Long COVID, genetic tests for cancer, and injuries in the hospital.

January 20, 2023

Happy Friday!

Today, I’ll cover an extensive review of Long COVID and news about genetic tests for cancer. I’ll review a report that demonstrates that many people who are hospitalized suffer adverse events, although many of these are not medical errors or preventable. I’ll also briefly survey the current COVID-19 landscape.

1.       Long COVID is painfully common, has many diverse presentations, and causes substantial disability. 

We’ve learned a lot about COVID-19 over the last three years, but many mysteries remain. Long COVID remains common and perplexing.  In the National Center for Health Statistics pulse survey (mid-December), 14.4% of adults reported they have ever had Long COVID symptoms, 5.8% reported that they currently had some symptoms of Long COVID, and 1.5% reported that they had significant limitations on their activities due to Long COVID.

Researchers published a major new review of Long COVID in Nature last week. They found that Long COVID affects at least 10% of those who are infected and identified 200 Long COVID symptoms, impacting multiple organ systems. They report that COVID infection can cause cardiovascular events (heart attacks and strokes), blood clots, ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome), and autonomic nervous problems such as a high heart rate and low blood pressure when standing up. Some sufferers have a decrease in cognitive function on par with drunk driving alcohol levels or increasing age by ten years.

There are multiple potential causes for Long COVID, and some patients might have more than one cause. Causes include persistent infection, the immune system not functioning correctly, a change in gut or other bacteria, or a signaling problem in the brain. Those at highest risk include women, those with type 2 diabetes, those with a history of Epstein-Barr virus, some connective tissue disorders, those with ADHD, and Latinx. Reinfection increases risk of Long COVID, even in those who are vaccinated. Nonetheless, a third of those with Long COVID have no known predisposition. While those who were critically ill with COVID-19 are more likely to have persistent symptoms, many with Long COVID had mild cases.

Kids get Long COVID, too, although more of them had negative PCR tests and so might not meet some criteria to be diagnosed. This review points out that for many the diagnosis of Long COVID will persist. A BMJ study of medical records in Israel, reported too late to be included in this review article, shows that “patients with mild COVID-19 are at risk for a small number of [adverse] health outcomes, most of which are resolved within a year from diagnosis.”

Some with Long COVID can be definitively diagnosed; however, many will not currently have a positive test result to “prove” the diagnosis. Some will respond to medical therapy for symptoms, and the antiviral, Paxlovid, is being studied as one potential treatment for Long Covid. But there is good evidence that physical activity worsens symptoms for many with the disease, and experts also recommend against cognitive behavioral therapy. The researchers also note that some with symptoms of Long COVID are initially misdiagnosed with a mental health disorder.

Paxlovid decreases the risk of Long COVID by about a quarter in both vaccinated and unvaccinated patients.

Implications for employers:

-          Employers are likely to face more workers with persistent symptoms due to Long COVID, some of whom will be disabled, and others who will need accommodations to return to work.

-          The best way to avoid Long COVID continues to be to avoid getting infected or reinfected, so promoting vaccination with bivalent boosters can reduce the future risk of Long COVID.

-          Employers should continue to make Paxlovid available for those within five days of their first symptoms, even after the drug is no longer provided free by the federal government later this year.

-          Long COVID can be a disability under the Americans with Disability Act (ADA) if it substantially limits one or more life activities. If so, employers must make reasonable accommodations to allow them to continue to perform their essential functions. Some employees could be eligible for unpaid leave as an accommodation under ADA. The ADA requires that employers review each employee’s circumstances individually.

-          Employers can train supervisors to recognize symptoms of Long COVID and to treat those who are suffering with empathy.

2.       A blood test proves as good as surgical staging at determining whether a patient with colon cancer will benefit from chemotherapy.  But that doesn’t mean it’s time to do a “blood biopsy” on everyone!

Source: Kotoni, D et al Nature Medicine, January 16, 2022 LINK

A new study shows that a blood test is more effective at identifying those with colon cancer who will benefit from chemotherapy than the way the tumor looks under the microscope or how far the cancer has spread as shown by imaging or surgery. This is big news and will likely mean that some with colon cancer that has spread locally but not to distant organs can safely avoid chemotherapy.

This study noted that a small portion of individuals with early colon cancer limited to the colon itself will have circulating tumor DNA (ctDNA) in the bloodstream, and chemotherapy could decrease their risk of metastatic disease. The study was large (over 800 people) and ctDNA was far more predictive of cancer spread than conventional blood tests. Chemotherapy made little difference in disease-free survival in those who had no ctDNA, but predicted increased survival from 22% to almost 62% in those who had ctDNA.

This is great news - and means that health plans will be wise to cover this type of genetic testing to help guide cancer treatment.

This technology is similar to that used by multi cancer early detection (MCED) testing to detect ctDNA in those not known to have cancer. This technology is being promoted to employers as a new method to screen for many deadly cancers for which we have not had adequate screening methods in the past. I’ll plan to dedicate more of a subsequent note to this technology. Right now, the majority of those who have positives on multi-cancer early detection tests are not found to have cancer after thorough workups, although they might still be proven to have cancer at some future point. Future MCED tests are likely to be less expensive and have a higher “predictive value of a positive,” and at some point may become the standard for cancer screening. 

This technology is different from tests which look for genetic markers that demonstrate increased genetic risk for cancer. These tests can help those with known familial genetic abnormalities like BRCA make important decisions regarding their care, such as those with BRCA 1 and 2 who choose to have surgery to reduce their risk of breast or ovarian cancer. But broad panels of genetic susceptibility tests generally identify 7-8% of people with a gene which gives them a higher risk of a certain cancer over their lifetimes. However, the overwhelming majority of such people would not have that cancer diagnosed in the next decade or more. Meanwhile, those with positive tests will generally need annual or more frequent testing (such as MRI scans or endoscopies) to check on their organs at genetic risk. This increased screening could have its own dangers, is likely to pick up some incidental abnormalities that would never have hurt the patient and could dramatically increase the cost of employer-sponsored health insurance.

Implications for employers:

-          Expect genetic tests to help identify which patients will benefit from more aggressive chemotherapy or other treatment for cancers that are already diagnosed.

-          Watch the market carefully. At some point in the future, blood tests to detect unsuspected cancer will become more accurate and affordable and could help many of us find deadly cancers when they are still curable.

-          Expect that insurance will cover follow-up tests for those who have purchased genetic cancer susceptibility tests on their own and had a positive result.

3.       The rate of many types of adverse events in hospitals fell dramatically, but the risk of a hospital adverse event remains high

The New England Journal of Medicine reported last week that an extensive chart review of almost 3000 randomly selected hospitalizations in eleven Massachusetts hospitals in 2018 demonstrated an adverse event in about 24% of hospitalizations. The researchers looked for a wide range of adverse events, including hospital acquired infections or injuries, unexpected surgery, drug reactions, blood clots, and complications of childbirth.

A third (316) of the 978 adverse events were considered serious, and 191 events were both serious and preventable (6.8%). Many adverse events that were excluded from the study happened in the outpatient setting prior to hospitalization.

The good news is that hospital acquired infections fell dramatically compared to earlier similar studies. The most common cause of adverse events was drugs (381 cases, 39% of all adverse events.)  Of these, 102 cases (27%) were preventable or potentially preventable.

Implications for employers:

-          Patients who are hospitalized continue to be at risk of adverse outcomes, although a small portion of these events are serious, and many are not preventable.

-          It’s best not to be too frightened by press headlines that point to the total number of adverse events, without clarifying that serious and preventable adverse events are relatively low and continue to decline.

-          Employers can ask their health plans what performance guarantees they have in place to decrease the risk of adverse events.

-          Employers can ask their health plan for a report on adverse events, and serious adverse events in their network.

-          Employers should insist that their health plans not pay for services associated with “never events,” the most serious adverse events which are clearly preventable. 

4.       Brief COVID-19 roundup

a)      COVID-19 wastewater numbers are down and Paxlovid cuts risk of hospitalization in half

The rate of COVID-19 hospitalizations and intensive care patients has declined in the last two weeks, although deaths remain high at over 500 per day.  Here is heartening wastewater data, showing a decrease in viral content in all regions of the US.

Source: Biobot, January 18, 2022 LINK Used by permission. Yellow is Northeast, Magenta is South, Purple is Midwest, and Green is West.

I’m hopeful this means that we’ll start to see decreasing rates of infection across the country. Rates of community transmission remain high in over 70% of counties (either >100 cases per 100,000 in 7 days or PCR test positivity rate of >10%), so I’ll keep wearing a mask in indoor spaces.

b)      Paxlovid decreases risk of hospitalization by half

The Annals of Internal Medicine published a cohort study of over 44,500 non-hospitalized patients who were prescribed Paxlovid (nirmatrelvir/ritonavir) for COVID-19. They found that treatment was associated with a 40% decrease in hospitalization rate, and a 71% decrease in death rate. The researchers weighted results to account for systematic differences in those who got prescriptions (for instance, Paxlovid was prescribed less often to people of color). The vaccination rate (>= 3 doses) in this cohort was over 90%, demonstrating that this medicine lowers risk of bad outcome regardless of vaccination status.

c)       CDC does not find evidence of Pfizer vaccine increased stroke risk in the elderly

The Centers for Disease Control and Prevention reported that it detected a statistical “safety signal” that suggested there might be an increased risk of stroke on those over 65 who were vaccinated with the Pfizer bivalent booster.  Review of databases from the Centers for Medicare and Medicaid Services (Medicare claims), the Veterans Administration (electronic medical records), the Vaccine Events Reporting System, and global data do not show an increased risk. I think this should reassure the public that the CDC is carefully monitoring the safety of the COVID-19 vaccines. I have had both Moderna and Pfizer/BioNTech vaccinations and will not hesitate to get the next booster when it is recommended.

Please check out my article on CFO.com yesterday, “10 Steps to Assess Vendor Programs that Promise to Lower Medical Costs.”

Have a great weekend when it comes! And please subscribe (if you haven’t) and share with a friend or colleague.

Jeff