key: cord-0724587-syow6p4f
authors: Chong, Woon H.; Saha, Biplab K.; Conuel, Edward; Chopra, Amit
title: The Incidence of Pleural Effusion in COVID-19 Pneumonia: State-of-the-Art Review
date: 2021-02-27
journal: Heart Lung
DOI: 10.1016/j.hrtlng.2021.02.015
sha: 1f647f4eff7d18bcd35601401883717e4108bc82
doc_id: 724587
cord_uid: syow6p4f

BACKGROUND: COVID-19-related pleural effusions are frequently described during the ongoing pandemic. OBJECTIVES: We described the incidence, characteristics, and outcomes of COVID-19-related pleural effusions based on the current evidence available in the literature. METHODS: We searched MEDLINE, Pubmed, and Google Scholar databases using keywords of “coronavirus disease 2019 (COVID-19),” “severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),” “pleural effusion,” “pleural fluid,” and “pleura” from January 1(st), 2020 to January 31(st), 2021. RESULTS: The incidence of pleural effusions was low at 7.3% among the 47 observational studies. Pleural effusions were commonly observed in critically ill patients and had Multisystem Inflammatory Syndrome (MIS). COVID-19-related pleural effusions were identified 5-7 days and 11 days, after hospital admission and onset of COVD-19 symptoms. The characteristic findings of pleural fluid were exudative, lymphocytic or neutrophilic-predominant pleural fluid with markedly elevated lactate dehydrogenase (LDH) levels and pleural fluid to serum LDH ratio. CONCLUSION: A well-designed study is required to assess the significance of COVID-19-related pleural effusions during this current pandemic.

The incidence of pleural effusions was low at 7.3% among the 47 observational studies.

Pleural effusions were commonly observed in critically ill patients and had Multisystem Inflammatory Syndrome (MIS). COVID-19-related pleural effusions were identified 5-7 days and 11 days, after hospital admission and onset of COVD-19 symptoms. The characteristic findings of pleural fluid were exudative, lymphocytic or neutrophilic-predominant pleural fluid with markedly elevated lactate dehydrogenase (LDH) levels and pleural fluid to serum LDH ratio.

A well-designed study is required to assess the significance of COVID-19-related pleural effusions during this current pandemic.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is known to cause coronavirus disease 2019 (COVID- 19) , resulting in the ongoing pandemic 1 . SARS-CoV-2 belongs to the same family of betacoronaviruses involving severe acute respiratory syndrome coronavirus (SARS-CoV-1) and middle east respiratory syndrome coronavirus (MERS-CoV) that are responsible for previous global outbreaks of respiratory illnesses such as severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS), respectively. 1 COVID-19 has been well described to present with a wide variety of respiratory complications that range from self-limiting upper respiratory tract infection to severe acute respiratory failure in the form of acute respiratory distress syndrome (ARDS) from underlying pneumonia. 2, 3 The significance of pleural effusions in COVID-19 pneumonia has not been well assessed due to the rarity of the disease limited to case reports/series; no systematic review/meta-analysis has analyzed the importance of pleural effusions in the setting of the ongoing pandemic. [4] [5] [6] [7] [8] [9] [10] [11] [12] The purpose of our review is to discuss the incidence, risk factors, outcomes, onset, and pleural fluid characteristic of pleural effusions in patients with COVID-19 pneumonia based on the current evidence available in the medical literature.

A literature search was performed through MEDLINE, Pubmed, and Google Scholar databases using keywords of "coronavirus disease 2019 (COVID- 19) ," "severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)," "pleural effusion," "pleural fluid," and "pleura" from January 1 st , 2020 to January 31 st , 2021. Articles published in the English language were selected, and any cited references were reviewed to identify relevant literature. All specified keywords were combined using the "OR" operator and "AND" operator for searching the literature. We selected articles that describe pleural effusions on chest imaging [using chest computed tomography (CT)] in adults and children due to COVID-19 infections from observational studies and case reports/series. We excluded articles that did not report pleural effusion in COVID -19 patients. All included studies in this review were analyzed for: study design (e.g., retrospective or prospective and cross-sectional, case-control, or cohort); study type (clinical or radiological characteristic); month/year; country; the number of patients; patient type (adults or adults and children); age of the patient (e.g., mean +/-standard deviation or median [interquartile range]); incidence of pleural effusions; location of pleural effusions (e.g., unilateral or bilateral); days to the diagnosis of first pleural effusion from admission; and other co-existing radiological features (e.g., frequency of pleural thickening, pleural retraction, pericardial effusion, and hilar/mediastinal lymphadenopathy) were described in Table 1 for COVID-19 observational  studies and Table 2 for COVID-19 case reports/series. We similarly compared pleural effusions observed in other SARS and MERS viruses that were briefly summarized in Table 2 . Lastly, we described the pleural effusions characteristics observed after pleural drainage was performed in four case reports/series as shown in Table 3 .

We screened a total of 141 studies ( Figure 1 ) and included 65 studies involving 47 observational studies and 18 case reports/series that described pleural effusion in either adults and/or children diagnosed with COVID-19 pneumonia ( Figure 1 ). Observational studies were divided into either clinical studies that described both the clinical and radiologic findings in COVID-19 patients or radiological studies that only reported the radiologic chest findings in COVID-19 patients. Among the 47 observational studies included in our review, 70 observational studies that assessed adults and children, the exact number of adults and children was not discussed further. The patient's age group ranged from 7.9 to 70.0 (Table 1) .

According to eight observational studies, the location of reported pleural effusions was unilateral in 66.8% (443/663) of cases, with the remainder bilateral in 33.2% (220/663) of patients. [13] [14] [15] [16] [17] [18] [19] In the two largest observational studies included in our review by Majidi et al. and Feng et al., the incidence of pleural effusions were 7.6% and 5.7% among 552 and 442 COVID-19 patients, respectively. 20,21 A high incidence of pleural effusions ranging from 13.3% to 62.5% was reported in 14 observational studies reviewed ( Table 1 ). The possible explanation for the high incidence of pleural effusions were: a) Seven observational studies had a small sample size ranging between 16 to 55 COVID-19 patients, 22-28 b) eight observational studies were single-center studies that focused on describing the radiological characteristics of COVID-19 patients, 24, 25, 27, [29] [30] [31] [32] [33] and c) five observational studies involved COVID-19-related pleural effusions among children. 23, 26, 28, 32, 34 The similarities in the overall incidence of pleural effusions encountered in COVID-19 to SARS were observed in several radiological observational studies at 7.5% (16/212). However, in MERS, the incidence substantially increased to 37.7% (29/77) that was likely due to selection bias and small sample size [ Table 2 ]. Pleural diseases such as pleural effusions and pneumothoraces may also suggest a more severe clinical course in critically ill MERS patients. [35] [36] [37] The presence of pleural effusion in the setting of other infections causing pneumonia (parapneumonic effusions) has been well described among viral pathogens such as communityacquired influenza virus (A and B), adenovirus, measles, hantavirus, herpes simplex virus (HSV), Epstein-Barr virus (EBV), cytomegalovirus (CMV). Less frequently in varicella-zoster virus and human metapneumovirus. [38] [39] [40] During zoonotic influenza outbreaks, the incidence of pleural effusions varies according to the influenza strain, such as swine influenza A H1N1 (7.7-8.3%), avian influenza A H5N1 (33.3%), and avian influenza A H7N9 (75-88.9%). 38 Other additional chest CT findings related to pleural disease noted in COVID-19 patients were pleural thickening and pleural retraction. The incidence of pleural thickening was 46.9% (534/1,139) in 11 observational studies (Table 1) . Pleural retraction was only noted in three observational studies with a reported incidence of 41.7% (75/180). 14, 32, 46 Although pleural thickening was commonly observed in elderly COVID-19 patients who were age 60 years and older (71.4% versus 40.9%; p = 0.011), which might indicate higher disease severity such as ARDS with greater radiologic lung involvement, the incidence of pleural traction and effusion remained similar, regardless of age group. 47 In SARS patients, chest imaging during the latestage of ARDS (two weeks and more) consisting of lung fibrosis and pleural thickening/retraction are similar to those seen in late-stage ARDS from alternative etiologies. 48 It is also not unusual for patients with avian influenza A (H5N1) pneumonia to develop lung and pleural fibrosis (retraction) during the convalescent stage of ARDS. 41 It has been suggested that to distinguish between patients with non-COVID-19 pneumonia and COVID-19 pneumonia, the radiologic finding of pleural effusion likely favors the diagnosis of former such as rhinovirus/enterovirus, human metapneumovirus, and influenza A H1N1 pneumonia; however, the significance of pleural thickening remains uncertain according to several observational studies by Bai et al. and Yin et al.. 27, 40, 49 

The frequency of pleural effusions varies with age, according to a large observational study by patients. 21 In this study, although the overall rate of pleural effusions detected was 7.3%, a higher amount of COVID-19 patients age 50 years and older (10% versus 5.2%; p = 0.037) developed pleural effusions than those 50 years and under.

However, this result was not replicated in other smaller observational studies. Several observational studies comparing the clinical presentation between adults and children (18 years and younger) with COVID-19 pneumonia demonstrated that although adults tend to present with more severe clinical symptoms and chest CT involvement, the incidence of pleural effusion was not different. 28, 50 Similar findings were replicated in a separate observational study comparing elderly COVID-19 patients (age 60 years and older) versus younger COVID-19 patients where despite a greater chest CT involvement, the incidence of pleural effusion remained similar. 47 A large, well-designed study controlling for confounding factors is required to assess whether age is a risk factor for developing COVID-19-related pleural effusions.

During the early course in the COVID-19 pandemic, data suggested that children appeared less likely to develop an infection or severe illness than adults. 23 However, a new entity termed Multisystem Inflammatory Syndrome in Children (MIS-C) has been increasingly described in the current medical literature defined as a condition that primarily occurs in children that features both Kawasaki disease and toxic shock syndrome. 51-53 MIS-C is often postulated to be an immune-mediated delayed host response triggered by a previous COVID-19 infection (postinfectious phenomenon) that occurs 2-4 weeks after the initial infection. Though, this hyperinflammatory disorder may even be a direct extension of active COVID-19 infections (cytokine storm). 23, 51 Several observational studies with various sample sizes demonstrated that the radiological findings of pleural effusions, pericardial effusions, and even ascites were highly variable at 13.9-62.5%, 12.5-47.6%, and 19.0-37.5%, respectively, in MIS-C patients. 23, 26, 34 According to case reports/series, MIS was not just confined to children and has also been described in adults (aged 21 years and more) referred to as Multisystem Inflammatory Syndrome in Adults (MIS-A) who presented with pleural effusions. 54, 55 In the existing medical literature, the oldest COVID-19 patient ever diagnosed with pleural effusion secondary to MIS-A was a 50-year-old man who presented with three days of symptoms, tested positive for COVID- 19 IgG antibodies with small pleural effusions noted on chest imaging, and improved clinically with immunosuppressive therapies of corticosteroids. 54 It has even been suggested that radiologic findings that may help distinguish between MIS from COVID-19 infections are pleural effusions, pericardial effusions, ascites, and hilar/mediastinal lymphadenopathies that favor MIS, reflecting any underlying multisystemic inflammatory process. 53, 56, 57 Case series by Rostad et al. described an incidence of pleural effusions in children was 81.8% for MIS-C compared to 6.3% (p < 0.01) during COVID-19 infections. 57 In conclusion, as our knowledge continues to grow during this current pandemic, pleural effusions should be recognized as part of the constellation of imaging findings in MIS-C and even MIS-A to assist with early diagnosis and allow prompt treatment.

According to Liu et al., the incidence of pleural effusions was up to 29.3% (12/41) in pregnant COVID-19 patients versus 7.1% (1/14) in those who were not pregnant, but their study was underpowered to detect any significant difference. 28 Pregnant COVID-19 patients who developed pleural effusions were in later stages of pregnancy at 35-41 weeks of gestation or during the postpartum period. 10, 28, 58 In pregnant COVID-19 patients, the higher incidence of pleural effusion could be due to benign postpartum pleural effusion that occurs within 24 hours of normal vaginal delivery due to transudation of fluid into the pleural space from a pregnancyinduced increase in systemic circulation hydrostatic pressure/blood volume and decreased oncotic pressure from hypoalbuminemia state. 10, 59 The repeated Valsalva maneuver during spontaneous delivery and elevated intraabdominal pressure from the gravid uterus will further increase intrathoracic pressure while impairing lymphatic drainage, promoting pleural effusion formation. Taking into consideration of other comorbidities, there was no association found between COVID-19 patients and the risk of developing pleural effusions in those with or without concurrent acute pulmonary embolism, according to a retrospective cohort study by Gervaise et al.. 60 When patients with active COVID-19 infections and those with MIS present with sepsis-like illness, aggressive IV fluid will be administered, leading to a clinical state of fluid overload that may precipitate the development of diffuse bilateral lung infiltrates with pleural effusions, attributable to depressed cardiac function, overwhelming systemic inflammatory response, and third spacing of fluids. 6, 17, 22, 29, 56, 57, 61 At least 15% and more of COVID-19 patients developed either acute heart failure or kidney failure during their clinical course, increasing to more than 50% in critically ill patients. 62, 63 The clinical state of fluid overload has been described as a potential etiology in SARS-related pleural effusions. 64 However, no study has been performed to determine the pre-existing comorbidities of congestive heart failure, hypoalbuminemia, chronic liver disease, and chronic renal failure with the risk of pleural effusions development in COVID-19 patients. The presence of SARS-CoV-2 was found in pleural effusions of 10 deceased COVID-19 patients during postmortem examination. 65 However, the location of pleural effusions (unilateral/bilateral), time of development, and pleural fluid characteristics/cultures were not described. At the same time, many of the deceased COVID-19 patients had comorbidities of metastatic malignancies, cardiac, liver, and renal dysfunction, which are common etiologies of pleural effusions. The concomitant presence of co-infection such as active TB or stage IV lung malignancy has been described as predisposing factors for developing pleural effusions that are commonly lymphocytic-predominant with elevated LDH in COVID-19 patients, although limited to case reports/series. 66, 67 Therefore, a well-designed study is required to assess the relationship between pre-existing comorbidities against the risk of developing COVID-19-related pleural effusions.

The current overall mortality rate was around 3% for COVID-19 compared to other zoonotic outbreaks such as 2003 SARS outbreak and 2012 MERS outbreak, with an observed mortality rate of 6-11% and 43-60%, respectively. 1, [35] [36] [37] [68] [69] [70] [71] [72] [73] Pleural effusions had been associated as an independent predictor for poor outcome in critically ill patients with ARDS from infectious and non-infectious etiologies. 74 A large observational study of 476 COVID-19 patients by Feng et al. reported that although the overall incidence of pleural effusions was 5.7%, the incidence of pleural effusions was 18% in critically ill patients versus 3.1% (p < 0.001) in non-critically ill patients. 32 Similar findings were noted collectively in several observational studies where critically ill COVID-19 patients had a greater likelihood of around 3.2-fold of developing pleural effusions at 33-43% versus 3-13% (p < 0.05) than non-critically ill COVID-19 patients. 14, 19, 29, 32, 75 Moreover, studies by Li et al. and Liu et al. described that pleural effusions were solely seen on chest CT in critically ill COVID-19 patients. 76, 77 Although the inflammatory stress response in pregnant women towards viral pneumonia increased significantly during the middle and late stages of pregnancy, resulting in a rapid progression of the disease and severity of illness that may cause maternal-fetal death, the relationship between COVID-19-related pleural effusions and mortality in pregnancy were not assessed in observational studies and case series included in our review likely due to the small sample size. 10, 28 The association between pleural effusion and increased mortality has been described in MERS patients, where 63.2% of deceased than 13.9% of survivors (p = 0.001) developed pleural effusion. 36 Influenza A H1N1 patients with ARDS and who suffered a poor clinical outcome have a greater likelihood of displaying pleural effusions. 44 When comparing patients with avian influenza A, H7N9 infection lead to a higher incidence of pleural effusion (88.9%) versus H1N1 infection (7.7%) [p < 0.01] with an 8-fold increased risk of developing ARDS. However, this did not translate to significant mortality in that study. 43 In patients with community-acquired pneumonia from both viral and bacterial microorganisms, bilateral pleural effusions and moderate to large pleural effusions are associated with a 7-fold and 3.4-fold increase in 30-day mortality. 78 Therefore, more studies are required to confirm or refute the association between critically ill COVID-19 patients and the development of pleural effusions.

Pleural effusions likely represent a more severe inflammatory radiological evolution of COVID-19 pneumonia with increasing frequency during the hospital course and concomitant progression of opacities from ground-glass opacifications (GGOs) to consolidations on chest imaging. 3, 13, 15, 46, 69, 79 From the day of admission, the overall time to diagnosis of COVID-19related pleural effusions using chest imaging was 5-7 days and more according to two observational studies. 5, 15, 80 In contrast, when compared to the time of COVID-19 symptoms onset, it was 11 days and after (Table 1) . A single-center, cross-sectional study utilizing serial chest CT scans demonstrated that pleural effusion incidence increased significantly from 12% to 38% (p = 0.01) when performed on day five and day 12 after the onset of COVID-19 symptoms. 79 Ding et al. reported that the incidence of pleural effusions identified on chest imaging increased from 9.2% (5-9 days from onset of COVID-19 symptoms) to 27.9% (15) (16) (17) (18) (19) (20) (21) days from onset of COVID-19 symptoms) in their observational study. 31 A single-center, retrospective study by Han et al. reported that the incidence of pleural effusions increases from 11.8% on week 2 to 23.5% on week 3 (p = 0.0071) of hospital admission. 24 Lastly, a singlecenter, retrospective cohort study comparing chest CT features in early-phase and advancedphase (eight days and more from symptoms onset) of COVID-19 pneumonia revealed that although there was no difference in the incidences of pleural thickening (42.5% versus 59.1%) and retraction (57.5% versus 54.5%), pleural effusions (2.5% versus 22.7%; p = 0.01) were predominantly seen in the advanced-phase. 46 The delay in recognizing pleural effusions could be from the limited use of chest imaging (chest radiograph and CT) and pleural ultrasonography during the ongoing pandemic. 81 The initial identification of pleural effusions on chest imaging is noted to be similar during the latter stages of SARS (14 days and more from the time of symptoms onset) and MERS (nine days and more from the time of symptoms onset) [ Table 2 ].

In avian influenza A H5N1 patients, pleural effusions are frequently observed around a median of seven days after the onset of symptoms. 41

Pleural effusions in many COVID-19 patients are under characterized due to concerns that pleural drainage is a potential aerosolized generating procedure leading to further transmission of the disease, although the evidence behind it remains poor. 82 As many COVID-19 patients (Table 3) (Table 2 ). As no pleural drainage was performed in the 47 observational studies included in our review, the pleural fluid characteristics in COVID-19 patients were limited to four case reports/series involving 7 COVID-19 patients (Table 3 ). In all four case reports/series, COVID-19-related pleural effusions were exudative in nature based on Light's criteria of pleural fluid to serum LDH ratio of 0.7 and more. 81, [83] [84] [85] [86] The white cell count differential in COVID-19related pleural effusions was either lymphocytic or neutrophilic-predominant (Table 3) Lymphocytic or neutrophilic-predominant white cell count differential has been noted in other viral-related pleural effusions such as adenovirus, influenza A H5N1, and human herpesvirus-6. 87 A markedly elevated pleural fluid to serum LDH ratio of 1.3 had been suggested to support the diagnosis of COVID-19-related pleural effusions that were observed in many COVID-19 patients who received pleural drainage (Table 3) . 81 However, multiple confounding variables could explain the floridly elevated LDH level observed in several case reports/series of COVID-19 patients. High levels of LDH could be secondary to various etiologies such as complicated parapneumonic effusions, rheumatoid pleurisy, tuberculosis (TB), and lymphoma/lung malignancy. 66, 67, 88 A few case reports/series reported of the concomitant findings of active TB and stage IV lung malignancy that were potential etiologies for pleural effusions in COVID-19 patients with pneumonia. 66, 67 A high pleural fluid to serum LDH ratio has also been observed in patients with other viral-related pleural effusions from influenza A H5N1, EBV, and adenovirus. 87, 89 Moreover, hemolysis of pleural fluid red blood cells (RBCs) might also contribute to elevation of pleural fluid LDH levels that were based on the serosanguineous and sanguineous pleural fluid appearance, commonly observed in the case series by Chong et al.. 81 However, a prospective study showed no increased risk in significant bleeding with drainage of pleural effusion in those receiving therapeutic anticoagulation. 90 Therefore, it is possible that hemorrhagic pleural effusions encountered in a case series by Chong et al. were due to endothelial dysfunction-related microthrombi formation leading to infarct and hemorrhage of lung parenchyma extending into the pleura. 81 

Our review had several limitations. First, the available data on pleural effusions in COVID-19 pneumonia was often limited due to the highly variable incidence reported across many observational studies compared to other common CT chest findings (Table 1) show an exudative, lymphocytic or neutrophilic-predominant cell differential with markedly elevated LDH and pleural fluid to serum LDH ratio. However, the evidence available in the current literature remained limited due to the variability in many observational studies reviewed on the actual incidence of pleural effusions and lack of pleural drainage. As our knowledge of COVID-19 disease continues to evolve during this current pandemic, we hope that more well-designed studies will be performed to describe the incidence, risk factors, outcomes, onset, and pleural fluid characteristics in COVID-19 patients with pleural effusions. 

The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health -The latest 2019 novel coronavirus outbreak in Wuhan

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet

Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. The Lancet Infectious Diseases

CT Imaging Features of 2019 Novel Coronavirus (2019-nCoV)

Early Clinical and CT Manifestations of Coronavirus Disease 2019 (COVID-19) Pneumonia

COVID-19 Associated Pneumonia and Pleural Effusion Masquerading as Heart Failure in Rheumatic Heart Disease

Asymptomatic novel coronavirus pneumonia patient outside Wuhan: The value of CT images in the course of the disease

A Novel Coronavirus from Patients with Pneumonia in China

2019-novel Coronavirus severe adult respiratory distress syndrome in two cases in Italy: An uncommon radiological presentation

CT characteristics and diagnostic value of COVID-19 in pregnancy

Novel Coronavirus (COVID-19) Pneumonia with Hemoptysis as the Initial Symptom: CT and Clinical Features

Clinical features of severe pediatric patients with coronavirus disease 2019 in Wuhan: a single center's observational study

Chest CT Findings in Coronavirus Disease-19 (COVID-19): Relationship to Duration of Infection

CT features of COVID-19 patients with two consecutive negative RT-PCR tests after treatment

Novel Coronavirus (2019-nCoV) Pneumonia

Radiographic findings in 240 patients with COVID-19 pneumonia: time-dependence after the onset of symptoms

Coronavirus Disease 2019: Initial Detection on Chest CT in a Retrospective Multicenter Study of 103 Chinese Patients

Imaging manifestations and diagnostic value of chest CT of coronavirus disease 2019 (COVID-19) in the Xiaogan area

CT image visual quantitative evaluation and clinical classification of coronavirus disease (COVID-19)

COVID-19 with Different Severities: A Multicenter Study of Clinical Features

High-resolution computed tomography finding in 552 patients with symptomatic COVID-19: first report from north of Iran

Characteristics and Outcomes of 21 Critically Ill Patients With COVID-19 in Washington State

Imaging Findings in Multisystem Inflammatory Syndrome in Children (MIS-C) Associated With Coronavirus Disease

Novel Coronavirus Disease 2019 (COVID-19) Pneumonia Progression Course in 17 Discharged Patients: Comparison of Clinical and Thin-Section Computed Tomography Features During Recovery

Characteristics of Chest CT Images in Patients With COVID-19 Pneumonia in London

Kawasaki-like multisystem inflammatory syndrome in children during the covid-19 pandemic

A Comparison of Clinical and Chest CT Findings in Patients With Influenza A (H1N1) Virus Infection

Clinical and CT imaging features of the COVID-19 pneumonia: Focus on pregnant women and children

CT Features and Short-term Prognosis of COVID-19 Pneumonia: A Single-Center Study from Kashan, Iran. Radiology: Cardiothoracic Imaging

CT features of coronavirus disease 2019 (COVID-19) pneumonia: experience of a single center in Southern Italy

Chest CT findings of COVID-19 pneumonia by duration of symptoms

Relation Between Chest CT Findings and Clinical Conditions of Coronavirus Disease (COVID-19) Pneumonia: A Multicenter Study

Well-aerated Lung on Admitting Chest CT to Predict Adverse Outcome in COVID-19 Pneumonia

Acute Cardiovascular Manifestations in 286 Children With Multisystem Inflammatory Syndrome Associated With COVID-19 Infection in Europe

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection: Chest CT Findings

Acute Middle East Respiratory Syndrome Coronavirus: Temporal Lung Changes Observed on the Chest Radiographs of 55 Patients

CT Correlation With Outcomes in 15 Patients With Acute Middle East Respiratory Syndrome Coronavirus

Viral Pneumonias in Adults: Radiologic and Pathologic Findings

Radiographic and CT Features of Viral Pneumonia

Performance of Radiologists in Differentiating COVID-19 from Non-COVID-19 Viral Pneumonia at Chest CT

The Radiologic Manifestations of H5N1 Avian Influenza

Chest Radiographic and CT Findings in Novel Swine-Origin Influenza A (H1N1) Virus (S-OIV) Infection

Comparison of patients with avian influenza A (H7N9) and influenza A (H1N1) complicated by acute respiratory distress syndrome: Medicine

Spectrum of clinical and radiographic findings in patients with diagnosis of H1N1 and correlation with clinical severity

Comparison of Clinical Features and Outcomes in Critically Ill Patients Hospitalized with COVID-19 versus Influenza

CT Features of Coronavirus Disease 2019 (COVID-19) Pneumonia in 62 Patients in Wuhan

A Comparative Study of Chest Computed Tomography Features in Young and Older Adults With Corona Virus Disease (COVID-19)

Late-Stage Adult Respiratory Distress Syndrome Caused by Severe Acute Respiratory Syndrome: Abnormal Findings at Thin-Section CT

Coronavirus Disease 2019 (COVID-19) CT Findings: A Systematic Review and Meta-analysis

Differences in Clinical and Imaging Presentation of Pediatric Patients with COVID-19 in Comparison with Adults

An adult with Kawasaki-like multisystem inflammatory syndrome associated with COVID-19. The Lancet

Hyperinflammatory shock in children during COVID-19 pandemic. The Lancet

Thoracic Imaging Findings of Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19: What Radiologists Need to Know Now

Case Series of Multisystem Inflammatory Syndrome in Adults Associated with SARS-CoV-2 Infection -United Kingdom and United States

COVID-19 associated Kawasaki-like multisystem inflammatory disease in an adult

Spectrum of Imaging Findings at Chest Radiography, US, CT, and MRI in Multisystem Inflammatory Syndrome in Children Associated with COVID-19

Chest radiograph features of multisystem inflammatory syndrome in children (MIS-C) compared to pediatric COVID-19

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection during late pregnancy: a report of 18 patients from Wuhan, China

Benign postpartum pleural effusion

Acute pulmonary embolism in non-hospitalized COVID-19 patients referred to CTPA by emergency department

CT chest findings in coronavirus disease-19 (COVID-19)

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet

Relationship Between Severe Acute Respiratory Syndrome Coronavirus 2 and The Etiology of Acute Kidney Injury. The American Journal of the Medical Sciences

Severe Acute Respiratory Syndrome: Radiographic Appearances and Pattern of Progression in 138 Patients

Postmortem Examination of Patients With COVID-19

Pleural effusion in a patient with COVID-19 pneumonia and lung cancer: A case report

Four Patients with COVID-19 and Tuberculosis

Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome. The Lancet

Imaging Features of Coronavirus disease 2019 (COVID-19): Evaluation on Thin-Section CT

Middle East Respiratory Syndrome Coronavirus (MERS-CoV): Announcement of the Coronavirus Study Group

Isolation of a Novel Coronavirus from a Man with Pneumonia in Saudi Arabia

Severe Acute Respiratory Syndrome

Thin-Section CT of Severe Acute Respiratory Syndrome: Evaluation of 73 Patients Exposed to or with the Disease

Influences of pleural effusion on respiratory mechanics, gas exchange, hemodynamics, and recruitment effects in acute respiratory distress syndrome

Clinical characteristics of refractory COVID-19 pneumonia in Wuhan, China. Clinical Infectious Diseases

The Clinical and Chest CT Features Associated With Severe and Critical COVID-19 Pneumonia: Investigative Radiology

CT manifestations of coronavirus disease-2019: A retrospective analysis of 73 cases by disease severity

Do Pulmonary Radiographic Findings at Presentation Predict Mortality in Patients With Community-Acquired Pneumonia

Clinical and High-Resolution CT Features of the COVID-19 Infection: Comparison of the Initial and Follow-up Changes. Investigative Radiology

Temporal Changes of CT Findings in 90 Patients with COVID-19 Pneumonia: A Longitudinal Study

Characteristics of Pleural Effusion in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Pneumonia. The American Journal of the Medical Sciences

Clarification on Pleural Effusions in COVID-19

A Case of Childhood COVID-19 Infection with Pleural Effusion Complicated by Possible Secondary Mycoplasma Pneumoniae Infection

First Detection of SARS-CoV-2 by Real-Time Reverse Transcriptase-Polymerase Chain Reaction Assay in Pleural Fluid

Pleural effusion as an isolated finding in COVID-19 infection

Pleural effusions: the diagnostic separation of transudates and exudates

Viral diseases affecting the pleura

Getting the most from pleural fluid analysis: Pleural fluid analysis

Clinical Course of Avian Influenza A(H5N1) in Patients at the Persahabatan Hospital

The Safety of Thoracentesis in Patients with Uncorrected Bleeding Risk

Pulmonary and cardiac pathology in African American patients with COVID-19: an autopsy series from New Orleans. The Lancet Respiratory Medicine

The clinical pathology of severe acute respiratory syndrome (SARS): a report from China

Pulmonary pathological features in coronavirus associated severe acute respiratory syndrome (SARS)

Co-infections in people with COVID-19: a systematic review and meta-analysis

Essentials for Radiologists on COVID-19: An Update-Radiology Scientific Expert Panel

Coronavirus Disease 2019 (COVID-19): A Systematic Review of Imaging Findings in 919 Patients

Contribution of CT Features in the Diagnosis of COVID-19. Vassilakopoulos TI

Chest CT manifestations of new coronavirus disease 2019 (COVID-19): a pictorial review

Pneumonia: high-resolution CT findings in 114 patients

 83 Chong et al. 81 Chong et al. 81 Chong et al. 81 Chong et al. 81 Chong et al. 81 Hussein et al. 85 Me al.