key: cord-0909728-gmfckewe
authors: Melhorn, James; Achaiah, Andrew; Conway, Francesca M.; Thompson, Elizabeth M. F.; Skyllberg, Erik W.; Durrant, Joseph; Hasan, Neda A.; Madani, Yasser; Naran, Prasheena; Vijayakumar, Bavithra; Tate, Matthew J.; Trevelyan, Gareth E.; Zaki, Irfan; Doig, Catherine A.; Lynch, Geraldine; Warwick, Gill; Aujayeb, Avinash; Jackson, Karl A.; Iftikhar, Hina; Noble, Jonathan H.; Ng, Anthony Y. K. C.; Nugent, Mark; Evans, Philip J.; Hastings, Robert A.; Bellenberg, Harry R.; Lawrence, Hannah; Saville, Rachel L.; Johl, Nikolas T.; Grey, Adam N.; Ellis, Huw C.; Chen, Cheng; Jones, Thomas L.; Maddekar, Nadeem; Khan, Shahul Leyakathali; Muhammad, Ambreen Iqbal; Ghani, Hakim; Myint, Yadee Maung Maung; Rafique, Cecillia; Pippard, Benjamin J.; Irving, Benjamin R. H.; Ali, Fawad; Asimba, Viola H.; Azam, Aqeem; Barton, Eleanor C.; Bhatnagar, Malvika; Blackburn, Matthew P.; Millington, Kate J.; Budhram, Nicholas J.; Bunclark, Katherine L.; Sapkal, Toshit P.; Dixon, Giles; Harries, Andrew J. E.; Ijaz, Mohammad; Karunanithi, Vijayalakshmi; Naik, Samir; Khan, Malik Aamaz; Savlani, Karishma; Kumar, Vimal; Gallego, Beatriz Lara; Mahdi, Noor A.; Morgan, Caitlin; Patel, Neena; Rowlands, Elen W.; Steward, Matthew S.; Thorley, Richard S.; Wollerton, Rebecca L.; Ullah, Sana; Smith, David M.; Lason, Wojciech; Rostron, Anthony J; Rahman, Najib M; Hallifax, Rob J
title: Pneumomediastinum in COVID-19: a phenotype of severe COVID-19 pneumonitis? The results of the United Kingdom (POETIC) survey
date: 2022-02-09
journal: Eur Respir J
DOI: 10.1183/13993003.02522-2021
sha: bb22b881430d625aba330442f43cf105f9c7e465
doc_id: 909728
cord_uid: gmfckewe

BACKGROUND: There is an emerging understanding that coronavirus disease 2019 (COVID-19) is associated with increased incidence of pneumomediastinum. We aimed to determine its incidence among patients hospitalised with COVID-19 in the United Kingdom and describe factors associated with outcome. METHODS: A structured survey of pneumomediastinum and its incidence was conducted from September 2020 to February 2021. United Kingdom-wide participation was solicited via respiratory research networks. Identified patients had SARS-CoV-2 infection and radiologically proven pneumomediastinum. The primary outcomes were to determine incidence of pneumomediastinum in COVID-19 and to investigate risk factors associated with patient mortality. RESULTS: 377 cases of pneumomediastinum in COVID-19 were identified from 58 484 inpatients with COVID-19 at 53 hospitals during the study period, giving an incidence of 0.64%. Overall 120-day mortality in COVID-19 pneumomediastinum was 195/377 (51.7%). Pneumomediastinum in COVID-19 was associated with high rates of mechanical ventilation. 172/377 patients (45.6%) were mechanically ventilated at the point of diagnosis. Mechanical ventilation was the most important predictor of mortality in COVID-19 pneumomediastinum at the time of diagnosis and thereafter (p<0.001) along with increasing age (p<0.01) and diabetes mellitus (p=0.08). Switching patients from continuous positive airways pressure support to oxygen or high flow nasal oxygen after the diagnosis of pneumomediastinum was not associated with difference in mortality. CONCLUSIONS: Pneumomediastinum appears to be a marker of severe COVID-19 pneumonitis. The majority of patients in whom pneumomediastinum was identified had not been mechanically ventilated at the point of diagnosis.

'Take Home Message' / ERS Social Media Roughly 0.6% of patients admitted with COVID-19 have pneumomediastinum identified. The finding is associated with severe COVID-19 and high mortality.

Pneumomediastinum is air around the heart and structures in the middle of the chest. This survey of hospitals from around the UK found that roughly 1 in every 160 patients (0.6%) admitted to hospital with COVID-19 had pneumomediastinum identified. Most of these patients were not mechanically ventilated when pneumomediastinum was diagnosed. However, by the end of their admissions more than three quarters (76.5%) of all patients with COVID-19 and pneumomediastinum who were eligible for mechanical ventilation had been mechanically ventilated. Half of all patients with COVID-19 and pneumomediastinum died. Pneumomediastinum occurs in patients with severe COVID-19 pneumonitis but it is not clear if pneumomediastinum is a contributory factor to the high death rate. There was no difference in outcome associated with removing patients from CPAP treatment after pneumomediastinum was identified.

There is an emerging understanding that coronavirus disease 2019 (COVID-19) is associated with increased incidence of pneumomediastinum. We aimed to determine its incidence among patients hospitalized with COVID-19 in the United Kingdom and describe factors associated with outcome.

A structured survey of pneumomediastinum and its incidence was conducted from September 2020 to February 2021. United Kingdom-wide participation was solicited via respiratory research networks. Identified patients had SARS-CoV-2 infection and radiologically proven pneumomediastinum. The primary outcomes were to determine incidence of pneumomediastinum in COVID-19 and to investigate risk factors associated with patient mortality.

Results 377 cases of pneumomediastinum in COVID-19 were identified from 58,484 inpatients with COVID-19 at 53 hospitals during the study period, giving an incidence of 0.64%. Overall 120-day mortality in COVID-19 pneumomediastinum was 195/377 (51.7%). Pneumomediastinum in COVID-19 was associated with high rates of mechanical ventilation. 172/377 patients (45.6%) were mechanically ventilated at the point of diagnosis. Mechanical ventilation was the most important predictor of mortality in COVID-19 pneumomediastinum at the time of diagnosis and thereafter (p < 0.001) along with increasing age (p < 0.01) and diabetes mellitus (p = 0.08).

Switching patients from continuous positive airways pressure support to oxygen or high flow nasal oxygen after the diagnosis of pneumomediastinum was not associated with difference in mortality.

Pneumomediastinum appears to be a marker of severe COVID-19 pneumonitis. The majority of patients in whom pneumomediastinum was identified had not been mechanically ventilated at the point of diagnosis.

Pneumomediastinum (PTM) is the abnormal presence of air or gas in the mediastinum. Spontaneous PTM is rare, appearing in approximately 1 in 33,000 hospital admissions [1] . PTM has a higher reported incidence among patients receiving positive pressure ventilation (PPV), particularly those with acute respiratory distress syndrome (ARDS) [2, 3] .

The COVID-19 pandemic has seen a remarkable increase in the number of patients receiving PPV within a given period with many patients with COVID-19 pneumonitis meeting ARDS criteria [4, 5] . The publication of several case reports and small series of PTM in patients with COVID-19 could be viewed in this context [5] [6] [7] [8] . There have however, been a number of reports of PTM occurring in COVID-19 pneumonitis without positive pressure ventilation [9] [10] [11] . The true incidence of PTM in COVID-19 and its relationship to PPV remains unclear. In addition, whether management should be altered after the identification of PTM is not known.

We report a multi-centre observational study of 377 cases of COVID-19 PTM from 53 hospitals in the United Kingdom between September 2020 and February 2021.

We describe the incidence and risk factors associated with PTM in COVID-19 and associations with mortality.

The study recruited across the United Kingdom (UK). It was advertised via national and regional trainee research networks including Pulmonary Research Inter-Site Matrix (PRISM) and North West Collaborative Respiratory Research (NCORR).

identified between 01/09/2020 to 31/01/2021. The diagnosis of PTM was based on a computed tomography (CT) or plain radiograph of chest and the diagnosis of COVID-19 was based on a positive SARS-CoV-2 PCR result or evidence of COVID-19 pneumonitis on CT imaging and a clear clinical history. All participating institutions searched radiology reports using the keywords 'pneumomediastinum', 'pneumothorax' or 'subcutaneous emphysema', and patient lists from medical and respiratory wards and intensive care units to ensure all cases were identified.

Anonymized data were collected for each case. These included; demographics; past medical history; radiological findings; clinical outcomes and respiratory settings from all respiratory support prior to and after diagnosis of PTM. Follow up at 120 days or more was recorded for all patients and all cases of interhospital transfer were crosschecked to ensure no duplication. In order to accurately estimate incidence data were collected on the total numbers of patients admitted during this period who were coronavirus positive on SARS-CoV-2 PCR testing and the proportion who underwent CT imaging of chest at each institution.

All data pertaining to fraction of inspired oxygen (FiO2) were normalized to a uniform scale prior to analyses. This is described in online supplementary table S2 (e.g., all patients receiving 15L of oxygen via a non-rebreather mask with reservoir were assigned an inspired FiO2 of 90%). A variety of devices were used to deliver high flow nasal oxygen (HFNO) and continuous positive airways pressure (CPAP).

Positive end expiratory pressure (PEEP) and FiO2 for patients receiving CPAP were normalized to values based on data from the Association of Respiratory Technology and Physiology (2020). PEEP for patients on HFNO was estimated and normalized based on published physiological data from [12] . Details of this can be found in online supplementary Tables S3a and S3b and supplementary We present the following article in accordance with the STROBE reporting checklist.

A total of 377 cases of pneumomediastinum were detected of whom 98.4% had a positive SARS-CoV-2 PCR and the remainder were diagnosed clinically. The diagnosis of PTM was made or confirmed on CT-scan of chest in 318 cases (84.4%).

For 147/318 (46.2%) of the cases diagnosed by CT scan, PTM had not been visible on a preceding chest radiograph. Outcome data were obtained for all patients and incidence data from all included hospitals. All other data was ≥ 95% complete for all parameters. The maximum respiratory support provided to all patients before and after diagnosis of PTM is described in Figure 1 . Four patients whose treatment was limited to non invasive respiratory support were switched from CPAP to Oxygen at the point of diagnosis of PTM as part of a decision to initiate palliative treatment. Two patients were managed on room air throughout.

Alteration of respiratory support at the time of diagnosis is illustrated in Figure 1 .

Most patients whose respiratory support was changed after diagnosis of PTM were on CPAP. At the point of diagnosis of PTM 93 patients eligible for mechanical ventilation were on CPAP. Fifty (53.8%) of these patients were switched immediately on diagnosis of PTM to either Oxygen or HFNO therapy creating two subgroups amenable to analysis; the 50 switched to Oxygen or HFNO and the 43 continuing on CPAP. These two subgroups were retrospectively well matched at the point of diagnosis by age (CPAP mean age 57.0 years vs Oxygen or HFNO 55.6 years, p = 0.51), by the maximum FiO2 they had received (CPAP mean FIO2 66% vs Oxygen or HFNO 68%, p = 0.15) or by the maximum PEEP they had received (CPAP mean PEEP 10.4cmH 2 0 vs Oxygen or HFNO 9.8cmH 2 0, p = 0.19). The subsequent trajectory of these two subgroups is illustrated in Figure 2 . Associations of change in mode of respiratory support and mortality for these patients was examined by ANOVA. There was no significant main effect of switching support from CPAP to Oxygen or HFNO on outcome. There was however, a main effect of mechanical ventilation as a factor associated with mortality for both subgroups (p < 0.001).

Co-occurrence of pneumothorax, subcutaneous emphysema and complications associated with pneumomediastinum Pneumothorax was seen concurrently in 154/377 patients (40.8%) and subcutaneous emphysema was seen in 280/377 (74.3%) of patients. The cooccurrence of pneumomediastinum with pneumothorax, subcutaneous emphysema and tension phenomena and the use of intercostal drains are displayed in Figure 3 .

The number and frequencies of intercostal chest drains inserted are presented in online supplementary Figure S5 . In cases associated with subcutaneous emphysema, subcutaneous drains were employed in 6 (1.6%) cases. In 5 of these 6 cases subcutaneous drains were inserted for threatened or actual tension subcutaneous emphysema. There were 4 (1.1%) instances of mediastinal drains being used. In 1 of these 4 cases the mediastinal drain was inserted as an emergency bedside procedure for suspected tension PTM and tension subcutaneous emphysema. In the other 3/4 cases the mediastinal drain was inserted to obviate possible tension PTM. These four mediastinal drains were inserted in patients at four different hospitals, each without on-site cardiothoracic services.

There were 14 cases of tension pneumothorax. During 10 cases of suspected tension phenomena bilateral intercostal drains were inserted as an emergency procedure. Seven of these 10 cases were performed without prior radiographic evidence of pneumothorax.

The development of pneumothorax was not associated with increased risk of death for our cohort (Table 1 ) including the subset of 16 patients who were mechanically ventilated before pneumothorax developed [11/116 (9.5%) were among those patients who subsequently died while 5/56 (8.9%) were among those discharged, p = 0.9] There were two cases of pneumoperitoneum. Both of these cases were in mechanically ventilated patients.

In 8 cases PTM appeared following an interventional procedure that could potentially represent a separate mechanism for occurrence e.g., tracheostomy, and these cases are included in the final analysis. Analyses were performed excluding these cases without any statistically significant deviation from the results presented. Factors of the presentation and association with outcome are presented for all patients in Table 1 . All factors significantly associated with mortality in univariate analyses were entered into binary regression prediction models with the exception of the use of ECMO which, was excluded as the direction of association for this variable was in favour of discharge rather than death. The variable 'radiographic progression of pneumomediastinum' was excluded where the model was conducted from the point of diagnosis.

A regression model comparing the predictive utility of variables for mortality at 120 days from the point of diagnosis for patients eligible for all treatment is presented in Table 2 . Further models looking at the predictive utility of the same variables for mortality across the duration of hospital admission are presented for patients eligible for all treatment in online supplementary Table S7 and for those limited to CPAP in online supplementary Table S8 .

These data comprise the largest series of PTM in COVID-19 to date. In comparison with other series we sought to accurately represent the incidence of PTM in COVID-19 during the period of the surveythe United Kingdom's 'second wave' of the pandemic. Hospital records and radiology reports were systematically reviewed in each centre. Hospitals that did not observe cases of PTM but provided accurate incidence data were included. However, hospital participation was sought via trainee research networks and this may have resulted in inclusion bias.

Our estimate of incidence is also subject to diagnostic biases. We identified cases through radiology reports which, may not always reference a relevant finding. The main mode of diagnosis of PTM was CT imaging and there was considerable variation in the use of CT by participating hospitals (online supplementary Figure   S4 ). Many CT scans of chest were pulmonary angiogram studies assaying for pulmonary emboli, not for PTM. For 46.2% of the patients diagnosed with PTM on thoracic CT the PTM was not visible on their preceding chest radiograph. As only 21.7% of our total denominator population of 58,484 COVID-19 positive inpatients had thoracic CT imaging performed during their admissions, there is likely to be a number of undetected cases of PTM in our denominator population. These unknown cases may have had a more benign disease trajectory than the cases identified.

With these caveats these data demonstrate an incidence of PTM in COVID-19 of 0.64% per inpatient admission and 3.0% per COVID-19 inpatients undergoing thoracic CT. This incidence is similar to rates reported by two other studies of PTM in hospitalized COVID-19 populations from Brazil and Romania, of 0.51% and 0.67% respectively [13, 14] . The incidence of 'spontaneous' PTM in COVID-19 in this cohort i.e., without any PPV via mechanical ventilation or CPAP, was 77/58,484 (0.13%). This is much higher than estimated background rates of non-COVID-19

'spontaneous' PTM. The largest study of non-COVID-19 'spontaneous' PTM in the literature with a defined denominator population, identified 41 cases of PTM from 1,824,967 emergency department admissions over 16 years (0.00002%) [15] .

The mean age of the cohort (59.1 years) is consistent with inpatient international COVID-19 PTM cohorts from Brazil, Romania, Turkey, Pakistan and the USA [13, [16] [17] [18] [19] . It is somewhat younger than the mean age of general COVID-19 inpatients in the UK, according to the largest epidemiological study (70.4 years) [20] . There could be pathophysiological reasons why COVID-19 inpatients who develop PTM are younger than the hospital population average (we note that background rates of non-COVID-19 PTM typically occur in younger adults) [1, [14] [15] . It could reflect bias towards more frequent imaging in younger patients who are usually eligible for all treatments, with an artificial reduction in the identification of PTM in older patient groups. A younger mean age is also representative of trends in patients hospitalized with COVID-19 during the 'second wave' in the UK [21] .

Pneumothorax was found to co-exist with PTM in 40.3% of cases. This compares to reported rates of between 20.0% and 72.7% in other series with more than 10 patients [6, 13, [16] [17] [18] 22] . There was no finding of an effect on mortality of pneumothorax within this cohort, nor specifically for those patients who were mechanically ventilated when pneumothorax occurred. This contrasts with the findings of Marciniak et al [23] who report an increased risk of mortality with COVID-19 pneumothorax in a large dataset of UK inpatients, and Chopra et al [24] Subcutaneous emphysema has been documented at rates of between 63.6% and 90.5% in other COVID-19 PTM series with more than 10 patients [13, [16] [17] . This result is in keeping with high reported rates of subcutaneous emphysema in spontaneous non-COVID PTM of up to 100% [1] and in excess of lower rates of cooccurrence between subcutaneous emphysema and non-COVID-19 pneumothorax of up to 20% [25] . It would suggest that subcutaneous emphysema is a feature strongly associated with PTM and not specifically to COVID-19 PTM. It is acknowledged however, that co-occurrence of subcutaneous emphysema and PTM may be subject to diagnostic bias with patients presenting with subcutaneous emphysema more likely to have CT imaging and subsequent revealing of a diagnosis of PTM.

It is not possible to determine the effect of different ventilatory strategies on outcome within an observational study such as this. However, we examined this for those patients eligible for mechanical ventilation who were on CPAP when PTM was diagnosed. The role of CPAP in patients with PTM is a clinically important question:

Analysis of changes in respiratory support after diagnosis of PTM permits an exploration of physician preferences regarding respiratory support, and by inference use of PEEP, in PTM. Those patients who remained on CPAP immediately after diagnosis of PTM were retrospectively well matched with those patients who were switched immediately to Oxygen or HFNO by age, maximum FiO2 and maximum PEEP. There was no difference in survival at 120 days between these subgroups.

Thus, the current data do not support a policy of taking patients off CPAP when PTM is diagnosed, although we acknowledge potential confounders.

The 120-day mortality rate for patients with COVID-19 PTM of 51.7% is in keeping with reported mortality rates of 47.7% -72.2% in other COVID-19 PTM cohorts [13, [16] [17] . The severity of COVID-19 illness is demonstrated by the high mean levels of FiO2 and PEEP before and after the diagnosis of PTM was made ( Figure 1 ). Only two patients (0.5%) were managed on room air throughout admission. The number of patients who were mechanically ventilated at some point during their admission was remarkable at 76.5% of those eligible, in comparison to the UK average for mechanical ventilation of COVID-19 inpatients of 8.8% [20] . Mechanical ventilation was unsurprisingly an important prognostic factor and dominant variable in outcome prediction models (Table 2) . It is a ubiquitous event in the trajectory of a deteriorating patient eligible for this support. Only one eligible patient in our cohort died without having been mechanical ventilated.

general hospital inpatient COVID-19 studies [13, 16] . This may reflect a confounding relationship between more severe illness and higher rates of CT scanning and detection in high-care environments. It may also indicate an important role for .50). Figure 1 . 

Prior to performing the current study we conducted a literature search of evidence on the subject. We searched MEDLINE and PubMed for original peer-reviewed cohort studies describing the incidence of pneumomediastinum in COVID-19 between March 2020 and June 2021. Search terms were "Pneumomediastinum" AND "COVID-19" OR "Barotrauma" AND "COVID-19" OR "Pneumothorax" AND "COVID-19". Only reports published in English that included at least 5 cases and with estimates of a background population were included. Our search yielded 15 studies. These are detailed in table S1 below Table S1 . Previously published cohort studies with ≥5 cases of pneumomediastinum (PTM) and an identified denominator population. Domiciliary devices which entrain room air have been widely used during the pandemic. Such devices lack an oxygen blender and could result in an unreliable fraction of inspired oxygen (FiO 2 ). 19 Using a series of "bench" studies the ARTP COVID Group 20 have identified that amount of oxygen delivered (FiO 2 ) is influenced by the amount of CPAP pressure used by the patient. Ultimately increasing CPAP pressure exerts a dilutional effect on FiO 2 . 20 Aware that many subjects in our data set did not have documented FiO 2 values we derived an estimate of FiO 2 for patients based upon data from ARTP COVID Group bench studies.

Using data from the ARTP Guidance for Oxygen Utilisation document, 20 we replicated a graph representing FiO 2 for varying CPAP pressure across 4 commonly used domiciliary devices at a flow rate of 15 L/min; Resmed Lumis 100, Resmed Lumis 150, Breas Vivo2 and Resmed AS10. In the figure below mean values of FiO2 for given CPAP pressures across these devices are plotted with a non-linear regression curve of best fit derived using GraphPad Prism version 9 (adapted from ARTP Guidance for Oxygen Utilisation, 2020). 20 Using the equation of this regression curve of mean values we estimated FiO 2 values for subjects in our dataset based on the assumption of 15L/min oxygen entrainment. Figure S4 given the highly selective patient intake. There were 17 cases of pneumomediastinum from 87 patients admitted to the Royal Brompton Hospital with COVID-19 of whom 67 had thoracic CT scans.

Three participating hospitals had no cases of pneumomediastinum but supplied incidence data and are included. There was a strong significant correlation between the number of COVID-19 inpatients and the number of cases identified r(50) = 0.61 p < .001 and a strong correlation between the number of COVID-19 inpatients who had CT Thoraces performed and the number of cases identified r(50) = 0.49 p < .001. The number of COVID-19 inpatients having CT-scans is an inferior predictor of the number of pneumomediastinum cases than the total number of COVID-19 inpatients at a hospital (3-way ANOVA; COVID-19 inpatients t(50) = 3.885 p < .001; CT-scans t(50) = 1.888 p < 0.65).

We believe these results reflect the alternate indications for CT imaging in our COVID-19 inpatient cohort during this period which, were likely to assay for thromboembolism and prognostication, not for pneumomediastinum. As illustrated above, there is wide variation in the amount of CT scanning in COVID-19 pneumonitis inpatients among our hospitals. This could reflect physician opinion on the utility of CT scanning in COVID-19 and possibly the varying availability of this resource at this time during the pandemic. Figure S5 . Bar chart illustrating the number and frequencies of intercostal chest drains employed according to whether pneumothoraces were unilateral or bilateral (n=154). Bilateral pneumothorax was ascribed to pneumothoraces occurring on both sides of the thorax within the same admission. (37.1) 0 0

A binary logistic regression model of factors predictive of death at 120 days constructed for patients for full escalation from the point of diagnosis of pneumomediastinum is presented in Table 2 of the main manuscript. A similar model examining the predictive utility of variables over the course of admission is presented below. Presenting this model separately is done (i) to include radiographic progression in predictive modelling as this variable is not available at the point of diagnosis and (ii) to demonstrate the dominance of mechanical ventilation as a predictor of mortality when considered across patients" admissions. Table S7 . Binary Logistic Regression Model of factors most predictive of death at 120 days over the course of admission for patients eligible for mechanical ventilation (n=315). All variables significantly associated with mortality in univariate analyses were entered into the model stepwise, backwards. The model produces prediction accuracy for outcome of 75.2% versus a 51.1% default accuracy.

Odds Ratio or % increase per unit with 95% CI p Notably, increasing age was not one of the variables associated with increased risk of death in this older subgroup. The four significantly associated variables in the univariate analyses (listed above) were entered into the regression model below. 

Spontaneous pneumomediastinum: experience in 18 adult patients

Incidence, risk factors and outcome of barotrauma in mechanically ventilated patients

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COVID-19-associated acute respiratory distress syndrome: is a different approach to management warranted?

Pneumomediastinum and subcutaneous emphysema in COVID-19: barotrauma or lung frailty?

Predictors of

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COVID-19 and Spontaenous Pneumomediastinum: A case series

Spontaneous subcutaneous emphysema and pneumomediastinum in non-intubated patients with COVID-19

Pneumothorax and Pneumomediastinum Secondary to COVID-19 Disease Unrelated to Mechanical Ventilation

High flow nasal oxygen generates positive airway pressure in adult volunteers

Spontaneous Pneumomediastinum, Pneumothorax, Pneumopericardium and Subcutaneous Emphysema-Not So Uncommon Complications in Patients with COVID-19 Pulmonary Infection-A Series of Cases

Spontaneous pneumomediastinum: Experience in 13 patients

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Is Spontaneous Pneumomediastinum a Poor Prognostic Factor in Covid-19?

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ggalluvial: Alluvial Plots in 'ggplot2

Area-Proportional Euler and Venn Diagrams with Ellipses

Welcome to the tidyverse

We would like to thank Pallav Shah, Lupei Cai, Muhammad Tariq, Benjamin Jones , and Emma Helm for their help with data collection, Maria Tsakok and Nick Tessier for assistance with imaging and Simon Couillard and Sanjay Ramakrishnan for review of the manuscript. 

De-identified participant data from the study will be made available with publication to medical researchers on a not for profit basis by email request to the corresponding author for the purposes of propensity matching or meta-analysis.

The authors declare no conflicts of interest.

Studies marked with an asterix (*) focused on identifying COVID-19 pneumothorax (PTX) rather than COVID-19 pneumomediastinum (PTM) therefore all cases were PTM/PTX overlap with likely underestimation of incidence of COVID-19 PTM. Studies marked with (**) describe "confirmed COVID-19 infection" rather than SARS-CoV-2 PCR positivity.

Hospitals within the POETIC consortium were a representative mix of secondary and tertiary hospitals throughout the UK including those within areas of high index of multiple deprivation. They are listed below in alphabetical order:Addenbrooke's Hospital, Cambridge Andover War Memorial Hospital Barnet Hospital Basingstoke and North Hampshire Hospital, Basingstoke