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Clinical Laboratories and Pathology Groups

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Dutch Patient with Longest COVID-19 Case of 612 Days Had More than 50 SARS-CoV-2 Mutations Before He Died

Study of the 50 Omicron variants could lead to new approaches to clinical laboratory testing and medical treatments for long COVID

Patients infected with SARS-CoV-2 can usually expect the COVID-19 illness to subside within a couple of weeks. However, one Dutch patient remained infected with the coronavirus for 612 days and fought more than 50 mutations (aka, variants) before dying late last year of complications due to pre-existing conditions. This extreme case has given doctors, virologists, microbiologists, and clinical laboratories new insights into how the SARS-CoV-2 virus mutates and may lead to new treatments for long COVID.

According to Scientific American, when the 72-year-old male patient was admitted to the Amsterdam University Medical Center (Amsterdam UMC) in 2022 with the Omicron variant of SARS-CoV-2, he was also found to have myelodysplastic syndrome (MDS) and myeloproliferative neoplasm (MPN) overlap syndromes. Thus, the patient was determined to be immunocompromised.

“This was complicated by the development of a post-transplant lymphoma for which he received rituximab [a monoclonal antibody medication used to treat certain autoimmune diseases and cancers] that depletes all available B-cells, including those that normally produce the SARS-CoV-2 directed antibodies,” according to a press release.

The medication the patient was taking for his pre-existing conditions may have contributed to his body being unable to produce antibodies in response to three shots of the Moderna mRNA COVID vaccine he received.

Magda Vergouwe, MD, PhD candidate at the Center for Experimental and Molecular Medicine (CEMM), Amsterdam UMC, who lead a study into the patient, theorized that some of the medications the patient was on for his pre-existing conditions could have destroyed healthy cells alongside the abnormal cancer-causing B cells the drugs were meant to target.

“This case underscores the risk of persistent SARS-CoV-2 infections in immunocompromised individuals,” the researchers said prior to presenting their report about the case at a meeting of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) in Barcelona, Spain, Time reported. “We emphasize the importance of continuing genomic surveillance of SARS-CoV-2 evolution in immunocompromised individuals with persistent infections.”

“Chronic infections and viral evolution [are] commonly described in [the] literature, and there are other cases of immunocompromised patients who have had [COVID] infections for hundreds of days,” Magda Vergouwe, MD, PhD candidate (above), Center for Experimental and Molecular Medicine at Amsterdam UMC, told Scientific American. “But this is unique due to the extreme length of the infection … and with the virus staying in his body for so long, it was possible for mutations to just develop and develop and develop.” Microbiologists, virologists, and clinical laboratories involved in testing patients with long COVID may want to follow this story. (Photo copyright: LinkedIn.)

Risks to Immunocompromised Patients

Pre-existing conditions increase the risk factor for COVID-19 infections. A 2021 study published in the Journal of the American Board of Family Medicine (JABFM) titled, “Prevalence of Pre-existing Conditions among Community Health Center Patients with COVID-19,” found that about 61% of that study’s test group had a pre-existing condition prior to the outbreak of the COVID-19 pandemic.

When the Dutch man was admitted to Amsterdam UMC with common and serious COVID-19 symptoms, such as shortness of breath, a cough, and low blood oxygen levels, he was prescribed sotrovimab (a monoclonal antibody) along with other COVID treatments.

About a month after being admitted his COVID-19 symptoms decreased, so he was first discharged to a rehab facility and then finally to his home. However, he continued to test positive for the coronavirus and developed other infections that may have been complicated by the persistent case of COVID-19.

The Amsterdam UMC doctors emphasized that the man ultimately succumbed to his pre-existing conditions and not necessarily COVID-19.

“It’s important to note that in the end he did not die from his COVID-19,” Vergouwe told Scientific American. “But he did keep it with him for a very long period of time until then, and this is why we made sure to sample [the virus in his body] as much as we could.”

One in Five Adults Develop Long COVID

Long COVID does not necessarily indicate an active infection. However, in as many as one in five US adults COVID symptoms persist after the acute phase of the infection is over, according to a study published recently in JAMA Network Open titled, “Epidemiologic Features of Recovery from SARS-CoV-2 Infection.”

“In this cohort study, more than one in five adults did not recover within three months of SARS-CoV-2 infection. Recovery within three months was less likely in women and those with pre-existing cardiovascular disease and more likely in those with COVID-19 vaccination or infection during the Omicron variant wave,” the JAMA authors wrote.

The origins of long COVID are not entirely clear, but according to the National Institutes of Health (NIH) it can develop when a patient is unable to sufficiently rest while battling off the initial virus. According to Vergouwe, the SARS-CoV-2 genome will always grow quicker when found in a patient with a compromised immune system.

Unique COVID-19 Mutations

More than 50 new mutations of the original Omicron variant were identified in the Dutch patient. According to Vergouwe, “while that number can sound shocking, mutations to the SARS-CoV-2 genome are expected to evolve more quickly in those who are immunocompromised (the average mutation rate of the virus is estimated to be two mutations per person per month),” Scientific American reported. “What does make these mutations unusual, she noted, is how their features differed vastly from mutations observed in other people with COVID. [Vergouwe] hypothesizes that the exceptional length of the individual’s infection, and his pre-existing conditions, allowed the virus to evolve extensively and uniquely.”

COVID-19 appears to be here to stay, and most clinical laboratory managers and pathologists understand why. As physicians continue to learn about the SARS-CoV-2 coronavirus, this is another example of how the knowledge about SARS-CoV-2 is growing as different individuals are infected with different variants of the virus.

—Ashley Croce

Related Information:

Longest-Ever COVID Infection Lasted More than 600 Days

COVID Patient’s Infection Lasts Record 613 Days—and Accumulated Over 50 Mutations

72-Year-Old Patient Had COVID for Record 613 Days, Accumulated over 50 Mutations from Virus Before It Killed Him

Prevalence of Preexisting Conditions among Community Health Center Patients with COVID-19: Implications for the Patient Protection and Affordable Care Act

The Risk Factors for Long COVID Have Finally Been Revealed

Prevalence of Pre-existing Conditions among Community Health Center Patients with COVID-19

Epidemiologic Features of Recovery from SARS-CoV-2 Infection

Genetic Testing of Wastewater Now Common in Detecting New Strains of COVID-19 and Other Infectious Diseases

Direct Primary Care a New Option for Patients to Receive High-Quality Medical Care at Affordable Prices

Medical laboratories prepared to receive direct payments for services rendered will have an advantage as more physicians’ practices convert to concierge medicine and stop taking insurance or Medicare

A growing number of physicians are looking at new care delivery models as increasing costs and narrow networks drive patients into high-deductible health plans (HDHPs). These can include concierge medicine and direct primary care. Clinical laboratories and anatomic pathology groups will need to  adapt to these new models of healthcare.

Concierge medicine is basically an alternative medical practice model. Its main benefit is providers see far fewer patients and can provide higher-quality care to patients who can afford to pay the fees. Dark Daily reported on this growing trend as far back as 10 years ago (see, “More Doctors Consider Concierge Medicine as Healthcare Reform Looms,” June 8, 2009), and as recently as this year (see, Some Hospitals Launch Concierge Care Clinics to Raise Revenue, Generating both Controversy and Opportunity for Medical Laboratories, April 23, 2018.)

Now, a new payment program called Direct Primary Care (DPC), which is emerging as an alternative to traditional health insurance plans, could further help patients in HDHPs—and the uninsured—afford quality healthcare.

The main difference between DPC and concierge medicine lies in how doctors get compensated. Monthly membership fees are usually the only source of revenue for DPC practices and they do not accept any type of insurance. Concierge practices, on the other hand, bill insurance companies and Medicare for covered medical services and collect membership fees for services that are not covered.

In general, if a third-party payer is not involved, the practice is considered Direct Primary Care.

DPC versus Concierge Medicine: How Do They Compare?

Direct Primary Care is an offshoot of concierge medicine and the two terms are often used interchangeably. Although similar, there are distinct differences between the two models of care.

Concierge medicine was created in the mid 1990’s and was originally used by wealthy patients who were willing to pay a high subscription fee for access to select physicians. However, this model has changed over the years, making concierge medicine economically available to lower income individuals as well.

According to Concierge Medicine Today, the majority of concierge medicine plans cost between $51 and $225 per month in 2017. Eleven percent of concierge plans charge less than $50, and 35% cost more than $226 per month. There are some high-end concierge plans that can cost upwards of $30,000 per year.

Direct Primary Care was started in the mid 2000’s as an insurance-free plan mainly for the uninsured. In 2015, the Journal of the American Board of Family Medicine reported that the average monthly cost for patients on a DPC plan was $93.26 among the 116 practices they surveyed. The range in costs at that time was $26.67 to $562.50 per month. They also found that practices that identified themselves as “Direct Primary Care” charged a lower fee on average than concierge practices.

The patient base also varies between the two types of practices. According to Cypress Concierge Medicine in Nashville, Tenn., DPC physicians usually treat younger patients with an annual household income of less than $50,000, while concierge medicine doctors typically treat patients over the age of 45 who have an annual household income of $75,000 or more.

Physicians in both plans try to limit the number of patients they serve to a few hundred to ensure they can provide the best possible care to their clients.

Physicians Like Direct Primary Care Programs

DPC physicians charge a monthly membership fee for their services based on the patient’s age, the type of practice, and the number of individual family members on the DPC plan. The monthly fee includes routine office visits—usually with no co-pays—and almost constant access to a physician through telemedicine technology.

DPC plans also provide same or next-day appointments for members and offer lower costs for pharmaceuticals and lab tests.

Direct Primary Care programs are attractive to physicians who often feel overworked by too many patients, too much tedious paperwork, too much time dealing with insurance companies and too little time to provide quality care.

“There are thousands of physicians in career crisis who are investigating new ways to practice medicine and in essence, love going to work again,” noted Michael Tetreault, Editor-in-Chief of The DPC Journal.

“I can understand why [direct primary care] would be appealing to some family physicians,” Dennis M. Dimitri, MD (above), Professor and Vice Chair of Family Medicine and Community Health at UMass Memorial Medical Center and President of the Massachusetts Medical Society, told the Boston Globe. “Many doctors feel terribly burdened by the administrative issues of dealing with insurers, referrals,” he stated. “They are unhappy that all of that gets in the way of them having sufficient time to help their patients the way they want to.” (Photo copyright: Massachusetts Medical Society.)

Jeffrey Gold, MD, a Family Practice specialist in Marblehead, Mass., left his position with a successful physicians group to launch his own DPC practice.

“It’s really blue-collar concierge medicine,” Gold told the Boston Globe. He added that his former practice model “was all about volume and coding and how many people a day you can see.”

“I couldn’t do it anymore,” he admitted. “It was not aligned with how I grew up thinking about medicine.”

DPC/Concierge Practices Expected to Increase in Numbers

With a growing number of patients in high-deductible health plans, concierge medicine and DPC practices are expected to increase in number. According to Direct Primary Care Frontier, an online resource that supports DPC, in 2014 there were only 125 DPC practices in the US. However, by April of 2017, that number had jumped to 620, and as of March 2018, the estimated number of DPC practices was 790.

Similarly, in 2010, there were between 2,400 and 5,000 concierge medical practices in the US, and by 2014, that number had increased to 12,000, according to the American Journal of Medicine.

Like concierge medicine, Direct Primary Care clients present a relatively new method for clinical laboratories to succeed and be profitable. Because there is no need to be in insurance networks—and patients pay cash for lab tests—DPC patients may prove to be an excellent source of business for medical laboratories that can adapt to DPC practices.

—JP Schlingman

Related Information:

A New Kind of Doctor’s Office That Doesn’t Take Insurance and Charges a Monthly Fee is ‘Popping up Everywhere’ and That Could Change How We Think About Healthcare

Medicine vs. Direct Primary Care

Direct Primary Care and Concierge Medicine: They’re Not the Same

4 Distinguishing Differences Between Direct Primary Care and Concierge Medicine

Direct Primary Care: Practice Distribution and Cost Across the Nation

List of What Worked and Didn’t in DPC from 2016

How These Doctors Bypass Insurance Companies

Concierge Medicine is Here and Growing!!

More Doctors Consider Concierge Medicine as Healthcare Reform Looms

Some Hospitals Launch Concierge Care Clinics to Raise Revenue, Generating both Controversy and Opportunity for Medical Laboratories

Findings Confirm What Pathologists Have Known for Years: Significant Number of Primary Care Doctors Are Uncertain about the Correct Clinical Laboratory Test to Order

National survey of 1,768 family practice and internal medicine specialists determines that they are struggling to stay current with changing guidelines for ordering and interpreting medical laboratory tests

Recent publication of a new study confirms what pathologists and medical laboratory professionals have known for years: a significant number of primary care physicians acknowledge that they sometimes are uncertain about which clinical laboratory test is the most appropriate one to order. These same doctors also admit that they are often also uncertain how to interpret the results of some medical laboratory tests.

Physicians Uncertain when Ordering Clinical Laboratory Tests

These are two conclusions resulting from a survey published in the March-April edition of the Journal of the American Board of Family Medicine (JABFM). It is important that clinical laboratory administrators and pathologists understand the survey findings for two important reasons.

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