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CME / ABIM MOC / CE

What Are the Systemic Effects of COVID-19? Multi-Organ Implications

  • Authors: News Author: Megan Brooks; CME Author: Laurie Barclay, MD
  • CME / ABIM MOC / CE Released: 7/8/2022
  • Valid for credit through: 7/8/2023
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  • Credits Available

    Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™

    ABIM Diplomates - maximum of 0.25 ABIM MOC points

    Nurses - 0.25 ANCC Contact Hour(s) (0 contact hours are in the area of pharmacology)

    Pharmacists - 0.25 Knowledge-based ACPE (0.025 CEUs)

    Physician Assistant - 0.25 AAPA hour(s) of Category I credit

    IPCE - 0.25 Interprofessional Continuing Education (IPCE) credit

    You Are Eligible For

    • Letter of Completion
    • ABIM MOC points

Target Audience and Goal Statement

This activity is intended for infectious disease clinicians, internists, cardiologists, critical care clinicians, gastroenterologists, family medicine and primary care clinicians, diabetologists/endocrinologists, hematologists/oncologists, nephrologists, nurses, pharmacists, pulmonologists, public health and prevention officials, physician assistants, and other members of the healthcare team for patients with COVID-19 who may be at risk for multi-organ complications.

The goal of this activity is for learners to be better able to describe objective measures of multisystem disease in patients hospitalized with COVID-19.

Upon completion of this activity, participants will:

  • Describe objective measures of multisystem disease in patients hospitalized with COVID-19, according to a prospective, multicenter, longitudinal clinical study (CISCO-19)
  • Identify clinical and public health implications of objective measures of multisystem disease in patients hospitalized with COVID-19, according to a prospective, multicenter, longitudinal clinical study (CISCO-19)
  • Outline implications for the healthcare team


Disclosures

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News Author

  • Megan Brooks

    Freelance writer, Medscape

    Disclosures

    Megan Brooks has no relevant financial relationships.

CME Author

  • Laurie Barclay, MD

    Freelance writer and reviewer
    Medscape, LLC

    Disclosures

    Laurie Barclay, MD, has the following relevant financial relationships:
    Formerly owned stocks in: AbbVie

Editor/Nurse Planner

  • Leigh Schmidt, MSN, RN, CMSRN, CNE, CHCP

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Leigh Schmidt, MSN, RN, CMSRN, CNE, CHCP, has no relevant financial relationships.

Compliance Reviewer

  • Yaisanet Oyola, MD

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Yaisanet Oyola, MD, has no relevant financial relationships.

Peer Reviewer

This activity has been peer reviewed and the reviewer has no relevant financial relationships.


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In support of improving patient care, Medscape, LLC is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

This activity was planned by and for the healthcare team, and learners will receive 0.25 Interprofessional Continuing Education (IPCE) credit for learning and change.

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    Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 0.25 MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

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    Medscape, LLC has been authorized by the American Academy of PAs (AAPA) to award AAPA Category 1 CME credit for activities planned in accordance with AAPA CME Criteria. This activity is designated for 0.25 AAPA Category 1 CME credits. Approval is valid until 7/8/2023. PAs should only claim credit commensurate with the extent of their participation.

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CME / ABIM MOC / CE

What Are the Systemic Effects of COVID-19? Multi-Organ Implications

Authors: News Author: Megan Brooks; CME Author: Laurie Barclay, MDFaculty and Disclosures

CME / ABIM MOC / CE Released: 7/8/2022

Valid for credit through: 7/8/2023

processing....

Note: The information on the coronavirus outbreak is continually evolving. The content within this activity serves as a historical reference to the information that was available at the time of this publication. We continue to add to the collection of activities on this subject as new information becomes available. It is the policy of Medscape Education to avoid the mention of brand names or specific manufacturers in accredited educational activities. However, manufacturer names related to COVID-19 vaccines may be provided in this activity to promote clarity. The use of manufacturer names should not be viewed as an endorsement by Medscape of any specific product or manufacturer.

Clinical Context

Understanding complications and outcomes of post-acute COVID-19 is essential to develop better management strategies to improve patient quality of life (QoL) and care and to expand the knowledge base of long-term effects of SARS-CoV-2 infection.

Research to date has included clinical studies, usually relying on patient recall, with potential selection bias, or lacking contemporary matched control participants. Disease classification is vulnerable to ascertainment bias, as hospitalized and community-based patients may differ in COVID-19 trajectory. The pathophysiology of post--COVID-19 syndrome (long COVID) has not been defined objectively, creating an information gap hindering development of management guidelines.

Study Synopsis and Perspective

One in eight adults hospitalized with COVID-19 subsequently develops myocarditis, often leading to impaired exercise capacity and health-related quality of life (HRQoL), according to an ongoing study looking at the clinical long-term effects of the SARS-CoV-2 virus.

The study also revealed evidence of persistent abnormalities in heart, lung, and kidney imaging, electrocardiography, and multisystem biomarkers after COVID-19 hospital discharge.

Importantly, said the researchers, it is the severity of a patient's COVID-19 condition, not their underlying health condition, that is most closely correlated to the severity of ongoing health issues after the patient leaves the hospital.

"We found that previously healthy patients, without any underlying health conditions, were suffering with severe health outcomes, including myocarditis, post hospitalization," principal investigator Colin Berry, MBChB, PhD, professor of cardiology and imaging, University of Glasgow, United Kingdom, said in a statement.

"The reasons for this are unclear, but it may be that a healthy person who is hospitalized with COVID-19 is likely to have a worse COVID infection than someone with underlying health conditions who is hospitalized," Berry said.

The study was published online May 23 in Nature Medicine.

A Multisystem Disease

The findings are based on 159 patients who are being followed after hospitalization for COVID-19 as part of the Scottish Cardiac Imaging in SARS CoV-2 (CISCO-19) study.

The mean age of the study participants was 55 years, 43% were women, and 47% had a history of cardiovascular disease (CVD) or treatment. Over an average post-discharge follow-up of 450 ± 88 days, 1 in 7 patients was readmitted to the hospital, and 2 in 3 required outpatient care.

Compared with a matched control group of patients without COVID-19, patients with COVID-19 showed evidence of cardiorenal inflammation, lung involvement, systemic inflammation, hemostatic pathway activation, and impairments in physical and psychologic function 28 to 60 days after discharge.

The likelihood of post--COVID-19 myocarditis (the primary outcome) was judged to be "very likely" in 13% of patients, "probable" in 41%, "unlikely" in 35%, and "not present" in 11%.

The etiology of myocarditis was predominantly SARS-COV-2 infection and less commonly myocardial ischemia due to coronary artery disease (CAD).

Myocardial scar was "surprisingly" common, affecting 1 in 5 patients with COVID-19, the researchers noted.

The fibrosis distribution in patients post--COVID-19 was "indicative of acute myocarditis, microvascular thrombosis, myocardial infarction, and preexisting scar with a nonischemic pattern. The prognostic implications of these findings should be clarified through longitudinal follow-up studies," the researchers said.

Almost one-quarter of the patients with COVID-19 were healthcare workers, and they had about a 3-fold higher likelihood of myocarditis, a finding that merits further investigation, the researchers said.

On univariate analysis, women had an increased likelihood of myocarditis, which, in turn, was linked to lower mental and physical well-being. This finding, they said, might provide a pathophysiologic basis for the physical limitations experienced by some women after severe COVID-19 that requires hospital care.

Myocarditis was associated with acute kidney injury during COVID-19 admission, with evidence of kidney inflammation 28 to 60 days after discharge.

"From a clinical perspective, cardiorenal injury was associated with persisting impairments in health-related quality of life, and poorer physical and psychological well-being during convalescence," the researchers said.

"Considering clinical translation, the results support a stratified management approach for post-COVID-19 patients early during convalescence," they added.

Chest abnormalities on computed tomography (CT) were also common 28 to 60 days after COVID-19 discharge.

The minimum patient-level fractional flow reserve on CT was lower in patients with COVID-19 than in 27 COVID-free control subjects, "consistent with flow-limiting [CAD]," the authors noted.

Magnetic resonance imaging (MRI) showed mild differences in ventricular function.

At baseline, circulating concentrations of C-reactive protein, ferritin, D-dimers, fibrinogen, factor VIII, and von Willebrand factor were higher in patients post-COVID than control participants, consistent with hemostatic pathway activation.

At 28 to 60 days after discharge, factor VIII concentrations remained high. Circulating concentrations of N-terminal pro B-type natriuretic peptide (NT-proBNP) were higher in patients with COVID-19 at baseline and 28 to 60 days after discharge.

Summing up, the researchers said their findings show that the illness trajectory of COVID-19 includes "persisting multisystem abnormalities that underlie impairments in health status, physical and psychological well-being during community convalescence."

The work was funded by the Scottish Government's Chief Scientist Office, and supported by the British Heart Foundation (BHF) as part of the University of Glasgow BHF Centre of Excellence. The authors have no relevant disclosures.

Study Highlights

  • Control participants were patients hospitalized with non--COVID-19 illness, patients with recent unscheduled secondary care attendance or scheduled outpatient clinical review, and volunteers with hypertension or other CV risk factors.
  • Compared with control participants, at 28 to 60 days post-discharge, patients with COVID-19 had increased incidence of cardiorenal and systemic inflammation, lung involvement and hemostasis pathway activation; worse HRQoL on EQ-5D-5L surveys; worse anxiety and depression on the 4 item Patient Health Questionnaire; and diminished maximal oxygen utilization and aerobic exercise capacity.
  • Healthcare workers (nearly one-quarter of patients with COVID-19) had ~ 3-fold higher likelihood of myocarditis.
  • Myocarditis etiology was predominantly SARS-COV-2 infection and less commonly CAD-related myocardial ischemia.
  • An unexpected, inverse, multivariable association between HbA1c blood concentration and myocarditis suggests that multisystem COVID-19 illness severity rather than preexisting comorbidities, is one of the leading factors driving long COVID.
  • Other factors associated with myocarditis were female sex and acute kidney injury during COVID-19 admission, with kidney inflammation 28 to 60 days after discharge.
  • Chest CT abnormalities were common at 28 to 60 days, suggesting flow-limiting CAD, with lower fractional flow reserve than in 27 COVID-19--free control participants.
  • MRI showed mild ventricular function differences.
  • Consistent with hemostatic pathway activation, baseline circulating concentrations of C-reactive protein, ferritin, D-dimers, fibrinogen, factor VIII, and von Willebrand factor were higher in patients post-COVID.
  • Factor VIII concentrations remained high at 28 to 60 days; circulating NT-proBNP concentrations were higher in patients with COVID-19 at baseline and 28 to 60 days.
  • Cardiorenal injury was associated with persistent impairments in HRQoL and worse physical and psychological well-being during convalescence.
  • The investigators concluded that the COVID-19 illness trajectory includes persistent cardiorenal inflammation, hemostatic pathway activation and lung involvement.
  • The findings indicate a link between post-COVID-19 syndrome and multisystem disease, partly explaining the lingering impairments in patient-reported HRQoL, physical function and psychological well-being after COVID-19, and merit prioritization of targeted preventive therapy development for post--COVID-19 syndromes in hospitalized patients.
  • Implication of multisystem injury pathways mediating long COVID should help inform clinical guideline updates.
  • Fibrosis distribution in patients post--COVID-19 suggested acute myocarditis, microvascular thrombosis, myocardial infarction, and preexisting scar with nonischemic pattern, meriting longitudinal follow-up to determine prognostic significance.
  • Increased risk for myocarditis in women and its association with lower mental and physical well-being may help explain physical limitations experienced by some women after severe COVID-19 requiring hospitalization.
  • Study limitations include most patients being unvaccinated during enrollment; diagnosis of myocarditis not biopsy-based; and possible selection and ascertainment bias, as patients too frail to comply with study procedures were excluded.
  • Participants were invited for longer-term follow-up to examine persistent health impairments, including cardiopulmonary exercise testing and stress perfusion CV MRI to provide objective measures of aerobic exercise capacity and myocardial blood flow.
  • The investigators also plan to assess multisystem disease pathways by quantifying circulating biomarkers using proteomics.

Clinical Implications

  • The COVID-19 illness trajectory includes persistent cardiorenal inflammation, hemostatic pathway activation, and lung involvement.
  • Implication of multisystem injury pathways mediating long COVID should help inform clinical guideline updates.
  • Implications for the Healthcare Team: The findings support stratified management approaches for patients post--COVID-19 early during convalescence, including vaccination and pharmacologic and lifestyle interventions. Members of the healthcare team should utilize a team-based approach to provide patient education on effective COVID-19 mitigation strategies.

 

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