Tag: Coronavirus

Diagnosis and Management of Coagulation Disorders Related to COVID-19

Although the clinical features of SARS-CoV-2 infection were first reported in 2019, it has also been established that hospitalized patients with COVID-19, especially those admitted to intensive care unit (ICU), have an increased risk for venous thromboembolism (VTE) despite prophylactic dose anticoagulation.1-4 As a result, some experts have suggested that higher anticoagulation targets may be necessary for critically ill patients with COVID-19 pneumonia.5 An ongoing challenge in treating these patients is the absence of high-quality evidence to guide clinical decision-making.

In a review published in the International Journal of Environmental Research and Public Health, Christian Zanza, MD, PhD, of the department of emergency medicine at the Catholic University of Rome in Italy, and colleagues, summarized current literature surrounding the treatment of coagulation abnormalities in patients with COVID-19.5

Coagulation Abnormalities in COVID-19

Infection with COVID-19 may predispose patients to both venous and arterial thrombotic events, thought to be the result of platelet activation, endothelial dysfunction, and hyperinflammation. Although bleeding is not commonly observed in patients, it may occur for other reasons, such as anticoagulation therapy or trauma, and if present, treatment consists of anticoagulant reversal or discontinuation, transfusions, or hemoderivatives for concurrent bleeding disorders. The presence of specific laboratory findings in COVID-19 may indicate a hypercoagulative state is present (Table 1).

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Table 1. List of laboratory findings indicative of a hypercoagulative state in COVID-195
D-dimer elevated
Fibrinogen elevated
aPTT and PT normal or slightly prolonged
Platelet counts normal or increased
Factor VIII activity increased
VWF antigen greatly increased
Small decreases in antithrombin and small increases in protein C
Abbreviations: aPTT, activated partial thromboplastin time; PT, prothrombin time; VWF, von Willebrand factor

Other laboratory findings include the presence of a lupus anticoagulant, which is common in those with prolonged aPTT. In addition, markedly elevated levels of D-dimer may correlate with illness severity, particularly if levels are increased several-fold.

Current evidence suggests the presence of a hypercoagulative state differs from disseminated intravascular coagulation (DIC); however, some patients with COVID-19 may also satisfy the criteria for probable DIC. Evidence of acute DIC includes increased plasma D-dimers, bleeding, thrombocytopenia, low plasma fibrinogen, prolonged aPTT and PT, and microangiopathic changes on peripheral blood smear.

The 2009 International Society of Thrombosis and Haemostasis (ISTH) scoring system may help diagnose DIC in patients with COVID-19 infection. For full details of the scoring system, readers should refer to the full publication in the International Journal of Environmental Research and Public Health.5

VTE in Patients With COVID-19

Critically ill and hospitalized patients with COVID-19 are at high risk for VTE primarily due to immobility, with pulmonary embolism (PE) being the most serious clinical manifestation of VTE. Clinical assessment for PE in these patients is challenging because the symptoms often overlap with COVID-19, and imaging studies may not be viable in all cases. The authors of this review recommended that the threshold for diagnosis of VTE should be low in patients with COVID-19.

With respect to anticoagulation, most medical societies still recommend using standard prophylactic dosing for hospitalized patients, but some physicians have advocated for empiric use of therapeutic anticoagulation, even in those without a documented diagnosis of VTE. Given the current state of evidence, the authors concluded that VTE prophylaxis with at least prophylactic dosing is appropriate in all hospitalized medical, surgical, and obstetric patients with COVID-19, unless there is a contraindication to anticoagulation, such as active or serious bleeding in the preceding 24 to 48 hours.

With respect to agent, low molecular weight heparin is preferred, but unfractionated heparin may also be used in patients with severe renal impairment. In cases of heparin-induced thrombocytopenia, an alternative therapy, such as fondaparinux, may be administered. In addition, therapeutic (full dose) anticoagulation for a minimum of three months is appropriate to treat VTE, and tissue plasminogen activator is suitable for massive PE, unless a contraindication is present.

Expert Perspective: The Importance of COVID-19 Vaccination

“It is very clear that COVID-19-related morbidity is substantial for patients with different malignant disorders, particularly in those with hematological malignancies,” commented Balazs Halmos, MD, of the department of medicine at the Albert Einstein College of Medicine in New York.

“Encouraging COVID-19 vaccinations amongst these patients is of paramount importance, and is strongly endorsed by all relevant agencies,” Dr Halmos further explained.


  1. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507-513. doi:10.1016/S0140-6736(20)30211-7
  2. Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020;18(5):1094-1099. doi:10.1111/jth.14817
  3. Longhitano Y, Racca F, Zanza C, et al. Venous thrombo-embolism in hospitalized SARS-CoV-2 patients treated with three different anticoagulation protocols: prospective observational study. Biology. 2020;9(10):310. doi:10.3390/biology9100310
  4. Demelo-Rodríguez P, Cervilla-Muñoz E, Ordieres-Ortega L, et al. Incidence of asymptomatic deep vein thrombosis in patients with COVID-19 pneumonia and elevated D-dimer levels. Thromb Res. 2020;192:23-26. doi:10.1016/j.thromres.2020.05.018
  5. Zanza C, Racca F, Longhitano Y, et al. Risk management and treatment of coagulation disorders related to COVID-19 infection. Int J Environ Res Public Health. 2021;18(3):1268. doi:10.3390/ijerph18031268.

What Does the Future of the Mental Health Pandemic Hold?

Health experts across the country agree: we are in the midst of a mental health pandemic and have good reason to believe that this mental health crisis will lead to increased cases of depression1 throughout the year.

This debilitating illness currently impacts more than 17.3 million American adults, with research2 showing rates have tripled as a result of the COVID-19 pandemic. Unfortunately, many sufferers — an astounding 6.2 million3 — do not find relief using antidepressant medications. Depression treatments are simply not one-size-fits-all. As we rebound from the COVID-19 pandemic, it is more critical than ever for clinicians to take a hard look at our patients and their needs to ensure we are exploring all available options as early as we can, to give them the best chance of relief — and potential remission — from this disease that plagues too many.

The Two Health Crises

Because the physical toll of COVID-19 is very visible, the mental health ramifications were often overlooked and not prioritized early on when fear of contracting the virus permeated every element of life. As businesses closed, schools turned virtual and quarantine orders extended, the impact of the pandemic snowballed. Young adults saw major milestone events, such as graduations or proms, cancelled and 46 percent of parents4 said their teen showed signs of worsening mental health. Parents were forced to juggle their careers and childcare, causing an increase in depression, stress, and loneliness.5 Job loss also contributed to an increase in rates of depression or anxiety1 at 53.4 percent. 

Unfortunately, depression and anxiety are not the only lingering effects. We’ve seen patients who have relapsed, leaning back on substance use in an effort to alleviate the feelings of hopelessness that the uncertainty of the pandemic has brought on. In fact, recent statistics show 13 percent of adults6 have turned to substances over the last year to help themselves cope. 

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What Happens Next?

Now that vaccines are rolling out and people are slowly resuming a bit of normalcy, many will likely start to feel better, but for others, the battle with mental health will continue. This pandemic has impacted us all, but our frontline workers, especially those in health care, have been the ones to experience unprecedented stress. As a result, I expect to see an increase in post-traumatic stress symptoms7 in frontline employees and long-term effects on their overall mental health.

Shifting back to pre-pandemic lifestyles without the opportunity to properly process what has happened over the last 15 months and the grief and pain associated with it can be dangerous. As depression rates rise, so too will the demand for treatment, ultimately resulting in a shortage of mental health professionals equipped to support those suffering. In my region, patient volume has exponentially increased. We are lucky to have been able to rely on telehealth technology that became popular last year to help keep us connected and providing that critical care.

Aaron M. Hawkins, MD, The Hawkins Group

As shelter in place orders began and people found themselves confined to their homes, many mental health professionals stayed open for in-person care. Clinicians in underserved areas began scheduling virtual appointments to reach patients who would not have otherwise been able to receive in-person care — and the use of telemedicine skyrocketed8 as a result.

Thanks to its benefits and convenience, this newer technology has become a more widely accepted method of care amongst my patients who understand the importance of seeking help but do not yet feel comfortable returning to in-person treatment. Since an increasing number of practices are safely seeing patients in-person, I do predict a majority of patients will return to in-person care in the coming months, and telemedicine is a great alternative in the meantime. I also believe the reliance on telemedicine for behavioral health care will outlast the pandemic, especially for those in less populated areas and with remote working expected to continue. 

A Rise in Alternative Treatment Options

While it does appear we are nearing the end of the COVID-19 pandemic, people are still struggling with mental health illnesses and searching for new treatment options. Because statistics  show medication therapy does not work for all depressed patients — in fact, research indicates9 the likelihood of remission drops in depressed patients who do not benefit from multiple antidepressant medication attempts — one of my top recommendations for adult patients struggling with depression who don’t benefit from antidepressants is TMS therapy. TMS therapy, or transcranial magnetic stimulation, is a non-drug, non-invasive treatment that uses magnetic pulses to stimulate areas of the brain that are underactive in depression. Of my patients who have been treated with NeuroStar Advanced Therapy since the opening of my practice in early 2020, we have seen a 70 percent response rate and more than a 50 percent remission rate. And this is only the beginning. It is important that both clinicians and patients alike are aware of this technology. Hope is not lost when drugs fail.

While the first TMS device received FDA approval back in 2008, it still seems to be a relatively unknown treatment option to patients and sometimes even clinicians. I’ve heard colleagues say they learned about electroconvulsive therapy in residency, but not TMS therapy — which means there is an opportunity to enhance our conversations about alternative treatments for depression. At my practice, we’ve recognized this critical need for education and have launched a campaign designed to raise awareness about TMS therapy among fellow health care professionals, resulting in interest from local universities who want information to help educate their students.

Given the growing prevalence of depression within the US, and the probability that cases will significantly increase, physicians would be wise to help mitigate the damage by making patients aware of non-drug treatment options, like TMS, as early on in their treatment journeys as possible. TMS is safe, effective and readily available. It is covered by most major insurers, free of the side effects often associated with antidepressants, and patients can drive themselves home after treatment.

We all agree that the “end” of the COVID-19 pandemic does not mean a magical and seamless switch back to pre-pandemic life. That transition will be a slow one as the impact of the past 15 months may be long-lasting, particularly for those who have felt an incredible weight on their mental health. The good news is that there is hope with TMS therapy. Remission from depression is possible when we look outside of antidepressants and think differently about how we approach mental health wellness.


  1. Panchal N, Kamal R, Cox C, Garfield R. The implications of COVID-19 for mental health and substance use. Kaiser Family Foundation. Published February 10, 2021. Accessed May 17, 2021. https://www.kff.org/coronavirus-covid-19/issue-brief/the-implications-of-covid-19-for-mental-health-and-substance-use/
  2. Ettman CK, Abdalla SM, Cohen GH, Sampson L, Vivier PM, Galeo S. Prevalence of depression symptoms in US adults before and during the COVID-19 pandemic. JAMA Network Open. Published September 2, 2020. doi:10.1001/jamanetworkopen.2020.19686
  3. Major Depression. National Institute of Mental Health. Updated February 2019. Accessed May 17, 2021. https://www.nimh.nih.gov/health/statistics/major-depression
  4. Mott Poll Report / How the pandemic has impacted teen mental health. C.S Mott Children’s Hospital. Published online March 15, 2021. Accessed May 17, 2021. https://mottpoll.org/reports/how-pandemic-has-impacted-teen-mental-health  
  5. Bargeron E. Survey shows single-parent households with young children bear the brunt of COVID-related stress. Georgetown University Health Policy Institute Center for Children and Families. Published online January 7, 2021. Accessed May 17, 2021. https://ccf.georgetown.edu/2021/01/07/survey-shows-single-parent-households-with-young-children-bear-the-brunt-of-covid-related-stress/
  6. Czeisler, MĖ, Lane RI, Petrosky E, et al. Mental health, substance use, and suicidal ideation during the COVID-19 pandemic — United States, June 24–30, 2020. Centers for Disease Control and Prevention. Published online August 14, 2021. Accessed May 17, 2021. https://www.cdc.gov/mmwr/volumes/69/wr/mm6932a1.htm
  7. Benfante A, Di Tella M, Romeo A, Castelli L. Traumatic stress in healthcare workers during COVID-19 pandemic: a review of the immediate impact. Front Psychol. Published online October 23, 2020. doi:10.3389/fpsyg.2020.569935
  8. Mochari-Greenberger H, Pande RL. Behavioral health in America during the COVID-19 pandemic: meeting increased needs through access to high quality virtual care. Am J Health Promot. Published February 8, 2021. doi.org:10.1177/0890117120983982d
  9. Haddad PM, Talbot PS, Anderson IM, McAllister-Williams RH. Managing inadequate antidepressant response in depressive illness. Br Med Bull. Published online August 26, 2015. doi:10.1093/bmb/ldv034

Multispecialty Perspectives on Long COVID-19

In the year since the global COVID-19 pandemic was declared in March 2020 by the World Health Organization,1 short-term treatments such as prone positioning of patients2 or the use of neutralizing antibody cocktails3 have been optimized, and strategies for patients who remain symptomatic for months or experience long-term sequelae4,5 are being developed. Although several effective vaccines6-9 have been developed and the end of the pandemic is now within sight, the long and laborious healing process for patients with long COVID and society as a whole is only just beginning.

“Politicians, key opinion leaders, and other stakeholders must realize that long-COVID-19 will have a big impact on society. If millions of people feel that they are unable to get back to work, it will mean a lot for society,” said Dr Daniel Kondziella, clinical research associate professor in the Department of Neurology at Rigshospitalet, Copenhagen University Hospital. “The after-effects [of the pandemic] will go on for many years to come.”

The Evidence

A detailed follow-up of 150 patients who were treated at the University of Tours Hospital in France showed that 2 months after symptom onset, more than half (68%) of patients presented with 1 or more lingering symptom of COVID-19. The most common symptoms included diarrhea (33.3%), anosmia/ageusia (22.7%), flu-like symptoms (21.5%), a greater than 5% weight loss (17.2%), arthralgia (16.3%), chest pain (13.1%), cutaneous signs (11.5%), palpitations (10.9%), and dyspnea (7.7%).8

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A longer-term, larger study of 1733 Chinese patients who were followed up at 6 months after hospital discharge revealed that most (63%) of the patients experienced fatigue and muscle weakness, and many reported difficulty sleeping (23%), below-average 6-minute walking distances (24%), anxiety or depression (23%), and diffusion impairments (22%).9

The Respiratory System

SARS-CoV-2 infection primarily affects the respiratory tract, causing pneumonia in severe cases with a proinflammatory response.10,11 “We categorize pneumonia as typical or atypical, involving different parts of the lungs. COVID-19 is an atypical pneumonia,” explained Dr Ali Gholamrezanezhad, a radiologist and assistant professor of clinical radiology with Keck Medicine of the University of Southern California, in Los Angeles.

Because COVID-19 may manifest as an atypical pneumonia, patients with severe disease can present with peripheral or posterior distribution of bilateral, multilobar ground-glass opacification, septal and/or pleural thickening, bronchiectasis, and subpleural involvement.11

In the long term, patients who present with complex lung manifestations seen on computed tomographic imaging are at increased risk for tissue scarring. “For patients who needed to be admitted into the hospital for COVID-19, the number [of patients with scarring] can be up to 30% to 40%. In patients who are not admitted, this number is much less, possibly less than 10%. It depends on the severity of the disease,” Dr Gholamrezanezhad added. For example, 6 weeks after discharge from University Hospital RWTH Aachen in Germany, 33 patients who did not require ventilation still presented with symptoms of fatigue (45%), cough (33%), and dyspnea (33%), but there was no evidence of widespread scarring.12

The Cardiovascular System

Although primarily a disease of the respiratory tract, extrapulmonary symptoms have been highly penetrant across tissue systems,10 and many of the lingering symptoms appear to involve other organs.8,9

Dr Valentina Püntmann, consultant physician, cardiologist, clinical pharmacologist, and assistant professor in the Department of Cardiology at the University Hospital Frankfurt, and colleagues recruited 100 patients who had recently recovered from COVID-19. Most patients had acute illness, with only 33% requiring hospitalization. Using cardiovascular magnetic resonance imaging a median of 71 days after their COVID-19 diagnosis, most patients presented with persistent cardiac involvement.13

“We actually thought we were not going to find anything because we were only permitted to scan patients later in their recovery,” said Dr Püntmann. “We also didn’t think at the time about COVID-19 as a cardiac condition. And yet, we were surprised to see myocardial inflammation, scarring, and also pericarditis persisting a few months after the original infection,” she continued.

In total, 78% of the patients had abnormal cardiovascular magnetic resonance scans, most commonly elevated myocardial native T1 (73%) and T2 (60%), myocardial late gadolinium (32%), and pericardial (22%) enhancement.13 These results are particularly intriguing, as they were sourced primarily from individuals who recovered at home, indicating that patients who experience even mild symptoms can have persistent myocardial inflammation and scarring for months.

“We are following up with these patients regularly, and for many patients, things do get better. They may not get better very quickly, which is perhaps something that is long-COVID specific,” stated Dr Püntmann. “But there is also a number of patients who don’t get better. I think we definitely need to get much better at understanding why some patients don’t improve, as well as work on developing effective treatments that we can administer early.”

The Nervous System

Throughout the pandemic, hospitalized patients have presented with a wide range of neurologic manifestations, thrombotic events, delirium, seizure-like events, encephalopathy, periodic discharges, ischemic lesions, and white matter lesions, among others.14,15 There has been little to no evidence collected during hospitalization to suggest there is widespread infiltration by the SARS-CoV-2 virus across the blood-brain barrier.14,16-17 With little direct evidence, it has been speculated these presentations occur as a result of neuroinflammation.15,18

During a 3-month follow-up of 61 patients admitted to Rigshospitalet, Copenhagen University Hospital in Denmark, nearly half (45.9%) of the patients had persistent central and peripheral nervous system complications.14

“Many patients actually still have affected cognitive ability. The average MOCA [Montreal Cognitive Assessment] score was 22 out of 30. Particularly, patients [who] were discharged from the intensive care unit had 19.5 out of 30, so they’re affected cognitively,” described Dr Michael E. Benros, professor of immuno-psychiatry in the Department of Immunology and Microbiology at the University of Copenhagen.

Dr Kondziella added, “There are 3 main ways by which COVID-19 might affect the nervous system. First, the virus itself has some sort of neurotropism. That means the virus crosses the blood-brain barrier and enters the brain, where it damages the tissue directly. The other option is that there is an autoimmune response by which cross-reaction toward the virus particles induces a neuroinflammatory pathway in the brain. We did find that in our study to a relatively lesser extent, compared to the third category, which is peripheral nervous system damage not directly caused by the virus or by autoimmune responses, but more because of treatment-related disorders.”

Because many of these nervous system manifestations were attributed to treatment-related complications (n=34 vs unresolved [n=4] vs para/postinfectious [n=3]),14 many of the younger, fitter patients likely will improve over time with rehabilitation after several months, predicted Dr Benros. However, patients who experience stroke or other thrombotic events may experience life-long COVID-19 complications.


The neurologic presentations observed among patients with COVID-19 may have psychiatric consequences. “Symptoms from long-term COVID-19 are commonly fatigue, headache, insomnia, and brain fog,” stated Dr Samoon Ahmad, professor in the Department of Psychiatry at New York University Grossman School of Medicine and Unit Chief of Inpatient Psychiatry at Bellevue Hospital Center. “However, we don’t know whether these symptoms are neurologic or caused by depression.”

Dr Ahmad explained that approximately 30% of patients who recovered from COVID-19 went on to develop post-traumatic stress disorder (PTSD).19,20 Symptoms of PTSD also have been reported in multiple studies of highly exposed individuals working in the healthcare sector.21

The observation of PTSD among healthcare workers is important because it brings to the forefront the fact that by no means do you need to be infected with the virus to be experiencing psychiatric consequences from SARS-CoV-2.

Dr Ahmad expounded, “Using data from 2019, on average we see that around 8% of people have anxiety disorders, and 6% [have] depressive disorders. If you look at the most recent data in a similar population, it is mind-boggling because rates of anxiety and depression have fluctuated between 34% and 42%. It’s just remarkable that during the pandemic, about 4 in 10 adults have reported symptoms of anxiety or depressive disorders.”

Dr Ahmad commented that the extent of the psychiatric consequences from the pandemic are likely far from being realized. Future research is needed to focus on the long-term psychiatric effects among patients who have recovered from severe illness, healthcare workers who were exposed to traumatic situations, the general public who experienced increased loneliness or the loss of loved ones, and children who were isolated because of the suspension of schools.

Future Perspectives

The need for ongoing collection of highly robust data and for the streamlining of definitions, data collection strategies, and patient stratification such that more consistent data become available is apparent. A more collaborative approach to conducting SARS-CoV-2 research would not only improve understanding but allow for more precise communication with the general public, which is imperative for successful vaccination campaigns and COVID-19 rule compliance.

In the meantime, Dr Püntmann implores fellow clinicians not to ignore the exercise intolerance that persists for weeks or months after infection among some COVID-19 patients. They may offer advice to patients to slow down for 3 to 6 months and not try to push themselves back to their former fitness too early. “By [not] doing that, they can make the symptoms a lot worse and slow down their recovery. This may feel very counterintuitive, especially to the young and fit patients because they are used to getting fit as soon as possible after a flu or a cold. Recovery after COVID-19 is a different, much more protracted process.”

The other largely protracted process will be to overcome the long-term stress associated with the pandemic. “In the short term it is easy to put mental health concerns on the back burner. This sort of constant stress will eventually have an impact on mental health in general,” cautioned Dr Ahmad. “At a certain point, people just reach their breaking point.” He stated that there is a great need for large-scale improved access to basic mental health support, such that everyone can be armed with basic tools to reduce stress and develop healthy routines.


1. World Health Organization. Report of the WHO-China joint mission on coronavirus disease 2019 (COVID-19). Published February 16-24, 2020. Accessed June 1, 2021. http://who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf

2. Guérin C, Albert RK, Beitler J, et al. Prone position in ARDS patients: why, when, how and for whom. Intensive Care Med. 2020;46(12):2385-2396. doi:10.1007/s00134-020-06306-w

3. Weinreich DM, Sivapalasingam S, Norton T, et al. REGN-COV2, a neutralizing antibody cocktail, in outpatients with Covid-19. N Engl J Med. 2021;384(3):238-251. doi:10.1056/NEJMoa2035002

4. Ella R, Vadrevu KM, Jogdand H, et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomised, phase 1 trial. Lancet Infect Dis. 2021;21(5):637-646. doi:10.1016/S1473-3099(20)30942-7

5. Voysey M, Clemens SAC, Madhi SA, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2021;397(10269):99-111. doi:10.1016/S0140-6736(20)32661-1

6. Baden LR, El Sahly HM, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021;384(5):403-416. doi:10.1056/NEJMoa2035389

7. Sadoff J, Le Gars M, Shukarev G, et al. Interim results of a phase 1–2a trial of Ad26.COV2.S Covid-19 vaccine. 2021;NEJMoa2034201. N Engl J Med. doi:10.1056/NEJMoa2034201

8. Carvalho-Schneider C, Laurent E, Lemaignen A, et al. Follow-up of adults with noncritical COVID-19 two months after symptom onset. Clin Microbiol Infect. 2021;27(2):258-263. doi:10.1016/j.cmi.2020.09.052

9. Huang C, Huang L, Wang Y, et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet. 2021;397(10270):220-232. doi:10.1016/S0140-6736(20)32656-8

10. Behzad S, Aghaghazvini L, Radmard AR, Gholamrezanezhad A. Extrapulmonary manifestations of COVID-19: radiologic and clinical overview. Clin Imaging. 2020;66:35-41. doi:10.1016/j.clinimag.2020.05.013

11. Salehi S, Abedi A, Balakrishnan S, Gholamrezanezhad A. Coronavirus disease 2019 (COVID-19): a systematic review of imaging findings in 919 Patients. AJR Am J Roentgenol. 2020;215(1):87-93. doi:10.2214/AJR.20.23034

12. Daher A, Balfanz P, Cornelissen C, et al. Follow up of patients with severe coronavirus disease 2019 (COVID-19): pulmonary and extrapulmonary disease sequelae. Respir Med. 2020;174:106197. doi:10.1016/j.rmed.2020.106197

13. Puüntmann VO, Carerj ML, Wieters I, et al. Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020;5(11):1265-1273. doi:10.1001/jamacardio.2020.3557

14. Nersesjan V, Amiri M, Lebech A-M, et al. Central and peripheral nervous system complications of COVID-19: a prospective tertiary center cohort with 3-month follow-up. J Neurol. Published online January 13, 202. doi:10.1007/s00415-020-10380-x

15. Lambrecq V, Hanin A, Munoz-Musat E, et al. Association of clinical, biological, and brain magnetic resonance imaging findings with electroencephalographic findings for patients with COVID-19. JAMA Netw Open. 2021;4(3):e211489. doi:10.1001/jamanetworkopen.2021.1489

16. Moriguchi T, Harii N, Goto J, et al. A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis 2020;94:55-58. doi:10.1016/j.ijid.2020.03.062

17. Domingues RB, Mendes-Correa MC, de Moura Leite FBV, et al. First case of SARS-COV-2 sequencing in cerebrospinal fluid of a patient with suspected demyelinating disease. J Neurol. 2020;267(11):3154-3156. doi:10.1007/s00415-020-09996-w

18. Boldrini M, Canoll PD, Klein RS. How COVID-19 affects the brain. JAMA Psychiatry. Published online March 26, 2021. doi:10.1001/jamapsychiatry.2021.0500

19. Forte G, Favieri F, Tambelli R, Casagrande M. COVID-19 pandemic in the Italian population: validation of a post-traumatic stress disorder questionnaire and prevalence of PTSD symptomatology. Int J Environ Res Public Health. 2020;17(11):4151. doi:10.3390/ijerph17114151

20. Janiri D, Carfì A, Kotzalidis GD, et al. Posttraumatic stress disorder in patients after severe COVID-19 infection. JAMA Psychiatry. 2021;78(5):567-569. doi:10.1001/jamapsychiatry.2021.0109

21. Tucker P, Czapla CS. Post-COVID stress disorder: another emerging consequence of the global pandemic. Psychiatric Times. 2021;38(1).

Discrimination and Harassment in the Cardiology Workplace

Along with the myriad challenges affecting healthcare providers since the coronavirus disease 2019 (COVID-19) pandemic began, some clinicians have the burden of dealing with various forms of discrimination and harassment that may contribute to a hostile work environment (HWE). Findings from 2 recent studies elucidated the extent of these issues within the field of cardiology.

In the first paper recently published in the Journal of the American College of Cardiology, researchers investigated the prevalence of HWE in medicine, addressing not only gender discrimination but also emotional harassment.1  Cardiologists from around the world were surveyed (n=5931, 77% men and 23% women). The survey responders self-identified as White (54%), Asian (17%), Hispanic (17%), and Black (3%). In addition, 73% of responding physicians were ≤54 years of age.

Over 40% of respondents reported experiencing HWE, with the highest rates reported among women (68% vs 37%; P <.001 odds ratio [OR], 3.58; 95% CI, 3.14-4.07) and Black cardiologists (53% vs 43%; OR, 1.46 vs Whites). Specific components of HWE affected women more often than men: Emotional harassment (43% vs 26%), discrimination (56% vs 22%), and sexual harassment (12% vs 1%). The most common reasons for discrimination were gender (44%), age (37%), race (24%), religion (15%), and sexual orientation (5%). Multivariate analysis demonstrated the highest odds of experiencing HWE among women (OR, 3.39; 95% CI, 2.97-3.86; P <.001) and early-career cardiologists (OR, 1.27; 95% CI, 1.14-1.43; P <.001) compared with other physicians surveyed.

Factors that independently protected against HWE included working in a physician-owned practice (OR, 0.75; 95% CI, 0.63-0.88; P =.001), being married (OR, 0.81; 95% CI, 0.71-0.92; P =.001), and White race (OR, 0.88; 95% CI, 0.79-0.98; P =.017). Respondents reported that HWE had adverse effects on interactions with patients (53%) and colleagues (75%), as well as several aspects of career satisfaction.

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In the second study published in the journal Heart2, London-based researchers examined the frequency and types of sexism affecting female and male cardiologists in the United Kingdom. Of the 174 cardiologists (24% female, 76% male) who completed a validated online survey, 61.9 of female physicians had experienced discrimination – most often focused on gender and parenting – compared with 19.7% of male physicians. The survey responses also showed that 35.7% of female cardiologists (vs 6.1% of male cardiologists) had “experienced unwanted sexual comments, attention or advances from a superior or colleague.” Sexual harassment had a greater negative impact on professional confidence in female vs male cardiologists (42.9% vs 3.0%), and 33.3% of female cardiologists (vs 2.3% of males) reported that sexism negatively affected opportunities for career advancement.

The results of these 2 studies are consistent with previous findings, including the American College of Cardiology third decennial Professional Life Survey published in 2017, which indicated that 65% of female cardiologists (vs 23% of males) experienced workplace harassment or discrimination.3 “Women are especially likely to experience gender harassment, which includes both verbal and nonverbal behaviors that treat women or men as inferior through hostility, objectification, disparagement, or exclusion”, noted researchers in the JACC study.1

Given the potential effects of these findings on providers and their patients, organizational structure and system processes should be examined to optimize patient care. We spoke with Laxmi Mehta, MD, lead study author of the JACC study and professor in the division of cardiovascular medicine, director of the Lipids Clinic, and director of Preventative Cardiology and Women’s Cardiovascular Health at The Ohio State University Wexner Medical Center in Columbus about how to address these findings.   

What are some of the factors believed to be driving the high levels of hostility in the cardiology workplace?

Women and minorities are underrepresented in cardiology. Organizational and individual practices and beliefs can contribute to the hostile work environment. Micro- and macro-aggressions also contribute to hostility in the workplace.

What are the potential effects of HWE on patient care and provider well-being? 

Working in a HWE can negatively impact professional activities with colleagues and patient care. HWE may also result in disengagement and burnout for some people when they feel discriminated against or threatened.

What actions are needed on the institutional and employer level to reduce HWE? 

There should be a zero-tolerance policy for egregious acts of discrimination and harassment. For serious incidents of such behavior, human resources interventions and legal interventions are necessary to curb the acts. People need to feel that it is safe to voice their concerns and seek help in a non-threatening fashion, and victims should not be blamed. External review of complaints can mitigate internal suspicion of favoritism. Creation of a culture of workplace wellbeing is essential.

What are suggestions for clinicians in terms of supporting and advocating for colleagues who may be experiencing HWE?  

The American College of Cardiology and the American Heart Association just published an online Professionalism and Ethics document that outlines recommendations to address bias, structural racism, and structural sexism.4 Everyone in the cardiovascular community is responsible and must do their part to recognize and eliminate structural racism and sexism.


  1. Sharma G, Douglas PS, Hayes SN, et al. Global prevalence and impact of hostility, discrimination, and harassment in the cardiology workplace. J Am Coll Cardiol. 2021;77(19):2398-2409.
  2. Jaijee SK, Kamau-Mitchell C, Mikhail GW, Hendry C. Sexism experienced by consultant cardiologists in the United Kingdom. Heart. 2021;107(11):895-901. doi:10.1136/heartjnl-2020-317837
  3. Lewis SJ, Mehta LS, Douglas PS, et al; American College of Cardiology Women in Cardiology Leadership Council. Changes in the professional lives of cardiologists over 2 decades. J Am Coll Cardiol. 2017;69(4):452-462. doi:10.1016/j.jacc.2016.11.027
  4. Executive Committee, Benjamin IJ, Valentine CM, Oetgen WJ, et al. 2020 American Heart Association and American College of Cardiology Consensus Conference on Professionalism and Ethics: a consensus conference report. Published online May 5, 2021. J Am Coll Cardiol. doi:10.1016/j.jacc.2021.04.004

Abdominal Pain, Diarrhea in COVID-19 Linked to H pylori Infection

Among patients with coronavirus disease 2019 (COVID-19) who experience abdominal pain and diarrhea, there is a significant likelihood of Helicobacter pylori (H pylori) infection, according to the results of a study published in the Journal of Pediatric Gastroenterology and Nutrition.1

It is currently understood that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), binds angiotensin-converting enzyme-2 (ACE-2) receptors.2 These receptors are highly expressed in the intestine, suggesting that SARS-CoV-2 infection may lead to gastrointestinal symptoms among patients with COVID-19.

As H pylori increases ACE-2 receptor expression in the gastrointestinal tract, a group of researchers in Turkey conducted an investigation from June 1, 2020, to July 20, 2020 to determine the effects of H pylori on the clinical presentation and course of COVID-19 infections.1

Patients who were COVID-19 positive, confirmed via polymerase chain reaction, were included in the analysis. Stool samples were collected and the presence of H pylori was determined via antigen screening tests.

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A total of 108 patients (mean age, 49.54 years) were included in the analysis: 77 patients tested negative for H pylori infection and 31 patients tested positive. Compared with patients who tested negative, patients with H pylori infection had significantly more frequent abdominal pain (P =.007) and diarrhea (P =.006). However, COVID-19 severity, outcomes of the disease, and the number of hospitalized days were not significantly associated with H pylori infection.

The investigators noted that the association between H pylori infection and abdominal pain and diarrhea in patients with COVID-19 is mediated by ACE-2 receptors. “[T]here is an urgent need for studies investigating the presence of H pylori and the expression of ACE-2 receptors in the lungs and upper respiratory system,” the investigators noted.1


  1. Balamtekin N, Artuk C, Arslan M, Gülşen M. The effect of Helicobacter pylori on the presentation and clinical course of coronavirus disease 2019 infection. JPGN. 2021;72(4):511-513. doi: 10.1097/MPG.0000000000003005
  2. Lan J, Ge J, Yu J, et al. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptorNature. 2020;581(7807):215–220. doi. 10.1038/s41586-020-2180-5

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Impact of the COVID-19 Pandemic on Adolescent Mental Health

Even before the COVID-19 pandemic began, concerning mental health trends and major treatment gaps were noted among adolescents in the United States. According to data from the National Survey on Drug Use and Health, an estimated 13.3% of US adolescents aged 12-17 experienced at least 1 episode of major depressive disorder in 2017, yet 60.1% of these individuals did not receive treatment for their illness.1

In addition, survey results from the Centers for Disease Control and Prevention demonstrated increasing rates of US high school students experiencing persistent sadness or hopelessness (from approximately 26% in 2009 to 37% in 2019), serious contemplation of suicide (from 14% to 19%), suicide planning (from 11% to 16%), and suicide attempts (from 6% to 9%). The highest risk levels were observed for White, female, and sexual minority students compared with non-White, male, and heterosexual students.2

Early findings indicate that these issues are being further exacerbated by the current crisis, with an especially high risk of worsening mental health among individuals with pre-existing psychological problems. These results have shown increased symptoms of depression, anxiety, and post-traumatic stress disorder among youth of various age groups.3,5 “The number, severity and duration of these symptoms are influenced by age, history of trauma, psychological status before the event, hours spent watching media coverage of the event, having a family member who died and the presence or absence of social and economic supports,” wrote Hertz and Barrios in a paper published in February 2021 in Injury Prevention.2

They noted that school closures may reduce access to mental health screening and care for vulnerable students, considering the large number of adolescents — nearly 3.5 million in 2018 — receiving such services in educational settings.2 These settings represent the only source of mental health services for many adolescents, particularly those from low‐income households and racial and ethnic minority groups. The authors thus emphasized the heightened importance of collaboration between schools and community health professionals to address the growing mental health needs of students.

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Adolescents and other youth are also affected by the impact of the pandemic on their caregivers, including unemployment, financial and emotional stress, and fear of infection, highlighting the need for adults to receive adequate care and support as well.6,7 Some youth have been forced to spend more time in abusive or otherwise dysfunctional homes due to quarantine requirements.

“Assessing the relative safety of a child at home is one of the major challenges posed to mental health professionals during a pandemic,” according to a November 2020 paper co-authored by Cécile Rousseau, MD, researcher, psychiatrist, and professor in the division of social and transcultural psychiatry at McGill University in Montreal, Canada.6 “Fueled by parental stress and in the absence of the benevolent gaze of the school or daycare, the risk of maltreatment is increasing as the rate of cases reported to youth protection is decreasing.”

Providers at hospitals across the US are reporting alarming increases in rates of attempted and completed suicides among youth — especially teenagers. One school district in Las Vegas has lost 19 children to suicide since the pandemic began. Regarding the increasing number of pediatric patients presenting to hospitals nationwide with suicidal ideation, clinicians have described them as having “worse mental states” compared to similar patients typically seen before the pandemic.8

Such trends underscore the vital importance of youth outreach and creative intervention and support during these times. Mental health providers “must continue to advocate to ensure that families and children get the mental health support that they need to support resilience, to decrease family conflict and child maltreatment, and to decrease risk-taking, unsafe, and dangerous behaviors,” as stated in the November 2020 article.6

We recently interviewed Dr Rousseau to further discuss these issues and potential solutions.

Cécile Rousseau, MD

What are believed to be the reasons for the generally low rates of mental health treatment among adolescents even pre-pandemic?

I believe there are 2 main reasons: First, MH services are overall difficult to access and often not very user-friendly for youth. Although some emerging models are addressing this, they are not generalized. Second, there is a widespread tendency to confound psychological distress and its expression — through sadness, anxiety, and anger — and mental disorder.

The first is associated with life being hurtful, which is very common, while the second is associated with more individual vulnerabilities. Of course, the 2 phenomena overlap, but in past times, distress was not medicalized or an object of treatment. Rather, it was addressed through interpersonal networks, spirituality, and so on. In the past decades there has been a shift in paradigm.

How has the pandemic affected and exacerbated mental health issues in this population?

The pandemic has generated first an acute stress response — which is normal, with fear and panic reactions, among others. To a certain extent, this has supported adherence to public health measures. As time passes, this becomes a chronic stress reaction with predominant avoidance symptoms such as denial and minimization of the pandemic risk. Frustration and anger regarding constraints have also increased, leading to scapegoating through conspiracy theories, and to legitimation of violence.

These are widespread reactions, which are not within the disorder range. For many people with vulnerabilities, however, the pandemic has exacerbated their symptoms, except for some cases of phobia — particularly school phobia — or cyberdependence, as these individuals may enjoy the confinement.

What are the relevant recommendations for clinicians about how to address these issues in practice and advocate for their adolescent patients?

Clinically, outreach to our patients to maintain continuity of care is crucial. In cases of frequent family conflict, virtual care should be used cautiously as it may not provide the needed confidentiality and safety and may aggravate the family conflict in some cases.

For new cases, management should include decreasing the impact of the collateral consequences of the pandemic — most commonly from social isolation and lack of stimulation — on adolescents’ development.

What are some of the broader, longer-term solutions that are also warranted?

Schools and colleges should be at the forefront of prevention. In Canada, pediatricians have advocated for the return of youth to school and the preservation of their social network (not partying, of course!). Youth need their peers to pursue their individuation-separation task, and this has been made impossible during confinement. We need to find a balance between the security of the elderly and the fulfillment of adolescent developmental needs.


  1. Major depression. National Institute of Mental Health. Updated February 2019. Accessed online February 7, 2021. https://www.nimh.nih.gov/health/statistics/major-depression.shtml
  2. Hertz MF, Barrios LC. Adolescent mental health, COVID-19, and the value of school-community partnerships. Inj Prev. 2021;27(1):85-86. doi:10.1136/injuryprev-2020-044050
  3. Rogers AA, Ha T, Ockey S. Adolescents’ perceived socio-emotional impact of COVID-19 and implications for mental health: results from a U.S.-based mixed-methods study. J Adolesc Health. 2021;68(1):43-52. doi:10.1016/j.jadohealth.2020.09.039
  4. Liang L, Ren H, Cao R, et al. The effect of COVID-19 on youth mental healthPsychiatr Q. 2020;91(3):841-852. doi:10.1007/s11126-020-09744-3
  5. Ma Z, Zhao J, Li Y, et al. Mental health problems and correlates among 746 217 college students during the coronavirus disease 2019 outbreak in China. Epidemiol Psychiatr Sci. 2020;29:e181. doi:10.1017/S2045796020000931
  6. Rousseau C, Miconi D. Protecting youth mental health during the COVID-19 pandemic: a challenging engagement and learning process. J Am Acad Child Adolesc Psychiatry. 2020;59(11):1203-1207. doi:10.1016/j.jaac.2020.08.007
  7. Chatterjee R. Make space, listen, offer hope: How to help a suicidal teen or child. NPR. Published online February 2, 2021. Accessed online February 7, 2021. https://www.npr.org/sections/health-shots/2021/02/02/962185779/make-space-listen-offer-hope-how-to-help-a-child-at-risk-of-suicide
  8. Chatterjee R. Child psychiatrists warn that the pandemic may be driving up kids’ suicide risk. NPR. Published online February 2, 2021. Accessed online February 7, 2021. https://www.npr.org/sections/health-shots/2021/02/02/962060105/child-psychiatrists-warn-that-the-pandemic-may-be-driving-up-kids-suicide-risk

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New Guidance: American College of Physicians Discusses Antibody Response in COVID-19 Immunity

Because of the novelty of the coronavirus that causes COVID-19, there is not enough evidence to determine whether antibodies produced after exposure are protective against reinfection. As such, the American College of Physicians (ACP) published rapid, evidence-based living practice points in the Annals of Internal Medicine discussing the role of antibodies in, tests for diagnosing, and tests for estimating the prevalence of COVID-19.

Practice Point 1: Antibody Tests for COVID-19 Diagnosis

The ACP does not recommend using SARS-CoV-2 antibody tests to diagnose COVID-19. This recommendation is based on the limited evidence that suggests not all patients with COVID-19 develop antibodies early in the course of their infection, as the presence and levels of antibodies can vary across patients and be dictated by certain disease characteristics.

The guideline panel adds that clinicians and patients should be mindful that some SARS-CoV-2 antibody tests may provide false-positive results, which are caused by cross-reactivity with antibodies of other coronaviruses.

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Studies also suggest that the sensitivity, specificity, and accuracy of currently available antibody tests widely vary, further complicating their use as reliable diagnostic tools. Variation in the sensitivity and specificity of these tests can also contribute to both false-negative and false-positive results, leading to inaccurate conclusions about infection and possibly inappropriate or insufficient treatment.

Practice Point 2: Antibody Tests for Estimating Community Prevalence

Studies suggest that patients develop immune responses following exposure to the novel coronavirus. The evidence shows immunoglobulin (Ig)A and IgM antibodies are detectable in the majority of patients who are infected with the SARS-CoV-2 virus. Nearly all patients also demonstrate detectable IgG and neutralizing antibodies.

Over time, the prevalence and levels of these antibodies may vary by different patient characteristics, disease symptoms, and disease severity. On average, the levels of each of the antibody types peak between 20 to 31 days following symptom onset or polymerase chain reaction diagnosis. Studies also show that the IgM antibodies may persist for up to 115 days and neutralizing antibodies may persist up to 152 days. Therefore, the ACP notes that antibody tests could be feasible options for estimating community prevalence of COVID-19.

Practice Point 3: The Protective Effect of SARS-CoV-2 Antibodies Against Reinfection

There is a paucity of evidence to suggest that natural immunity is conferred by SARS-CoV-2 antibodies. There is no evidence to suggest SARS-CoV-2 antibodies can predict the presence, level, or durability of any conferred natural immunity, especially as it relates to protection against reinfection.

Given that most patients exhibit detectable antibodies at least 100 days after infection, it may be plausible that natural immunity can occur. However, the panel reiterates that there is no direct evidence to answer the question of whether these antibodies can protect against reinfection.

Some literature indicates that both asymptomatic and symptomatic patients can develop an antibody response indicative of natural immunity following COVID-19, but variables such as disease severity, patient factors, type and amount of antibodies developed, as well as the longevity of those antibodies, play an important role.

The guideline panel cites a small study of hospitalized patients with COVID-19 that reported a single possible case of reinfection during the convalescence stage. This patient did not have IgM or IgG antibodies detected at the 4-week follow-up period.

Limitations of the Practice Points

According to the guideline authors, the practice points presented concern only the antibody-mediated natural immunity response in COVID-19 and do not particularly address the involvement of other natural immune responses, including cell-mediated immunity or vaccine-acquired immunity.

Currently, the only evidence-based recommendation for increasing immunity to the SARS-CoV-2 virus and preventing infection is to receive an authorized COVID-19 vaccine. Additional prevention strategies recommended in the guideline include social distancing, wearing a mask in public, quarantining, and regular hand washing.

“Given limited knowledge about the association between antibody levels and natural immunity,” the guideline authors wrote, “patients with SARS-CoV-2 infection and those with a history of SARS-CoV-2 infection should follow recommended infection prevention and control procedures to slow and reduce the transmission of SARS-CoV-2.”


Qaseem A, Yost J, Etxeandia-Ikobaltzeta I, et al; for the Scientific Medical Policy Committee of the American College of Physicians. What is the antibody response and role in conferring natural immunity after SARS-CoV-2 infection? Rapid, living practice points from the American College of Physicians (version 1). Ann Intern Med. Published online March 16, 2021. doi:10.7326/M20-7569

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Venous Thromboembolism Management in Patients With COVID-19

The severe systemic inflammatory processes and hypercoagulability occurring with COVID-19 illness increase the risk for atherosclerotic plaque disruption and acute myocardial infarction (AMI). Patients with a previous history of coronary disease and/or other significant comorbidities are particularly predisposed to cardiovascular complications with COVID-19 infection.1 In this installment, we will discuss a patient with COVID-19 and venous thromboembolism.

Case Presentation

A 61-year-old woman presents to a rural emergency department with complaints of progressively worsening dyspnea over the past 24 hours and pleuritic chest pain. On initial presentation, the patient is hypoxic with an oxygen saturation of 92% on 5 L/min supplemental oxygen via nasal cannula and exhibits sinus tachycardia (130-140 beats per minute).

The patient’s COVID-19 polymerase chain reaction (PCR) test is positive. Blood work reveals D-dimer is 3 times higher than normal (<0.4 mcg/mL), initial troponin within normal limits (0-0.1 ng/mL), hemoglobin 10.7 g/dL, hematocrit 33.1%, and platelet count 172 ×10/µL.

A massive saddle pulmonary emboli (PE) is present on spiral computed tomography (CT) arteriography with intravenous contrast of the pulmonary arteries. Echocardiogram demonstrates acute cor pulmonale with a right ventricular (RV) to left ventricular (LV) diameter ratio of 1.4. Venous ultrasound reveals a nonocclusive popliteal venous thromboembolism.

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The patient is given full-dose enoxaparin and is transferred to an acute care cardiac specialty hospital for further treatment. Upon arrival at the specialty hospital, she is taken to the catheterization laboratory where a right and left pulmonary angiogram is performed with thrombectomy of the right and left pulmonary arteries.

Significant Medical History

The patient’s medical history includes type 2 diabetes mellitus, hypertension, dyslipidemia, hypothyroidism, and a 60-pack/year history of smoking.

Physical Examination

The patient is a middle-aged woman with obesity who is in acute respiratory distress. She has labored breathing and is tachypneic, with a respiratory rate in the mid-30s. Lung examination reveals mild expiratory wheezing bilaterally; a cardiac summation gallop is noted.

Electrocardiography (ECG) monitoring may indicate findings of cor pulmonale (right-sided heart failure) identified by a new incomplete or complete right bundle branch block, right axis deviation, or right ventricular ischemia with ST-segment depression in right pericardial leads. Monitoring with ECG also helps with evaluating for atrial arrhythmias such as atrial fibrillation commonly seen with PE.1

Spiral CT arteriography of the chest with contrast is ordered to rule out pulmonary embolus, which can be a contributing factor to respiratory symptoms, elevation in biomarkers, and a sequela of COVID-19 infection.3

Ultrasound of the lower extremities (bilaterally) is used to rule out deep vein thrombosis (DVT) in the lower extremities.


The gold standard for confirmation of a PE is a spiral CT with arteriography. In this case, the test confirmed the presence of a massive saddle pulmonary embolus. Minimally invasive intervention is indicated if the patient is found to have right ventricular strain on echocardiogram (Table 1).

Table 1. Recommended Diagnostic/Laboratory Tests

Coagulation: elevation in PT/INR, D-dimer, platelet count, fibrinogen
Cardiac biomarkers: troponin
Factor V Leiden mutation
Prothrombin gene mutation
Anticardiolipin antibodies (including lupus anticoagulant)
Hyperhomocysteinemia (usually due to folate deficiency)1,2
PT/INR, prothrombin time/international normalized radio

Radionuclide lung scan, commonly known as ventilation-perfusion (VQ) scan, may serve as a diagnostic tool for inpatients who have elevation in renal indices and are not able to undergo contrast studies. A VQ scan with a high clinical suspicion confirms the diagnosis of PE in 40% of cases.1

Echocardiogram is a useful tool for performing risk stratification. The presence of right ventricular wall akinesis or hypokinesis with sparing of the apex has a high specificity for acute PE. Also, in cases of PE, the ratio of the right ventricular end-diastolic area (RVEDA) to left ventricular end-diastolic area (LVEDA) exceeds the upper limit of normal, which is 0.6 mm.1

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Potential Drug Interaction Between Warfarin, COVID-19 Treatment Reported

A probable drug interaction was observed in 2 patients taking warfarin who were initiated on remdesivir and dexamethasone for the treatment of COVID-19, according to a case series recently published in the Journal of Pharmacy Practice.

The patients, a 71-year-old man and a 62 year-old-man, both on long-term warfarin therapy, presented to the emergency department with symptoms of COVID-19. Per the report, each patient’s international normalized ratio (INR) was within their specific goal and both denied any diet, lifestyle, or medication changes prior to admission.

“During admission, both patients experienced a marked elevation in INR within 24 to 48 hours of the initiation of remdesivir with dexamethasone for COVID-19 pneumonia directed therapy,” the authors reported. After several days of modification to their warfarin doses, both patients were stable enough for discharge and were counseled to continue monitoring per the instructions of their outpatient pharmacist.

Although the exact mechanism of action resulting in the interaction between dexamethasone, remdesivir, and warfarin is unknown, the authors concluded that there is potential for interaction based on a calculated Drug Interaction Probability Scale score of 5. “This probable interaction is demonstrated by marked INR elevations within 24 to 48 hours of initiation of the combination in 2 cases with patients with historically stable INR history,” the authors stated.

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Landayan RP, Saint-Felix S, Williams A. Probable interaction between warfarin and the combination of remdesivir with dexamethasone for coronavirus disease 2019 (COVID-19) treatment: A 2 case report. J. Pharm. Pract. [Published online April 5, 2021]. doi: 10.1177/08971900211008623

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Inflammatory Heart Disease Prevalence in Professional Athletes With Prior COVID-19 Infection

Among professional athletes who have tested positive for coronavirus disease 2019 (COVID-19 infection 0.6% had imaging findings suggestive of inflammatory heart disease that resulted in restriction from participation, according to a screening protocol based on American Heart Association (AHA)/American College of Cardiology (ACC) guidelines, researchers reported in JAMA Cardiology.

In May 2020, a number of major North American professional sports leagues —including Major League Soccer, Major League Baseball, the National Hockey League, the National Football League, and the men’s and women’s National Basketball Association — implemented a conservative return-to-play (RTP) cardiac testing program according to the AHA/ACC recommendations for all athletes who test positive for severe acute respiratory syndrome coronavirus 2019 (SARS-CoV-2), the virus that causes COVID-19. In this cross-sectional study, investigators sought to assess the prevalence of detectable inflammatory heart disease in professional athletes with prior SARS-CoV-2 infection in accordance with the current RTP screening recommendations.

The analysis included 789 professional athletes who tested positive for SARS-CoV-2 from May 2020 to October 2020 and underwent RTP cardiac screening. The mean age of the cohort was 25±3 (range, 19-41) years, and 777 (98.5%) were men. Among the athletes, 460 (58.3%) had previous symptomatic COVID-19 illness, and 329 (41.7%) were asymptomatic or paucisymptomatic but had tested positive for SARS-CoV-2.

SARS-CoV-2 positivity was diagnosed by polymerase chain reaction (PCR) assay in 587 (74.4%) athletes and antibody testing in 202 (25.6%) athletes. For athletes who tested positive for SARS-CoV-2 with PCR assay, cardiac screening was performed a mean of 19±17 (range, 3-156) days after the positive SARS-CoV-2 test.

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A total of 30 athletes had initial abnormal screening results and were sent for additional testing. Cardiac magnetic resonance imaging (CMR) was performed in 27 athletes in this group. Downstream testing confirmed diagnosis of inflammatory heart disease in 5 (18.5%) of the 27 athletes (0.6% of the total cohort); 3 athletes had CMR-confirmed myocarditis (0.4% of the total cohort), and 2 athletes had CMR-confirmed pericarditis (0.3% of the total cohort).

The athletes with confirmed inflammatory heart disease were held out from participation in their sport according to the RTP screening recommendations. The remaining 25 (83.3%) athletes who underwent additional testing ultimately did not have findings that suggested acute cardiac injury and returned to play. No clinical cardiac events have occurred in any of the athletes who had cardiac screening and resumed full professional sporting activity, as of late December 2020.

This study has important limitations, according to the researchers. RTP screening examinations were performed in a clinical setting and were usually analyzed and adjudicated by team physicians and cardiologists across the United States and Canada, which may lead to varying determinations of potential cardiac pathology and need for downstream testing. There was also variability in the time between SARS-CoV-2 testing and cardiac screening, and 98.5% of the athletes were men.

“We observed only rare cases of athletes having potential cardiac involvement,” stated the study authors. “This reporting of systematic RTP cardiac screening, while not generalizable to all athletic populations, can provide clinical guidance for other athletic organizations who are preparing and optimizing RTP protocols.”

Disclosures: Some of the authors reported affiliations with sports leagues, associations, and teams. Please see the original reference for a full list of disclosures.


Martinez MW, Tucker AM, Bloom OJ, et al. Prevalence of inflammatory heart disease among professional athletes with prior COVID-19 infection who received systematic return-to-play cardiac screening. JAMA Cardiol. Published online March 4, 2021. doi: 10.1001/jamacardio.2021.0565

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