COVID-19 Presenting with Syncope

63 yr old otherwise healthy male in Northern Italy with syncope • Xray of the Week

The patient presented to the Emergency Department with syncope. He denied contact with COVID-19 positive people in the Italian “red zones”. Vital signs including temperature were normal. Physical exam was normal.

EKG: negative

LABORATORY: CBC: Lymphopenia, otherwise normal. D-dimer: Elevated.

LDH: Elevated at 365.

Oxygen saturation: Low at 92.

Influenza virus: Negative.

Respiratory syncytial virus: Negative.

Chlamydia serology: Negative.

ABG:↓PaO2 = 60 mm Hg (N=80-100 mm Hg)

RADIOLOGY:

CT brain: Normal Chest X-ray: Bilateral linear consolidation, in left upper and lower lobes. No pleural effusion. Normal heart size.

Due to the syncope, elevated D-Dimer, and chest X-ray the patient underwent a CT pulmonary angiogram which demonstrated no pulmonary embolism. However, there was bilateral subpleural consolidation and two small areas of ground glass opacification in the left upper lobe and lingula.

The patient was admitted with a diagnosis of nonspecific pulmonary inflammation and treated with ceftriaxone and azithromycin. During hospitalization the patient’s condition worsened with the onset of respiratory distress. Non-contrast chest CT was then performed and demonstrated widespread bilateral mosaic crazy paving pattern, resolution of sub-pleural consolidations and no pleural effusion or lymphadenopathy.

Figure 1. Chest CT scan upper chest. Initial images show bilateral subpleural linear consolidation and two small areas of ground glass opacification in the left upper lobe and lingula. One week later, there is crazy paving pattern with ground glass opacities.

Figure 2. Chest CT scan lower chest. Initial images show bilateral subpleural linear consolidation and two small areas of ground glass opacification in the left upper lobe and lingula. One week later, there is crazy paving pattern with ground glass opacities.

Discussion:

This case demonstrates how the lack of epidemiological criteria and atypical clinical presentation led to the hospitalization of a COVID-19 positive patient without standard quarantine precautions. Unfortunately, this led to a delayed diagnosis and the subsequent spread of the disease in the Hospital.

It is felt that the initial radiological studies were too non-specific for an early diagnosis of COVID-19, especially given that the city was in the early phase of the pandemic. The CT chest performed one week after admission did have the typical pattern of COVID-19 with crazy paving pattern with peripheral ground glass opacities. After this experience and due to the high prevalence in the community, during this pandemic most of the non-traumatic patients triaged in the Ospedale Castelli di Verbania Emergency Department have since been considered COVID-19 positive until proven otherwise.

COVID-19 Information as of February 5, 2021:

Epidemiology and Etiology

In December of 2019, there was a large outbreak of a new coronavirus (part of the Coronaviridae family) in Wuhan, Hubei Province, China. This novel virus was termed SARS-CoV-2 and the corresponding disease caused by the virus, coronavirus disease, has been termed COVID-19. Although possibly originating in bats with an intermediate host, the virus spreads through human-to-human contact and has been shown to be transmissible during the incubation period which is up to 14 days following exposure. It is likely that 40% of infected individuals remain asymptomatic. It has been estimated that the Ro of the virus is 2.5, thus each carrier of the virus goes on to infect 2-3 other individuals and the CDC estimates that 50% of transmission occurs before symptom onset (23). Based on data from New York City where on 5/2/20, they found 20% of the sampled population was positive for antibodies, the the case fatality rate is estimated at 0.5%-1%. Due to the high rate of transmissibility of SARS-CoV-2, some epidemiologists estimate that herd immunity will be only be achieved when about 60-70% of the population has been infected and has antibodies (22).

Current Best Estimate of Infection Fatality Ratio (ref. 23):

0-19 years: 0.003%

20-49 years: 0.02%

50-69 years: 0.5%

70+ years: 5.4%

Confirmed COVID-19 cases of February 5, 2021 (ref. 7):

Seen in 192 territories and six continents.

Global: >105 Million cases. >2.3 Million deaths.

USA: >26 Million cases. >460,000 deaths.

Brazil: >9 Million cases. >230,000 deaths.

UK: >3.9 Million cases. >111,00 deaths.

Spain: >2.9 Million cases. >61,00 deaths.

Italy: >2.6 Million cases. >90,000 deaths.

Ireland: >201,000 cases. >3600 deaths.

Fatality rate per million people by country. Source:

https://ourworldindata.org/grapher/total-covid-deaths-per-million?year=latest

Excess mortality during COVID-19: The number of deaths from all causes compared to previous years. Source:

https://ourworldindata.org/grapher/excess-mortality-p-scores

Share of people who received at least one dose of COVID-19 vaccine. This may not equal the share that are fully vaccinated if the vaccine requires two doses. Source: https://ourworldindata.org/covid-vaccinations

Clinical manifestations

Most cases manifest approximately four to five days after exposure and symptoms described in 138 patients with COVID-19 pneumonia in Wuhan included fever (99%), fatigue (70%), dry cough (59%), anorexia (40%), myalgias (35%), dyspnea (31%), sputum production (27%). In an Italian survey of 59 patients with COVID-19, 34% self-reported either olfactory dysfunction such as anosmia or taste aberration. Recent reports also indicate that the virus may cause nausea, abdominal pain or diarrhea and occasionally patients may present with gastrointestinal symptoms. Rare cases have also been associated with myocarditis or encephalopathy. A recent paper out of Ireland found that patients admitted to hospital with severe COVID-19 infection may develop an unusual coagulopathy resulting in micro-thrombosis within the pulmonary vasculature (19).

Imaging Features

Plain radiograph features are less sensitive than computed tomography and are highly variable and non-specific. Within infected individuals, chest radiography most often shows bilateral involvement with patchy or diffuse asymmetric opacities within the lungs, and ground glass opacification. Involvement is most often in the lower lung zones.

CT findings include interstitial thickening, crazy paving pattern, progressive ground glass opacification which may be rounded, consolidation with air bronchograms and the reverse halo sign. The findings are more likely to be bilateral, have a peripheral distribution, and involve the lower lobes. Pleural effusion and lymphadenopathy are uncommon. Follow up CT’s often illustrate progressive worsening. Mild ground glass opacities may be seen incidentally in asymptomatic patients.

While imaging findings are useful for showing disease activity, the findings are nonspecific and many mimic those seen in influenza, cytomegalovirus pneumonia, SARS or MERS pneumonia, pulmonary edema, various interstitial lung diseases, and atypical bacterial pneumonia.

Management of COVID-19 patients and persons under investigation in the radiology department are evolving and vary depending on the needs and resources of each facility. Priorities center around early detection and limiting exposure of healthcare workers, employees and patients, as well as maintenance of radiology department operations.

Labs

The diagnosis is made by a nasopharyngeal swab specimen collected for reverse-transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2. In a study conducted on 138 hospitalized COVID-19 positive patients, the most common laboratory findings were increased PT, increased LDH, and lymphopenia. Laboratory features which have been associated with worse outcomes include lymphopenia and acute kidney injury. Elevated blood work including liver enzymes, LDH, CRP, D-dimer, PT, troponin, CPK also portend a worse prognosis.

Treatment

While many different treatment modalities are currently in the pipeline, no regimen has yet to be shown to effectively treat COVID-19. On March 28, 2020 in the United States, the FDA issued an emergency use authorization (EUA) to allow the use of hydroxychloroquine and chloroquine for COVID-19. However, this EUA was revoked on June 15, 2020 stating "Based on its ongoing analysis of the EUA and emerging scientific data, the FDA determined that chloroquine and hydroxychloroquine are unlikely to be effective in treating COVID-19." An emergency-use authorization is a lower regulatory bar than full FDA approval.

The antiviral drug remdesivir, which was developed to treat the Ebola virus has shown promise in laboratory settings to inhibit the ability of Coronavirus to infect cells in vitro. It has been effective in treating coronavirus within animals. Large randomized clinical trials with the antiviral are currently underway. The FDA issued an EUA on May 1, 2020 to treat hospitalized patients with severe COVID-19 stating the benefits of the drug outweigh its risks in patients (20).

COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU) Source: https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6

References:

1. Xiong Y, Sun D, Liu Y, et al. Clinical and High-Resolution CT Features of the COVID-19 Infection: Comparison of the Initial and Follow-up Changes. Investigative Radiology. 2020;Publish Ahead of Print. doi:10.1097/RLI.0000000000000674

2. CDC. Coronavirus Disease 2019 (COVID-19) – Symptoms. Centers for Disease Control and Prevention. https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html. Published March 29, 2020. Accessed April 5, 2020.

3. CDC. Coronavirus Disease 2019 (COVID-19). Information for Clinicians on Therapeutic Options for COVID-19 Patients. https://www.cdc.gov/coronavirus/2019-ncov/hcp/therapeutic-options.html#r7. Accessed April 5, 2020.

4. Li Y, Xia L. Coronavirus Disease 2019 (COVID-19): Role of Chest CT in Diagnosis and Management. American Journal of Roentgenology. March 2020:1-7. doi:10.2214/AJR.20.22954

5. Publishing HH. Coronavirus Resource Center. Harvard Health. https://www.health.harvard.edu/diseases-and-conditions/coronavirus-resource-center. Accessed April 5, 2020.

6. Bell DJ. COVID-19 | Radiology Reference Article | Radiopaedia.org. Radiopaedia. https://radiopaedia.org/articles/covid-19-3?lang=us. Accessed April 5, 2020.

7. Coronavirus COVID-19 Global Cases by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins. Interactive online map. https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6 Accessed April 8, 2020.

8. Hosseiny M, Kooraki S, Gholamrezanezhad A, Reddy S, Myers L. Radiology Perspective of Coronavirus Disease 2019 (COVID-19): Lessons From Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome. American Journal of Roentgenology. February 2020:1-5. doi:10.2214/AJR.20.22969

9. Gautret P, Lagier J, Parola P, Hoang V, Meddeb L, Mailhe M, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. International Journal of Antimicrobial Agents. In Press.

10. Hu Z, Song C, Xu C, et al. Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China. Sci China Life Sci. 2020 Mar 4. doi: 10.1007/s11427-020-1661-4. [Epub ahead of print]

11. Shi H, Han X, Jiang N, et al. Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect Dis. 2020 Apr;20(4):425-434. doi: 10.1016/S1473-3099(20)30086-4. Epub 2020 Feb 24.

12. Zhao W, Zhong Z, Xie X. et al. Relation Between Chest CT Findings and Clinical Conditions of Coronavirus Disease (COVID-19) Pneumonia: A Multicenter Study. AJR Am J Roentgenol. 2020 Mar 3:1-6. doi: 10.2214/AJR.20.22976. [Epub ahead of print]

13. Poyiadji N, Shahin G, Noujaim D, et al. COVID-19–associated Acute Hemorrhagic Necrotizing Encephalopathy: CT and MRI Features. Published Online: Mar 31 2020 https://doi.org/10.1148/radiol.2020201187

14. Mossa-Basha M, Meltzer CC , Kim DC, et al. Radiology Department Preparedness for COVID-19: Radiology Scientific Expert Panel. Published Online: Mar 16 2020 https://doi.org/10.1148/radiol.2020200988

15. RSNA COVID-19 Resources. Radiological Society of North America. Published online. Accessed April 5, 2020. https://www.rsna.org/covid-19

16. Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Feb 7. doi: 10.1001/jama.2020.1585. [Epub ahead of print]

17. Up to Date online. Coronavirus disease 2019 (COVID-19). https://www.uptodate.com/contents/coronavirus-disease-2019-covid-19

18. Giacomelli A, Pezzati L, Conti F, et al. Self-reported olfactory and taste disorders in SARS-CoV-2 patients: a cross-sectional study. Clin Infect Dis. 2020 Mar 26. pii: ciaa330. doi: 10.1093/cid/ciaa330. [Epub ahead of print]

19. Fogarty H, Townsend L, Ni Cheallaigh C, et al. COVID-19 Coagulopathy in Caucasian patients. British Journal of Haematology, 2020; First published online:24 April 2020 DOI: https://doi.org/10.1111/bjh.16749

20. Coronavirus (COVID-19) Update: FDA Issues Emergency Use Authorization for Potential COVID-19 Treatment. Online FDA news release. Accessed May 2, 2020. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-issues-emergency-use-authorization-potential-covid-19-treatment

21. 21 Percent Of NYC Residents Tested In State Study Have Antibodies From COVID-19. Date of publication April 23, 2020. https://gothamist.com/news/new-york-antibody-test-results-coronavirus​

22. Kwok KO, Lai F, Wei WI, et al. Herd immunity – estimating the level required to halt the COVID-19 epidemics in affected countries. J Infect. 2020 Mar 21.[Epub ahead of print] doi: 10.1016/j.jinf.2020.03.027

23. CDC. Coronavirus Disease 2019 (COVID-19) – COVID-19 Pandemic Planning Scenarios. https://www.cdc.gov/coronavirus/2019-ncov/hcp/planning-scenarios.html#definitions

Gianluca Firullo is a Radiologist at Ospedale Castelli di Verbania (Maggiore Lake), Azienda Sanitaria Locale Verbano-Cusio-Ossola Italy.

He graduated from the ancient Alma Ticinensis Univesitas of Pavia, after experiences in Northern Italy Public Hospitals of Pavia and Cuneo with responsibility roles of CT body and MSK MRI. Dr. Firullo currently carries out his radiology practice at Ospedale Castelli of Verbania (Maggiore Lake) with body MRI responsibility role. He is author and coauthor of scientific works on MRI, mammography, lung screening X-ray tomo. He has also lectured at several congresses and conferences, and is a past docent at the degree course for radiologist technicians.

Neal Shah is a medical student at The Edward Via College of Osteopathic Medicine (VCOM)–Carolinas and intends on completing his residency within the field of radiology. Prior to medical school, he completed his undergraduate studies at the University of North Carolina at Chapel Hill where he majored in economics and chemistry. During his 4 years there he worked in UNC’s Biomedical Research Imaging Center where he helped develop formulations for iron-oxide nanoparticles used for MRI; it was here that his love for the field of radiology developed. He eventually wishes to also pursue his MBA and hopes to use it to help advance the field of medicine in terms of medical innovation.

Follow Neal Shah on Twitter @nealshah95

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Kevin M. Rice, MD is the president of Global Radiology CME

Dr. Rice is a radiologist with Renaissance Imaging Medical Associates. and is currently the Vice Chief of Staff at Valley Presbyterian Hospital in Los Angeles, California. Dr. Rice has made several media appearances as part of his ongoing commitment to public education. Dr. Rice's passion for state of the art radiology and teaching includes acting as a guest lecturer at UCLA. In 2015, Dr. Rice and Natalie Rice founded Global Radiology CME to provide innovative radiology education at exciting international destinations, with the world's foremost authorities in their field. In 2016, Dr. Rice was nominated and became a semifinalist for a "Minnie" Award for the Most Effective Radiology Educator.

Follow Dr. Rice on Twitter @KevinRiceMD

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Fabio Di Stefano was proudly born in Sicily in 1964. A specialist in geriatrics, he has been the Director of Internal Medicine Department of Ospedale Castelli of Verbania since 2017. He has authored many publications on geriatrics,with a special interest in Alzheimer’s disease and osteoporosis management. Currently he is strongly committed in the struggle with SARS-CoV-2 since his department was changed into a sub-intensive COVID-19 unit.

Dr. Gabriella Traballi is in the Department of Internal Medicine at Ospedale Castelli di Verbania (Maggiore Lake), Azienda Sanitaria Locale Verbano-Cusio-Ossola Italy.