Are monoclonal antibodies effective in patients with severe obesity in SARS-CoV-2 infected?

It is important to block SARS-CoV-2 infection immediately with early therapies, such as monoclonal antibodies (MonoAbs). Also, several studies show that obesity is associated with a high risk of severe COVID-19 disease. We enrolled 32 SARS-CoV-2 infected patients who received MonoAbs, all patients were not vaccinated for SARS-CoV-2, and they received therapy after 7 ± 2 days from the onset of COVID-19 symptoms. In the days following administration, patients followed home therapy with Pidotimod 800 mg bid for 10 days and cholecalciferol 2000 UI for 20 days, prescribed the same day they received MonoAbs therapy. Our study found that there are no differences in the therapeutic response between obese and nonobese patients with SARS-CoV-2 infection undergoing MonoAbs therapy, in fact, none of them underwent hospitalization. Furthermore, the effect of the immunostimulant Pidotimod and cholecalciferol may have contributed to the resolution of COVID-19 symptoms in these patients.

Are monoclonal antibodies effective in patients with severe obesity in SARS‐CoV‐2 infected?

It is important to block SARS‐CoV‐2 infection immediately with early therapies, such as monoclonal antibodies (MonoAbs). Also, several studies show that obesity is associated with a high risk of severe COVID‐19 disease. We enrolled 32 SARS‐CoV‐2 infected patients who received MonoAbs, all patients were not vaccinated for SARS‐CoV‐2, and they received therapy after 7 ± 2 days from the onset of COVID‐19 symptoms. In the days following administration, patients followed home therapy with Pidotimod 800 mg bid for 10 days and cholecalciferol 2000 UI for 20 days, prescribed the same day they received MonoAbs therapy. Our study found that there are no differences in the therapeutic response between obese and nonobese patients with SARS‐CoV‐2 infection undergoing MonoAbs therapy, in fact, none of them underwent hospitalization. Furthermore, the effect of the immunostimulant Pidotimod and cholecalciferol may have contributed to the resolution of COVID‐19 symptoms in these patients. There are no differences in the therapeutic response between obese and nonobese patients with SARS‐CoV‐2 infection undergoing MonoAbs therapy The effect of the immunostimulant Pidotimod and cholecalciferol may contribute to the resolution of COVID‐19 symptoms in patients with SARS‐CoV‐2 infection. Early therapies in COVID‐19, such as monoclonal antibodies, reduce the risk of progression to severe disease.

Iron Dyshomeostasis in COVID-19: Biomarkers Reveal a Functional Link to 5-Lipoxygenase Activation.

Coronavirus disease 2019 (COVID-19) is characterized by a broad spectrum of clinical symptoms. After acute infection, some subjects develop a post-COVID-19 syndrome known as long-COVID. This study aims to recognize the molecular and functional mechanisms that occur in COVID-19 and long-COVID patients and identify useful biomarkers for the management of patients with COVID-19 and long-COVID. Here, we profiled the response to COVID-19 by performing a proteomic analysis of lymphocytes isolated from patients. We identified significant changes in proteins involved in iron metabolism using different biochemical analyses, considering ceruloplasmin (Cp), transferrin (Tf), hemopexin (HPX), lipocalin 2 (LCN2), and superoxide dismutase 1 (SOD1). Moreover, our results show an activation of 5-lipoxygenase (5-LOX) in COVID-19 and in long-COVID possibly through an iron-dependent post-translational mechanism. Furthermore, this work defines leukotriene B4 (LTB4) and lipocalin 2 (LCN2) as possible markers of COVID-19 and long-COVID and suggests novel opportunities for prevention and treatment.

Predictive Value of Echocardiographic Pulmonary to Left Atrial Ratio for In-Hospital Death in Patients with COVID-19.

Background: Echocardiographic Pulmonary to Left Atrial Ratio (ePLAR) represents an accurate and sensitive non-invasive tool to estimate the trans-pulmonary gradient. The prognostic value of ePLAR in hospitalized patients with COVID-19 remains unknown. We aimed to investigate the predictive value of ePLAR on in-hospital mortality in patients with COVID-19. Methods: One hundred consecutive patients admitted to two Italian institutions for COVID-19 undergoing early (<24 h) echocardiographic examination were included; ePLAR was determined from the maximum tricuspid regurgitation continuous wave Doppler velocity (m/s) divided by the transmitral E-wave: septal mitral annular Doppler Tissue Imaging e'-wave ratio (TRVmax/E:e'). The primary outcome measure was in-hospital death. Results: patients who died during hospitalization had at baseline a higher prevalence of tricuspid regurgitation, higher ePLAR, right-side pressures, lower Tricuspid Annular Plane Systolic Excursion (TAPSE)/ systolic Pulmonary Artery Pressure (sPAP) ratio and reduced inferior vena cava collapse than survivors. Patients with ePLAR > 0.28 m/s at baseline showed non-significant but markedly increased in-hospital mortality compared to those having ePLAR ≤ 0.28 m/s (27% vs. 10.8%, p = 0.055). Multivariate Cox regression showed that an ePLAR > 0.28 m/s was independently associated with an increased risk of death (HR 5.07, 95% CI 1.04−24.50, p = 0.043), particularly when associated with increased sPAP (p for interaction = 0.043). Conclusions: A high ePLAR value at baseline predicts in-hospital death in patients with COVID-19, especially in those with elevated pulmonary arterial pressure. These results support an early ePLAR assessment in patients admitted for COVID-19 to identify those at higher risk and potentially guide strategies of diagnosis and care.

New Therapeutic Options in Mild Moderate COVID-19 Outpatients.

BACKGROUND: In recent years, the therapeutic options for COVID have significantly improved; however, the therapies are expensive with restricted access to drugs, and expeditious and difficult to manage at home. We investigated the effect of pidotimod in preventing hospitalization in patients with mild-moderate COVID-19. METHODS: A total of 1231 patients between January and June 2021 were screened. A total of 184 patients with mild-moderate COVID-19 were enrolled and divided into two groups: group-A (97) had undergone therapy with pidotimod 800 mg bid for 7-10 days and group-B (87) had other therapies. We excluded those who had undergone complete vaccination course, monoclonal anti-spike/antivirals or the co-administration of pidotimod-steroid. The primary outcome chosen was the emergency room, hospitalization, and deaths for COVID-related causes; the secondary outcome chosen was the duration of COVID-19 illness. RESULTS: A total of 34 patients (18.5%) required hospital treatment, 11 in group-A and 23 in group-B (11.3% vs. 26.4%, p = 0.008). The median disease duration in group-A was 21 days (IQR 17-27) vs. 23 (IQR 20-31) in group-B (p = 0.005). Patients in the pidotimod group had higher SpO2 in the walking test (IQR 96-99% vs. IQR 93-98%, p = 0.01) and a lower need for steroid rescue therapy (11.5% vs. 60.9%, p < 0.001). CONCLUSIONS: In the first phase of disease, pidotimod can represent an effective, low-cost, weapon, without restrictions of use, that is able to prevent a second aggressive phase and promote faster virological recovery.

Molnupiravir as an Early Treatment for COVID-19: A Real Life Study.

OBJECTIVES: Below we report our experience in the use of molnupiravir, the first antiviral drug against SARS-CoV-2 available to us, in the treatment of patients with COVID-19. MATERIALS AND METHODS: We enrolled patients diagnosed with COVID-19 and comorbidities who were candidates for antiviral drug therapy. All patients received molnupiravir (800 mg twice daily). Blood chemistry checks were carried out at T0 and after 7/10 days after starting therapy (T1). RESULTS: There were enrolled within the cohort 100 patients. There was 100.0% compliance with the antiviral treatment. No patient required hospitalization due to worsening of respiratory function or the appearance of serious side effects. The median downtime of viral load was ten days (IQR 8.0-13.0), regardless of the type of vaccination received. The patients who had a shorter distance from vaccination more frequently presented vomiting/diarrhea. During baseline and T1 we found significant differences in the median serum concentrations of the main parameters, in particular of platelets, RDW CV, neutrophils and lymphocytes, the eGFR, liver enzymes, as well as of the main inflammatory markers, CRP and Ferritin. CONCLUSION: Participants treated with molnupiravir, albeit in risk categories, demonstrated early clinical improvement, no need for hospitalization, and a low rate of adverse events.

Atypical Sites of Lymphadenopathy after Anti-COVID-19 Vaccine: Ultrasound Features.

Background and Objectives: Several authors have reported cervical and axillary lymphadenopathies as known side effects following anti-COVID-19 vaccine administration. Few data are available about atypical locations of post-anti-COVID-19 vaccine lymphadenopathy. In this investigation, we evaluated the incidence and prevalence of postvaccine lymphadenopathy ultrasound (US) features in atypical sites. Materials and Methods: In this retrospective study, we retrospectively selected 64 patients on whom US was performed between January and October 2021 due to COVID-19 vaccine-related lymphadenopathy. We investigated lymph node anatomical sites, presence, number, size, shape, cortical profile, hilum outline, superb microvascular imaging (SMI), and elastosonography. Results: A total of 170 nodes were assessed. Atypical location was demonstrated in 5/64 patients (7.8%). In all these cases, atypical nodal involvement was associated with lymphadenopathy in a typical site (axillary, supraclavicular) ipsilateral to the vaccine injection site. Two patients presented lymphadenopathy in the infraclavicular station (3.1%), one in the pectoralis major muscle (1.6%), one in the left arm (1.6%), and one in the nuchal site (1.6%). All lymphadenopathies were oval-shaped, with a median size of 0.9 ± 0.2 cm. US features included a symmetric cortex with hilum evidence (4/6, 60%), vascular signal at SMI in both the hilar region and periphery of lymph node (5/6, 83.3%), and a US elastography pattern resembling that of adjacent tissues (5/6, 83.3%). The median age of patients with lymphadenopathies in an atypical location was 23 years. The main type of vaccine associated with lymph node appearance in atypical sites was Moderna's mRNA-1273 (60% of patients, 4/6 lymph nodes accounting for 66.7% among atypical locations). Conclusion: Post-COVID-19 vaccine administration lymphadenopathies in an atypical location represent an intense immune response to antigenic stimuli and they may show alarming US traits superimposed on malignant pathologies, which may complicate the patient's clinical and diagnostic pathway. Despite no distinctive US features between reactive post-COVID-19 vaccination and malignant lymph nodes being available, careful examination of atypical lymph node locations associated with accurate knowledge of patients' clinical background and delay of US exam to four to six weeks after vaccine injection should be considered.

BNT162b2 mRNA Vaccination Leads to Long-Term Protection from COVID-19 Disease.

The efficacy of SARS-CoV-2 mRNA-based vaccines in preventing COVID-19 disease has been extensively demonstrated; however, it is of uttermost importance to acquire knowledge on the persistence of immune-protection both in terms of levels of neutralizing antibodies and specialized memory cells. This can provide important scientific basis for decisions on the need of additional vaccine doses and on when these should be administered thus resulting in an improvement in vaccination schedules. Here, we briefly report the changes in antibody levels and cellular immunity following BNT162b2 administration. We show an important fall in anti S1-Spike antibodies in BNT162b2 vaccinated subjects overtime, paralleled by a contextual consolidation of specific spike (S) T-cells, mainly of the CD8+ compartment. Contrariwise, CD4+ S-specific response shows a considerable interindividual variability. These data suggest that the well-known antibody drop in vaccinated subjects is replaced by memory cell consolidation that can protect from severe adverse effects of SARS-CoV-2 infection.

COVID-19 in a patient with SISTEMIC sclerosis: The role of ruxolitinib

We describe the case of a 78-year-old Italian woman with COVID-19 affected by Systemic Sclerosis with pulmonary fibrosis treated with Ruxolitinib (Ruxolitinib was provided free of charge by Novartis International AG). We chose Ruxolitinib, as a second-line treatment, after administering a standard therapy with hydroxychloroquine and lopinavir/ritonavir, due to a rapid deterioration in the patient's lung function. Ruxolitinib is a janus kinase inibithor with selectivity for subtypes JAK1 and JAK2. A rapid improvement in the patient's respiratory function, objectified with an increase in PO2/FiO2 value, has been observed in the 10 days after the introduction of Ruxolitinib. Surprisingly we noticed a reduction in pulmonary fibrosis by comparing the chest- CT made before and after the COVID-19 diagnosis. JAK/STAT signalling is involved both in pathogenesis of the second part of COVID-19 and in the modulation of fibrosis in patients with SSc. The use of ruxolitinib should be a new therapeutic option in patients with COVID-19 and lung fibrosis. [ABSTRACT FROM AUTHOR] Copyright of European Journal of Inflammation (Sage Publications, Ltd.) is the property of Sage Publications, Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

It is Not Always COVID-19: Case Report about an Undiagnosed HIV Man with Dyspnea.

BACKGROUND: The current COVID-19 pandemic has attracted great attention from the medical world. In the past year, there have been reports of missed or delayed treatments for conditions that mimic COVID-19. The main symptoms caused by SARS-CoV-2, such as fever and cough, belong to different clinical conditions. It is of the utmost importance that the diagnostic thinking used to analyze data and information to reach a COVID-19 diagnosis does not overlook the plethora of different diagnoses related to these symptoms. CASE REPORT: The aim of this work is to present the clinical case of a patient having unrecognized HIV infection with a 4-week history of fever, cough, and hypoxia. When tests were allowed to highlight HIV-related immunodeficiency status, a CMV assay was performed in order to evaluate opportunistic pneumonia. Through this, diagnosis of HIV combined with CMV pneumonia was made, thus excluding COVID-19 respiratory insufficiency. CONCLUSION: The diagnosis of the two conditions in the COVID-19 era is challenging due to overlapping clinical and radiological features and limitations of current diagnostic assays. This causes clinical implications due to diagnostic delays.

JAK Inhibition with Ruxolitinib in Patients with COVID-19 and Severe Pneumonia: Multicenter Clinical Experience from a Compassionate Use Program in Italy.

Jak inhibitors are potent anti-inflammatory drugs that have the potential to dampen the hyperactive inflammatory response associated with severe COVID-19. We reviewed the clinical outcomes of 218 patients with COVID-19 hospitalized for severe pneumonia and treated with ruxolitinib through a compassionate use program. Data on the duration of treatment; outcomes at 4, 7, 14, and 28 days; oxygen support requirements; clinical status; and laboratory parameters were retrospectively collected. Overall, according to the physician evaluation, 66.5% of patients showed improvement at follow-up; of these, 83.5% showed improvement by day 7. Oxygen support status also showed improvement, and by day 7, 21.6% of patients were on ambient air, compared with 1.4% at baseline, which increased to 48.2% by day 28. Significant decreases in C-reactive protein and increases in the lymphocyte total count were already observed by day 4, which seemed to correlate with a positive outcome. At the end of the observation period, 87.2% of patients were alive. No unexpected safety findings were observed, and grade 3/4 adverse events were reported in 6.9% of patients.

Parameters associated with diagnosis of COVID-19 in emergency department.

OBJECTIVES: We designed this study to identify laboratory and radiological parameters, which could be useful to guide the clinician, in the evaluation of a suspected case of coronavirus disease 19 (COVID-19). METHODS: This retrospective, observational, single-center-study recruited patients with a suspect of COVID-19 data were extracted from electronic medical records using a standardized data collection form. RESULTS: A total of 566 patients with suspect COVID-19 infection were enrolled (280 were COVID-19+). The COVID-19 population was characterized with bilateral-pneumonia, a lower count of neutrophil, lymphocyte and monocyte, a lower neutrophil to lymphocyte-ratio (NLR). Lower of platelet count, d-dimer, troponin I, and serum calcium were in COVID-19 patients. The occurrence of COVID-19 diagnosis increased, independently of other variables, with pneumonia (odds ratio [OR]: 3.60; p < .001), neutrophil below normal range (OR: 4.15; p < .05), lactate dehydrogenase (OR: 2.09; p < .01) and sodium above normal range (OR: 2.34; p < .01). In patients with possible respiratory acute affections we found a higher neutrophil, higher monocyte, a higher NLR and a more elevation in d-dimer. In the Sepsis group showed higher level of white blood cell, C-reactive protein, d-dimer, and procalcitonin. CONCLUSIONS: Our study confirms that patients with COVID-19 have typical radiological and laboratory characteristics. The parameters highlighted in the study can help identify COVID-19 patients, also highlighting which are the main differential diagnoses to be made and the parameters that facilitate the differential diagnosis.

Normal breathing releases SARS-CoV-2 into the air.

This study tests the release of SARS-CoV-2 RNA into the air during normal breathing, without any sign of possible risk of contagion such as coughing, sneezing or talking. Five patients underwent oropharyngeal, nasopharyngeal and salivary swabs for real-time reverse transcriptase PCR (RT-PCR) detection of SARS-CoV-2 RNA. Direct SARS-CoV-2 release during normal breathing was also investigated by RT-PCR in air samples collected using a microbiological sampler. Viral RNA was detected in air at 1 cm from the mouth of patients whose oropharyngeal, nasopharyngeal and salivary swabs tested positive for SARS-CoV-2 RNA. In contrast, the viral RNA was not identified in the exhaled air from patients with oropharyngeal, nasopharyngeal and salivary swabs that tested negative. Contagion of SARS-CoV-2 is possible by being very close to the mouth of someone who is infected, asymptomatic and simply breathing.

Clinical characteristics and cardiovascular implications of the dead patients for COVID-19

Coronavirus Disease 2019 (COVID-19) caused by 2019 novel coronavirus (named SARS-CoV-2), has become a global pandemic. Aged population with cardiovascular diseases is usually more susceptible to SARS-CoV-2 infection with an increased risk of severe complications and elevated case-fatality rate. Despite of several researches about COVID-19, cardiovascular implications related to this infection still remain largely unclear. The aim of this study is to evaluate the clinical characteristics of dead patients with COVID-19. We enrolled all patients with more than 50 years of age with laboratory confirmed COVID-19, admitted to infectious clinical diseases PO SS Annunziata of Chieti (Italy) from March 2020 to April 2020 who died during hospitalization. Demographics, underlying comorbidities, clinical symptoms and signs, laboratory results, computed tomography of the chest, treatment measures, and outcome data were collected. We enrolled eight patients, the age was 82 ± 9.7 years, four female and four male. All patients had comorbidity, such as hypertension (7 [87.5%]), diabetes (1 [12.5%]), and heart disease (6 [75%]). Common symptoms included fever [8 (100%)], dry cough (1[12.56%]), and dyspnea (3 [37.5%]). All patients [8 (100%)] showed local and/or bilateral patchy shadowing on chest computed tomography that is the typical radiological finding in COVID-19. Lymphopenia was observed in seven patients (87.5%). All patients showed elevated troponin and prolongation of the QTc interval (p < 0.05). In this study we demonstrated that in SARS-CoV-2 infection, the deaths occurred in the non-ICU population with more than 50 years are related to cardiac causes. In our cases elongation of QTc and alteration in troponin are present in all patients who died and could represent a data to better stratify the population at risk. More detailed research on cardiovascular involvement in COVID-19 patients with sudden deaths showed a predictive role of troponin and QTc elongation. [ABSTRACT FROM AUTHOR] Copyright of European Journal of Inflammation (Sage Publications, Ltd.) is the property of Sage Publications, Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Air and surface measurements of SARS-CoV-2 inside a bus during normal operation.

Transmission pathways of SARS-CoV-2 are aerosol, droplet and touching infected material. The diffusion of the virus contagion among people is easier in indoor location, but direct detection of SARS-CoV-2 in air or on surfaces is quite sparse, especially regarding public transport, while it would be important to know how and if it is safe to use them. To answer these questions we analysed the air and the surfaces most usually touched by passengers inside a city bus during normal operation, in order to understand the possible spreading of the virus and the effectiveness of the protective measures. The measurements were carried out across the last week of the lockdown and the first week when, gradually, all the travel restrictions were removed. The air and surface samples were analysed with the RT-PCR for the detection of SARS-CoV-2 virus. After two weeks of measurements and more than 1100 passenger travelling on the bus the virus was never detected both on surfaces and on air, suggesting that the precautions adopted on public transportation are effective in reducing the COVID-19 spreading.

Role of monoclonal antibody drugs in the treatment of COVID-19.

Currently clinicians all around the world are experiencing a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical presentation of this pathology includes fever, dry cough, fatigue and acute respiratory distress syndrome that can lead to death infected patients. Current studies on coronavirus disease 2019 (COVID-19) continue to highlight the urgent need for an effective therapy. Numerous therapeutic strategies have been used until now but, to date, there is no specific effective treatment for SARS-CoV-2 infection. Elevated inflammatory cytokines have been reported in patients with COVID-19. Evidence suggests that elevated cytokine levels, reflecting a hyperinflammatory response secondary to SARS-CoV-2 infection, are responsible for multi-organ damage in patients with COVID-19. For these reason, numerous randomized clinical trials are currently underway to explore the effectiveness of biopharmaceutical drugs, such as, interleukin-1 blockers, interleukin-6 inhibitors, Janus kinase inhibitors, in COVID-19. The aim of the present paper is to briefly summarize the pathogenetic rationale and the state of the art of therapeutic strategy blocking hyperinflammation.

Duration of COVID-19: Data from an Italian Cohort and Potential Role for Steroids.

The diffusion of SARS-CoV-2, starting from China in December 2019, has led to a pandemic, reaching Italy in February 2020. Previous studies in Asia have shown that the median duration of SARS-CoV-2 viral shedding was approximately 12-20 days. We considered a cohort of patients recovered from COVID-19 showing that the median disease duration between onset and end of COVID-19 symptoms was 27.5 days (interquartile range (IQR): 17.0-33.2) and that the median duration between onset of symptoms and microbiological healing, defined by two consecutive negative nasopharyngeal swabs, was 38 days (IQR: 31.7-50.2). A longer duration of COVID-19 with delayed clinical healing (symptom-free) occurred in patients presenting at admission a lower PaO2/FiO2 ratio (p < 0.001), a more severe clinical presentation (p = 0.001) and a lower lymphocyte count (p = 0.035). Moreover, patients presenting at admission a lower PaO2/FiO2 ratio and more severe disease showed longer viral shedding (p = 0.031 and p = 0.032, respectively). In addition, patients treated with corticosteroids had delayed clinical healing (p = 0.013).

Factors associated with hospital admission for COVID-19 in HIV patients.

: This study reports on hospital admission and outcomes of 69 HIV-infected individuals who were diagnosed with SARS-CoV-2 infection between February and May 2020, in a network of Italian centres. Patients' characteristics and median days between symptoms and diagnosis were similar by hospital admission, whereas admitted patients had lower nadir CD4 cells and current lymphocytes count. These values were also correlated to worse COVID-19 outcome. Antiretroviral drugs did not seem to be associated with disease severity.