“Long COVID” continues to evade diagnosis

Embargoed for release until 5:00 p.m. ET on 12 August 2024    
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Below please find summaries of new articles that will be published in the next issue of Annals of Internal Medicine. The summaries are not intended to substitute for the full articles as a source of information. This information is under strict embargo and by taking it into possession, media representatives are committing to the terms of the embargo not only on their own behalf, but also on behalf of the organization they represent.    
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1. “Long COVID” continues to evade diagnosis

Of 25 routine clinical lab tests, not one can aid in diagnosing post-acute sequelae of SARS-CoV-2

Abstract:

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A national cohort study of adult participants with and without prior SARS-CoV-2 infection found that there are no objective tests to accurately diagnose post-acute sequelae of SARS-CoV-2 infection (PASC), also known as Long COVID. Data also suggested that many of the long-term PASC symptoms are due to ongoing inflammation, rather than viral invasion of the affected area. The findings are published in Annals of Internal Medicine.  

Researchers from the National Institutes of Health studied more than 10,000 adult patients enrolled in the RECOVER (Researching COVID to Enhance Recovery) trial to investigate clinical laboratory markers of SARS-CoV-2 and PASC. Because a baseline was necessary to compare variables, adults were eligible to participate in the study regardless of prior infection of SARS-CoV-2. The researchers compared questionnaire responses and routine clinical laboratory results from participants to determine if SARS-CoV-2 led to persistent laboratory abnormalities, whether or not symptoms were present. The researchers found that none of the 25 routine clinical laboratory values assessed in the study could serve as a clinically useful biomarker of PASC. Additionally, they found evidence to support the idea that SARS-CoV-2 may contribute to diabetes risk independent of PASC symptoms, a connection that had been made early in the pandemic. Those with prior SARS-CoV-2 also had higher urine albumin to creatinine ratio, a marker of early kidney disease that has been associated with cardiovascular disease in other populations. The data also showed that ongoing inflammation is a potential mechanism underlying anosmia (smell/taste disturbances) and PASC.

The authors of an accompanying editorial from Johns Hopkins University say that some of the greatest unsolved challenges of the COVID pandemic relate to understanding, diagnosing, and treating long COVID. Extremely large observational studies like RECOVER are a once-in-a-lifetime opportunity to study an infection-associated chronic illness that occurred simultaneously in millions triggered by the same pathogen. The findings are a reminder that physicians should consider long COVID in differential diagnoses for symptoms or conditions without apparent etiology.

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak with corresponding author, Kristine M. Erlandson, MD, MSc, please email Wendy Meyer at wendy.meyer@cuanschutz.edu or Julia Milzer at julia.milzer@cuanschutz.edu.

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2. More than one fifth of Medicare Advantage users classified as homebound or semi-homebound

Homebound status a powerful predictor of hospitalization and health care utilization

Abstract:

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A large cross-sectional study of Medicare Advantage (MA) plan beneficiaries found that more than one fifth of participants are homebound or semi-homebound, which is a powerful independent predictor of hospitalization and health care utilization. As MA becomes the majority payer source for Medicare beneficiaries, attention to providing appropriate care delivery to this high-need, high-cost population is warranted. The findings are published in Annals of Internal Medicine. 

 

Researchers from Johns Hopkins University, Harvard Medical School, and Humana surveyed more than 514,000 Humana MA beneficiaries to determine the prevalence, characteristics, predictors, health service use, and mortality outcomes of homebound beneficiaries. To keep the focus on homebound status, the sample was limited to beneficiaries who completed an in-home health and well-being assessment (IHWA) and were alive and continuously enrolled in a large national MA plan between January and December 2022. The data showed that the overall prevalence of homebound status was 22%. Compared to those who were not homebound, participants who were homebound or semi-homebound were more likely to be older than 85 years old, female, and low-income, and factors associated with homebound status included dementia and moderate-severe frailty. Homebound status was associated with increased odds of emergency department visits, inpatient hospital admissions, skilled nursing facility admissions and mortality. In fact, homebound status was a more powerful predictor of hospitalization than any sociodemographic variable or measure of morbidity burden except level of frailty. Similarly, homebound status was the strongest predictor of skilled-nursing facility admission other than frailty and having an abnormal gait. According to the study authors, these findings can be used to inform strategic initiatives to identify and manage care for homebound beneficiaries.

 

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak with corresponding author, Bruce Leff, MD, please email Zachary Fulwood at zfulwoo1@jhu.edu. 

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3. Researchers warn of dangers associated with rising kratom use

Abstract:

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Researchers from the University of New Mexico School of Medicine and WorkIt Health suggest it’s time for physicians to embrace asking patients about kratom use, the same as they would cannabis, cocaine, methamphetamines, or heroin. While widely available and largely unregulated, recreational use of kratom has been associated with dangerous side effects, including risk for cardiac arrest, seizures, aphasia, and death, and it has been implicated in numerous studies as a highly addictive substance. The authors suggest that physicians need more education and better tools to help them deal with this growing clinical threat. The commentary is published in Annals of Internal Medicine.

 

In 2022, it was estimated that 1.9 million people in the US had used kratom, a legal drug that offers stimulant effects at low doses and opioid-like effects at higher doses. Despite being considered a drug of concern by the Drug Enforcement Administration, kratom is available in tobacco, vape, tea, and vitamin shops.  While some use it to manage pain, increase energy levels, or in place of illegal substances, a recent survey found that at least 12% of people who use kratom would qualify as having a use disorder, but other research finds that more than half of patients using kratom do not feel comfortable disclosing use to a health care professional. As such, the authors highlight the need for caution on kratom use among the public until the DEA or FDA regulates it. They urge physician education about kratom use and potential harm reduction strategies for patients and suggest a research agenda that can better quantify the risks posed by kratom use and how to mitigate them. Evidence-based guidelines regarding the care of people who use kratom are needed, as well as an evidence-informed public health response.

 

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To reach the lead author, Eileen Barrett, MD, MPH, please email barrett.eileen@gmail.com. 

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4. Physicians debate best management strategies for inpatient glycemic control

‘Beyond the Guidelines’ features are based on the Department of Medicine Grand Rounds at Beth Israel Deaconess Medical Center.

Abstract:

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In a new Annals “Beyond the Guidelines” feature, two expert diabetologists discuss their approach to inpatient management of type 2 diabetes mellitus (T2DM), specifically regarding inpatient glycemic goals on the medical ward, the use of noninsulin antihyperglycemic medications, and patient safety strategies for patients receiving long-acting insulin. All “Beyond the Guidelines” features are based on selected clinical conferences at Beth Israel Deaconess Medical Center (BIDMC) and include multimedia components published in the Annals of Internal Medicine.

 

More than 38 million Americans have T2DM, leading to $307 billion in direct healthcare costs annually. T2DM is associated with multiple microvascular and macrovascular complications. In the inpatient setting, T2DM is associated with hyperglycemia (blood glucose above a healthy range) and hypoglycemia (blood glucose below a healthy range). Both carry dangers—inpatient hypoglycemia is associated with prolonged length of stay and increased rates of in-hospital and 1-year mortality, while hyperglycemia is associated with higher rates of surgical site infections and electrolyte abnormalities. Several antihyperglycemic medications have come to market in the last decade, but insulin remains the backbone of inpatient glycemic control. Guidelines on management of inpatient hyperglycemia in T2DM from the American Diabetes Association (ADA) and Endocrine Society (ES) have slight differences in their evidence-based recommendations about glycemic control, although both express a preference for insulin over other agents and make commentary relevant to patients receiving long-acting insulin.

 

Diabetologists Florence Brown, MD, Assistant Professor of Medicine at Harvard Medical School and Co-Director of the Joslin and BIDMC Diabetes in Pregnancy Program, Boston, Mass., and Zachary Taxin, MD, Instructor of Medicine at Harvard Medical School and Director of the Inpatient Diabetes Service at Beth Israel Deaconess Medical Center, Boston, Mass., responded to questions concerning ideal patient management of patients with T2DM and made recommendations for Mr. D, a patient with T2DM admitted with a foot infection. They expressed contrasting views, with Dr. Brown favoring the ES glycemic target of 100 to 180 mg/dL and Dr. Taxin preferring a more liberal target than ADA and ES guidelines, aiming initially for a fingerstick blood glucose range of 100 to 250 mg/dL and eventually tightening up to 100 to 200 mg/dL if able to do so without causing hypoglycemia. To refute Dr. Brown’s tighter glycemic goals, Dr. Taxin cites numerous trials and studies showing the lack of harm of liberal glycemic goals and demonstrating that tight glycemic goals increases hypoglycemia. The diabetologists also have differing views on noninsulin antihyperglycemic medications, with Dr. Brown highlighting the risks of medication such as metformin and GLP-1RA, supporting low-dose insulin. Meanwhile, Dr. Taxin emphasizes insulin’s risks and presents outpatient evidence showing the metformin risks Dr. Brown introduced are rare, and the medication can be continued for stable patients. They agree on patient safety suggestions, and both diabetologists avoid new inpatient initiation of GLP-1RA due to gastrointestinal concerns.

 

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak with one of the discussants, please contact Kendra McKinnon at Kmckinn1@bidmc.harvard.edu.

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