different -  the ones with ApoE2 and ApoE4 proteins had notably worse courses of disease and lower survival rates. The outcomes were particularly severe in the male mice, where 100% of the ApoE4 homozygotes died (as opposed to 30% death in the corresponding ApoE3 ones). The disease progressed more quickly in the variant mice, with higher viral loads, and a close look at their immune cell profiles strongly suggests that an impaired immune response to the virus is one of the factors. This (as with human patients with bad outcomes) seems to be part of the problem, with too much immune response (perhaps because other pathways are diminished) doing some of the damage all by itself. But just as mentioned above, working out the exact mechanisms underlying this problem will take a lot of effort.

All this is very suggestive of what goes on in human infections, but although animal models of infectious disease are in many ways about as good as we can get in this work, they can still only take you so far. So the authors here make the connection to human clinical data in the UK. As before, they find that older men are at the most risk for bad outcomes, but when they brought in data from the UK Biobank, it showed that homozygous APOE4 patients had a twofold higher risk of death on top of that. (APOE2 homozygotes had a trend toward increased mortality, but it did not reach statistical significance). The APOE4 result stood up to a number of statistical tests (looking at patients of different genetic backgrounds, adjusting for age and ApoE effects on longevity, etc.) So it appears that ApoE4 homozygosity is the very opposite of a gift that keeps on giving - it's associated not only with increasing risk in chronic diseases such as Alzheimer's, but with increasing risk in response to acute ones like coronavirus infection. Knowing the ApoE status of coronavirus patients, particularly older males, could provide an early warning.

https://www.science.org/content/blog-post/apoe-and-coronavirus