Air Leak in COVID-19 Patients

Jonathan Nieves*, Tarig S. Elhakim, Valentina Rojas Ortiz, Gabriell Silva, Robert Hernandez, Jose Gascon

Department of Internal Medicine, Kendall Regional Medical Center, Miami, Florida, USA

COVID-19 has been associated with multiple complications including Acute Respiratory Distress Syndrome (ARDS), thrombo-embolism, and septic shock. A rare complication is a Spontaneous pneumomediastinum (SPM), pneumothorax (PNX), and subcutaneous emphysema (SCE) unrelated to positive pressure ventilation. These complications can become life threatening if a large amount of air is present and cannot escape to the neck or retroperitoneum causing obstructive shock or tension pneumothorax. Studies suggest that the cytokine storm in COVID-19 can result in diffuse alveolar injury, which can result in the alveolar wall being vulnerable to rupture. It is also speculated that the cause of the alveolar rupture is due to the diffuse alveolar damage resulting in air leak to the mediastinum. A recent case series of COVID19 autopsies have identified the microthrombi formation and the mononuclear response that leads to diffuse alveolar damage. In addition, recent studies have shown that COVID 19 infected patients are associated with worse clinical outcomes and increase intra and postoperative pulmonary complications and mortality risk. Meaning that patients with SPM had a higher chance of intubation and a higher chance of death. For anesthesiologists, the preoperative evaluation and risk assessment have always been a crucial step in determining whether it is safe to take a patient for surgery. Studies have shown that patients who test positive for COVID 19 are associated with worse clinical outcomes and increase postoperative complications and mortality. Obtaining accurate information, using clinical judgement and having open communication with surgeons may help reduce these risks.

About COVID-19

Towards the end of 2019, health officials from Wuhan City of China identified multiple cases of pneumonia with unknown etiology complicated by Acute Respiratory Distress Syndrome(ARDS)1. Later on, nucleic acid sequence tests of samples from lung, posterior pharynx, and blood demonstrated a novel coronavirus, later named SARS-CoV2. It was determined that most of these patients visited an outdoor market that sells fish and wild animals2. It is thought that the most common route of transmission is in droplet form human to human, although aerosol transmission is possible3. The virus can remain viable and infectious on different surfaces for hours after being shed4-5.

Coronavirus is a positive-stranded RNA virus with spike glycoproteins on its envelope, which gives it the appearance of a crown6-7. The incubation period is typically 2-14 days and it typically precedes symptoms like fever, fatigue, cough, myalgia, dyspnea, headache, dizziness, loss of taste and smell, abdominal discomfort, nausea, vomiting, and diarrhea8. In general, most cases present with mild symptoms while others can progress to pneumonia, sepsis, ARDS, and multi-organ failure8

Spike proteins on SARS-COV2 bind directly to angiotensin-converting enzyme 2 (ACE2) expressed on alveolar epithelium type 2 cells9. Analysis has shown that ACE2 can facilitate viral invasion and replication in the lungs. ACE2 is also seen in other organ tissues like the gut epithelium, which is implicated in fecal-oral route transmission and severe complications leading to multi-organ failure9. Moreover, the pro-inflammatory cytokine storms seem to be the culprit for lung and tissue inflammation which leads to fibrosis10. Interferon-alpha, tumor necrosis factor and interleukin 6 are among the most commonly implicated10. Meta-analyses have shown that high LDH levels are commonly seen in patients infected with MERS-CoV11. This may be due to different mechanisms like upregulation of glycolysis due to decreased oxygen supply and cell death which releases LDH11. Serum levels of LDH are associated with an increased risk of SPM in patients with COVID1912. Damage can be seen on imaging as bilateral peripheral ground glass appearance is best seen on CT scan and can be identified early in the disease process13.

Spontaneous pneumomediastinum, Pneumothorax, and Subcutaneous emphysema in COVID-19

The presence of air within the mediastinum is known as pneumomediastinum (PM) or mediastinal emphysema. In 1819, this condition was originally described by Lannec in the setting of chest trauma14. It was further characterized by Hamman in 1939, who described the typical findings of crackles or rub sounds heard on auscultation with each contraction of the heart16. Patients usually present with chest pain, dyspnea, and subcutaneous emphysema, which is due to the continuous connection of cervical fascial planes which is seen as crepitus on physical exam. PM is typically considered benign and patients usually recover spontaneously15. However, there is a risk for severe complications which may occur when the mediastinal pressure increases resulting in obstructive shock15. There is also a risk of bilateral tension pneumothorax after air dissecting into bilateral pleural spaces. The list of possible causes of PM is extensive, but it includes barotrauma from the use of mechanical ventilation or injuries directed to the chest wall16. It can also arise spontaneously or as secondary causes of lung or airway disease that include but are not limited to cystic fibrosis or asthma increasing the risk of pneumothorax17. Other risk factors include smoking tobacco or marijuana, drug use, lung infection, and interstitial lung disease18-19

Air Leak and The Macklin Phenomenon

Air leak is referred to the escape of air from cavities that contain air into spaces that normally do not contain air. The pathophysiology of pneumomediastinum involves alveolar rupture leading to air leak through the broncho-vascular sheath to the mediastinum16. The mediastinal air can take the path of the low resistance cervical fascial planes resulting in subcutaneous emphysema which is associated with significant relief of the patient's symptoms20. This is usually a consequence of overinflated marginal alveoli causing an increased pressure gradient between alveoli and the surrounding connective tissue16. Potential causes of increased intrathoracic pressure can occur with coughing, vomiting, defecating, sneezing, or asthma exacerbations20. Another mechanism of air leak is caused by a reduction in the caliber of pulmonary vessels without a corresponding reduction in alveolar pressures as seen with vigorous Valsalva maneuver which can decrease blood return and increase alveolar pressure16.


Prior to the covid 19 pandemic lung infections caused by staphylococcal, mycoplasma, fungal, bronchiolitis obliterans organizing pneumonia, and severe pertussis had been known to cause air leaks leading to SPM and PNX21-23. Other causes of PNX have been seen in HIV patients infected with PCP or tuberculosis24.

Further review of the literature identified 13 patients who developed SPM with or without PNX or SCE during a community outbreak of SARS-CoV in Hong Kong 200312. All patients were treated with a standard protocol of broad spectrum antibiotics, ribavirin and corticosteroids12. In every patient SPM occurred before assisted ventilation being non related to invasive or noninvasive positive pressure ventilation12. Patients had a mean of 19.6 +/- 4.6 days from onset of symptoms for the development of SPM, and those who survived took an average of 28 days to completely resolve. Most patients were managed in a conservative manner, but bilateral tube thoracostomies were needed in five patients complicated by bilateral pneumothoraces12. There was a total of 4 deaths. Two of the five total patients intubated died and two additional patients without intubation on surrogates’ requests. Meaning that patients with SPM had a higher chance of intubation and a higher chance of death12. It was speculated by the authors that the cause of the alveolar rupture is due to the diffuse alveolar damage resulting in air leak to the mediastinum17.

There are many complications reported with COVID-19 positive patients that demonstrate the potential and severity posed by this deadly virus. We have identified 16 cases of SPM occurring in patients confirmed as COVID19 positive25-35. Of the 15  patients, 6 patients developed associated PNX and SCE and one case of pneumopericardium was reported25-35. Some patients presented with these complications initially while others developed them during the hospital stay. A common factor shared among these patients is that none of them required the use of an invasive or noninvasive positive pressure ventilation before the development of these complications25-35. All patients were nonsmokers and had no significant comorbidities that would place them at a high risk. This may suggest that the disease process of COVID19 can directly result in air leaks. Prior studies have shown that the exaggerated immune response to SARS-CoV could be the cause of such severe lung changes that may lead to ARDS32. A recent case series of COVID19 autopsies have identified the microthrombi formation and the mononuclear response that leads to diffuse alveolar damage33. This suggests that the exaggerated immune response is responsible for the diffuse alveolar damage which makes the alveoli prone to rupture especially with uncontrolled cough or the use of positive pressure ventilation as explained by the Macklin effect. Fortunately, 11 patients spontaneously recovered with conservative management. However, four patients did not recover and eventually expired due to respiratory failure and acute respiratory distress syndrome21-31. Although most of the patients with SPM tend to do well, they should be closely monitored for any sudden change in respiratory status or circulatory dysfunction. An early chest CT scan may help identify these complications in any patients whose respiratory status rapidly declines. 

There are certain types of surgeries that increase the chances of subcutaneous emphysema for example during laparoscopic surgery if the trocar is misplaced and CO2 is insufflated into the peritoneal cavity36. This may even cause gas to take the path of least resistance and track up into the thorax and mediastinum37. Additional risk factors are surgeries that take more than 200 minutes, or the use of additional surgical ports37. Although most cases resolve after the abdomen is deflated, caution for laryngeal edema should be taken by delaying extubation36-37. Physical exams may show crepitus in the neck and audible crunch on auscultation. Patients typically transition to a higher level of care for closer observation and tend to recover with bed rest, analgesia and oxygen therapy including mitigation of factors that increase alveolar pressure such as cough and forced expiration. 

For anesthesiologists, the preoperative evaluation and risk assessment has always been a critical step for safe surgery. New studies show that patients who test positive for COVID 19 are associated with worse clinical outcomes and increase postoperative complications and mortality38. Recovery from COVID 19 may be slow and there is a new syndrome known as “post-COVID” resulting in deconditioning of lung function due to inflammation that may lead to fibrosis38-39. Some of these patients may require surgery and are at a higher risk of intra-postoperative complications. The use of lung protective strategies and peep optimization has shown to be beneficial studies are still not conclusive to its application when it comes to patients with ARDs40. A recent international, multicenter cohort study identified patients who tested positive for SARS-CoV-2 within 7 days prior or 30 days after surgery found an increase rate of pulmonary complications, pulmonary embolism, intensive care unit admission, reoperation, 7-day mortality, and length of hospital stay41.

It showed that 30-day mortality was as high as 23.8% (268 of 1128) with men having higher mortality rates than women41. Age was also a predictor as men and women aged 70 years or older had higher rates than those younger than 70 years39,41. Pulmonary complications occurred in 219 (81.7%) of 268 patients who died. Among patients who developed pulmonary complications, 30-day mortality was highest in those who developed ARDS (102 [63.0%] of 162)39,41.

Postoperative pulmonary complications may result in reintubation and/or unplanned intensive care unit admission39. Based on available literature COVID-19 can also cause subcutaneous emphysema and should therefore be included in your differential diagnosis as a separate reason for air leak.

In some circumstances, delaying surgery in some patients greatly outweighs the risk associated with SARS-CoV-2 infection39. Certain groups of patients were highly vulnerable to adverse outcomes, such as men, people aged 70 years or older, ASA grades 3-5 or with comorbidities, cancer surgeries, emergency surgeries or major39,41.

COVID 19 continues to affect our daily life, and it is vital to keep building our understanding of the problem and investigate methods to minimize the risk for intra or postoperative pulmonary complication in COVID 19 infected patients where the surgery cannot be delayed.

Conflict of Interest

The Authors declare no conflicts of interest.

Funding information

None of the authors has any financial interests, relationships or affiliations relevant to the subject of this manuscript.

This research was supported (in whole or in part) by HCA Healthcare and/or an HCA Healthcare affiliated entity. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA Healthcare or any of its affiliated entities. 


  1. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395: 497-506. doi:10.1016/S0140-6736(20)30183-5
  2. Lu H, Stratton CW, Tang Y-W. Outbreak of pneumonia of unknown etiology in Wuhan, China: the mystery and the miracle. J Med Virol. 2020; 92: 4012. doi:10.1002/jmv.25678
  3. Hui DS, I Azhar E, Madani TA, et al. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health - The latest 2019 novel coronavirus outbreak in Wuhan, China. Int J Infect Dis. 2020; 91: 264-6. doi:10.1016/j.ijid.2020.01.009
  4. WHO pneumonia of unknown cause – China. Available:
  5. van Doremalen N, Bushmaker T, Morris DH, et al. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. N Engl J Med. 2020; 382: 1564-7. doi:10.1056/NEJMc2004973
  6. Chan JF-W, Kok K-H, Zhu Z, et al. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microbes Infect. 2020; 9: 221-36. doi:10.1080/22221751.2020.1719902
  7. Cascella M, Rajnik M, Cuomo A. Features, Evaluation and Treatment Coronavirus (COVID-19). In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing, 2020.
  8. 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; 323: 1061-9. doi:10.1001/jama.2020.1585
  9. Zhang H, Penninger JM, Li Y, et al. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020; 46: 586-90. doi:10.1007/s00134-020-05985-9
  10. Conti P, Ronconi G, Caraffa A, et al. Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies. J Biol Regul Homeost Agents. 2020; 34: 1. doi:10.23812/CONTI-E
  11. Hariyanto T I, Japar K V, Kwenandar F, et al. Inflammatory and Hematologic markers as predictors of severe outcomes in COVID-19 infection: a systematic review and meta-analysis. The American Journal of Emergency Medicine. 2021; 41: 110-119.
  12. Chu CM, Leung YY, Hui JYH, et al. Spontaneous pneumomediastinum in patients with severe acute respiratory syndrome. Eur Respir J. 2004; 23: 802-4. doi:10.1183/09031936.04.00096404
  13. Vancheri SG, Savietto G, Ballati F, et al. Radiographic findings in 240 patients with COVID-19 pneumonia: time-dependence after the onset of symptoms. Eur Radiol. 2020: 30(11): 6161-6169. doi:10.1007/s00330-020-06967-7
  14. Jougon JB, Ballester M, Delcambre F, et al. Assessment of spontaneous pneumomediastinum: experience with 12 patients. Ann Thorac Surg. 2003; 75: 1711-4. doi:10.1016/S0003-4975(03)00027-4
  15. Mason R. Chapter 72: Pneumomediastinum and mediastinitis. In: Murray and Nadel’s textbook of respiratory medicine. 4th edn. Elsevier Health Sciences, 2005. Google Scholar
  16. Macklin MT, Macklin CC. Malignant interstitial emphysema of the lungs and mediastinum as an important occult complication in many respiratory diseases and other conditions: interpretation of the clinical literature in the light of laboratory experiment. Medicine. 1944; 23: 281-358. Google Scholar
  17. Jougon JB, Ballester M, Delcambre F, et al. Assessment of spontaneous pneumomediastinum: experience with 12 patients. Ann Thorac Surg. 2003; 75: 1711-4. doi:10.1016/S0003-4975(03)00027-4
  18. Mattox KL. Pneumomediastinum in heroin and marijuana users. JACEP. 1976; 5: 26-8. doi:10.1016/S0361-1124(76)80162-1
  19. Sahni S, Verma S, Grullon J, et al. Spontaneous pneumomediastinum: time for consensus. N Am J Med Sci. 2013; 5: 460-4. doi:10.4103/1947-2714.117296
  20. Kouritas VK, Papagiannopoulos K, Lazaridis G, et al. Pneumomediastinum. J Thorac Dis. 2015; 7: S44-9. doi:10.3978/j.issn.2072-1439.2015.01.11
  21. Ödev K, Çalışkan Ü, Emlik D, et al. Pneumomediastinum and pneumopericardium due to intracavitary aspergilloma: an unusual complication of fungal pneumonia. Ped Radiol. 2002; 32: 143-145.
  22. Vázquez JL, Vázquez I, González ML, et al. Pneumomediastinum and pneumothorax as presenting signs in severe Mycoplasma pneumoniae pneumonia. Pediatr Radiol. 2007; 37: 1286-1288.
  23. Yates SP, Morcos SK. Delayed tension pneumothorax complicating staphylococcal pneumonia. Postgraduate Medical Journal. 1988; 64: 796-798.
  24. Tumbarello M, Tacconelli E, Pirronti T, et al. Pneumothorax in HIV-infected patients: role of Pneumocystis carinii pneumonia and pulmonary tuberculosis. European Respiratory Journal. 1997; 10(6): 1332-1335. doi:10.1183/09031936.97.10061332
  25. Wang J, Su X, Zhang T, et al. Spontaneous pneumomediastinum: a probable unusual complication of coronavirus disease 2019 (COVID-19) pneumonia. Korean J Radiol. 2020; 21: 627-8. doi:10.3348/kjr.2020.0281
  26. Wang W, Gao R, Zheng Y, et al. COVID-19 with spontaneous pneumothorax, pneumomediastinum and subcutaneous emphysema. J Travel Med. 2020; 27: taaa062. doi:10.1093/jtm/taaa062
  27. Zhou C, Gao C, Xie Y, et al. COVID-19 with spontaneous pneumomediastinum. Lancet Infect Dis. 2020; 20: 510. doi:10.1016/S1473-3099(20)30156-0
  28. Mohan V, Tauseen RA. Spontaneous pneumomediastinum in COVID-19. BMJ Case Rep. 2020; 13: e236519. doi:10.1136/bcr-2020-236519
  29. Romano N, Fischetti A, Melani EF. Pneumomediastinum related to Covid-19 pneumonia. Am J Med Sci. 2020. doi:10.1016/j.amjms.2020.06.003
  30. Sun R, Liu H, Wang X. Mediastinal emphysema, giant bulla, and pneumothorax developed during the course of COVID-19 pneumonia. Korean J Radiol. 2020; 21: 541-4. doi:10.3348/kjr.2020.0180
  31. Murillo Brito DA, Villalva CEA, Simón AS, et al. COVID-19 pneumonia associated with spontaneous pneumomediastinum and pneumopericardium. CTSNET. 2020: 12485831. Google Scholar
  32. Brogna B, Bignardi E, Salvatore P, et al. Unusual presentations of COVID-19 pneumonia on CT scans with spontaneous pneumomediastinum and loculated pneumothorax: a report of two cases and a review of the literature. Heart Lung. 2020. doi:10.1016/j.hrtlng.2020.06.005
  33. López Vega JM, Parra Gordo ML, Diez Tascón A, et al. Pneumomediastinum and spontaneous pneumothorax as an extrapulmonary complication of COVID-19 disease. Emerg Radiol. 2020: 27(6): 727-730. doi:10.1007/s10140-020-01806-0
  34. Kolani S, Houari N, Haloua M, et al. Spontaneous pneumomediastinum occurring in the SARS-COV-2 infection. IDCases. 2020; 21: e00806. doi:10.1016/j.idcr.2020.e00806
  35. Lei P, Mao J, Wang P. Spontaneous pneumomediastinum in a patient with coronavirus disease 2019 pneumonia and the possible underlying mechanism. Korean J Radiol. 2020; 21: 929-30. doi:10.3348/kjr.2020.0426
  36. Murdock CM, Wolff AJ, Van Geem T. Risk factors for hypercarbia, subcutaneous emphysema, pneumothorax, and pneumomediastinum during laparoscopy. Obstet Gynecol. 2000; 95(5): 704-9.
  37. Wolf JS Jr, Monk TG, McDougall EM, et al. The extraperitoneal approach and subcutaneous emphysema are associated with greater absorption of carbon dioxide during laparoscopic renal surgery. J Urol. 1995; 154(3): 959-63.
  38. Bui N, Coetzer M, Schenning, KJ, et al. Preparing previously COVID-19-positive patients for elective surgery: a framework for preoperative evaluation. Perioperative Medicine. 2021.
  39. COVID Surg Collaborative. Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study. Lancet. 2020; 396(10243): 27-38.
  40. Marcos VM, Matthias E. Protect the Lungs during Abdominal Surgery: It May Change the Postoperative Outcome. Anesthesiology. 2013; 118: 1254-1257.
  41. COVID Surg Collaborative. Delaying surgery for patients with a previous SARS-CoV-2 infection. British Journal of Surgery. 2020; 107(12): e601–e602.

Article Info

  • Journal of Anesthesiology and Pain Therapy
  • Article Type : Mini Review
  • View/Download pdf

Article Notes

  • Published on: September 29, 2021


  • SARS-CoV

  • COVID-19
  • Pneumomediastinum
  • Pneumothorax
  • Subcutaneous emphysema
  • Air leak


Dr. Jonathan Nieves,
Department of Internal Medicine, Kendall Regional Medical Center, Miami, Florida, USA;