Lung ultrasound in the COVID-19 era: a lesson to be learned for the future.

Lung Ultrasound (LUS) is a reliable, radiation free and bedside imaging technique to assess several pulmonary diseases. Although the diagnosis of COVID-19 is made with the nasopharyngeal swab, detection of pulmonary involvement is key for a safe patient management. LUS is a valid alternative to explore, in paucisymptomatic self-presenting patients, the presence and extension of pneumonia compared to High Resolution Computed Tomography (HRCT) that represent the gold standard. This is a single-centre prospective study with 131 patients enrolled. Twelve lung areas were explored reporting a semiquantitative assessment to obtain the LUS score. Each patient performed reverse-transcription polymerase chain reaction test (rRT-PCR), hemogasanalysis and HRCT. We observed an inverse correlation between LUSs and pO2, P/F, SpO2, AaDO2 (p value < 0.01), a direct correlation with LUSs and AaDO2 (p value < 0.01). Compared with HRCT, LUS showed sensitivity and specificity of 81.8% and 55.4%, respectively, and VPN 75%, VPP 65%. Therefore, LUS can represent an effective alternative tool to detect pulmonary involvement in COVID-19 compared to HRCT.

Interoperator Reliability of Lung Ultrasound during the COVID-19 Pandemic.

AIM: Lung ultrasound (LUS) is a reliable, radiation-free, and bedside imaging technique used to assess several pulmonary diseases. Although COVID-19 is diagnosed with a nasopharyngeal swab, detection of pulmonary involvement is crucial for safe patient discharge. Computed tomography (CT) is currently the gold standard. To treat paucisymptomatic patients, we have implemented a "fast track" pathway in our emergency department, using LUS as a valid alternative. Minimal data is available in the literature about interobserver reliability and the level of expertise needed to perform a reliable examination. Our aim was to assess these. MATERIALS AND METHODS: This was a single-center prospective study. We enrolled 96 patients. 12 lung areas were explored in each patient with a semiquantitative assessment of pulmonary aeration loss in order to obtain the LUS score. Scans were performed by two different operators, an expert and a novice, who were blinded to their colleague's results. RESULTS: 96 patients were enrolled. The intraclass correlation coefficient (ICC) showed excellent agreement between the expert and the novice operator (ICC 0.975; 0.962-0.983); demographic features (age, sex, and chronic pulmonary disease) did not influence the reproducibility of the method. The ICC was 0.973 (0.950-0.986) in males, 0.976 (0.959-0.986) in females; 0.965 (0.940-0.980) in younger patients (≤ 46 yrs), and 0.973 (0.952-0.985) in older (> 46 yrs) patients. The ICC was 0.967 (0.882-0.991) in patients with pulmonary disease and 0.975 (0.962-0.984) in the other patients. The learning curve showed an increase in interobserver agreement. CONCLUSION: Our results confirm the feasibility and reproducibility of the method among operators with different levels of expertise, with a rapid learning curve.

Can Lung Ultrasound be Used to Screen for Pulmonary Embolism in Patients with SARS-CoV-2 Pneumonia?

Thromboembolic disease is strongly associated with, or even an integral part of, COVID-19 pneumonia. Indeed, endothelial/microvascular damage to pulmonary capillaries seems to be the main trigger of the pneumonia. Here we report a case of pulmonary embolism in a COVID-19 patient with an atypical clinical presentation. Blood gas analysis and lung ultrasound allowed the correct diagnosis to be reached. LEARNING POINTS: COVID-19 pneumonia is associated with cardiovascular complications and pulmonary embolisms.Lung ultrasound can aid diagnosis by visualizing small peripheral pulmonary embolisms.

Platelet Count in Patients with SARS-CoV-2 Infection: A Prognostic Factor in COVID-19.

COVID-19 patients may manifest thrombocytopenia and some of these patients succumb to infection due to coagulopathy. The aim of our study was to examine platelet count values in patients infected with SARS-CoV-2, comparing them to a control group consisting of non-COVID-19 patients. Moreover, we evaluated the correlation between the platelet value and the respiratory alteration parameters and the outcome (hospitalization and mortality) in COVID-19 patients. The mean platelet values (×109/L) differed between patients with positive or negative SARS-CoV-2 swabs (242.1 ± 92.1 in SARS-CoV-2 negative vs. 215.2 ± 82.8 in COVID-19 patients, p < 0.001). In COVID-19 patients, the platelet count correlated with the A-aO2 gradient (p = 0.001, rho = -0.149), with its increase over the expected (p = 0.013; rho = -0.115), with the PaO2 values (p = 0.036; rho = 0.093), with the PCO2 values (p = 0.003; rho = 0.134) and with the pH values (p = 0.016; rho = -0.108). In COVID-19 negative patients, the platelet values correlated only with the A-aO2 gradient: (p = 0.028; rho = -0.101). Patients discharged from emergency department had a mean platelet value of 234.3 ± 68.7, those hospitalized in ordinary wards had a mean value of 204.3 ± 82.5 and in patients admitted to sub-intensive/intensive care, the mean value was 201.7 ± 75.1. In COVID-19 patients, the survivors had an average platelet value at entry to the emergency department of 220.1 ± 81.4, while that of those who died was 206.4 ± 87.7. Our data confirm that SARS-CoV-2 infection may induce thrombocytopenia, and that the reduction in platelet counts could be correlated with the main blood gas parameters and with clinical outcome; as a consequence, platelet count could be an important prognostic factor to evaluate and stratify COVID-19 patients.

CovHos score for predicting severe respiratory failure in COVID-19 patients presenting at the emergency department.

Hospitalization of COVID-19 patients in low-intensity wards may put patients at risk in case of clinical deterioration. We tested CovHos score in predicting severe respiratory failure (SFR) at emergency department (ED) admission. This is a monocentric observational prospective study enrolling adult COVID-19 patients admitted to the ED of IRCCS AOU di Bologna Policlinico S.Orsola in October 2020, both discharged and hospitalized. Patients were then dichotomized based on days from symptoms onset. Main outcome was the occurrence of SRF. Receiver operating characteristic (ROC) analysis was used to identify cut-off and corresponding accuracy. A CovHos cut-off of 22 yielded a sensitivity of 84.7% and specificity of 75.3% in predicting SRF (AUROC 0.856; CI 95% 0.813-0.898). In patients with symptoms onset up to 8 days, a CovHos cut-off of 22 was able to predict SRF with a sensitivity of 91.7% and a specificity of 78.6% (AUROC 0.901; CI 95% 0.861-0.941). Negative predictive value (NPV) was 97.1%. A CovHos score lower than 22, in patients with COVID-19 symptoms onset dated 8 or less days prior to the ED admittance, had a NPV of 97.1% for the development of SRF, meaning that almost none of those patients will evolve into SRF and could be therefore suitable for a lower intensity of care.

Role of Lung Ultrasound in the Management of Patients with Suspected SARS-CoV-2 Infection in the Emergency Department.

BACKGROUND: The lung ultrasound (LUS) score has been proposed as an optimal scheme for the ultrasound study of patients with suspected/confirmed COVID-19 pneumonia. The aims of our study were to evaluate the use of lung ultrasound as a diagnostic tool for diagnosing SARS-CoV-2 pneumonia, to examine the validity of the LUS score for the diagnosis of COVID-19 pneumonia, and to correlate this score with hospitalization rate and 30-day mortality. MATERIALS AND METHODS: A retrospective analysis was performed on 1460 patients who were referred to the General Emergency Department of the S. Orsola-Malpighi Hospital from April 2020 to May 2020 for symptoms suspected to indicate SARS-CoV-2 infection. The ultrasound examination was based on a common execution scheme called the LUS score, as previously described. RESULTS AND CONCLUSIONS: The LUS score was found to correlate with the degree of clinical severity and respiratory failure (paO2/FiO2 ratio and the alveolar-arterial gradient increase than expected for age). It was shown that COVID-19 patients with an LUS score of >7 require the use of oxygen support, and a value of >10 is associated with an increased risk of oro-tracheal intubation. The LUS score was found to present higher values in hospitalized patients, increasing according to the degree of care intensity. Patients who died from COVID-19 were characterized by a mean LUS score of 11 at presentation to the emergency department. An LUS score of >7.5 was found to indicate a sensitivity of 83% and a specificity of 89% for 30-day mortality in COVID-19 patients. The use of LUS seems to be an optimal first level method for pneumonia detection and risk stratification in patients with suspected SARS-CoV-2 infection.

Sickle Cell Trait and SARS-CoV-2-Induced Rhabdomyolysis: A Case Report.

BACKGROUND Rhabdomyolysis is a syndrome characterized by muscle necrosis and the subsequent release of intracellular muscle constituents into the bloodstream. Although the specific cause is frequently evident from the history or from the immediate events, such as a trauma, extraordinary physical exertion, or a recent infection, sometimes there are hidden risk factors that have to be identified. For instance, individuals with sickle cell trait (SCT) have been reported to be at increased risk for rare conditions, including rhabdomyolysis. Moreover, there have been a few case reports of SARS-CoV-2 infection-related rhabdomyolysis. CASE REPORT We present a case of a patient affected by unknown SCT and admitted with SARS-CoV-2 pneumonia, who suffered non-traumatic non-exertional rhabdomyolysis leading to acute kidney injury (AKI), requiring acute hemodialysis (HD). The patients underwent 13 dialysis session, of which 12 were carried out using an HFR-Supra H dialyzer. He underwent kidney biopsy, where rhabdomyolysis injury was ascertained. No viral traces were found on kidney biopsy samples. The muscle biopsy showed the presence of an "open nucleolus" in the muscle cell, which was consistent with virus-infected cells. After 40 days in the hospital, his serum creatinine was 1.62 mg/dL and CPK and Myoglobin were 188 U/L and 168 ng/mL, respectively; therefore, the patient was discharged. CONCLUSIONS SARS-CoV-2 infection resulted in severe rhabdomyolysis with AKI requiring acute HD. Since SARS-CoV-2 infection can trigger sickle-related complications like rhabdomyolysis, the presence of SCT needs to be ascertained in African patients.

Prediction of Conventional Oxygen Therapy Failure in COVID-19 Patients With Acute Respiratory Failure by Assessing Serum Lactate Concentration, PaO2/FiO2 Ratio, and Body Temperature.

One of the challenges that emerged during the coronavirus disease 2019 (COVID-19) pandemic and is still relevant today is the need to identify patients with acute respiratory failure (ARF) who could benefit from conventional oxygen therapy (COT) - oxygen supplementation with nasal cannulas, Venturi masks, and non-rebreather masks - without recurring to advanced respiratory therapy, such as high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), non-invasive ventilation (NIV), or invasive mechanical ventilation. The aim of the study was to develop a clinical tool able to predict the failure of COT in COVID-19 patients presenting to the emergency department (ED) with ARF. This was a retrospective monocentric cohort study carried out in the ED of the University Hospital of Bologna Sant'Orsola-Malpighi Polyclinic, Italy. The cohort comprised 101 COVID-19 patients with ARF from the first pandemic wave who received COT. This cohort was used to develop a scale that considers serum lactate concentration, partial arterial oxygen pressure/inspired oxygen fraction (PaO2/FiO2) ratio, and body temperature to predict COT failure, referred to as the Lactate, Oxygenation, and Temperature (LOT) score. The highest possible score was 17 points. The LOT score was associated with COT failure (area under the receiver operating curve or AUROC = 0.79, 95% CI 0.69 - 0.89, p < 0.001); the cut-off value of > 5 points had optimal predictive power and showed significantly higher 30-day mortality (log-rank χ2 = 28,828, p < 0.0001). The LOT score was able to effectively predict COT failure in COVID-19 patients with ARF. Patients with LOT score > 5 had a very high risk of therapy failure, and more advanced respiratory therapies must be considered in these patients.

Non-COVID-19 patients in times of pandemic: Emergency department visits, hospitalizations and cause-specific mortality in Northern Italy.

The COVID-19 pandemic forced healthcare services organization to adjust to mutating healthcare needs. Not exhaustive data are available on the consequences of this on non-COVID-19 patients. The aim of this study was to assess the impact of the pandemic on non-COVID-19 patients living in a one-million inhabitants' area in Northern Italy (Bologna Metropolitan Area-BMA), analyzing time trends of Emergency Department (ED) visits, hospitalizations and mortality. We conducted a retrospective observational study using data extracted from BMA healthcare informative systems. Weekly trends of ED visits, hospitalizations, in- and out-of-hospital, all-cause and cause-specific mortality between December 1st, 2019 to May 31st, 2020, were compared with those of the same period of the previous year. Non-COVID-19 ED visits and hospitalizations showed a stable trend until the first Italian case of COVID-19 has been recorded, on February 19th, 2020, when they dropped simultaneously. The reduction of ED visits was observed in all age groups and across all severity and diagnosis groups. In the lockdown period a significant increase was found in overall out-of-hospital mortality (43.2%) and cause-specific out-of-hospital mortality related to neoplasms (76.7%), endocrine, nutritional and metabolic (79.5%) as well as cardiovascular (32.7%) diseases. The pandemic caused a sudden drop of ED visits and hospitalizations of non-COVID-19 patients during the lockdown period, and a concurrent increase in out-of-hospital mortality mainly driven by deaths for neoplasms, cardiovascular and endocrine diseases. As recurrencies of the COVID-19 pandemic are underway, the scenario described in this study might be useful to understand both the population reaction and the healthcare system response at the early phases of the pandemic in terms of reduced demand of care and systems capability in intercepting it.

CovHos, a New Score to Predict the Need of Hospitalization for Coronavirus Disease 2019 (COVID-19) Patients at the Emergency Department.

INTRODUCTION AND AIM: As first receivers of suspected coronavirus disease 2019 (COVID-19) patients, clinicians of the Emergency Department (ED) have to rapidly perform the first clinical assessment evaluating the intensity of care needed. So far, clear management guidelines still lack. We identified variables associated with hospitalization in order to give a quick tool to assist clinicians in stratifying cases based on the severity at their arrival at the ED and in predicting the need for hospital care.  Methods: This is a monocentric observational prospective study enrolling COVID-19 patients. A score for hospitalization prediction (CovHos Score) was created using variables associated with hospitalization at multivariate analysis and then validated on an internal subsequent cohort. RESULTS: A total of 667 patients were included; 465 (69.7%) were hospitalized and 108 (16.2%) died at 30-days follow-up. In a multivariate analysis, male sex, age>65, alveolar-to-arterial oxygen gradient percentage increase compared to that expected for age, neutrophils/lymphocytes ratio and C-reactive protein levels were significantly associated with a higher rate of hospital admission. A CovHos score cut-off of 12 points predicted hospitalization with 85% sensitivity and 82.4 % specificity (area under a receiver operating characteristic curve [AUROC] = 0.909, 95% CI 0.884 - 0.935). Similar results were obtained in the validation court. A cut-off of 22 has 79% sensitivity and 77% specificity in predicting mortality (AUROC = 0.824; 95% CI 0.782-0.866); sensitivity and specificity were respectively 71.4% and 71.3% in the validation group. CONCLUSIONS: Although medical judgment still remains crucial, the CovHos score is an effective tool to assist emergency clinicians in predicting the need for hospitalization or to optimize allocation in a shortage of hospital resources.

Patterns of Emergency Department visits for acute and chronic diseases during the two pandemic waves in Italy.

BACKGROUND: Evidence is lacking about the impact of subsequent COVID-19 pandemic waves on Emergency Departments (ED). We analyzed the differences in patterns of ED visits in Italy during the two pandemic waves, focusing on changes in accesses for acute and chronic diseases. METHODS: We conducted a retrospective study using data from a metropolitan area in northern Italy that includes twelve ED. We analyzed weekly trends in non-COVID-19 ED visits during the first (FW) and second wave (SW) of the pandemic. Incidence rate ratios (IRRs) of triage codes, patient destination, and cause-specific ED visits in the FW and SW of the year 2020 vs. 2019 were estimated using Poisson regression models. MAIN FINDINGS: We found a significant decrease of ED visits by triage code, which was more marked for low priority codes and during the FW. We found an increased share of hospitalizations compared to home discharges both in the FW and in the SW. ED visits for acute and chronic conditions decreased during the FW, ranging, from -70% for injuries (IRR = 0.2862, p < 0.001) to -50% and - 60% for ischemic heart disease and heart failure. CONCLUSIONS: The two pandemic waves led to a selection of patients with higher and more urgent needs of acute hospital care. These findings should lead to investigate how to improve systems' capacity to manage changes in population needs.

One year of SARS-CoV-2 and lung ultrasound: what has been learned and future perspectives.

A first screening by ultrasound can be relevant to set a specific diagnostic and therapeutic route for a patient with a COVID-19 infection. The finding of bilateral B-lines and white lung areas with patchy peripheral distribution and sparing areas is the most suggestive ultrasound picture of COVID-19 pneumonia. Failure to detect bilateral interstitial syndrome (A pattern) on ultrasound excludes COVID-19 pneumonia with good diagnostic accuracy, but does not exclude current infection. The use of shared semiotic and reporting schemes allows the comparison and monitoring of the COVID-19 pulmonary involvement over time. This review aims to summarise the main data on pulmonary ultrasound and COVID-19 to provide accurate and relevant information for clinical practice.

Lung ultrasound for the early diagnosis of COVID-19 pneumonia: an international multicenter study.

PURPOSE: To analyze the application of a lung ultrasound (LUS)-based diagnostic approach to patients suspected of COVID-19, combining the LUS likelihood of COVID-19 pneumonia with patient's symptoms and clinical history. METHODS: This is an international multicenter observational study in 20 US and European hospitals. Patients suspected of COVID-19 were tested with reverse transcription-polymerase chain reaction (RT-PCR) swab test and had an LUS examination. We identified three clinical phenotypes based on pre-existing chronic diseases (mixed phenotype), and on the presence (severe phenotype) or absence (mild phenotype) of signs and/or symptoms of respiratory failure at presentation. We defined the LUS likelihood of COVID-19 pneumonia according to four different patterns: high (HighLUS), intermediate (IntLUS), alternative (AltLUS), and low (LowLUS) probability. The combination of patterns and phenotypes with RT-PCR results was described and analyzed. RESULTS: We studied 1462 patients, classified in mild (n = 400), severe (n = 727), and mixed (n = 335) phenotypes. HighLUS and IntLUS showed an overall sensitivity of 90.2% (95% CI 88.23-91.97%) in identifying patients with positive RT-PCR, with higher values in the mixed (94.7%) and severe phenotype (97.1%), and even higher in those patients with objective respiratory failure (99.3%). The HighLUS showed a specificity of 88.8% (CI 85.55-91.65%) that was higher in the mild phenotype (94.4%; CI 90.0-97.0%). At multivariate analysis, the HighLUS was a strong independent predictor of RT-PCR positivity (odds ratio 4.2, confidence interval 2.6-6.7, p < 0.0001). CONCLUSION: Combining LUS patterns of probability with clinical phenotypes at presentation can rapidly identify those patients with or without COVID-19 pneumonia at bedside. This approach could support and expedite patients' management during a pandemic surge.

Use of non-invasive ventilation in acute respiratory failure due to SARS-CoV-2 pneumonia: typing of patients and choice of respiratory support, the role of internal medicine

The use of non-invasive ventilation (NIV) during de novo acute hypoxemic respiratory failure is not recommended by the guidelines because NIV does not improve the prognosis. With the advent of the new coronavirus, many cases of acute hypoxemic respiratory failure associated with the infection (severe acute respiratory infection) have been observed: data are missing regarding the use of NIV in this particular clinical condition, but a correct typing of patients based on different clinical, pathophysiological and radiological characteristics, could help in prognostic stratification and choice of respiratory support (invasive versus non-invasive). During NIV in these patients, particular attention is paid to the possibility of environmental dissemination of the virus, and consequently, adequate technical precautions are taken.

COVID-19 and Immunological Dysregulation: Can Autoantibodies be Useful?

Coronavirus disease 2019 (COVID-19) is often associated with interstitial pneumonia. However, there is insufficient knowledge on the presence of autoimmune serological markers in patients with COVID-19. We analyzed the presence and role of autoantibodies in patients with COVID-19-associated pneumonia. We prospectively studied 33 consecutive patients with COVID-19, 31 (94%) of whom had interstitial pneumonia, and 25 age-matched and sex-matched patients with fever and/or pneumonia with etiologies other than COVID-19 as the pathological control group. All patients were tested for the presence of antinuclear antibodies (ANAs), anti-antiphospholipid antibodies, and anti-cytoplasmic neutrophil antibodies (ANCAs). Clinical, biochemical, and radiological parameters were also collected. Fifteen of 33 patients (45%) tested positive for at least one autoantibody, including 11 who tested positive for ANAs (33%), 8 who tested positive for anti-cardiolipin antibodies (immunoglobulin (Ig)G and/or IgM; 24%), and 3 who tested positive for anti-ß2-glycoprotein antibodies (IgG and/or IgM; 9%). ANCA reactivity was not detected in any patient. Patients that tested positive for auto-antibodies had a significantly more severe prognosis than other patients did: 6 of 15 patients (40%) with auto-antibodies died due to COVID-19 complications during hospitalization, whereas only 1 of 18 patients (5.5%) who did not have auto-antibodies died (P = 0.03). Patients with poor prognosis (death due to COVID-19 complications) had a significantly higher respiratory rate at admission (23 breaths per minute vs. 17 breaths per minute; P = 0.03) and a higher frequency of auto-antibodies (86% vs. 27%; P = 0.008). In conclusion, auto-antibodies are frequently detected in patients with COVID-19 possibly reflecting a pathogenetic role of immune dysregulation. However, given the small number of patients, the association of auto-antibodies with an unfavorable prognosis requires further multicenter studies.