Imaging profile after treatment with Tocilizumab in COVID-19: a case series.

INTRODUCTION- COVID-19 is a pandemic disease, mainly affecting the respiratory tract, triggering an inflammatory cascade complicated by multiorgan failure up to death. Among the tested medications for this disease, tocilizumab appears to act directly on the inflammatory cascade, improving COVID-19 outcomes. For this reason, we have tested the efficacy of tocilizumab on lung damage using chest computed tomography (CT). CASE Presentation: The study was conducted on twenty-one hospitalised COVID-19 patients between March-June 2020. Patients were divided into 2 groups according to the therapies administered (TCZ group= treatment with tocilizumab and NTZ group= other therapies). At admission, TCZ group presented worse laboratory test values, respiratory profile (PaO2/FiO2 ratio: 145.37±38.16 mmHg vs 257.9±95.3 mmHg of NTZ group, P<0.01) and radiological signs (multifocal opacity at chest-X-ray: 88% vs 23% of NTZ group, P<0.01). After performing chest CT at the clinical recovery, the scans of the 2 groups were compared and we observed that some features (e.g., ground glass opacity, consolidation and parenchymal bands) were less marked in the TCZ group. CONCLUSION- In our study, patients treated with tocilizumab presented a worse overall clinical and radiological profile at admission, but the control CT showed a similar imaging profile to patients treated with standard therapy. Based on this evidence, we may suggest that tocilizumab plays an important role in COVID-19 patients reducing lung inflammation.

Real life experience of molnupiravir as a treatment of SARS-CoV-2 infection in vaccinated and unvaccinated patients: a letter on its effectiveness at preventing hospitalization.

BACKGROUND: The SARS-CoV-2 pandemic has prompted clinicians to develop an early and effective treatment of viral infections. To date, vaccines, monoclonal antibodies, and antivirals are the cornerstone of therapy for SARS-CoV-2. AIFA approved the prescription of molnupiravir on 30/12/2021. Molnupiravir is a prodrug that causes the accumulation of errors in the viral genome. METHODS: We prescribed molnupiravir to a total of 74 patients in a range between 26 and 96 years old and followed-up them for 30 days. 10 patients affected by idiopathic pulmonary fibrosis (IPF) were treated. RESULTS: The follow-up showed that all of the treated patients presented a regression of symptoms. No patients were hospitalized and/or showed sequelae after the infection by SARS-CoV-2, even though the examined population was older and with more co-morbidities than other patients treated with different antivirals. CONCLUSION: Molnupiravir is safe and well-tolerated by patients with high-risk of progression to severe COVID. No patients were hospitalized or showed sequelae, including all patients affected by IPF.

SARS-CoV-2 Gamma and Delta Variants of Concern Might Undermine Neutralizing Activity Generated in Response to BNT162b2 mRNA Vaccination.

The Delta variant raised concern regarding its ability to evade SARS-CoV-2 vaccines. We evaluated a serum neutralizing response of 172 Italian healthcare workers, three months after complete Comirnaty (BNT162b2 mRNA, BioNTech-Pfizer) vaccination, testing their sera against viral isolates of Alpha, Gamma and Delta variants, including 36 subjects with a previous SARS-CoV-2 infection. We assessed whether IgG anti-spike TRIM levels and serum neutralizing activity by seroneutralization assay were associated. Concerning Gamma variant, a two-fold reduction in neutralizing titres compared to the Alpha variant was observed, while a four-fold reduction of Delta virus compared to Alpha was found. A gender difference was observed in neutralizing titres only for the Gamma variant. The serum samples of 36 previously infected SARS-CoV-2 individuals neutralized Alpha, Gamma and Delta variants, demonstrating respectively a nearly three-fold and a five-fold reduction in neutralizing titres compared to Alpha variant. IgG anti-spike TRIM levels were positively correlated with serum neutralizing titres against the three variants. The Comirnaty vaccine provides sustained neutralizing antibody activity towards the Alpha variant, but it is less effective against Gamma and even less against Delta variants.

Impact of smoking, COPD and comorbidities on the mortality of COVID-19 patients.

The prognosis of the coronavirus disease 2019 (COVID-19) patients is variable and depends on several factors. Current data about the impact of chronic obstructive pulmonary disease (COPD) and smoking on the clinical course of COVID-19 are still controversial. This study evaluated the prevalence and the prognosis of COPD patients and smokers in a cohort of 521 patients admitted to four intermediate Respiratory Intensive Care Units (Puglia, Italy) with respiratory failure due to COVID-19 pneumonia. The prevalence of COPD and current smokers was 14% and 13%, respectively. COPD patients had a higher 30-day all-cause mortality than non-COPD patients. Former smokers compared to never smokers and current smokers had higher 30-day all-cause mortality. COPD patients and former smokers had more comorbidities. This study described the prevalence and the outcomes of COPD patients and smokers in a homogenous cohort of COVID-19 patients. The study showed that the prevalence of COPD and current smokers was not high, suggesting that they were not at increased risk of getting the infection. However, when SARS-CoV-2 infection occurred, COPD patients and former smokers were those with the highest all-cause mortality, which seemed to be mainly related to the presence of comorbidities and not to COPD and smoking itself.

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.

Dysphagia in non-intubated patients affected by COVID-19 infection.

PURPOSE: Patients affected by COVID-19 are assumed to be at high risk of developing swallowing disorders. However, to our best knowledge, data on the characteristics and incidence of dysphagia associated with COVID-19 are lacking, especially in non-intubated patients. Therefore, we investigated the onset of swallowing disorders in patients with laboratory-confirmed COVID-19 infection who have not been treated with invasive ventilation, in order to evaluate how the virus affected swallowing function regardless of orotracheal intubation. METHODS: We evaluated 41 patients admitted to the COVID department of our Hospital when they had already passed the acute phase of the disease and were therefore asymptomatic but still positive for SARS-CoV-2 RNA by RT-PCR. We examined patients' clinical history and performed the Volume-Viscosity Swallow Test (VVST). Each patient also answered the Swallowing Disturbance Questionnaire (SDQ). After 6 months, we performed a follow-up in patients with swallowing disorders. RESULTS: Eight of 41 patients (20%) presented with dysphagia symptoms during hospitalization and 2 of them (25%) still presented a SDQ high score and swallowing disorders with liquid consistency after 6 months. CONCLUSION: Non-intubated patients can experience various grades of swallowing impairment that probably directly related to pulmonary respiratory function alterations and viral direct neuronal lesive activity. Although these symptoms show natural tendency to spontaneous resolution, their impact on a general physical impaired situation should not be underestimated, since it can adversely affect patients' recovery from COVID-19 worsening health outcomes.

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.

Possible role of higher serum level of myoglobin as predictor of worse prognosis in Sars-Cov 2 hospitalized patients. A monocentric retrospective study.

BACKGROUND: Limited data on myoglobin and infectious diseases are available. In this study, we evaluate the potential role of myoglobin in predicting poor outcome in patients with Sars-Cov2 pneumonia. METHODS: One hundred and twenty-one Sars-Cov 2 patients with an average age of 69.9 ± 13.2 years, and symptoms duration of 8.8 ± 7.9 days were enrolled in the study. At the admission, the serum levels of myoglobin, erythrocyte sedimentation rate, C reactive protein (CRP), procalcitonin, ferritin, creatine phosphokinase, creatinine, fibrinogen, d-dimers, lactic dehydrogenase, troponin (Tn-I), creatine kinase myocardial band (CK-MB), complement fractions C3 and C4, immunoglobulins, interleukin 6 were evaluated. We also assessed the patients' complete clinical history and performed a thorough physical examination including age, disease history, and medications. RESULTS: Twenty-four (20%) patients died, and 18 (15%) patients required intensive care. The mean time between symptoms onset and death was 12.4 days ± 9.1. Univariate analysis of the patients' data highlighted some independent risk factors for mortality in COVID-19, including higher neutrophils rate (HR: 1.171), lower lymphocyte rate (HR: 0.798), high CK-MB serum levels (HR: 1.6), high Tn-I serum levels (HR: 1.03), high myoglobin serum levels (HR: 1.014), Alzheimer (HR 5.8), and higher CRP values (HR: 1.011). Cox regression analysis model revealed that higher serum values of myoglobin (HR 1.003; 95%CI: 1.001-1.006; p = 0.01), and CRP (HR 1.012; 95% CI: 1.001-1.023; p = 0.035) could be predictors of mortality in COVID-19 patients. The value of the myoglobin level for predicting 28 days-mortality using ROC curve was 121.8 ng/dL. Lower survival rate was observed in patients with serum levels of myoglobin>121.8 ng/dL (84% vs 20% respectively, p = 0.0001). CONCLUSION: Our results suggest that higher serum levels of myoglobin could be a considerable and effective predictor of poor outcomes in COVID-19 patients; a careful follow-up in these patients is strongly suggested. The possibility of enhancing these findings in other cohorts of COVID-19 patients could validate the clinical value of myoglobin as a biomarker for worse prognosis in COVID-19.

Surgical mask and N95 in healthcare workers of Covid-19 departments: clinical and social aspects.

Introdution. In order to prevent or slow down the transmission of COVID-19, various public health measures have been introduced, including social distancing, environmental disinfection and the use of personal protective equipment (PPE). In this perspective, the clinical practice of healthcare professionals has changed dramatically. As a matter of fact, the use of surgical masks and N95 has significantly worsened the job performance of workers who deal directly with COVID-19 disease. METHODS: The study included 116 health workers employed in the pulmonology, intensive care and infectious diseases departments of Bari and Foggia Hospital, directly involved in the healthcare of patients affected by COVID-19. Between May 1, 2020 and May 31, 2020, each participant completed an online questionnaire aimed to investigate the impact of the COVID-19 pandemic on workers' lifestyle changes and job performances. We compared the results based on the type of mask used by each participant (surgical mask vs N95). RESULTS: Although disturbances related to the use of the mask arose earlier in subjects who wore the N95 (p = 0.0094), healthcare workers that wore surgical masks reported a statistically higher average score for a greater number of disorders. CONCLUSIONS: This is the first study that compares the effects of the two most used PPE on the quality of life of health workers and which highlights the greater discomfort caused by surgical masks. This result brings to light a serious social problem, being surgical masks widely used in everyday life by ordinary people and non-healthcare workers.

Real Time PCR and Culture-Based Virus Isolation Test in Clinically Recovered Patients: Is the Subject Still Infectious for SARS-CoV2?

BACKGROUND: The highly variable manifestation of the COVID-19 disease, from completely asymptomatic to fatal, is both a clinical and a public health issue. The criteria for discharge of hospitalized patients have been based so far on the negative result of Real-Time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) tests, but the persistence of viral fragments may exceed that of the integral virus by weeks. The aim of our study was to verify the clearance of the virus at viral culture in patients hospitalized for COVID-19 that have clinically recovered but are still positive on nasopharyngeal swab. METHODS: The study was conducted in hospitalized patients with positive RT-PCR on nasopharyngeal swab. Patients included were from asymptomatic to severe cases and performed nasopharyngeal control swabbing on day 14 for asymptomatic patient or at least three days after remission of symptoms. RT-PCR positive specimens were sent to a biosafety level 3 laboratory for viral culture. RESULTS: We performed a combined analysis of RT-PCR and a highly sensitive in vitro culture from 84 samples of hospitalized patients. The average age was 46 ± 20.29, and 40.5% of the subjects had radiologically confirmed pneumonia, with average PaO2 of 72.35 ± 12.12and P/F ratio of 315 ± 83.15. Ct values for the N gene were lower in the first swab than in the control one (p < 0.001). The samples from 83 patients were negative at viral culture, and RT-PCR on the respective supernatants always confirmed the absence of viral growth. CONCLUSIONS: Our preliminary results demonstrate that patients clinically recovered for at least three days show the viral clearance at viral culture, and presumably they continued to not be contagious.

Tocilizumab and liver injury in patients with COVID-19.

Current mortality rate in patients with COVID-19 disease is about 2%, whereas 5% of patients require admission to the intensive care unit. It is assumed that interleukin (IL)-6 may be involved in the pathogenesis of severe COVID-19 infections; therefore, in the absence of a specific antiviral therapy, some authors have suggested that tocilizumab - a drug used to block the signal transduction pathway of IL-6 - could have beneficial effects in the management of severe COVID-19 disease. However, mild-to-moderate elevation in transaminases and drug-induced liver injury have been observed in patients treated with tocilizumab. We present seven cases of patients with elevated liver enzymes [up to five times the upper limit of normal (ULN)] at baseline who received tocilizumab for life-threatening COVID-19 disease. All patients had no history of liver or pulmonary disease and were admitted for acute hypoxemic respiratory failure, dyspnea and fever due to COVID-19 bilateral pneumonia. IL-6 was available in six patients, and was significantly increased particularly in those with severe impairment of lung function. All patients received tocilizumab (8 mg/kg/day) for two consecutive days because of lack of improvement after hydroxychloroquine, azithromycin and lopinavir/ritonavir treatment. After tocilizumab administration, clinical condition rapidly improved and liver function test normalized within 3 weeks of treatment. Tocilizumab may be effective for the treatment of severe COVID-19 disease, even in patients with elevated liver function tests. Further studies are needed to evaluate the impact of tocilizumab use on liver function tests in patients with pre-existing chronic liver disease.

Covid-19 and the role of smoking: the protocol of the multicentric prospective study COSMO-IT (COvid19 and SMOking in ITaly).

The emergency caused by Covid-19 pandemic raised interest in studying lifestyles and comorbidities as important determinants of poor Covid-19 prognosis. Data on tobacco smoking, alcohol consumption and obesity are still limited, while no data are available on the role of e-cigarettes and heated tobacco products (HTP). To clarify the role of tobacco smoking and other lifestyle habits on COVID-19 severity and progression, we designed a longitudinal observational study titled COvid19 and SMOking in ITaly (COSMO-IT). About 30 Italian hospitals in North, Centre and South of Italy joined the study. Its main aims are: 1) to quantify the role of tobacco smoking and smoking cessation on the severity and progression of COVID-19 in hospitalized patients; 2) to compare smoking prevalence and severity of the disease in relation to smoking in hospitalized COVID-19 patients versus patients treated at home; 3) to quantify the association between other lifestyle factors, such as e-cigarette and HTP use, alcohol and obesity and the risk of unfavourable COVID-19 outcomes. Socio-demographic, lifestyle and medical history information will be gathered for around 3000 hospitalized and 700-1000 home-isolated, laboratory-confirmed, COVID-19 patients. Given the current absence of a vaccine against SARS-COV-2 and the lack of a specific treatment for -COVID-19, prevention strategies are of extreme importance. This project, designed to highly contribute to the international scientific debate on the role of avoidable lifestyle habits on COVID-19 severity, will provide valuable epidemiological data in order to support important recommendations to prevent COVID-19 incidence, progression and mortality.

Prolonged Low-Dose Methylprednisolone in Patients With Severe COVID-19 Pneumonia.

BACKGROUND: In hospitalized patients with coronavirus disease 2019 (COVID-19) pneumonia, progression to acute respiratory failure requiring invasive mechanical ventilation (MV) is associated with significant morbidity and mortality. Severe dysregulated systemic inflammation is the putative mechanism. We hypothesize that early prolonged methylprednisolone (MP) treatment could accelerate disease resolution, decreasing the need for intensive care unit (ICU) admission and mortality. METHODS: We conducted a multicenter observational study to explore the association between exposure to prolonged, low-dose MP treatment and need for ICU referral, intubation, or death within 28 days (composite primary end point) in patients with severe COVID-19 pneumonia admitted to Italian respiratory high-dependency units. Secondary outcomes were invasive MV-free days and changes in C-reactive protein (CRP) levels. RESULTS: Findings are reported as MP (n = 83) vs control (n = 90). The composite primary end point was met by 19 vs 40 (adjusted hazard ratio [aHR], 0.41; 95% CI, 0.24-0.72). Transfer to ICU and invasive MV were necessary in 15 vs 27 (P = .07) and 14 vs 26 (P = .10), respectively. By day 28, the MP group had fewer deaths (6 vs 21; aHR, 0.29; 95% CI, 0.12-0.73) and more days off invasive MV (24.0 ±â€…9.0 vs 17.5 ±â€…12.8; P = .001). Study treatment was associated with rapid improvement in PaO2:FiO2 and CRP levels. The complication rate was similar for the 2 groups (P = .84). CONCLUSION: In patients with severe COVID-19 pneumonia, early administration of prolonged MP treatment was associated with a significantly lower hazard of death (71%) and decreased ventilator dependence. Treatment was safe and did not impact viral clearance. A large randomized controlled trial (RECOVERY trial) has been performed that validates these findings. Clinical trial registration. ClinicalTrials.gov NCT04323592.