key: cord-1042374-7vkdg0qk
authors: Chowdhary, Anisa; Nirwan, Lalit; Abi-Ghanem, Alain S.; Arif, Uroosa; Lahori, Simmy; Kassab, Mohamad B.; Karout, Samar O.; Itani, Rania Mazen; Abdalla, Rasha; Naffaa, Lena; Karout, Lina
title: Spontaneous Pneumomediastinum in Patients Diagnosed with COVID-19: a Case Series with Review of Literature
date: 2021-07-31
journal: Acad Radiol
DOI: 10.1016/j.acra.2021.07.013
sha: 89e9f7c4b07bf3696350c7a747b6028970045ebc
doc_id: 1042374
cord_uid: 7vkdg0qk

Spontaneous pneumomediastinum is a rare condition defined by the presence of air in the mediastinum in the absence of traumatic or iatrogenic. Although the imaging findings and complications of SARS-CoV-2 infection have been reported many times, there are few reports of the prevalence and outcomes of patients with spontaneous pneumomediastinum. In this paper, we aimed to illustrate the different manifestations, management, and outcome of three cases of SPM in COVID-19 patients and provide an extensive review of 22 related published case reports and series of 35 patients. Statistical analysis of the reviewed articles showed that SPM in COVID-19 occurs in patients with a mean age of 55.6 ± 16.7 years. Furthermore, 80% of the 35 patients are males and almost 60% have comorbidities. Intriguingly, SPM in COVID-19 is associated with a 28.5% mortality rate. These findings are consistent with our case series and are different from previous reports of SPM in non-COVID-19 cases where it most commonly occurs in younger individuals and has a self-limiting course with a good outcome. Therefore, SPM in COVID-19 patients occurs in older patients and is potentially associated with a higher mortality rate. Further studies are necessary to assess its role as a prognostic marker of poor outcome.

On March 11, 2020 , the World Health Organization (WHO) declared a pandemic caused by the novel Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) 1-3 . This virus is responsible for the novel coronavirus disease-19 which as of July 13, 2021, has infected almost 190 million people and led to the death of more than 4 million 4 . Although the definitive diagnosis of SARS-Cov-2 infection is made by a positive reverse transcriptase-polymerase chain reaction assay (RT-PCR), high false-negative results are observed due to suboptimal specimen collection, inadequate detection, and extraction techniques during nasopharyngeal swabs, variability in viral shedding or testing in the early stage of disease 5 . This has resulted in the need for alternative diagnostic tools such as chest computed tomography which currently plays a major role in the diagnosis, assessment, and surveillance of COVID-19 [5] [6] [7] . Several publications have described the radiological manifestations of COVID-19 in the chest, with one of the most common findings being the detection of bilateral multilobar peripheral ground-glass opacities (GGO) 8 . Chest CT allows the clear detection of ground-glass opacities and other COVID-19 complications such as pneumomediastinum.

Pneumomediastinum, also known as "mediastinal emphysema", is the presence of air in the mediastinum 9 .

Spontaneous pneumomediastinum (SPM) is a rare condition characterized by the presence of free air in the mediastinum without any causative factor such as trauma, mechanical ventilation, or iatrogenic injury 10 . The pathophysiology of SPM was first described by Macklin et al and known as the Mackling effect where SPM was suggested to result from alveolar rupture due to high intra-alveolar pressure or low perivascular pressure or due to both 11 . Common risk factors include underlying asthma, COPD, bronchiectasis, interstitial lung disease, vomiting, pneumonia, and malignancy 12, 13 . The use of recreational drugs such as cocaine, methamphetamine, and marijuana are also identified as risk factors 14, 15 . In this study, we illustrate the clinical manifestation, management, and outcome of three cases of SPM in COVID-19 patients. We additionally provide a literature review of 22 related case reports and series consisting of 35 COVID-19 patients who developed SPM.

A 71-year-old man with a past medical history of DM and HTN of 10 years duration presented to the ER on August 22, 2020, with 8-day history of fever, productive cough, and SOB. The patient was conscious and hypoxemic on arrival at the hospital (SpO2=80%). He was immediately started on BIPAP with moderate improvement (SpO2=89%). Pulmonary examination showed bilateral crepitations. On admission, laboratory findings were remarkable for hyponatremia (117 mEq/L), normocytic anemia, and elevated BUN (29 mg/dL), LDH (711 U/L), D-dimer (1013 ng/mL), ferritin (868 ng/mL), ESR (32 mm/hr) and CRP (40 mg/L). The patient was diagnosed with COVID-19 by RT-PCR of nasopharyngeal swabs and had reactive IgM and non-reactive IgG antibodies with ELISA. Chest radiograph showed bilateral consolidations and air space haziness in the mid to lower lung zones ( Figure 3 ). Chest CT demonstrated extensive peripheral ground-glass opacities with consolidations in both lungs affecting multiple segments, predominantly in the lower lobes, and bronchiectasis.

The CT CO-RADS was 6 and the CT severity score was 16/25. In addition, pneumomediastinum, bilateral pleural effusions, cardiomegaly, and subcentimeter mediastinal reactive lymph nodes were noted ( Figure 4 ).

The patient was admitted to the ICU and treated with Remdesivir (100 mg once per day), clexane (0.6 mg twice per day), claribid (500 mg twice per day), dexamethasone (6 mg thrice per day), ivermectin (12 mg once per day), zinc (once per day), perfinex (200 mg twice per day), mucomix (600 mg twice per day), Tazar (4.5 mg thrice per day), solumedrol (80 mg once per day) and nebulization of duoline and budecort (once and twice per day respectively). The patient was put on NIV and on day 3 of hospital admission, the patient improved and was taken off NIV and was transferred to the hospital ward on oxygen. On day 6, patient was discharged after follow-up chest CT showing resolving changes.

A 61-year-old man with a past medical history of diabetes mellitus (DM) and hypertension (HTN) of 5 years duration presented to the emergency department (ER) on September 4, 2020, with a 9-day history of fever, nonproductive cough, shortness of breath (SOB) and weakness. On admission, his vital signs were remarkable for tachycardia (heart rate=109 beats/minute) and hypoxemia (SpO2=80%). Laboratory tests showed normocytic anemia, hypernatremia (158 mEq/L) and hyperglycemia (random blood glucose= 308 mg/dL) and elevated urea After COVID-19 diagnosis, the patient was admitted to the intensive care unit (ICU) and was given, Remdesivir (100 mg once per day), Meropenem (1 mg thrice per day), clexane (0.6 mg twice per day), doxycycline (100 mg twice per day), dexamethasone (6 mg thrice per day), ivermectin (12 mg once per day), zinc (once per day), perfinex (200 mg twice per day) and nebulization of duoline and budecort (once and twice per day respectively).

Despite being placed on non-invasive ventilator (NIV), his clinical condition deteriorated on day 3 of hospitalization due to labored breathing. The patient was then intubated and placed on mechanical ventilation, however, he developed bradycardia followed by cardiac arrest and expired after unsuccessful CPR attempts.

A 30-year-old man, previously healthy, presented to the ER on October 9, 2020, with a 5-day history of fever, productive cough, and SOB. On admission, the patient was conscious and oriented. Respiratory examination showed bilateral crepitations with decreased air entry. SpO2 was 88% which improved to 92% after BIPAP. No and budecort (twice per day). The patient was placed on NIV support. On day 5 of hospitalization, his shortness of breath increased, and a chest CT was performed showing multilobar peripheral ground-glass attenuation with consolidations in both lungs, predominantly in the lower lobes. Additionally, moderate pneumomediastinum with soft tissue emphysema in the neck spaces was noted. The CO-RADS was 6 and CT Severity Score was 16/25 ( Figure 5 ). The patient was transferred to the ICU for further management. On day 11 th of admission, the patient showed significant improvement in shortness of breath and was tapered off from NIV. The patient was discharged on day 16th"

The literature search was employed through March 2021 using Pubmed and Google scholar databases. The search strategy consisted of the following keywords and MeSH terms ["spontaneous pneumomediastinum" or "SPM" or "spontaneous mediastinal emphysema"] and ["COVID-19" or "COVID 19" or "SARS-CoV-2" or "SARS Cov 2" or "novel coronavirus" or "SARS-CoV"]. Case reports and series published in English were included in our review.

All articles were initially screened by title and abstract by two independent authors. In case of different opinions in a specific article, a third author screened it for inclusion or exclusion. Therefore, the most recent 22 screened articles were included in our review.

Analyses were conducted using SPSS 24 for Windows (SPSS Inc, IBM). Patients' demographics, chronic disease, clinical presentation, radiological and laboratory findings, and outcomes were calculated. Categorical variables were presented as frequencies with percentages, and continuous variables were presented as means +/-standard deviations.

SPM is a rare condition associated with an incidence rate of 1/25,000 patients. It commonly affects patients aged 5-34 years with 76% of the cases being males 16 . It usually resolves by itself with conservative treatment such as oxygen, bed rest, and analgesics, however, protracted cases up to 2 months, although rare, have also been reported 12, 17 . In the context of viral infection, SPM has been reported in patients with influenza virus and severe acute respiratory syndrome coronavirus (SARS-CoV-1) 18 . The mechanism of SPM in viral infection is suggested to be attributed to inflammation and diffuse alveolar injury which is combined with an increased intra-alveolar pressure due to coughing resulting in alveolar rupture and alveolar air to pass to the lung interstitium which flows to the hilum and mediastinum 19, 20 . This pathophysiology is suggested to be responsible for the increased incidence of SPM in SARS-COV2 infected patients 21 .

In our manuscript, we illustrated the demographic characteristics, clinical presentation, hospital management, radiological and laboratory findings and outcomes of three patients diagnosed with COVID-19 who developed SPM. Additionally, we reviewed similar data from 22 published case reports and case series of 35 COVID-19 patients who developed SPM (Table 1) However, this age discrepancy can be a true difference or result from selection bias of elderly patients who tend to have a more severe course of COVID-19 prompting more imaging and SPM detection than in the younger population. Additionally, studies have reported SPM usually as a benign self-limiting condition with minimal mortality 11 . However, reports of SPM in SARS-CoV-1 infected patients have been associated with a more severe course of the disease and portends a poor outcome 18 . Similarly, our literature review of SPM in COVID-19 patients showed a high mortality rate which reached 28.5% (10 of 35 patients) of the published cases and 33.3%

(1 of 3) of our cases and suggested that SPM may potentially be a prognostic marker of an adverse event in COVID-19 patients. The high mortality rate could also be attributed to COVID-19 where SPM is associated with poor outcome when it occurs on a background of extensive pulmonary parenchymal damage 22 . It is worth noting, that a definitive conclusion should not be drawn from our review and small case series.

SPM occurs in older COVID-19 patients and could potentially be associated with a severe course of disease and a high mortality rate. Further studies are needed to assess whether SPM is an indicator of disease severity and poor outcome.

All authors had nothing to declare. 

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