key: cord-270628-jtj30v0r
authors: Alharthy, Abdulrahman; Faqihi, Fahad; Abuhamdah, Mohamed; Noor, Alfateh; Naseem, Nasir; Balhamar, Abdullah; Al Saud, Ahad Alhassan Al Saud Bin Abdulaziz; Brindley, Peter G.; Memish, Ziad A.; Karakitsos, Dimitrios; Blaivas, Michael
title: Prospective Longitudinal Evaluation of Point‐of‐Care Lung Ultrasound in Critically Ill Patients With Severe COVID‐19 Pneumonia
date: 2020-08-14
journal: J Ultrasound Med
DOI: 10.1002/jum.15417
sha: 
doc_id: 270628
cord_uid: jtj30v0r

OBJECTIVES: To perform a prospective longitudinal analysis of lung ultrasound findings in critically ill patients with coronavirus disease 2019 (COVID‐19). METHODS: Eighty‐nine intensive care unit (ICU) patients with confirmed COVID‐19 were prospectively enrolled and tracked. Point‐of‐care ultrasound (POCUS) examinations were performed with phased array, convex, and linear transducers using portable machines. The thorax was scanned in 12 lung areas: anterior, lateral, and posterior (superior/inferior) bilaterally. Lower limbs were scanned for deep venous thrombosis and chest computed tomographic angiography was performed to exclude suspected pulmonary embolism (PE). Follow‐up POCUS was performed weekly and before hospital discharge. RESULTS: Patients were predominantly male (84.2%), with a median age of 43 years. The median duration of mechanical ventilation was 17 (interquartile range, 10–22) days; the ICU length of stay was 22 (interquartile range, 20.2–25.2) days; and the 28‐day mortality rate was 28.1%. On ICU admission, POCUS detected bilateral irregular pleural lines (78.6%) with accompanying confluent and separate B‐lines (100%), variable consolidations (61.7%), and pleural and cardiac effusions (22.4% and 13.4%, respectively). These findings appeared to signify a late stage of COVID‐19 pneumonia. Deep venous thrombosis was identified in 16.8% of patients, whereas chest computed tomographic angiography confirmed PE in 24.7% of patients. Five to six weeks after ICU admission, follow‐up POCUS examinations detected significantly lower rates (P < .05) of lung abnormalities in survivors. CONCLUSIONS: Point‐of‐care ultrasound depicted B‐lines, pleural line irregularities, and variable consolidations. Lung ultrasound findings were significantly decreased by ICU discharge, suggesting persistent but slow resolution of at least some COVID‐19 lung lesions. Although POCUS identified deep venous thrombosis in less than 20% of patients at the bedside, nearly one‐fourth of all patients were found to have computed tomography–proven PE.

Europe. [1] [2] [3] [4] [5] [6] Lung US was suggested to be particularly useful during the COVID-19 pandemic because of its ability to identify subtle lung parenchymal changes early in the course of disease, monitor the evolution of pulmonary lesions in hospitalized patients, and guide mechanical ventilation therapy in critically ill patients with acute respiratory failure and acute respiratory distress syndrome. [7] [8] [9] [10] Although the role of traditional portable chest radiography, especially in this era of crisis and resource limitations, cannot be unheeded, lung US could represent a flexible diagnostic solution in COVID-19 pneumonia. 11, 12 Unlike lung US, some reports indicate the sensitivity of chest radiography for COVID-19 pneumonia to be as slow at 20%. 13 Lung US is a portable bedside imaging tool, which has been previously used in the diagnosis and monitoring of acute respiratory distress syndrome in the intensive care unit (ICU). [14] [15] [16] [17] [18] [19] [20] [21] [22] Chest computed tomography (CT) rapidly became the mainstream imaging method in the diagnosis and monitoring of COVID-19 pneumonia by identifying the typical pattern of ground glass opacities with variable infiltrates and consolidations, while showing a high correlation with laboratory detection of the virus by real-time polymerase chain reaction (RT-PCR) assays. [23] [24] [25] [26] [27] [28] [29] [30] Compared to CT, point-ofcare ultrasound (POCUS) still has limited evidence supporting its diagnostic utility in COVID-19 but could be helpful with proper expertise. Since most lung parenchymal lesions in COVID-19 are distributed peripherally, these lesions should theoretically be detected by POCUS. [23] [24] [25] [26] [27] [28] [29] [30] Hence, in this study, the primary end point was to analyze the lung US findings in critically ill patients with severe COVID-19 pneumonia or admission to the ICU longitudinally throughout their disease course.

We prospectively enrolled consented patients with confirmed COVID-19 pneumonia admitted to a polyvalent ICU (King Saud Medical City) throughout May 2020. Inclusion criteria were age older than 18 years, ICU admission, and serious COVID-19 pneumonia. The latter was defined as acute respiratory failure: dyspnea, a respiratory rate of 30 breaths per minute or higher, blood oxygen saturation of 93% or less, a partial arterial pressure of oxygen-tofractional inspired concentration of oxygen ratio of less than 300, development of bilateral pulmonary infiltrates within 24 to 48 hours, or a combination thereof. [30] [31] [32] [33] [34] [35] Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was determined by RT-PCR assays on throat swab samples using a QuantiNova Probe RT-PCR kit (Qiagen, Hilden, Germany) in a Light-Cycler 480 real-time PCR system (Roche, Basel, Switzerland). [36] [37] [38] [39] [40] [41] [42] Exclusion criteria were patients with COVID-19 who did not undergo a POCUS examination (reasons included unavailability of operators on the patient's admission and transfer to other COVID-19-targeted hospitals per the Saudi Ministry of Health surge plan) and 2 consecutive negative RT-PCR test results for SARS-CoV-2 taken at least 24 hours apart. The study was conducted according to the principles of the Declaration of Helsinki and approved by our Institutional Review Board. 43 Written informed consent was obtained from patients or their legal representatives.

On ICU admission, a POCUS examination was performed with phased array (2-4-MHz), convex (2-6-MHz), and linear (10-15-MHz) transducers connected to portable US machines assigned exclusively to the study of patients with COVID-19, (Figure 1 ). The US examination was performed by a single operator with the assistance of a single ICU nurse. Both entered the ICU isolation room wearing personal protective equipment adhering to preventive infection control measures for respiratory, droplet, and contact isolation in COVID-19 as detailed elsewhere. [44] [45] [46] All transducers were placed inside sterile sheaths, and US machines were dressed in sterile covers to perform each examination. At the end of the examination, machines and transducers were sterilized in a designated isolation room and were placed into new sterile covers. [44] [45] [46] The thorax was scanned in 12 lung areas in total: anterior-superior and anterior-inferior, lateral-superior and lateral-inferior, and posterior-superior and posterior-inferior bilaterally. [1] [2] [3] [4] [5] [6] 14, 15, 19 Ultrasound examinations targeted detection of B-lines, lung consolidations, and pleural line abnormalities in each lung ( Figure 2 ). [14] [15] [16] [17] [18] [19] [20] [21] [22] Due to the high risk of thromboembolic disease in ICU patients with COVID-19, during the POCUS session, a vascular US examination of the lower limbs was performed in search of potential deep venous thrombosis (DVT). 6, 47, 48 Per hospital policy and regardless of POCUS results, all patients with COVID-19 who had a high suspicion of pulmonary embolism (PE; ie, elevated D-dimer levels or refractory hypoxia for >48 hours) underwent chest computed tomographic angiography (CCTA) to exclude PE. [49] [50] [51] [52] [53] [54] [55] The incidence of acute kidney injury, as defined per the "risk," "injury," and "failure" criteria, and the prevalence of comorbidities were documented. 56 Data regarding invasive mechanical ventilation and oxygen therapy by means of a high-flow nasal cannula (HFNC), which has shown promise in the management of serious COVID-19 pneumonia, were tracked. 57 Outcome measures such as the duration of mechanical ventilation, ICU length of stay, and raw (not adjusted for disease severity) mortality on day 28 after ICU admission were recorded. Follow-up POCUS examinations were performed weekly in all patients and once before hospital discharge in survivors. All POCUS examinations were performed by experienced operators. Point-of-care US images were electronically stored and analyzed. Medical records were used to obtain demographic, clinical, and laboratory data for enrolled patients with COVID-19. 

Continuous variables were expressed as medians with interquartile ranges (IQR). Categorical variables were expressed as proportions. A power analysis suggested that a minimum sample size of 80 patients would be required with a significance level of 5% to achieve power of 80%. The Fisher exact test was used to compare differences between proportions. A 2-tailed significance level of .05 was regarded statistically significant. All data were stored on a spreadsheet (Excel 2011; Microsoft Corporation, Redmond, WA), and analyses were performed with a commercially available statistical package (SPSS version 24; IBM Corporation, Armonk, NY).

One hundred consecutive patients with COVID-19 were admitted to the ICU during the study period. Eleven patients were excluded from study enrolment because of transfer to other COVID-19 centers according to the Saudi Ministry of Health surge plan. Eighty-nine consented patients with COVID-19 were finally enrolled. All patients had portable chest radiography, which was performed in the emergency department. Ten of 89 patients (11.2%) had admission chest CT scans. All recruited patients underwent POCUS examinations on study enrollment. Table 1 summarizes main baseline parameters and outcome measures of the study population. Most of the patients with COVID-19 were male (84.2%) with a median age of 43 (IQR, 32.1-53.9) years. Table 2 summarizes patient symptoms and comorbidities before hospital admission. The most common symptoms were cough (100%), fever (84.2%), and dyspnea (47.1%). On ICU admission, 84.2% of patients were intubated, and 15.7% were receiving oxygen via an HFNC with median flow of 60 L/min and a median fraction of inspired oxygen of 40%. However, after 48 hours, all patients were intubated and mechanically ventilated.

A high admission Sequential Organ Function Assessment score was documented (9.4 [IQR, 8.9-10.5]). Venovenous extracorporeal membrane oxygenation was attempted in 5 cases (5.6%), of which 2 patients died. All patients received acute respiratory distress syndrome net ventilation, prone positioning, lung recruitment, and empiric therapy for COVID-19 with lopinavir/ritonavir, ribavirin, and interferon β 1b for 14 days, dexamethasone for 7 days, prophylactic anticoagulation, and ICU supportive care per current recommendations for the treatment of severe COVID-19 pneumonia. 35, 36, 58 Computed Tomography, Laboratory Results, and Illness Severity Twenty-five patients were screened for PE by CCTA within the first 48 hours of ICU admission because of resistant hypoxemia. Twenty-two of 89 (24.7%) patients were found to have positive results for PE by CCTA (Table 1 ). Acute kidney injury was documented in 11 cases (12.3%), of which 3 received continuous renal replacement therapy, as they had anuria, Values are medians (IQRs) where applicable. PaO 2 /FiO 2 ratio indicates partial arterial pressure of oxygen-to-fractional inspired concentration of oxygen ratio; SOFA, Sequential Organ Function Assessment; and VV-ECMO, venovenous extracorporeal membrane oxygenation. Table 3 . On ICU admission, all patients with COVID-19 had an abnormal aeration pattern (B-lines). In most cases, coexistent confluent and separated B-lines were documented ( Figure 3 ). Bilateral involvement and pleural line irregularities in more than 6 lung areas were evident in most cases (Table 3) . However, the right lung (73%) was more frequently affected compared to the left lung (61.7%). Confluent B-lines originating from regular pleural lines, previously characterized as "beam line" or "waterfall" (Figure 4 ) artifacts and suggested to represent an early stage of actively spreading COVID-19 pneumonia alternating with areas of normal lung parenchyma, were observed only in a minority of cases (31.4%). 59, 60 Of note, the aforementioned sign was best visualized with the convex transducer because of its large scanning surface and low frequency (Figure 4 ). In contrast, confluent and separate B-lines originating from irregular pleural lines were evident in most cases (69.6%), which may reflect a late stage of COVID-19 pneumonia. Variable consolidations, which were mainly identified in the posterior lung areas, were recorded (Table 3) . A "starry sky" pattern of consolidation (bright infiltrates) was evident in most cases (49.4%; Figures 5 and 6 ). Less-prevalent consolidation patterns were subpleural consolidations (26.9%) and lung parenchymal hepatization pattern (22.4%). Pleural and pericardial effusions were observed less frequently (Table 3) . Small pneumothoraxes were detected by lung US in the first week of hospitalization in 3 cases (3.37%), although the median positive end-expiratory pressure used in this study was relatively low: 10 (IQR, [8] [9] [10] [11] [12] cm H 2 O (Figure 7 ). On ICU admission, DVT was detected in 16.8% of cases compared to the confirmed rate of PE ( Figure 8 ) by CCTA (24.7%) in this study. The follow-up POCUS examinations in the upcoming weeks (weeks 1-4) showed an initial increase of the incidence of lung US findings in weeks 1 to 2, followed by a gradual decrease of these finding in weeks 3 and 4 after ICU admission (Table 4 ). Ten patients died in the first week, 9 in the second week, 3 in the third week, and 3 in the fourth week of hospitalization. The 64 survivors were examined again before hospital discharge, approximately 32 (IQR, [26] [27] [28] [29] [30] [31] [32] [33] [34] [35] [36] [37] [38] [39] [40] days after ICU admission. At that time, lung abnormalities were still present (Tables 3 and 4 ). However, the incidence of lung abnormalities on hospital discharge was significantly lower (P < .05, 2-tailed Fisher exact test) compared to baseline findings (Table 3 ).

Due to the sudden and rapid onset of the COVID-19 pandemic with its disruptive effect on medical systems, prospective data regarding POCUS use on critically ill patients has been slow to emerge. Our study provides additional important data on the utility of POCUS in the population of critically ill patients with COVID-19. We found that POCUS effectively detected lung abnormalities such as B-lines, pleural line abnormalities, variable consolidations, and pleural effusions. Additionally, our standardized POCUS Percentages were derived from the total numbers of patients examined at each point in time on admission, during follow-up, and on discharge. Ten patients died in the first week, 9 in the second week, 3 in the third week, and 3 in the fourth week of hospitalization. The total number of survivors who were examined in the fifth to sixth weeks before hospital discharge was 64.

approach identified other critical conditions such as pericardial effusions and DVT in critically ill patients with COVID-19.

Early depictions of COVID-19 lung US findings have suggested that the extent of lung involvement and typical appearances of patient lungs differ from one patient population to another. Descriptions of lung US findings on emergency department presentation, including scattered areas of pleural involvement adjacent to normal lung, are less common among patients seen by ICU providers and represent an earlier stage of COVID-19 development. In our study, lung US examinations, performed on ICU admission, identified bilateral lung abnormalities mainly in the posterior lung areas for most of the patients studied. [1] [2] [3] [4] [5] [6] In most of our patients, severe COVID-19 pneumonia had already evolved, as their clinical picture and lung US findings suggested (Figure 9 ). The beam line artifact (integrating a pattern of regular pleural lines with accompanying confluent Blines), which has been reported in publications focused on patient populations with early stages of active COVID-19 pneumonia, was noted only in a minority of our cases, again supporting a steady progression of US findings as disease severity progresses. [1] [2] [3] [4] [5] [6] 59, 60 Our patient group showed rather extensive lung parenchymal involvement on POCUS examinations on ICU admission (Table 3) .

Depicting the natural course of the disease process in the ICU population with lung US is an important task. Our weekly follow-up scans of all patients showed that an increasing number of lung abnormalities were observed in weeks 1 and 2 after ICU admission ( Figure 10) . A gradual improvement of the lung parenchymal abnormalities was then observed in weeks 3 and 4 after ICU admission and before hospital discharge in survivors (>30 days after ICU admission). These findings were consistent with a previous study, which used a similar but less-detailed lung US scanning protocol. 6 We have documented pleural line irregularities (in >6 lung areas) with accompanying B-lines in most our patients ( Figure 11 ). 1-6 Additionally, we found several consolidation patterns. The most prevalent one (starry sky pattern: bright infiltrates) could be a reflection of the severe lung parenchymal inflammation of COVID-19 pneumonia (Figure 10) , which is also visualized on chest CT as ground glass opacities and infiltrates and was mainly distributed in peripheral and posterior lung zones.

Notably, on ICU admission, clinical and laboratory data showed a high Sequential Organ Function Assessment admission score, as well as lymphocytopenia, with elevated levels of C-reactive protein, lactate dehydrogenase, D-dimers, and ferritin, which are predictors of severe COVID-19 pneumonia, a cytokine storm, and death. [32] [33] [34] [56] [57] [58] Our findings regarding the ICU length of stay, days receiving mechanical ventilation, and the raw 28-day mortality were comparable to the published literature. [32] [33] [34] 56, 57 Of particular interest was the low rate of DVT identified as part of our POCUS evaluation: just 16.8%. This was in contrast to CCTA-confirmed PE in nearly one-fourth of our study population, at 24.7%. These rates were much lower compared to findings reported by a previous study. 6 The difference may be partially attributed to the fact that all of our patients received aggressive prophylactic anticoagulation per hospital policy. Furthermore, we speculate that in COVID-19, PE may be due to predominantly local growth of microthrombi within the lung vasculature, which may not necessarily be linked to DVT formation and could be another reason for our findings related to DVT and PE frequencies. [49] [50] [51] [52] [53] [54] [55] The pathophysiologic mechanisms of lung microthrombosis in serious COVID-19 are highly complex and may be related to the development of cytokine release syndrome. [61] [62] [63] [64] [65] Notwithstanding, lung abnormalities were still present on hospital discharge in a minority of patients, suggesting that lung US findings correlate with resolution of severe COVID-19 pneumonia in ICU patients. However, the lack of clearance of lung findings in all patients, even on hospital discharge, suggests that the resolution of lung parenchymal abnormalities depicted by imaging techniques in COVID-19 pneumonia requires considerable time. Moreover, lung parenchymal damage and changes may persist for a long time (lung tissue scarring), highlighting potentially chronic issues for long-term rehabilitation of survivors.

This prospective study had a number of limitations. The number of recruited patients was relatively small; hence, no meaningful subgroup analysis could be performed. We could not relate the US findings with pertinent laboratory findings and chest CT scans in all studied cases; however, that was not an end point of this study. Although it is an operator-dependent modality, the advantages of POCUS cannot be underestimated, even in contrast to CT scanning. Point-ofcare US is a bedside diagnostic tool that could minimize the risk of cross-infection related to transport of patients with COVID-19. It is less resource intensive and delivers no ionizing radiation. More studies are clearly required to explore the role of POCUS in the diagnosis and treatment of critically ill patients with COVID-19, bearing in mind that the absence of imaging signs cannot entirely rule out the infection.

In conclusion, this study illustrated that POCUS may be an alternative imaging modality in the diagnosis and monitoring of critically ill patients with COVID-19. Lung US detected extensive lung involvement, featured by B-lines, pleural line irregularities, and variable consolidation patterns in patients with serious COVID-19 pneumonia. Lung involvement progression was successfully tracked with US as well as disease resolution on improvement. Our rate of confirmed PE by CCTA was high but could not be related to POCUS-detected DVT. Lung US confirmed the gradual improvement of COVID-19 pneumonia in survivors approximately 5 to 6 weeks after ICU admission. The putative correlation of POCUS to CT and laboratory findings in COVID-19 warrants further attention.

Chinese Critical Care Ultrasound Study Group (CCUSG). Finding of lung ultrasonography of novel coronavirus pneumonia during the 2019-2020 epidemic

A preliminary study on the ultrasonic manifestations of peripulmonary lesions of non-critical novel coronavirus pneumonia (COVID-19). Social Science Research Network website

Point-of-care lung ultrasound findings in novel coronavirus disease-19 pnemoniae: a case report and potential applications during COVID-19 outbreak

Lung ultrasound findings in a 64-year-old woman with COVID-19

Our Italian experience of using lung ultrasound for identification, grading and serial follow-up of severity of lung involvement for management of patients with COVID-19

Lung ultrasound findings in patients with COVID-19 pneumonia

Can lung US help critical care clinicians in the early diagnosis of novel coronavirus (COVID-19) pneumonia?

Is there a role for lung ultrasound during the COVID-19 pandemic?

Proposal for international standardization of the use of lung ultrasound for COVID-19 patients; a simple, quantitative, reproducible method

Point-of-care lung ultrasound in patients with COVID-19: a narrative review

It's not over until it's over: the chameleonic behavior of COVID-19 over a six-day period

COVID-19 outbreak: less stethoscope, more ultrasound

Extension of coronavirus disease 2019 (COVID-19) on chest CT and implications for chest radiograph interpretation

Relevance of lung ultrasound in the diagnosis of acute respiratory failure

Bedside ultrasound assessment of positive end-expiratory pressureinduced lung recruitment

Training for lung ultrasound score measurement in critically ill patients

Ultrasound of the lungs more than a room with a view

Ultrasonography for the assessment of lung recruitment maneuvers

Ultrasound assessment of lung aeration loss during a successful weaning trial predicts postextubation distress

Inter-rater reliability of quantifying pleural B-lines using multiple counting methods

Diagnostic accuracy of chest radiograph, and when concomitantly studied lung ultrasound, in critically ill patients with respiratory symptoms: a systematic review and meta-analysis

Lung ultrasound in the diagnosis and follow-up of community-acquired pneumonia: a prospective, multicenter, diagnostic accuracy study

Clinical and computed tomographic imaging features of novel coronavirus pneumonia caused by SARS-CoV-2

Chest CT for typical 2019-nCoV pneumonia: relationship to negative RT-PCR testing

Correlation of chest CT and RT-PCR testing in coronavirus disease 2019 (COVID-19) in China: a report of 1014 cases

Performance of radiologists in differentiating COVID-19 from viral pneumonia on chest CT

Clinical and high-resolution CT features of the COVID-19 infection: comparison of the initial and follow-up changes

Proposal of a low-dose, long-pitch, dual-source chest CT protocol on third-generation dual-source CT using a tin filter for spectral shaping at 100 kVp for coronavirus disease 2019 (COVID-19) patients: a feasibility study

Time course of lung changes on chest CT during recovery from 2019 novel coronavirus (COVID-19) pneumonia

Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study

Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

China Medical Treatment Expert Group for COVID-19. Clinical characteristics of coronavirus disease 2019 in China

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

Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy region

Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspectedinterim guidance

Coronavirus diseases 19 (COVID-19) guidelines (revised version 1.7). Riyadh, Saudi Arabia: Saudi Ministry of Health website

Comparative performance of SARS-CoV-2 detection assays using seven different primer/probe sets and one assay kit

Virological assessment of hospitalized patients with COVID-2019

Detection of SARS-CoV-2 in different types of clinical specimens

Positive rate of RT-PCR detection of SARS-CoV-2 infection in 4880 cases from one hospital in

Improved molecular diagnosis of COVID-19 by the novel, highly sensitive and specific COVID-19-RdRp/Hel real-time reverse transcription-PCR assay validated in vitro and with clinical specimens

Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR

World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects

publicationsdetail/infection-prevention-and-controlduring-health-care-when-novel-coronavirus-(ncov)-infection-issuspected-20200125

Air, surface, environmental, and personal protective equipment contamination by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from a symptomatic patient

World Federation for Ultrasound in Medicine and Biology Safety Committee. World Federation for Ultrasound in Medicine and Biology position statement: how to perform a safe ultrasound examination and clean equipment in the context of COVID-19

Lower-extremity Doppler for deep venous thrombosis: can emergency physicians be accurate and fast?

Accuracy of ultrasonography performed by critical care physicians for the diagnosis of DVT

Incidence of thrombotic complications in critically ill ICU patients with COVID-19

ISTH interim guidance on recognition and management of coagulopathy in COVID-19

Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia

Autopsy findings and venous thromboembolism in patients with COVID-19

Post-mortem examination of COVID-19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings of lungs and other organs suggesting vascular dysfunction

Severe pulmonary embolism in COVID-19 patients: a call for increased awareness

Thrombotic and hemorrhagic events in critically ill COVID-19 patients: a French monocenter retrospective study

Acute kidney injury in the intensive care unit according to RIFLE

Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72,314 cases from the Chinese Center for Disease Control and Prevention

A trial of lopinavir-ritonavir in adults hospitalized with Severe COVID-19

Sonographic signs and patterns of COVID-19 pneumonia. Version 2

What's new in lung ultrasound during the COVID-19 pandemic

Immune response to SARS-CoV-2 and mechanisms of immunopathological changes in COVID-19

Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)?

Tocilizumab treatment in COVID-19: a single center experience

Cytokine release syndrome in severe COVID-19

Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia