29. Long COVID Roundtable

Posted on November 15, 2022 by Pulm PEEPs

This week on Pulm PEEPs, Dave and Kristina are joined by Jason Maley and Ann Parker, two pulmonary and critical care physicians who are leaders in treating patients with Long COVID, or Post-Acute Sequelae of SARS-CoV-2. Both of them help run the Long COVID clinics at their respective institutions and are part of broader consortiums dedicated to patient care. They also both participate in research to improve outcomes for patients with Long COVID and Post-Intensive Care Syndrome. In this conversation, we cover the diagnosis of Long COVID, common symptoms, abnormal test findings, possible mechanisms of disease, the impacts of variants and vaccines, treatments, and the natural history of this condition. We hope this will be helpful for providers, patients, and family members.

Meet Our Guests

Jason Maley is an Assistant Professor of Medicine at Beth Israel Deaconess Medical Center and Harvard Medical School. He is the Director of the BIDMC Critical Illness and COVID-19 Survivorship Program, and the Co-Chair of the American Academy of Physical Medicine and Rehabilitation Postacute Sequeleae of SARS-CoV-2 infection (PASC) initiative. He is NIH funded to study post-COVID patients.

Ann Parker is an Assistant Professor of Medicine at Johns Hopkins and is the Co-Director of the Johns Hopkins Post-Acute COVID-19 team. She is NIH funded with her research focusing on survivors of respiratory failure and critical illness.

Key Learning Points

Long COVID or Post-Acute Sequelae of SARS-CoV-2 or Post-COVID condition

Long COVID was first described this way by patients so this is the common nomenclature that is used. It is also referred to as Post-Acute Sequelae of SARS-CoV-2 or Post-COVID condition
Defined by patients that have not returned to their baseline health 3 months after their acute episode of COVID-19
Major organizations in describing this disease and doing research are:
- World Health Organization
- Multiple patient-led organizations
- CDC – INSPIRE
- NIH – RECOVER

Post-COVID Clinic

Seeing patients across the spectrum of illness. Not all patients had to be critically ill or hospitalized
- The standard patient has changed over time and now the vast majority had a mild initial illness, but afterward had unusual and persistent symptoms
Patients are generally referred by their PCP or self-referred
The criteria for being seen in clinic are very loose to make sure patients are not excluded
- Many patients do not have a confirmed case of COVID since patients early in the pandemic often did not have a positive test available, and now many people are testing positive at home
Initial records review to make sure that can help patients
Standardized questionnaires
- Screening for physical impairment, mental health impairment, and cognitive impairment
Rehabilitation and multi-disciplinary based approach
It is extremely important to be aware of the bias in patient populations in Post-COVID clinics
- The population that can make it to clinic may not, and does not, represent all patients who have had COVID or have Long COVID. Patients may be limited in their ability to get to clinic based on their physical condition, financial resources, location, support, and language barriers.

Overlap of Long COVID and PICS

These conditions are very similar and certainly have a lot of overlap
For patients coming out of the ICU, screening should start with looking for known PICS symptoms.
- These domains are mental health, physical impairment, and cognitive function
There may be some unique aspects, such as:
- Severe persistent fatigue
- Extreme changes in taste and smell

Common symptoms

Many symptoms are complex and multifactorial
Neuropsycholgoicl impairment – termed “brain fog”
- Difficulty with concentration, and cognition
Anxiety
Depression
Persistent shortness of breath
- Dyspnea can be reported even with just talking for long periods of time
- “Deep breaths are just not satisfying”
Cough
Chest pain
Dysautonomia
- Palpitations, dizziness, orthostasis
Fatigue
Post-exertional malaise
Cognitive blunting or “brain fog”
Changes in sleep
Headaches

Common findings on testing in patients with Long COVID

Shortness of breath
- Some may have impaired diffusion (low DLCO) on PFTs
- However, often patients have normal or near-normal PFTs
- 10 – 20 % have air trapping on inspiratory/expiratory chest CTs that could indicate bronchiolitis
- One study showed that CPETs showed impaired oxygen extraction
  - Preserved cardiac output to exercise and no evidence of deconditioning
  - This study indicated an issue at the peripheral level (ex: vascular, mitochondrial) with oxygen extraction.

Variants

It is very difficult to say if variants differ in rates of Long COVID given that often patients do not get sequencing to know the variant and because there is overlap in the timing of variants
Further testing will continue on this going forward

Vaccines

Reduced risk of Long COVID with vaccination
- Boosting further decreases the risk compared to just the initial vaccination
There is a variable response to getting vaccinated if a patient has Long COVID
- Most patients tolerate it well and some patients have relief of symptoms
- There are some patients who can develop worsened Long COVID symptoms

References and further reading

Chippa V, Aleem A, Anjum F. Post Acute Coronavirus (COVID-19) Syndrome. In: StatPearls. StatPearls Publishing; 2022. Accessed November 14, 2022. http://www.ncbi.nlm.nih.gov/books/NBK570608/
Crook H, Raza S, Nowell J, Young M, Edison P. Long covid—mechanisms, risk factors, and management. BMJ. 2021;374:n1648. doi:10.1136/bmj.n1648
Durstenfeld MS, Sun K, Tahir P, et al. Use of Cardiopulmonary Exercise Testing to Evaluate Long COVID-19 Symptoms in Adults: A Systematic Review and Meta-analysis. JAMA Network Open. 2022;5(10):e2236057. doi:10.1001/jamanetworkopen.2022.36057
Nalbandian A, Sehgal K, Gupta A, et al. Post-acute COVID-19 syndrome. Nat Med. 2021;27(4):601-615. doi:10.1038/s41591-021-01283-z
Soriano JB, Murthy S, Marshall JC, Relan P, Diaz JV. A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect Dis. 2022;22(4):e102-e107. doi:10.1016/S1473-3099(21)00703-9
Sudre CH, Murray B, Varsavsky T, et al. Attributes and predictors of long COVID. Nat Med. 2021;27(4):626-631. doi:10.1038/s41591-021-01292-y

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Radiology Rounds – 11/8/22

Posted on November 8, 2022 by Pulm PEEPs

This week’s #RadiologyRounds is brought to you by our newest contributor, Nick Ghionni! We’ll dive into a classic Radiology Sign and talk about what it represents, and how it helps inform your differential.

In this case, the patient underwent a biopsy that showed no malignancy but grew NTM! Given that NTM can be superimposed on malignancy, repeated biopsies were done that corroborated. She is being treated with close monitoring.

28. Fellows’ Case Files: Harvard – MGH & BIDMC

Posted on November 1, 2022 by Pulm PEEPs

Welcome back to our Pulm PEEPs Fellows’ Case Files series! We are joined this week by a fellow and the program director from the Harvard combined PCCM fellowship at Massachusettes General Hospital and Beth Israel Deaconess Medical Center. Listen in for a great learning case and let us know on Twitter, if you have a great case to share!

Meet our Guests

Brian Rosenberg is a third year fellow at the Harvard MGH/BI program. He completed his undergraduate degree at Harvard, received his MD from Yale where he also got a PhD in cell biology, and then did his internal medicine residency at Columbia University Medical Center in NYC.

Asha is an Assistant Professor Medicine at Beth Israel Deaconess Medical Center and Harvard Medical School, and is the Program Director of the Harvard MGH/BI combined fellowship. She is also the Director of the Pulmonary Consult Service at BIDMC, was a Rabkin Fellow in Medical Education and has received multiple leadership and teaching awards

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Radiology Rounds – 10/25/22

Posted on October 25, 2022 by Pulm PEEPs

This week’s #RadiologyRounds is coming from the pulmonary clinic. Follow us on Twitter to see the case and answer our polls live!

Given the patient’s weight loss and persistent symptoms despite trying some empiric therapies, a chest CT was obtained. PFTs were also ordered 🙂

The patient’s CT had tree-in-bud opacities, nodular consolidations, scattered micronodular opacities, and airway thickening.

The pt had an induced sputum but could not produce a sample. She underwent bronchoscopy + lavage and her AFB smear was positive with negative TB NAAT. The culture ended up growing M. chimaera! Does that explain her symptoms? Here are the diagnostic criteria for pulmonary NTM:

All other testing was negative and the patient was diagnosed with pulmonary NTM. After a long discussion about treatment (an interesting topic for another day!!) she was started on triple antibiotic therapy and after 9 months her cough had resolved and she was gaining weight.

27. Live from CHEST 2022

Posted on October 17, 2022 by Pulm PEEPs

We are thrilled today here at Pulm PEEPs to be coming to you live from the CHEST 2022 Annual Meeting. We are joined by three fantastic speakers, and CHEST leaders to discuss the highlights and events of the conference, and to share some great learning points along the way. The episode is being released immediately after recording this morning, Monday 10/17/22, so if you’re at the conference now make sure to listen for some extremely timely recommendations. If you’re not here in Nashville, we’ve highlighted some learning points that you can take away and some wisdom on how to maximize your conference experience for the next time!

Meet Our Guests

Subani Chandra is an Associate Professor at Columbia University. She is the Vice Chair of Medicine for Education and the internal medicine residency program director. She is also the incoming Chair of the Training and Transitions Committee at CHEST, and the chair of the CHEST Scientific Program Committee for CHEST 2022.

Matt Siuba is an Assistant Professor of Medicine and intensivist at the Cleveland Clinic, where he is the associate program director for the Critical Care Medicine fellowship. He founded and runs the website Zentensivist.com, and is well known as a fantastic educator both in person via many different online formats.

Todd Rice is an Associate Profess of Medicine at Vanderbilt University, where he is also the Medical Director of the ICU. In addition, he is the Vice President for Clinical Trial Innovation and Operations in the Vanderbilt Institute for Clinical and Translational Research. He is also a past president of The American Society of Parenteral and Enteral Nutrition, and most relevant to today, the Associate Editor of Critical Care for Chest.

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Radiology Rounds – 10/11/22

Posted on October 11, 2022 by Pulm PEEPs

For #RadiologyRounds this week we have a mystery case from the pulmonary clinic complete with imaging and exploration of PFTs. Follow along for some great clinical pearls and teaching points about lung function tests. Graphics made with the help of outstanding educator Kaitlin Seitz.

What imaging views would you get next?

A) Supine and prone

B) Inspiratory and expiratory

C) High resolution

D) With contrast

What test would you get next?

A) Bronchoscopy

B) ECHO

C) PFTs

D) Lung US

What do these PFTs show?

A) Restriction concerning for ILD

B) Restriction concerning for obesity

C) Restriction concerning for weakness

D) Mixed obstruction and restriction

The patient was referred to neurology and ultimately diagnosed with severe mixed sensory and motor chronic axonal polyneuropathy.

26. A Case of AMS, Renal Failure, and Hemolysis

Posted on October 4, 2022 by Pulm PEEPs

This week on Pulm PEEPs, we have another great case episode. We’re switching up the format a bit, and instead of introducing our guests in the beginning, we’ll bring them in consultants as we need to. Luckily, we’re joined by Pulm PEEPs Associated Editor Luke Hedrick to walk us through the case. Let us know your thoughts and if you have any other pearls to add!

Meet Our Guests

Rakhi Naik an Associate Professor of Medicine at Johns Hopkins Hospital and the Associate Director for the Hematology / Oncology Fellowship program. She also has a Masters in Health Sciences from the Johns Hopkins Bloomberg School of Public Health. She has expertise in an array of non-malignant hematology disorders and focuses specifically on sickle cell in her research. She is also an outstanding and dedicated educator and serves as the Chair of the American Society of Hematology Hematology-Focused Training Program Consortium to develop innovative training pathways for non-malignant heme.

Patient Presentation

A 60-year-old woman with a past medical history of hypertension, diabetes, stage 4 chronic kidney disease, COPD, HFpEF, chronic pain on methadone, hyperparathyroidism s/p parathyroidectomy that was c/b hypothyroidism now on thyroid hormone replacement, and a recent admission for nonconvulsive status epilepticus is brought to an outside hospital by EMS with encephalopathy and shaking.

When EMS gets her to the other hospital her GCS was 5, so she was intubated for airway protection and started on fentanyl and midazolam drips. Details of labs and imaging are scarce, but we know that she had a CT head that was normal, a CXR with a report of pulmonary edema, and labs with a Cr of 2.4, serum bicarbonate of 14, and a pH from a VBG of 7.1 with pCO2 of 38.

Key Learning Points

*Spoilers ahead* The infographic below highlighting key points gives away the diagnosis in this case so if you want to work through the case on your own, we recommend listening to the episode first.

References and further reading

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Radiology Rounds – 9/27/22

Posted on September 27, 2022 by Pulm PEEPs

This week’s #RadiologyRounds and tutorial is authored by Huzaifah Salat, our newest PulmPEEPs contributor! See if you can figure out the case and check out our high-yield points at the end. Follow us on Twitter to answer live polls about the case.

25. ARDS Precision Medicine & Phenotypes Roundtable

Posted on September 20, 2022 by Pulm PEEPs

We’re very excited this week on Pulm PEEPs to be resuming our Roundtable series. We are joined by two outstanding critical care doctors to discuss precision medicine in the ICU, specifically ARDS phenotypes. This is a topic of increasing clinical and research interest, and personalized medicine in the ICU will certainly change the landscape of how care is delivered in the coming years and decades. We are honing in on ARDS today and how phenotyping can influence future research and clinical care.

Meet Our Guests

Carolyn Calfee is a Professor of Medicine and Anesthesia at the University of California, San Francisco. She is a leader in the field of ARDS research and a pioneer in the field of ARDS phenotyping research. She has received numerous NIH grants and has literally 100s of publications on ARDS and other topics. She is also a previous ATS CC Assembly chair, and in 2022 received the ATS Recognition Award for Scientific Accomplishments.

Annette Esper is an Associate Professor of Medicine at Emory University School of Medicine. She works clinically in critical care and is the Medical Director of the stepdown Intensive Care Unit at Grady Memorial Hospital. In addition to her clinical activities, Annette does both clinical and translational research in ARDS, and was the Assembly Chair for the ATS Critical Care Assembly from 2021 – 2022.

Key Learning Points

Berlin Criteria of ARDS:

— Acute symptoms developing within 7 days of a known insult

— Bilateral airspace opacites on chest imaging

— Hypoxemia not fully explained by cardiogenic pulmonary edema

— P:F ratio < 300 on a PEEP of 5

Heterogeneity in ARDS

— ARDS has a broad definition so it is comprised of people with a wide range of disease characteristics and severity

— There is heterogeneity in clinical characteristics, but also underlying biological drivers of disease

— Heterogeneity stymies research efforts to identify effective therapies in ARDS

Phenotyping in ARDS

— There are many ways of phenotyping for critical illness and ARDS

1. Etiology. Examples: COVID vs non-COVID, pulmonary vs non-pulmonary, bacterial vs viral

2. Physiologic phenotypes: Severity (Berlin criteria P:F ratio); Compliance, Ventilatory ratio

3. Biological phenotypes: Different underlying drivers of disease

— The motivation for phenotyping is to find treatment-responsive subgroups within the broader heterogeneous subgroups

— Phenotyping embodies more than risk factors, because it includes information about the host response, not just predictors of outcome

Biomarkers in ARDS

— There is probably a role for biomarkers in ARDS clinically and in research

> Prognostication

> Identify who will be responsive to specific therapies

> May not be one biomarker, will likely be a panel

— What is the perfect ARDS biomarker?

> Specific: identify a group of patients that are at risk, or respond to therapies differently

> Easily measurable at the bedside

> Reliable

> Reproducible

— Challengers in identifying useful biomarkers

> Heterogeneity of disease

> Real world applicability. For example, can you get IL-6 back in real-time? Can you apply it consistently when labs have different testing techniques and scales?

> Temporal stability – how do biomarkers change over the time course of ARDS?

— Biomarkers of interest

> Inflammatory markers (IL-6, IL-8, TNF)

> sRAGE – Soluble receptor for advanced glycation end products

> Highest levels on type 1 alveolar epithelial cells

> Seems to be a marker of alveolar epithelial injuries

> Meta-genomic sequencing of patients in a real-time environment

Latent class analysis

— Clustering technique that, agnostic to outcomes, looks for existing groups within the data

— Ideally, identifies biologically distinct phenotypes that may have different prognoses or response to therapy

Omics in ARDS

— Existing risk scores are quite limited, so using biological data to distinguish patients seems promising.

— Unbiased approach to identifying subgroups to identify patients that behave similarly biologically

— Omics is really thinking about endotyping patients and identifying the biological processes that are driving phenotypes

Hypo and hyperinflammatory phenotypes in ARDS

— Described by LCA incorporating demographics, clinical data, labs, vital signs, 6-8 plasma protein biomarkers

— Importantly, the groups were identified agnostically to outcomes.

— Distinguished by:

> Inflammatory biomarkers (IL-6, IL-8, TNF 1)

> Acidosis

> Shock, vasopressor requirement, and multi-system organ failure

— Consistently across 8 different data sets

— Both RCTs and observational cohorts

— Hyperinflammatory phenotype has dramatically worse clinically outcomes (higher mortality, fewer VFD)

— The different phenotypes respond differently to therapies retrospectively in RCTs

— The phenotypes did respond differently to PEEP, fluids conservative therapy, and simvastatin.

— This was not seen universally (rosuvastatin did not have differential treatment response)

— Note: We don’t really know that inflammation is at the heart of the pathogenesis of what distinguishes these two groups. The “hypoinflammatory” phenotype still has elevated levels of inflammatory biomarkers compared to controls.

What is next?

— This is all just subgroup analysis.

— These hypotheses still need to be tested prospectively

— Need to be able to easily identify the phenotypes quickly and easily

— Working on biomarker-based and non-biomarker-based clinical classifications

Key Quote:

Dr. Calfee “My takeaway point would be, there is no one best or one right way to phenotype these patients. I think there are numerous different approaches that we’re probably going to be using over the years. But I would say that what we want to focus on is what has the potential to change outcomes for our patients and to really identify individual patients or groups of patients that respond differently to therapies. And I think if we can keep that goal in mind and start testing some of these hypotheses prospectively we’re going to make progress.”

References and links for further reading

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Radiology Rounds – 9/13/22

Posted on September 13, 2022 by Pulm PEEPs

This week’s #RadiologyRounds is authored by Leon Mirson, one of our amazing Associate Editors. Follow us on Twitter to answer live polls about the case and future Radiology Rounds cases!