key: cord-0749924-pny5ya8o authors: Basille, Damien; Auquier, Marie-Anne; Andréjak, Claire; Rodenstein, Daniel Oscar; Mahjoub, Yazine; Jounieaux, Vincent title: Dissociation between the clinical course and chest imaging in severe COVID-19 pneumonia: a series of five cases date: 2021-06-30 journal: Heart Lung DOI: 10.1016/j.hrtlng.2021.06.008 sha: d9cdbc39cfe2a2fb474c91d6fc52bc214010afd1 doc_id: 749924 cord_uid: pny5ya8o BACKGROUND: Although an RT-PCR test is the “gold standard” tool for diagnosing an infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), chest imaging can be used to support a diagnosis of coronavirus disease 2019 (COVID-19) – albeit with fairly low specificity. However, if the chest imaging findings do not faithfully reflect the patient's clinical course, one can question the rationale for relying on these imaging data in the diagnosis of COVID-19. AIMS: To compare clinical courses with changes over time in chest imaging findings among patients admitted to an ICU for severe COVID-19 pneumonia. METHODS: We retrospectively reviewed the medical charts of all adult patients admitted to our intensive care unit (ICU) between March 1, 2020, and April 15, 2020, for a severe COVID-19 lung infection and who had a positive RT-PCR test. Changes in clinical, laboratory and radiological variables were compared, and patients with discordant changes over time (e.g. a clinical improvement with stable or worse radiological findings) were analyzed further. RESULTS: Of the 46 included patients, 5 showed an improvement in their clinical status but not in their chest imaging findings. On admission to the ICU, three of the five were mechanically ventilated and the two others received high-flow oxygen therapy or a non-rebreather mask. Even though the five patients’ radiological findings worsened or remained stable, the mean ± standard deviation partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO(2):FiO(2)) ratio increased significantly in all cases (from 113.2 ± 59.7 mmHg at admission to 259.8 ± 59.7 mmHg at a follow-up evaluation; p=0.043). INTERPRETATION: Our results suggest that in cases of clinical improvement with worsened or stable chest imaging variables, the PaO2:FiO2 ratio might be a good marker of the resolution of COVID-19-specific pulmonary vascular insult. -Guarantor statement: DB is is the guarantor of the content of the manuscript, including the data and analysis -Authors contribution: DB, MAA, YM, CA, DOR, and VJ contributed substantially to the study design, data analysis and interpretation, and the writing of the manuscript. -Financial/nonfinancial disclosures: the authors do not report any conflict of interest. Early diagnosis of COVID-19 is crucial for disease treatment and control, and the detection of viral nucleic acid in a reverse-transcription polymerase chain reaction (RT-PCR) test remains the gold standard diagnostic tool. However, it has been suggested that the RT-PCR test's lack of sensitivity, insufficient stability and relatively long processing time weaken our ability to control the COVID-19 pandemic. 5 Moreover, RT-PCR assays for SARS-CoV-2 were not available in several countries during the epidemic period. 6 In this context, chest imaging can be used to support the diagnosis of COVID-19 pneumonia. 7,8 There is currently no consensus among the main radiology societies on the type of chest imaging to use in the diagnosis of COVID-19 pneumonia. The British Society of Thoracic Imaging and the Canadian Society of Radiologists suggested that a chest X-ray should be the first-line tool in stable patients. 9, 10 Chest computed tomography (CT) is typically used to (i) assess patients with comorbidities and/or a high risk of disease progression and (ii) screen for complications. Chest CT can reveal early pneumonia with greater sensitivity than a chest X-ray. However, the sensitivity and the specificity of CT are lower in non-pandemic areas. [11] [12] [13] Therefore, the choice of the imaging modality depends on the judgment of clinical teams, the availability of local resources, and the expertise of local radiologists. Relative to RT-PCR, chest CT offers good sensitivity, positive predictive values and negative predictive values, although the specificity is fairly low (97%, 65%, 83%, and 25%, respectively). 5 We therefore decided to compare clinical courses with changes over time in chest imaging findings among patients admitted to an ICU for severe COVID-19 pneumonia. This study was conducted in Amiens-Picardie University Medical Center (Amiens, with chest X-rays, we used the scoring system described by Borghesi and Maroldi. 15 Variables assessed: The following data were obtained from the patients' medical charts: age, sex, comorbidities, self-reported smoking status, and body mass index (BMI). Following admission to the ICU, the results of arterial blood gas, ventilatory support mode and concomitant thoracic imaging data were recorded. The time interval between symptom onset and the initial evaluation was noted. The ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO 2 :FiO 2 ) was computed for each patient. These data were also collected at the follow-up radiological evaluation (chest CT when it had been available for the initial evaluation, or a chest X-ray). In patients to whom oxygen was delivered through nasal prongs, the delivered FiO 2 was estimated using the equation published by Markovitz et al. (21% + 2.5% per L/min of additional oxygen). 16 Wilcoxon's paired test was used to compare the PaO 2 :FiO 2 ratio at baseline and at follow-up. Eighty-one patients with a positive SARS-CoV-2 RT-PCR test were admitted to our ICU and included in the study. In line with our exclusion criteria, thirty-five patients were excluded from the study (lack of radiological data at follow-up: n=22; non-severe COVID-19 pneumonia: n=7; COVID-19 without respiratory signs or symptoms: n=2; loss to follow-up: n=4). Of the 46 patients with severe COVID-19 pneumonia, the change in radiological status was assessed with a chest X-ray in 28 cases (60.9%) and with chest CT in 18 cases (39.1%). Twenty-seven patients showed a clinical and radiological improvement, 14 had clinical and radiological worsening, and 5 patients showed a discordant change (i.e. clinical improvement in the absence of radiological improvement) and were analyzed further ( Figure 1 and Table 1 ). The mean ± standard deviation age of the study population was 65.0 ± 7.8, and the mean BMI was 31.6 ± 6.1 kg/m². Three patients presented at least one comorbidity, and only one was a former smoker. The mean time from disease onset to ICU admission was 10.0 ± 6.1 days. At ICU admission, three patients were intubated and mechanically ventilated with a lung-protective strategy, whereas the other two patients were given high-flow oxygen therapy or a non-rebreather mask. The clinical course, blood gas levels, and chest imaging findings were then evaluated between 9 and 28 days after admission. pneumonia. 21 The time to radiological resolution of the pneumonia appears to be correlated with older age and the number of lobes involved. 22 In these situations, however, the change in the PaO2:FiO2 ratio is correlated with the radiological change. Gattinoni et al. have described two time-dependent chronological phenotypes among patients suffering from COVID-19 pneumonia. 23 The five cases reported here raise questions about the mechanism of the increase in the PaO2:FiO2 ratio during COVID-19 pneumonia. In fact, our observations suggest that the hypoxemia was due not only to lung parenchyma lesions but also to another pathophysiological mechanism. The discordant changes observed in our five patients (a dramatic increase in the PaO2:FiO2 ratio in the absence of a radiological improvement) support our "intrapulmonary shunt" hypothesis. Indeed, we recently hypothesized that all stages of COVID-19 are characterized by an elevated pulmonary blood flow and an intrapulmonary right-to-left shuntprompting us to introduce the acronym AVDS for "acute vascular distress syndrome". 24 These patients should not be considered as being asymptomatic, since their pulmonary vascular insult might lead to an intrapulmonary shunt that can be only evidenced by contrastenhanced echocardiography. 25 One can assume that hypoxemia will decrease upon recovery from the pulmonary vascular insult, regardless of the course of the lung's parenchymal lesions. The clear-cut PaO 2 :FiO 2 ratio improvement observed in our five patients (despite stable or worsening chest imaging results) argues in favor of this hypothesis. Our study also had some limitations. Notably, the change in chest imaging findings was assessed with CT in only 18 of the 46 patients. For patients assessed with a chest X-ray, some radiological features (such as vascular enlargement and GGOs) may have been misclassified. Our observation of five cases of significant clinical and blood gas improvements in patients with stable or worsening radiological findings suggests that chest imaging is not a reliable means of assessing the initial vascular damage and the likely outcome of some ICU patients with severe COVID-19 disease. The PaO2:FiO2 ratio could then be considered as a good marker of the resolution of the COVID-19-specific pulmonary vascular insult. Further clinical studies will be useful to confirm this result. 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Severe Covid-19 disease: rather AVDS than ARDS? Pure SARS-CoV-2 related AVDS (Acute Vascular Distress Syndrome) Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19 Pulmonary Vascular Manifestations of COVID-19 Pneumonia Pulmonary Vascular Pathology in Covid-19 VCV: volume-controlled ventilation; ECMO: extracorporeal membrane oxygenation; PCV: pressure-controlled ventilation; PIP: peak inspiratory pressure; PSV: pressure support ventilation; GFR: glomerular filtration rate; CRP: C reactive protein; BNP: brain natriuretic peptide NA: not available † For patients assessed with chest CT, our evaluation of the extension of pneumonia was based on the guidelines issued by the European Society of Radiology and the European Society of Thoracic Imaging. 14 For patients assessed with a chest X-ray, we used the scoring system published by Borghesi et Maroldi. 15 * In patients treated with oxygen via nasal prongs, we considered that the effective FiO 2 increased by 2.5% per additional liter of oxygen flow.