Lung ultrasound in the follow-up of severe COVID-19 pneumonia: six months evaluation and comparison with CT.

While lung ultrasonography (LUS) proved to be a useful diagnostic and prognostic tool in acute phase of COVID 19 pneumonia, its role in detecting long-term pulmonary sequelae has yet to be explored. In our prospective observational study we assessed the potential of LUS in detecting the presence of computed tomography (CT) fibrotic-like changes after 6 months from COVID-19 pneumonia. Patients who were discharged with a diagnosis of severe COVID-19 pneumonia were enrolled. After 6 months from hospital discharge they underwent LUS, chest CT scan and pulmonary function tests. A logistic regression analysis was performed to assess the association between presence of symptoms, LUS score and diffusing capacity for carbon monoxide (DLCO) at 6-month after hospital discharge and CT scan fibrotic-like changes. A second logistic model was performed to assess the value of some predefined baseline factors (age, sex, worst PaO2/FiO2, ventilator support, worst CRP value, worst D-dimer value and worst LUS score during hospitalization) to predict fibrotic-like changes on 6-month CT scan. Seventy-four patients were enrolled in the study. Twenty-four (32%) showed lung abnormalities suitable for fibrotic-like changes. At multivariate logistic regression analysis LUS score after 6 months from acute disease was significantly associated with fibrotic-like pattern on CT scan. The second logistic model showed that D-dimer value was the only baseline predictive variable of fibrotic-like changes at multivariate analysis. LUS performed after 6 months from severe COVID-19 pneumonia may be a promising tool for detection and follow-up of pulmonary fibrotic sequelae.

Examination of the relationship between emergency department presentations and population mortality: a multicenter analysis of emergency department presentations during the COVID-19 pandemic.

BACKGROUND: In the spring of 2020, Italy experienced a significant reduction in the number of emergency department (ED) presentations during the first wave of the COVID-19 pandemic. If ED access has an impact on patients' prognosis, such a reduction in ED presentations would be expected to correlate with a parallel increase in the mortality rate of the corresponding population. The aim of the present study was to evaluate the impact of reduced ED presentations on the all-cause mortality of the general population. METHODS: Absolute and relative variation in ED accesses from March 1 to April 30 of both 2019 and 2020 in three hub hospitals in areas with different COVID-19 prevalence and age-standardized mortality data from January 1 to June 30 in 2019 and 2020 of the same areas were evaluated. RESULTS: During March and April 2020, ED consults were decreased of approximately 50% in all three hospitals, as compared with the same months in 2019. There was a marked increase in cumulative mortality in Milan (high SARS-CoV2 infection spread zone) compared with the same period in 2019. In the other two municipalities (Ferrara and Perugia), which had intermediate and low levels of infection spread, the mortality in 2020 was not substantially changed from that of 2019. CONCLUSIONS: Taking into account the increase in mortality due to SARS-CoV-2, reductions in ED access did not seem to affect death rates. If this finding will be confirmed, ED organization and access would need to be reconsidered.

Diagnostic performance of chest radiography in high COVID-19 prevalence setting: experience from a European reference hospital.

PURPOSE: The study's aim is to analyse the diagnostic performance of chest radiography (CXR) in patients with suspected coronavirus disease 19 (COVID-19). METHODS: We retrospectively considered 826 consecutive patients with suspected COVID-19 presenting to our emergency department (ED) from February 21 to March 31, 2020, in a high disease prevalence setting. We enrolled patients who underwent CXR and rhino-oropharyngeal swab for real-time reverse transcription-polymerase chain reaction (rRT-PCR). CXRs were evaluated by an expert radiologist; a second independent analysis was performed by two residents in consensus. All readers, blinded to rRT-PCR results, classified CXRs positive/negative depending on presence/absence of typical findings of COVID-19, using rRT-PCR as reference standard. RESULTS: We finally analysed 680 patients (median age 58); 547 (80%) tested positive for COVID-19. The diagnostic performance of CXR, interpreted by the expert reader, was as follows: sensitivity (79.0%; 95% CI: 75.3-82.3), specificity (81.2%; 95% CI: 73.5-87.5), PPV (94.5%;95% CI: 92.0-96.4), NPV (48.4%; 95% CI: 41.7-55.2), and accuracy (79.3%; 95% CI: 76.0-82.2). For the residents: sensitivity (75.1%; 95% CI: 71.2-78.7), specificity (57.9%; 95% CI: 49.9-66.4), PPV (88.0%; 95% CI: 84.7-90.8), NPV (36.2%; 95% CI: 29.7-43.0), and accuracy (71.6%; 95% CI: 68.1-75.0). We found a significant difference between the reporting sensitivity (p = 0.013) and specificity (p < 0.0001) of expert radiologist vs residents. CXR sensitivity was higher in patients with symptom onset > 5 days before ED presentation compared to ≤ 5 days (84.4% vs 70.7%). CONCLUSIONS: CXR showed a sensitivity of 79% and a specificity of 81% in diagnosing viral pneumonia in symptomatic patients with clinical suspicion of COVID-19. Further studies in lower prevalence settings are needed.

Early evidence of SARS-CoV-2 in Milan, Jan-Feb 2020.

BACKGROUND: A few studies have suggested that the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) was present in Northern Italy several weeks before its official detection on February 21, 2020. On the other hand, no clinical data have been provided so far to support such hypothesis. We investigated clinical-epidemiological evidence of SARS-CoV-2 infection among children and adults referring to emergency department (ED) in the main hospital of the center of Milan (Italy) before February 21, 2020. METHODS: A retrospective analysis of medical records of ED visits at the Fondazione Ca' Granda Policlinico, Milan between January 11 and February 15 in 2017, 2018, 2019 and in 2020 was performed. The number of subjects referring with fever, cough or dyspnea was compared between the studied period of 2020 and the previous 3 years, by calculating a standardized referral ratio (SRR, number of observed cases in 2020 divided by the number of expected cases according to 2017-2019) and the corresponding 95% confidence interval (CI). RESULTS: In the pediatric ED, 7709 (average 2570/year) and 2736 patients were visited during the period 2017-2019 and in the 2020, respectively. Among adults, 13,465 (average 4488/year) and 4787 were visited during the period 2017-2019 and in the 2020, respectively. The SRR was 1.16 (95% CI 1.10-1.23) in children and 1.25 (95% CI 1.16-1.35) in adults. The ratio for the two (children and adults) SRRs was 0.93 (0.84-1.02), suggesting a trend towards a higher frequency in adults compared to children. CONCLUSIONS: This study suggests that SARS-CoV-2 might have spread in Milan before February 21, 2020 with a minor trend among children.

Laryngotracheal aspiration test reduce the false negative rate in patients with suspected SARS-COV-2 pneumonia despite a negative nasopharyngeal swab.

BACKGROUND: In the emergency department (ED) definitive diagnosis of SARS-COV-2 pneumonia is challenging as nasopharyngeal swab (NPS) can give false negative results. Strategies to reduce false negative rate of NPS have limitations. Serial NPSs (24-48 h from one another) are time-consuming, sputum can not be collected in the majority of patients, and bronchoalveolar lavage (BAL), the most sensitive test, requires specific expertise. Laryngotracheal aspiration (LTA) is easy to perform and showed a similar accuracy to BAL for diagnosis of other pulmonary diseases, however it was not studied to diagnose SARS-COV-2 pneumonia. OBJECTIVE: An observational cross-sectional study was performed to evaluate the negative predictive value of LTA in patients with suspected SARS-COV-2 pneumonia despite a negative NPS. METHODS: In the EDs of two university hospitals, consecutive patients with suspected SARS-COV-2 pneumonia despite a negative NPS underwent LTA performed with a nasotracheal tube connected to a vacuum system. Final diagnosis based on all respiratory specimen tests (NPS, LTA and BAL) and hospital data was established by two reviewers and in case of discordance by a third reviewer. RESULTS: 117 patients were enrolled. LTA was feasible in all patients and no patients experienced adverse events. Fifteen (12.7%) patients were diagnosed with community-acquired SARS-COV-2 pneumonia: 13 LTA positive and only 2 (1.7%) LTA negative. The negative predictive value of NPS and LTA was 87.3% (79.9% - 92.7%) and 98.1% (93.3%99.8%) respectively. CONCLUSIONS: LTA resulted feasible, safe and reduced false negative rate in patients with suspected SARS-COV-2 pneumonia despite a negative NPS.

Utility of hospitalization for elderly individuals affected by COVID-19.

BACKGROUND: During the COVID-19 pandemic, the number of individuals needing hospital admission has sometimes exceeded the availability of hospital beds. Since hospitalization can have detrimental effects on older individuals, preference has been given to younger patients. The aim of this study was to assess the utility of hospitalization for elderly affected by COVID-19. We hypothesized that their mortality decreases when there is greater access to hospitals. METHODS: This study examined 1902 COVID-19 patients consecutively admitted to three large hospitals in Milan, Italy. Overall mortality data for Milan from the same period was retrieved. Based on emergency department (ED) data, both peak and off-peak phases were identified. The percentage of elderly patients admitted to EDs during these two phases were compared by calculating the standardized mortality ratio (SMR) of the individuals younger than, versus older than, 80 years. RESULTS: The median age of the patients hospitalized during the peak phase was lower than the median age during the off-peak phase (64 vs. 75 years, respectively; p <0.001). However, while the SMR for the younger patients was lower during the off-peak phase (1.98, 95% CI: 1.72-2.29 versus 1.40, 95% CI: 1.25-1.58, respectively), the SMR was similar between both phases for the elderly patients (2.28, 95% CI: 2.07-2.52 versus 2.48, 95% CI: 2.32-2.65, respectively). CONCLUSIONS: Greater access to hospitals during an off-peak phase did not affect the mortality rate of COVID-19-positive elderly patients in Milan. This finding, if confirmed in other settings, should influence future decisions regarding resource management of health care organizations.

Mortality in Patients with COVID-19 on Renin Angiotensin System Inhibitor Long-Term Treatment: An Observational Study Showing that Things Are Not Always as They Seem.

INTRODUCTION: At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, controversial data were reported concerning angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) that induced a number of physicians to stop using them in patients with COVID-19. Although large-scale studies have ruled out this concern, it is common experience that patients with COVID-19 taking ACE inhibitors or ARBs are at increased risk of death. The aim of this study was to investigate the reasons for this apparently high mortality rate. METHODS: During the first wave of the pandemic, we conducted a field study of 427 consecutive patients with COVID-19 upon their admission to the emergency department of a hospital in one of the most severely hit cities in northern Italy, and 30 days later. The disease was defined as being mild, moderate or severe on the basis of clinical, laboratory and imaging data, and a multivariate model was used to analyse the determinants of mortality. RESULTS: Within 30 days of admission, 31.6% of the patients treated with ACE inhibitors or ARBs and 15.2% of those not treated with these drugs had died. Multivariate analysis showed that the determinants of mortality were age (p = 0.0001), hypertension (p = 0.0120) and diabetes (p = 0.0129), whereas ACE inhibitors or ARBs had no effect on mortality. There was no significant difference between the patients treated with ACE inhibitors and those treated with ARBs. CONCLUSION: The apparently increased mortality of patients with COVID-19 receiving long-term treatment with ACE inhibitors or ARBs is not due to the drugs themselves, but to the conditions associated with their use.

The clinical spectrum of COVID-19-associated cutaneous manifestations: An Italian multicenter study of 200 adult patients.

BACKGROUND: COVID-19 is associated with a wide range of skin manifestations. OBJECTIVE: To describe the clinical characteristics of COVID-19-associated skin manifestations and explore the relationships among the 6 main cutaneous phenotypes and systemic findings. METHODS: Twenty-one Italian Dermatology Units were asked to collect the demographic, clinical, and histopathologic data of 200 patients with COVID-19-associated skin manifestations. The severity of COVID-19 was classified as asymptomatic, mild, moderate, or severe. RESULTS: A chilblain-like acral pattern was significantly associated with a younger age (P < .0001) and, after adjusting for age, significantly associated with less severe COVID-19 (P = .0009). However, the median duration of chilblain-like lesions was significantly longer than that of the other cutaneous manifestations taken together (P < .0001). Patients with moderate/severe COVID-19 were more represented than those with asymptomatic/mild COVID-19 among the patients with cutaneous manifestations other than chilblain-like lesions, but only the confluent erythematous/maculo-papular/morbilliform phenotype was significantly associated with more severe COVID-19 (P = .015), and this significance disappeared after adjustment for age. LIMITATIONS: Laboratory confirmation of COVID-19 was not possible in all cases. CONCLUSIONS: After adjustment for age, there was no clear-cut spectrum of COVID-19 severity in patients with COVID-19-related skin manifestations, although chilblain-like acral lesions were more frequent in younger patients with asymptomatic/pauci-symptomatic COVID-19.

Sensitivity of SARS-CoV-2 Detection With Nasopharyngeal Swabs.

Background: SARS-CoV-2-infected subjects have been proven contagious in the symptomatic, pre-symptomatic and asymptomatic phase. The identification of these patients is crucial in order to prevent virus circulation. No reliable data on the sensitivity of nasopharyngeal swabs (NPS) are available because of the lack of a shared reference standard to identify SARS-CoV-2 infected patients. The aim of our study was to collect data on patients with a known diagnosis of COVID-19 who underwent serial testing to assess NPS sensitivity. Methods: The study was a multi-center, observational, retrospective clinical study with consecutive enrollment. We enrolled patients who met all of the following inclusion criteria: clinical recovery, documented SARS-CoV-2 infection (≥1 positive rRT-PCR result) and ≥1 positive NPS among the first two follow-up swabs. A positive NPS not preceded by a negative nasopharyngeal swab collected 24-48 h earlier was considered a true positive. A negative NPS followed by a positive NPS collected 24-48 h later was regarded as a false negative. The primary outcome was to define sensitivity of SARS-CoV-2 detection with NPS. Results: Three hundred and ninety three NPS were evaluated in 233 patients; the sensitivity was 77% (95% CI, 73 to 81%). Sensitivity of the first follow-up NPS (n = 233) was 79% (95% CI, 73 to 84%) with no significant variations over time. We found no statistically significant differences in the sensitivity of the first follow-up NPS according to time since symptom onset, age, sex, number of comorbidities, and onset symptoms. Conclusions: NPS utility in the diagnostic algorithm of COVID-19 should be reconsidered.

High rates of pulmonary artery occlusions in COVID-19. A meta-analysis.

BACKGROUND: COVID-19 patients are considered at high risk of venous thromboembolism (VTE). The real nature of pulmonary artery occlusions (PAO) in COVID-19 has been questioned, suggesting that it is caused also by in situ thrombi, rather than only by emboli (PE) from peripheral thrombi. METHODS: We searched MEDLINE for studies published until 6 June 2020 that included COVID-19 patients or non-COVID-19 medical patients at VTE risk, treated with heparins, in whom VTE (PE and deep vein thrombosis, DVT) had been reported. Systematic review and results reporting were conducted in accordance with PRISMA guidelines. Data were independently extracted by two observers, and estimates were pooled using random-effects meta-analysis. RESULTS: We identified 17 studies including 3224 COVID-19 patients and 7 including 11 985 non-COVID-19 patients. Two analyses were performed: in all COVID-19 patients and only in those (n = 515) who, like non-COVID-19 patients, were screened systematically for DVT. The latter analysis revealed that the prevalence of DVT was 15.43% (95%CI, 4.08-31.77) in COVID-19 and 4.21% (2.27-6.68) in non-COVID-19 patients (P = .0482). The prevalence of PE was 4.85% (40.33-13.01) in COVID-19 patients and 0.22% (0.03-0.55) in non-COVID-19 patients (P = .0128). The percentage of PE among VTE events was 22.15% (5.31-44.60) in COVID-19 and 6.39% (3.17-10.41) in non-COVID-19 patients (P = .0482). Differences were even more marked when all COVID-19 patients were analysed. CONCLUSIONS: The results of our meta-analysis highlight a disproportion in the prevalence of PE among all VTE events in COVID 19 patients, likely reflecting PAO by pulmonary thrombi, rather than emboli from peripheral vein thrombi.