Respiratory Investigation 62 (2024) 137–141

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Respiratory Investigation
journal homepage: www.elsevier.com/locate/resinv

Clinical features of pneumothorax associated with COVID-19: A

retrospective analysis of two centres
Kohei Fujita a, b, *, Toshiyuki Iwata c, Osamu Kanai a, b, Hiroaki Hata b, d, Hiroyuki Tanaka e,
Takuma Imakita a, Issei Oi a, Takao Odagaki b, Akihiro Aoyama f, Satoru Sawai g, Tadashi Mio a
a
Division of Respiratory Medicine, Center for Respiratory Diseases, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
b
Department of Infectious Diseases, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
c
Department of Respiratory Medicine, Kyoto Katsura Hospital, Kyoto, Japan
d
Department of Surgery, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
e
Department of Emergency and Critical Care Medicine, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
f
Department of Thoracic Surgery, Kyoto Katsura Hospital, Kyoto, Japan
g
Department of Thoracic Surgery, National Hospital Organization Kyoto Medical Center, Kyoto, Japan

A R T I C L E I N F O A B S T R A C T

Keywords: Background: Pneumothorax is a known sequela of coronavirus disease 2019 (COVID-19). However, the clinical
COVID-19 features of pneumothorax associated with COVID-19 have not been fully elucidated.
Pneumothorax Methods: Patients who developed pneumothorax within 6 months of being diagnosed with COVID-19 were
Long-COVID
retrospectively analysed at two institutions. We investigated the background factors, COVID-19 severity and
Chest drainage
treatment, timing of pneumothorax onset, treatment modalities, treatment duration, and prognosis of these
patients.
Results: A total of 21 patients were diagnosed with pneumothorax within 6 months of COVID-19 diagnosis. The
combined incidence rate of pneumothorax at two institutions was 0.89 %. The mean age of these patients was
72.5 years, and they were predominantly male (90.5 %), with a history of smoking (76.1 %). The most frequent
comorbidity was hypertension, followed by type 2 diabetes mellitus, COPD, and malignancy. Approximately 76
% of the patients had moderate or severe disease requiring oxygenation. Moreover, 90.5 % of these patients were
taking antiviral drugs; 52.4 %, immunosuppressant agents (baricitinib/tocilizumab); and 66.7 % were on
dexamethasone. The median time to the onset of pneumothorax was 15.0 days, and 86 % of cases occurred
within 1 month of COVID-19 diagnosis. Bilateral pneumothorax and pneumomediastinum were noted in one
patient each. Chest drainage was performed in 71.4 % of the patients. The mean treatment duration for pneu­
mothorax was 14.1 days, and the 30-day mortality rate was 28.6 %.
Conclusion: Pneumothorax associated with COVID-19 was more common in patients with moderate or severe
disease requiring oxygenation, and occurred within 1 month of COVID-19 diagnosis. Pneumothorax associated
with COVID-19 is a serious complication with a high mortality rate and clinicians should pay attention to it.

1. Introduction mechanical ventilation management (during positive pressure ventila­

Coronavirus disease 2019 (COVID-19), caused by infection with se­
vere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rapidly
spread worldwide, after the first case was reported in Wuhan, China, in
December 2019, causing an instant pandemic [1,2]. The pandemic
persisted in Japan until February 2020 [3,4]. Pneumothorax occurs as a
complication of severe COVID-19, ranging from its occurrence during
tion), to accidental pneumothorax in patients with mild-to-moderate
disease [5–7]. Pneumothorax has been reported to be more frequent
in COVID-19 than any other viral infections [8]. It is estimated to occur
in approximately 1 % of mild COVID-19 cases, and up to 10 % of patients
with severe COVID-19 require ICU management [5–8]. Studies have also
suggested cyst formation in the course of the disease [9]. A single-centre
observational study in Japan reported that 0.79 % of COVID-19 patients

* Corresponding author. Division of Respiratory Medicine, Center for Respiratory Diseases, National Hospital Organization Kyoto Medical Center, Fukakusa-
Mukaihata, 612, Kyoto, Japan.
E-mail address: kfujita.acd@gmail.com (K. Fujita).

https://doi.org/10.1016/j.resinv.2023.12.001
Received 5 July 2023; Received in revised form 21 November 2023; Accepted 1 December 2023
Available online 19 December 2023
2212-5345/© 2023 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.
K. Fujita et al. Respiratory Investigation 62 (2024) 137–141

had pneumothorax, and the mortality was significantly higher in pa­ Table 1
tients with pneumothorax [10]. However, there are only a few coherent Characteristics of the patients.
reports regarding the clinical presentation of this complication; hence, N = 21
further research is needed to study its various clinical aspects.
Age 72.5 ± 11.9
In this study, we aimed to evaluate the clinical characteristics of Sex (Male) 19 (90.5)
pneumothorax associated with COVID-19 at two medical centres. Smoking status
Never 5 (23.8)
2. Patients and methods Ex 12 (57.1)
Current 4 (19.0)
Respiratory comorbidities
This study was conducted at the National Hospital Organization Asthma 2 (9.5)
Kyoto Medical Center (NHOKMC: 600-bed, Kyoto, Japan) and Kyoto COPD 7 (33.3)
Katsura Hospital (KKH: 557-bed, Kyoto, Japan). These two hospitals are Interstitial pneumonia 2 (9.5)
Bronchiectasis 1 (4.8)
teaching hospitals in Kyoto City that serve the southern and western
Other comorbidities
parts of the city, respectively. During the COVID-19 pandemic, they Hypertension 11 (52.4)
treated COVID-19 patients from mild to severe, depending on the Kyoto Type 2 diabetes mellitus 7 (33.3)
City administrative sorting. The observation period of this study was Hemodialysis 2 (9.5)
from April 2020 to March 2023. We conducted a chart review of patients Malignancy 4 (19.0)
Use of systemic corticosteroid (≥10 mg/daily) 2 (9.5)
admitted with COVID-19 and identified those who developed pneumo­ Laboratory at pneumothorax onset
thorax within 6 months of being diagnosed with COVID-19. All patients WBC 9553.8 ± 3546.1
were diagnosed by COVID-19 PCR or antigen testing. Patient back­ RBC, × 106 3.7 ± 0.7
ground factors, comorbidities, severity of the disease, treatment Haemoglobin, g/dl 11.4 ± 2.0
Platelet, × 103 19.8 ± 11.1
administered, and the treatment course were collected from the medical
CRP, mg/dl 4.2 ± 7.2
records. Regarding the duration of pneumothorax treatment, the treat­
ment period was defined as the period from insertion to drain removal if Data are shown as number (%) or mean ± SD.
chest drainage was performed; or the follow-up period if only follow-up Abbreviations: COPD, chronic obstructive pulmonary disease; WBC, white blood
cell; RBC, red blood cell; CRP, C-reactive protein.
was performed.
The Ministry of Health, Labour and Welfare, Japan (MHLW) criteria
were used to determine the severity of COVID-19 [11]. Specifically, mild
Table 2
disease: only minor respiratory symptoms, no pneumonia, and no need Clinical details of COVID-19 illness.
for oxygen administration (SpO2: ≥96 %); moderate disease 1: pneu­
N = 21
monia, but no need for oxygen administration (93 % < SpO2<96 %);
moderate disease 2: pneumonia and need for oxygen administration Severity (MHWL criteria)
(SpO2≤93 %); severe disease: ICU management or mechanical venti­ Mild 3 (14.3)
Moderate 1 2 (9.5)
lator required. Moderate 2 9 (42.9)
Severe 7 (33.3)
2.1. IRB approval and patient’s consent Presence of COVID-19 pneumonia 17 (81.0)
Respiratory/oxygen support
Oxygen administration 18 (85.7)
This study was approved by the Institutional Review Boards of
HFNC 4 (19.0)
NHOKMC (approval number: 22–063) and KKH (approval number: Mechanical ventilation 5 (23.8)
886). The institutional committee waived the informed consent ECMO 3 (14.3)
requirement due to the study’s retrospective nature. Vaccination
1 2 (9.5)
2≤ 7 (33.3)
2.2. Statistical analyses Unknown 1 (4.8)
Treatment for COVID-19
Patient data are presented as number, percentage, median (range), or Antiviral agents
mean ± SD. A bar chart was constructed using Microsoft Excel version Remdesivir 16 (76.2)
2021. Molnupiravir 2 (9.5)
Ritonavir-boosted nirmatrelvir 1 (4.8)
Anti-SARS-CoV-2 monoclonal antibody 1 (4.8)
3. Results
Dexamethasone 14 (66.7)
Immunosuppressant agents
3.1. Characteristics and treatment course of the COVID-19 Baricitinib 5 (23.8)
Tocilizumab 6 (28.6)
During the study period, 21 cases of pneumothorax were identified in Anticoagulant agent 10 (47.6)

patients with COVID-19. Data on 19 and 2 cases were collected from the
NHOKMC and KKH, respectively. The NHOKMC treated 1614 and the
KKH treated 739 hospitalised COVID-19 patients during the study
period. The incidence of pneumothorax at the respective hospitals was
1.18 % and 0.27 %. The combined incidence rate of pneumothorax for
both hospitals was 0.89 %. Table 1 presents the patient characteristics.
The mean age of patients was 72.5 years, predominantly males. Almost
80 % of patients smoked or had a history of smoking. The most common
comorbidities were hypertension (52.4 %), COPD (33.3 %), type 2 dia­
betes mellitus (33.3 %), and malignancy (19.0). Two patients (9.5 %)
were taking prednisolone at a dose of ≥10 mg of per day.
Table 2 presents the clinical details of patients with COVID-19. Ac­
cording to the MHLW COVID-19 severity classification, 76 % of the
Data are shown as number (%).
Abbreviations: MHWL, Ministry of Health, Wealth and Labour, COVID-19 =
coronavirus disease 2019; HFNC, high-flow nasal cannula; ECMO, extra­
corporeal membrane oxygenation, SARS-CoV-2 = severe acute respiratory
syndrome coronavirus 2.
patients had moderate 2 or severe illness. Approximately 85 % of the
patients presented with hypoxaemia, and required oxygen administra­
tion during the treatment. Of the patients who required oxygen
administration, four required HFNC, five required mechanical ventila­
tory management, and three required ECMO management. Approxi­
mately 90 % of the patients received antiviral agents, with the highest
number of patients receiving remdesivir. Eleven patients were treated

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K. Fujita et al. Respiratory Investigation 62 (2024) 137–141

with immunosuppressive drugs: five (23.8 %) with baricitinib and six stress”, are presumed to be particularly relevant in the development of
(28.6 %) with tocilizumab. pneumothorax associated with COVID-19. The classic “Macklin effect” is
also back in the spotlight as a cause of pneumothorax and pneumo­
mediastinum occurring in COVID-19 patients [14,15]. Reports of
3.2. Characteristics and treatment course of the pneumothorax
pneumothorax and pneumomediastinum, possibly caused by the
Macklin effect, have been published in recent years in rapid succession
Among the patients with COVID-19 who developed pneumothorax,
[6,8,16–18]. All three of our cases with pneumothorax more than one
52.4 % had cysts/bullae in the lungs before the onset of pneumothorax
month after the onset of COVID-19 also showed persistent COVID-19
(see Table 3). Fig. 1 shows images of pneumothorax in patients who had
pneumonia, which resembled interstitial pneumonia. As mentioned
cysts/bullae before the onset of pneumothorax, and in patients who did
above, the Macklin effect is considered to be one of the pathogenic
not have cysts before the onset of pneumothorax. Of the 21 patients, four
mechanisms of pneumothorax associated with interstitial pneumonia.
patients did not have COVID-19 pneumonia. Of these four, three patients
The mechanism of Macklin effects is described as “increased
had pre-existing bulla in the lungs.
intra-alveolar pressure causes a breakdown of the alveolar walls around
The median time from the diagnosis of COVID-19 to the onset of
the pulmonary vessels and bronchioles, and the leaked air passes
pneumothorax was 15 days (range 0, 175). The variation in the time
through the pulmonary hilum and mediastinum to the subcutaneous
period is shown in Fig. 2. The bar chart shows that 86 % of the cases
area” [19]. It is speculated that the prolonged COVID-19 pneumonia in
occurred within 1 month of COVID-19 diagnosis. The site of occurrence
our case may also have led to the Maclin effect, resulting pneumothorax.
of pneumothorax was the left or right side in nine patients, and no sig­
In any case, pneumothorax in COVID-19 patients is increasingly recog­
nificant differences were observed between the two sites. Fifteen pa­
nised as a serious complication. This study evaluated the incidence of
tients had a thoracic drain inserted, and six patients were treated with
pneumothorax associated with COVID-19 in two medical centres located
follow-up only. Seventeen patients recovered from the pneumothorax,
in Kyoto City, Japan. In previous studies, the complication rate of
while four did not. All four patients who did not recover, died. These are
pneumothorax in patients with COVID-19 ranged from 1 % to nearly 10
four patients, one of whom had an exacerbation of respiratory failure
% in many cases [5,7,10]. Pneumothorax occurs in 24.1 % of COVID-19
after a pneumothorax, with pneumothorax as the cause of death. The
patients requiring mechanical ventilation [6]. Our combined incidence
other three patients have COVID-19 pneumonia as the direct cause of
rate of pneumothorax in both centres was lower than that reported
death due to exacerbation of COVID-19 pneumonia. Total six patients,
overseas [5,7], but similar to that reported from Japan [10]. In the
(28.6 %) who developed pneumothorax died; the causes being pneu­
present study, COVID-19 patients who developed pneumothorax
mothorax and exacerbation of the underlying disease in one patient
exhibited several characteristics.
each, and exacerbation of COVID-19 in four patients.
Firstly, many patients had a high severity of COVID-19 or severity
factors. Patients with moderate 2 and severe disease according to the
4. Discussion
MHLW severity classification, patients with moderate to severe disease
accounted for 76.2 % of all patients. The most common comorbidities
Three years after the COVID-19 pandemic began, various post-
were hypertension, COPD, type 2 diabetes mellitus and malignancy, in
COVID-19 complications have been reported. It has been hypothesised
that order, all of which are also COVID-19 severity factors. Previous
that post-COVID-19 complications are caused by the combined effects of
reports have shown that COVID-19 patients with severe illness, or those
four factors: “genetic/physical predisposition”, “biological effects of
at risk of severe illness are more prone to pneumothorax [6,7,10].
chronic stress”, “personality” and “poor social support” [12]. Reports
Secondly, 77 % of our patients did not receive positive pressure
from the Netherlands indicate that symptoms such as painful muscles,
ventilation during treatment, indicating that most patients with COVID-
chest pain, ageusia/anosmia, and general tiredness persist after
19 associated pneumothorax do not have barotrauma. Several inter­
COVID-19 [13]. Recently, several reports on post-COVID-19 pneumo­
esting reports support this finding. For instance, Everden et al. reported
thorax have been published, suggesting that pneumothorax may be a
a case of cyst formation after COVID-19 leading to pneumothorax and
post-COVID-19 complication. Two of the four factors mentioned above,
mediastinal emphysema [9]. Kawachi et al. suggested that COVID-19
“genetic/physical predisposition” and “biological effects of chronic
may contribute to alveolar fragility in patients with a smoking history,
resulting in pneumothorax [10]. Our study revealed that 11 patients
Table 3 (52.4 %) had pre-existing cysts/bullae in their lungs before the onset of
Clinical details of pneumothorax associated with COVID-19.
pneumothorax, indicating that approximately half of the cases devel­
N = 21 oped in the absence of cysts, on the other hand, the remaining 10 pa­
a
Days from COVID-19 diagnosis to pneumothorax onset, Days 15 (0–175) tients (47.6 %) had no obvious cysts/bullae. Of these 10 patients, 3
Pre-existing pulmonary cysts/bullae 11 (52.4) patients had cyst formation after COVID-19 infection. Cyst formation in
Site of pneumothorax these three patients is similar to that previously reported by Everden
Left 9 (42.9)
et al. [9] Cyst formation due to COVID-19 may be also a significant
Right 9 (42.9)
Bilateral 2 (9.5) factor.
Mediastinum 1 (4.8) The third issue to be addressed is the timing of the onset of pneu­
Treatment for pneumothorax mothorax, which often occurs within 1 month of COVID-19 onset
Chest drain 15 (71.4)
(Fig. 2). The most common time of onset of pneumothorax in COVID-19
Observation 6 (28.6)
b
Duration of pneumothorax treatment, Days 14.1 ± 11.1
patients is within one week to one month, followed by one week. In
Treatment outcome other words, 86 % of cases occurred within 1 month of COVID-19
Recover 17 (81.0) diagnosis. In a previous report, similar to our study, many cases
Unrecovered 4 (19.0) occurred within 1 month, and 1 month after the onset of COVID-19 is
Mortality
considered a favourable period for pneumothorax [10]. However, 14 %
Total 6 (28.6)
Pneumothorax 1 (4.8) of our patients developed pneumothorax after 1 month, with a
COVID-19 4 (19.0) maximum onset time of 6 months, suggesting that cases may also
Others 1 (4.8) develop after a long period of time and this should be taken into
Abbreviation: COVID-19 = coronavirus disease 2019. consideration.
a
Data are presented as median (range). Mortality is a crucial issue that must be addressed, as it is a serious
b
Data are shown as mean ± SD. complication of the procedure. Our study revealed a 30-day mortality

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K. Fujita et al. Respiratory Investigation 62 (2024) 137–141

Fig. 1. A, B: CT scan image shows an illustrative pneumothorax in a patient with pre-existent pulmonary cysts/bullae.
1C, 1D: CT scan image shows an illustrative pneumothorax in a patient without pre-existent pulmonary cysts/bullae.

Fig. 2. The bar chart shows the number of patients per time period from COVID-19 diagnosis to pneumothorax onset. The time period was divided into four cat­
egories: within 1 week, within 1 week to 1 month, within 1–3 months and within 3–6 months.

rate of 28.6 %, indicating the controversy surrounding the topic. Some
studies suggest that complications of pneumothorax have no effect on
mortality [5,7], whereas others have shown a higher mortality rate [6,
10,17]. Notably, our data showed that pneumothorax is a significant
complication of COVID-19, with a mortality rate of 28.6 %.
Furthermore, 28.6 % of patients in our study received tocilizumab,
and recent reports indicate that tocilizumab administration is a risk
factor for the development of pneumothorax, with a hazard date of 10.7
[7], Therefore, attention should be paid to any signs suggesting the
development of pneumothorax complications in patients receiving
tocilizumab.
This study had several limitations, including its retrospective nature

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K. Fujita et al.
and small sample size, which may have been biased by regional char­
acteristics. There were significant differences in the number of cases per
centre, likely due to KKH being a secondary emergency centre, whereas
NHOKMC is a tertiary emergency centre that admits more severely ill
patients. Additionally, indications for mechanical ventilation manage­
ment vary according to the COVID-19 pandemic. During the early stages
of the pandemic, patients were moved to ventilatory management with
as early as 5 L of oxygen, and the original severity of illness and in­
dications for mechanical ventilation management may have differed
from the present situation. In this retrospective study, the attending
physician had discretion over indications for thoracic drainage, timing,
and duration of treatment, leading to variations in care. Moreover, post-
COVID-19 patients are not always regularly followed up, and imaging
studies are only performed when symptoms appear, making the onset of
pneumothorax difficult to determine accurately. Despite these limita­
tions, few coherent reports exist on COVID-19 associated pneumo­
thorax, and our experience is valuable.
5. Conclusions
In conclusion, the COVID-19 pandemic is ongoing and likely to
persist sporadically. Pneumothorax is a life-threatening complication
that requires urgent recognition by clinicians in the context of COVID-
19.
Author contributions
Conceptualization: Kohei Fujita and Toshiyuki Iwata. Data collec­
tion: Kohei Fujita, Toshiyuki Iwata and Osamu Kanai. Investigation:
Kohei Fujita and Toshiyuki Iwata. Supervision: Hiroaki Hata, Takao
Odagaki, Akihiro Aoyama, Satoru Sawai, Tadashi Mio. Writing original
draft: Kohei Fujita and Toshiyuki Iwata. Writing, review, and editing:
Osamu Kanai, Hiroaki Hata, Hiroyuki Tanaka, Takuma Imakita, Issei Oi,
Takao Odagaki, Akihiro Aoyama, Satoru Sawai, and Tadashi Mio.
Project administration: Kohei Fujita, Toshiyuki Iwata, Takao Odagaki,
Akihiro Aoyama and Tadashi Mio. Patients care: All authors.
Availability of data and materials
The data used in this study can be obtained upon reasonable request
after obtaining approval from the ethics committee. Please contact the
corresponding author if necessary.
Declaration of competing interest
KF received research funding from AstraZeneca and Merck & Co.,
Inc, these are not directly related to this study. Other authors have no
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Respiratory Investigation 62 (2024) 137–141
conflict of interest.
Acknowledgements
We thank all the health professionals involved in COVID-19 treat­
ment at NHOKMC and KKH for their dedicated medical care.
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