Remdesivir significantly reduces SARS-CoV-2 viral load on nasopharyngeal swabs in hospitalized patients with COVID-19: A retrospective case-control study.

Remdesivir is a broad-spectrum antiviral agent able to inhibit the RNA polymerase of SARS-CoV-2. At present, studies focusing on the effect of remdesivir on viral load (VL) are few and with contrasting results. Aim of the present study was to evaluate the effect of remdesivir on SARS-CoV-2 VL from nasopharyngeal swabs (cycle threshold criterion) in a sample of patients treated with the drug, compared with patients who did not receive the antiviral treatment. This retrospective analysis evaluated patients with (1) real-time polymerase chain reaction (RT-PCR) confirmed COVID-19 diagnosis and (2) availability of at least two positive nasopharyngeal swabs analysed with the same analytic platform (ORF target gene, Ingenius ELITe, ELITechGroup, Puteaux, France). Upper respiratory specimens from nasopharyngeal swabs were collected at admission (T0) and 7-14 days after treatment, upon clinical decision. A total of 27 patients treated with remdesivir (Group A) met the inclusion criteria and were compared with 18 patients (Group B) treated with standard care, matched for baseline clinical characteristics. At baseline, both remdesivir-treated and nontreated patients showed comparable VLs (21.73 ± 6.81 vs. 19.27 ± 5.24, p = 0.348). At the second swab, remdesivir-treated patients showed a steeper VL reduction with respect to controls (34.28 ± 7.73 vs. 27.22 ± 3.92; p < 0.001). Longitudinal linear model estimated a mean decrease in cycle threshold equal to 0.61 (SE: 0.09) per day in remdesivir-treated versus 0.33 (SE: 0.10) per day in remdesivir nontreated patients (p for heterogeneity = 0.045). The present study shows that the administration of remdesivir in hospitalized COVID-19 patients significantly reduces the VL on nasopharyngeal swabs.

Factors Associated with Delirium in COVID-19 Patients and Their Outcome: A Single-Center Cohort Study.

BACKGROUND: A significant proportion of patients with coronavirus disease 2019 (COVID-19) suffer from delirium during hospitalization. This single-center observational study investigates the occurrence of delirium, the associated risk factors and its impact on in-hospital mortality in an Italian cohort of COVID 19 inpatients. METHODS: Data were collected in the COVID units of a general medical hospital in the South of Italy. Socio-demographic, clinical and pharmacological features were collected. Diagnosis of delirium was based on a two-step approach according to 4AT criteria and DSM5 criteria. Outcomes were: dates of hospital discharge, Intensive Care Unit (ICU) admission, or death, whichever came first. Univariable and multivariable proportional hazards Cox regression models were estimated, and risks were reported as hazard ratios (HR) along with their 95% confidence intervals (95% CI). RESULTS: A total of 47/214 patients (22%) were diagnosed with delirium (21 hypoactive, 15 hyperactive, and 11 mixed). In the multivariable model, four independent variables were independently associated with the presence of delirium: dementia, followed by age at admission, C-reactive protein (CRP), and Glasgow Coma Scale. In turn, delirium was the strongest independent predictor of death/admission to ICU (composite outcome), followed by Charlson Index (not including dementia), CRP, and neutrophil-to-lymphocyte ratio. The probability of reaching the composite outcome was higher for patients with the hypoactive subtype than for those with the hyperactive subtype. CONCLUSIONS: Delirium was the strongest predictor of poor outcome in COVID-19 patients, especially in the hypoactive subtype. Several clinical features and inflammatory markers were associated with the increased risk of its occurrence. The early recognition of these factors may help clinicians to select patients who would benefit from both non-pharmacological and pharmacological interventions in order to prevent delirium, and in turn, reduce the risk of admission to ICU or death.

Low eGFR Is a Strong Predictor of Worse Outcome in Hospitalized COVID-19 Patients.

BACKGROUND: The clinical course of COVID-19 is more severe in elderly patients with cardio-metabolic co-morbidities. Chronic kidney disease is considered an independent cardiovascular risk factor. We aimed to evaluate the impact of reduced eGFR on the composite outcome of admission to ICU and death in a sample of consecutive COVID-19 hospitalized patients. METHODS: We retrospectively evaluated clinical records of a consecutive sample of hospitalized COVID-19 patients. A total of 231 patients were considered for statistical analysis. The whole sample was divided in two groups on the basis of eGFR value, e.g., ≥ or <60 mL/min/1.73 m2. Patients with low eGFR were further divided among those with a history of chronic kidney disease (CKD) and those without (AKI, acute kidney injury). The primary outcome was a composite of admission to ICU or death, whichever occurred first. The single components were secondary outcomes. RESULTS: Seventy-nine (34.2%) patients reached the composite outcome. A total of 64 patients (27.7%) died during hospitalization, and 41 (17.7%) were admitted to the ICU. A significantly higher number of events was present among patients with low eGFR (p < 0.0001). Age (p < 0.001), SpO2 (p < 0.001), previous anti-platelet treatment (p = 0.006), Charlson's Comorbidities Index (p < 0.001), serum creatinine (p < 0.001), eGFR (p = 0.003), low eGFR (p < 0.001), blood glucose levels (p < 0.001), and LDH (p = 0.003) were significantly associated with the main outcome in univariate analysis. Low eGFR (HR 1.64, 95% CI 1.02-2.63, p = 0.040) and age (HR per 5 years 1.22, 95% CI 1.10-1.36, p < 0.001) were significantly and independently associated with the main outcome in the multivariate model. Patients with AKI showed an increased hazard ratio to reach the combined outcome (p = 0.059), while those patients with both CKD had a significantly higher probability of developing the combined outcome (p < 0.001). CONCLUSIONS: Patients with reduced eGFR at admission should be considered at high risk for clinical deterioration and death, requiring the best supportive treatment in order to prevent the worst outcome.

Sepsis: New Challenges and Future Perspectives for an Evolving Disease-Precision Medicine Is the Way!

Sepsis still remains the leading cause of in-hospital death in the world [...].

COVID-19 Pneumonia: The Great Ultrasonography Mimicker.

The pandemic spread of the new severe acute respiratory syndrome coronavirus 2 has raised the necessity to identify an appropriate imaging method for early diagnosis of coronavirus disease 2019 (COVID-19). Chest computed tomography (CT) has been regarded as the mainstay of imaging evaluation for pulmonary involvement in the early phase of the pandemic. However, due to the poor specificity of the radiological pattern and the disruption of radiology centers' functionality linked to an excessive demand for exams, the American College of Radiology has advised against CT use for screening purposes. Lung ultrasound (LUS) is a point-of-care imaging tool that is quickly available and easy to disinfect. These advantages have determined a "pandemic" increase of its use for early detection of COVID-19 pneumonia in emergency departments. However, LUS findings in COVID-19 patients are even less specific than those detectable on CT scans. The scope of this perspective article is to discuss the great number of diseases and pathologic conditions that may mimic COVID-19 pneumonia on LUS examination.

Risk of burnout and stress in physicians working in a COVID team: A longitudinal survey.

BACKGROUND AND AIMS: The COVID-19 pandemic represents a source of stress and potential burnout for many physicians. This single-site survey aimed at assessing perceived stress and risk to develop burnout syndrome among physicians operating in COVID wards. METHODS: This longitudinal survey evaluated stress and burnout in 51 physicians operating in the COVID team of Gemelli Hospital, Italy. Participants were asked to complete the Maslach Burnout Inventory (MBI) and the Perceived Stress Questionnaire on a short run (PSQs) (referring to the past 7 days) at baseline (T0) and then for four weeks (T1-T4). Perceived Stress Questionnaire on a long run (PSQl) (referring to the past 2 years) was completed only at T0. RESULTS: Compared with physicians board-certified in internal medicine, those board-certified in other disciplines showed higher scores for the Emotional Exhaustion (EE) score of the MBI scale (P < .001). Depersonalisation (DP) score showed a reduction over time (P = .002). Attending physicians scored lower than the resident physicians on the DP scale (P = .048) and higher than resident physicians on the Personal Accomplishment (PA) scale (P = .04). PSQl predicted higher scores on the EE scale (P = .003), DP scale (P = .003) and lower scores on the PA scale (P < .001). PSQs showed a reduction over time (P = .03). Attending physicians had a lower PSQs score compared with the resident physicians (P = .04). CONCLUSIONS: Medical specialty and clinical position could represent risk factors for the development of burnout in a COVID team. In these preliminary results, physicians board-certified in internal medicine showed lower risk of developing EE during the entire course of the study.

Lung Ultrasound in the Diagnosis of COVID-19 Pneumonia: Not Always and Not Only What Is COVID-19 "Glitters".

Background: In the current coronavirus disease-2019 (COVID-19) pandemic, lung ultrasound (LUS) has been extensively employed to evaluate lung involvement and proposed as a useful screening tool for early diagnosis in the emergency department (ED), prehospitalization triage, and treatment monitoring of COVID-19 pneumonia. However, the actual effectiveness of LUS in characterizing lung involvement in COVID-19 is still unclear. Our aim was to evaluate LUS diagnostic performance in assessing or ruling out COVID-19 pneumonia when compared with chest CT (gold standard) in a population of SARS-CoV-2-infected patients. Methods: A total of 260 consecutive RT-PCR confirmed SARS-CoV-2-infected patients were included in the study. All the patients underwent both chest CT scan and concurrent LUS at admission, within the first 6-12 h of hospital stay. Results: Chest CT scan was considered positive when showing a "typical" or "indeterminate" pattern for COVID-19, according to the RSNA classification system. Disease prevalence for COVID-19 pneumonia was 90.77%. LUS demonstrated a sensitivity of 56.78% in detecting lung alteration. The concordance rate for the assessment of abnormalities by both methods increased in the case of peripheral distribution and middle-lower lung location of lesions and in cases of more severe lung involvement. A total of nine patients had a "false-positive" LUS examination. Alternative diagnosis included chronic heart disease (six cases), bronchiectasis (two cases), and subpleural emphysema (one case). LUS specificity was 62.50%. Collateral findings indicative of overlapping conditions at chest CT were recorded also in patients with COVID-19 pneumonia and appeared distributed with increasing frequency passing from the group with mild disease (17 cases) to that with severe disease (40 cases). Conclusions: LUS does not seem to be an adequate tool for screening purposes in the ED, due to the risk of missing some lesions and/or to underestimate the actual extent of the disease. Furthermore, the not specificity of LUS implies the possibility to erroneously classify pre-existing or overlapping conditions as COVID-19 pneumonia. It seems more safe to integrate a positive LUS examination with clinical, epidemiological, laboratory, and radiologic findings to suggest a "virosis." Viral testing confirmation is always required.

A "Galactic" Chest X-ray.

Clinical manifestations accompanying respiratory failure with insidious and rapidly progressive onset are often non-specific. Symptoms such as a cough, dyspnea, and fever are common to a large number of inflammatory, infectious, or neoplastic diseases. During the COVID-19 pandemic it is essential to limit the use of hospital services and inappropriate diagnostic techniques. A particular radiological pattern can orient the clinical and laboratory scenario and guide the diagnostic workup. A 58-year-old woman was admitted to our COVID-19 unit for suspected coronavirus infection. She was complaining of worsening dyspnea, tachycardia, and low grade fever. A chest X-ray showed diffuse, alveolar, and interstitial lung involvement with micronodules tending to coalescence. This radiographic pattern known as "galaxy sign", consistent with diffuse, coalescing nodular miliary pulmonary involvement, simulating a non-specific alveolar opacification of the lungs is typical of a few pneumological differential diagnoses, represented by sarcoidosis, tuberculosis, pneumoconiosis, and metastatic lesions, and virtually excludes an interstitial viral pneumonitis. The use of endoscopic techniques can, in such cases, confirm the clinical suspicion for initiating appropriate targeted therapies.

Low Sensitivity of Admission Lung US Compared to Chest CT for Diagnosis of Lung Involvement in a Cohort of 82 Patients with COVID-19 Pneumonia.

Background and Objectives: The potential role of lung ultrasound (LUS) in characterizing lung involvement in Coronavirus disease 2019 (COVID-19) is still debated. The aim of the study was to estimate sensitivity of admission LUS for the detection of SARS-CoV-2 lung involvement using Chest-CT (Computed Tomography) as reference standard in order to assess LUS usefulness in ruling out COVID-19 pneumonia in the Emergency Department (ED). Methods: Eighty-two patients with confirmed COVID-19 and signs of lung involvement on Chest-CT were consecutively admitted to our hospital and recruited in the study. Chest-CT and LUS examination were concurrently performed within the first 6-12h from admission. Sensitivity of LUS was calculated using CT findings as a reference standard. Results: Global LUS sensitivity in detecting COVID-19 pulmonary lesions was 52%. LUS sensitivity ranged from 8% in case of focal and sporadic ground-glass opacities (mild disease), to 52% for a crazy-paving pattern (moderate disease) and up to 100% in case of extensive subpleural consolidations (severe disease), although LUS was not always able to detect all the consolidations assessed at Chest-CT. LUS sensitivity was higher in detecting a typical Chest-CT pattern (60%) and abnormalities showing a middle-lower zone predominance (79%). Conclusions: As admission LUS may result falsely negative in most cases, it should not be considered as a reliable imaging tool in ruling out COVID-19 pneumonia in patients presenting in ED. It may at least represent an expanded clinical evaluation that needs integration with other diagnostic tests (e.g., nasopharyngeal swab, Chest-CT).

Diagnosis of COVID-19 in Patients with Negative Nasopharyngeal Swabs: Reliability of Radiological and Clinical Diagnosis and Accuracy Versus Serology.

BACKGROUND: The diagnosis of Coronavirus disease 2019 (COVID-19) relies on the positivity of nasopharyngeal swab. However, a significant percentage of symptomatic patients may test negative. We evaluated the reliability of COVID-19 diagnosis made by radiologists and clinicians and its accuracy versus serology in a sample of patients hospitalized for suspected COVID-19 with multiple negative swabs. METHODS: Admission chest CT-scans and clinical records of swab-negative patients, treated according to the COVID-19 protocol or deceased during hospitalization, were retrospectively evaluated by two radiologists and two clinicians, respectively. RESULTS: Of 254 patients, 169 swab-confirmed cases and one patient without chest CT-scan were excluded. A total of 84 patients were eligible for the reliability study. Of these, 21 patients died during hospitalization; the remaining 63 underwent serological testing and were eligible for the accuracy evaluation. Of the 63, 26 patients showed anti-Sars-Cov-2 antibodies, while 37 did not. The inter-rater agreement was "substantial" (kappa 0.683) between radiologists, "moderate" (kappa 0.454) between clinicians, and only "fair" (kappa 0.341) between radiologists and clinicians. Both radiologic and clinical evaluations showed good accuracy compared to serology. CONCLUSIONS: The radiologic and clinical diagnosis of COVID-19 for swab-negative patients proved to be sufficiently reliable and accurate to allow a diagnosis of COVID-19, which needs to be confirmed by serology and follow-up.