Search

During the COVID-19 pandemic, the scientific literature related to SARS-COV-2 has been growing dramatically. These literary items encompass a varied set of topics, ranging from vaccination to protective equipment efficacy as well as lockdown policy evaluations. As a result, the development of automatic methods that allow an in-depth exploration of this growing literature has become a relevant issue, both to identify the topical trends of COVID-related research and to zoom-in on its sub-themes. This work proposes a novel methodology, called LDA2Net, which combines topic modelling and network analysis, to investigate topics under their surface. More specifically, LDA2Net exploits the frequencies of consecutive words pairs (i.e. bigram) to build those network structures underlying the hidden topics extracted from large volumes of text by Latent Dirichlet Allocation (LDA). Results are promising and suggest that the topic model efficacy is magnified by the network-based representation. In particular, such enrichment is noticeable when it comes to displaying and exploring the topics at different levels of granularity. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters cells by binding to the angiotensin-converting enzyme 2 (hACE2) receptor. This process is aided by the transmembrane protease serine 2 (TMPRSS2), which enhances entry efficiency and infectiousness by cleaving the SARS-CoV-2 surface glycoprotein (Spike). The cleavage primes the Spike protein, promoting membrane fusion instead of receptor-mediated endocytosis. Despite the pivotal role played by TMPRSS2, our understanding of its non-protease distinct domains remains limited. In this report, we present evidence indicating the potential phosphorylation of a minimum of six tyrosine residues within the cytosolic tail (CT) of TMPRSS2. Via the use of TMPRSS2 CT phospho-mimetic mutants, we observed a reduction in TMPRSS2 protease activity, accompanied by a decrease in SARS-CoV-2 pseudovirus transduction, which was found to occur mainly via the endosomal pathway. We expanded our investigation beyond TMPRSS2 CT and discovered the involvement of other non-protease domains in regulating infection. Our co-immunoprecipitation experiments demonstrated a strong interaction between TMPRSS2 and Spike. We revealed a 21 amino acid long TMPRSS2-Spike-binding region (TSBR) within the TMPRSS2 scavenger receptor cysteine-rich (SRCR) domain that contributes to this interaction. Our study sheds light on novel functionalities associated with TMPRSS2's cytosolic tail and SRCR region. Both of these regions have the capability to regulate SARS-CoV-2 entry pathways. These findings contribute to a deeper understanding of the complex interplay between viral entry and host factors, opening new avenues for potential therapeutic interventions. [ABSTRACT FROM AUTHOR]

Coronavirus disease of 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may be complicated by life-threatening interstitial pneumonia. SARS-CoV-2 infection may also damage several tissues and/or organs beyond the lungs, including the liver. However, controversy still exists as to whether SARS-CoV-2-induced liver alterations can have an impact on the outcome of COVID-19. The aim of this study was therefore to assess whether SARS-CoV-2-infected patients with liver abnormalities at the time of hospital referral had a worse outcome with respect to patients with no liver biochemistry alterations. To this end, the medical records of 123 patients admitted to our COVID center between the end of 2020 and spring 2021 were retrospectively reviewed. Patients were divided into two groups: those with normal liver biochemistries (group 1, 77 patients) and those with altered liver function tests (group 2, 46 patients). Serum levels of aminotransferases (AST and ALT) and bile duct cell injury markers (γ-GT and ALP) were used to dichotomize patients. A higher percentage of patients with liver enzyme alterations were found to develop COVID-19 pneumonia with respect to group 1 patients (74% vs. 65%); moreover, they needed more days of respiratory support and, more importantly, more intensive administration of supplemental oxygen. A statistically significant correlation was also found between aminotransferase levels and duration of respiratory support. The mortality rate was not superior in group 2 vs. group 1 patients. In conclusion, liver abnormalities on admission predisposed COVID-19 patients to development of more severe interstitial pneumonia, because of a longer requirement for supplemental oxygen and a more intensive respiratory support, indicative of a worse disease evolution in these patients. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic resulted from the global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since its first appearance in 2019, new SARS-CoV-2 variants of concern (VOCs) have emerged frequently, changing the infection's dynamic. SARS-CoV-2 infects cells via two distinct entry routes; receptor-mediated endocytosis or membrane fusion, depending on the absence or presence of transmembrane serine protease 2 (TMPRSS2), respectively. In laboratory conditions, the Omicron SARS-CoV-2 strain inefficiently infects cells predominantly via endocytosis and is phenotypically characterized by decreased syncytia formation compared to the earlier Delta variant. Thus, it is important to characterize Omicron's unique mutations and their phenotypic manifestations. Here, by utilizing SARS-CoV-2 pseudovirions, we report that the specific Omicron Spike F375 residue decreases infectivity, and its conversion to the Delta S375 sequence significantly increases Omicron infectivity. Further, we identified that residue Y655 decreases Omicron's TMPRSS2 dependency and entry via membrane fusion. The Y655H, K764N, K856N and K969N Omicron revertant mutations, bearing the Delta variant sequence, increased the cytopathic effect of cell–cell fusion, suggesting these Omicron-specific residues reduced the severity of SARS-CoV-2. This study of the correlation of the mutational profile with the phenotypic outcome should sensitize our alertness towards emerging VOCs. [ABSTRACT FROM AUTHOR]

Affek et al. [[13]] also proved that both the type of biofilter bed and the number of microorganisms in the bed affected the final bioaerosol emission only for biofilters that treated waste gases with low microbial concentrations. The characterization and the main properties of biogenic airborne particles (or bioaerosols) comprising both living and dead microorganisms (such as bacteria, fungi, viruses, pollen, and microbial fragments) are currently of increasing interest in the scientific community. No correlation between the number of microorganisms and the respiratory activity in the biofilter beds was determined, while biofilters were seen to reduce or increase bioaerosol emissions from industrial plants, depending on the microbial content in the waste gases. In the scientific community devoted to bioaerosol characterization, the study of pathogenic species identified in aerosol samples is a topic of increasing interest. [Extracted from the article]

Summary: COVID‐19 is associated with high mortality in patients with haematological malignancies (HM) and rate of seroconversion is unknown. The ITA‐HEMA‐COV project (NCT04352556) investigated patterns of seroconversion for SARS‐CoV‐2 IgG in patients with HMs. A total of 237 patients, SARS‐CoV‐2 PCR‐positive with at least one SARS‐CoV‐2 IgG test performed during their care, entered the analysis. Among these, 62 (26·2%) had myeloid, 121 (51·1%) lymphoid and 54 (22·8%) plasma cell neoplasms. Overall, 69% of patients (164 of 237) had detectable IgG SARS‐CoV‐2 serum antibodies. Serologically negative patients (31%, 73 of 237) were evenly distributed across patients with myeloid, lymphoid and plasma cell neoplasms. In the multivariable logistic regression, chemoimmunotherapy [odds ratio (OR), 3·42; 95% confidence interval (CI), 1·04–11·21; P = 0·04] was associated with a lower rate of seroconversion. This effect did not decline after 180 days from treatment withdrawal (OR, 0·35; 95% CI: 0·11–1·13; P = 0·08). This study demonstrates a low rate of seroconversion in HM patients and indicates that treatment‐mediated immune dysfunction is the main driver. As a consequence, we expect a low rate of seroconversion after vaccination and thus we suggest testing the efficacy of seroconversion in HM patients. [ABSTRACT FROM AUTHOR]

Coronaviruses, including SARS-CoV-2 (the etiological agent of the current COVID-19 pandemic), rely on the surface spike glycoprotein to access the host cells, mainly through the interaction of their receptor-binding domain (RBD) with the human angiotensin-converting enzyme 2 (ACE2). Therefore, molecular entities able to interfere with the binding of the SARS-CoV-2 spike protein to ACE2 have great potential to inhibit viral entry. Starting from the available structural data on the interaction between SARS-CoV-2 spike protein and the host ACE2 receptor, we engineered a set of soluble and stable spike interactors, here denoted as S-plugs. Starting from the prototype S-plug, we adopted a computational approach by combining stability prediction, associated to single-point mutations, with molecular dynamics to enhance both S-plug thermostability and binding affinity to the spike protein. The best developed molecule, S-plug3, possesses a highly stable α-helical con-formation (with melting temperature Tm of 54 °C) and can interact with the spike RBD and S1 domains with similar low nanomolar affinities. Importantly, S-plug3 exposes the spike RBD to almost the same interface as the human ACE2 receptor, aimed at the recognition of all ACE2-accessing coronaviruses. Consistently, S-plug3 preserves a low nanomolar dissociation constant with the delta B.1.617.2 variant of SARS-CoV-2 spike protein (KD = 29.2 ± 0.6 nM). Taken together, we provide valid starting data for the development of therapeutical and diagnostic tools against coronaviruses accessing through ACE2. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal agent of the COVID-19 pandemic. More than 274 million individuals have suffered from COVID-19 and over five million people have died from this disease so far. Therefore, there is an urgent need for therapeutic drugs. Repurposing FDA approved drugs should be favored since evaluation of safety and efficacy of de-novo drug design are both costly and time consuming. We report that imatinib, an Abl tyrosine kinase inhibitor, robustly decreases SARS-CoV-2 infection and uncover a mechanism of action. We show that imatinib inhibits the infection of SARS-CoV-2 and its surrogate lentivector pseudotype. In latter, imatinib inhibited both routes of viral entry, endocytosis and membrane-fusion. We utilized a system to quantify in real-time cell–cell membrane fusion mediated by the SARS-CoV-2 surface protein, Spike, and its receptor, hACE2, to demonstrate that imatinib inhibits this process in an Abl1 and Abl2 independent manner. Furthermore, cellular thermal shift assay revealed a direct imatinib-Spike interaction that affects Spike susceptibility to trypsin digest. Collectively, our data suggest that imatinib inhibits Spike mediated viral entry by an off-target mechanism. These findings mark imatinib as a promising therapeutic drug in inhibiting the early steps of SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

In January 2022, our genomic surveillance network identified a SARS-CoV-2 BA.1 and BA.2 coinfection in a sample from a patient residing in Brazil. Our results suggest that the true number of SARS-CoV-2 coinfections remains largely underestimated. [ABSTRACT FROM AUTHOR]

Hemothorax (HT) and pulmonary hematoma represent rare complications of anticoagulant therapy. We present a rare case of a 53-year-old man with COVID-19 pneumonia who showed, in a follow-up computed tomography (CT) scan 13 days after hospitalization, a left HT and a small hyperdense area in a subpleural location and compatible with a small subpleural hematoma. This patient was being treated with a subcutaneous administration of low-molecular-weight heparin (100UI/kg/BID). No vascular malformations were visualized on the CT pulmonary angiography. Herein, we report the first case of both a spontaneous HT and a lung subpleural hematoma in a COVID-19 patient, probably caused by anticoagulant therapy. [ABSTRACT FROM AUTHOR]

The article discusses the emergence of the SARS-CoV-2 KP.2 variant, which is a descendant of the BA.2.86 variant. While the KP.2 variant has shown an increase in cases, there is no evidence suggesting that it is a significantly concerning new variant. The article provides information on the global prevalence of the KP.2 variant, highlighting regions where it has been detected and its relative prevalence in different countries. The KP.2 variant carries mutations of interest, including K417N, S477N, N501Y, and P681R, which may pose potential risks. Additionally, it shares the E484K mutation, which has been associated with the ability to evade immune responses. However, the lasting immunity conferred by natural immune responses to these mutations has not been explicitly documented. The KP.2 variant of SARS-CoV-2, also known as the Omicron variant, carries three additional mutations in the spike protein genes compared to its ancestor, the JN.1 variant. These mutations, R346T, F456L, and V1104L, have been observed in other Omicron subvariants and are associated with increased transmission and evasion of neutralizing antibodies. The F456L mutation, in particular, enhances the spike protein's affinity for the ACE2 receptor, allowing the virus to better evade immune responses. The V1104L mutation, located within a T cell epitope, may enhance protein stability. However, it is [Extracted from the article]

Background Evidence is accumulating of coronavirus disease 2019 (COVID-19) vaccine effectiveness among persons with prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods We evaluated the effect against incident SARS-CoV-2 infection of (1) prior infection without vaccination, (2) vaccination (2 doses of Pfizer-BioNTech COVID-19 vaccine) without prior infection, and (3) vaccination after prior infection, all compared with unvaccinated persons without prior infection. We included long-term care facility staff in New York City aged <65 years with weekly SARS-CoV-2 testing from 21 January to 5 June 2021. Test results were obtained from state-mandated laboratory reporting. Vaccination status was obtained from the Citywide Immunization Registry. Cox proportional hazards models adjusted for confounding with inverse probability of treatment weights. Results Compared with unvaccinated persons without prior infection, incident SARS-CoV-2 infection risk was lower in all groups: 54.6% (95% confidence interval, 38.0%–66.8%) lower among unvaccinated, previously infected persons; 80.0% (67.6%–87.7%) lower among fully vaccinated persons without prior infection; and 82.4% (70.8%–89.3%) lower among persons fully vaccinated after prior infection. Conclusions Two doses of Pfizer-BioNTech COVID-19 vaccine reduced SARS-CoV-2 infection risk by ≥80% and, for those with prior infection, increased protection from prior infection alone. These findings support recommendations that all eligible persons, regardless of prior infection, be vaccinated against COVID-19. [ABSTRACT FROM AUTHOR]

Purpose: To assess the clinical and retinal imaging features of patients in whom retinal vascular occlusion (VO) had developed in temporal associations with COVID-19 vaccination. Methods: In this retrospective case series, all consecutive adult patients with new onset VO within 6 weeks of vaccination against COVID-19 were included in the study between May 1 and October 31, 2021. All patients had a systemic medical health assessment, full ophthalmic evaluation, and complete fundus imaging. Results: Fifteen eyes of VO (14 patients) after COVID-19 vaccinations were identified. The median time between vaccination and symptoms onset was 14 days (range 7–42 days). The mean best-corrected visual acuity (BCVA) was 20/55 with a range of 20/20 to 20/200. Eleven of 15 eyes (73.3%) had visual acuity improvement after intravitreal treatment at 60–90 days (range, 45–105 days) from the presentation. Four of 5 cases without systemic risk factors for VO had a mean BCVA > 20/32 at presentation and > 20/25 at the latest evaluation. Between May 1 and October 31, 2021, a temporal association was found between the 15 reported cases and COVID-19 vaccination out of a total of 29 VO (p = 0.05). The incidence of VO was higher in the considered period compared to the equivalent 6-month period in 2019 (1.17% vs 0.52%, respectively; p = 0.0134). Conclusions: Retinal vascular occlusion with different grades of severity are reported in temporal association with COVID-19 vaccination. The exact pathogenic mechanism needs to be further studied. No certain causal relationship can be established from this case series. [ABSTRACT FROM AUTHOR]

Repurposing of remdesivir and other drugs with potential antiviral activity has been the basis of numerous clinical trials aimed at SARS-CoV-2 infection in adults. However, expeditiously designed trials without careful consideration of dose rationale have often resulted in treatment failure and toxicity in the target patient population, which includes not only adults but also children. Here we show how paediatric regimens can be identified using pharmacokinetic-pharmacodynamic (PKPD) principles to establish the target exposure and evaluate the implications of dose selection for early and late intervention. Using in vitro data describing the antiviral activity and published pharmacokinetic data for the agents of interest, we apply a model-based approach to assess the exposure range required for adequate viral clearance and eradication. Pharmacokinetic parameter estimates were subsequently used with clinical trial simulations to characterise the probability target attainment (PTA) associated with enhanced antiviral activity in the lungs. Our analysis shows that neither remdesivir, nor anti-malarial drugs can achieve the desirable target exposure range based on a mg/kg dosing regimen, due to a limited safety margin and high concentrations needed to ensure the required PTA. To date, there has been limited focus on suitable interventions for children affected by COVID-19. Most clinical trials have defined doses selection criteria empirically, without thorough evaluation of the PTA. The current results illustrate how model-based approaches can be used for the integration of clinical and nonclinical data, providing a robust framework for assessing the probability of pharmacological success and consequently the dose rationale for antiviral drugs for the treatment of SARS-CoV-2 infection in children. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 infection has been recently shown to induce cellular senescence in vivo. A senescence-like phenotype has been reported in cystic fibrosis (CF) cellular models. Since the previously published data highlighted a low impact of SARS-CoV-2 on CFTR-defective cells, here we aimed to investigate the senescence hallmarks in SARS-CoV-2 infection in the context of a loss of CFTR expression/function. We infected WT and CFTR KO 16HBE14o-cells with SARS-CoV-2 and analyzed both the p21 and Ki67 expression using immunohistochemistry and viral and p21 gene expression using real-time PCR. Prior to SARS-CoV-2 infection, CFTR KO cells displayed a higher p21 and lower Ki67 expression than WT cells. We detected lipid accumulation in CFTR KO cells, identified as lipolysosomes and residual bodies at the subcellular/ultrastructure level. After SARS-CoV-2 infection, the situation reversed, with low p21 and high Ki67 expression, as well as reduced viral gene expression in CFTR KO cells. Thus, the activation of cellular senescence pathways in CFTR-defective cells was reversed by SARS-CoV-2 infection while they were activated in CFTR WT cells. These data uncover a different response of CF and non-CF bronchial epithelial cell models to SARS-CoV-2 infection and contribute to uncovering the molecular mechanisms behind the reduced clinical impact of COVID-19 in CF patients. [ABSTRACT FROM AUTHOR]

Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system (CNS), clinically defined by an acute polyfocal neurological syndrome usually with monophasic course. ADEM often occurs after infections, but 5%–10% of cases are preceded by vaccinations. Several cases of ADEM have been described after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, whereas no case has been reported after adenovirus-vectored or mRNA COVID-19 vaccine administration. Here we describe a case of ADEM presenting 2 weeks after receiving the first dose of ChAdOx1 nCoV-19 vaccine. Patient clinical/magnetic resonance imaging (MRI) status spontaneously improved and rapidly resolved with corticosteroids. A 4-month follow-up showed complete recovery and no relapses. [ABSTRACT FROM AUTHOR]

Background: SARS-CoV-2 quickly spreads in the worldwide population, imposing social restrictions to control the infection, being the massive testing another essential strategy to break the chain of transmission. Aim: To compare the performance of at-home self-collected samples – saliva and combined nasal-oropharyngeal swabs (NOP) – for SARS-CoV-2 detection in a telemedicine platform for COVID-19 surveillance. Material and methods: We analyzed 201 patients who met the criteria of suspected COVID-19. NOP sampling was combined (nostrils and oropharynx) and saliva collected using a cotton pad device. Detection of SARS-COV-2 was performed by using the Altona RealStar® SARS-CoV-2 RT-PCR Kit 1.0. Results: There was an overall significant agreement (κ coefficient value of 0.58) between saliva and NOP. Considering results in either sample, 70 patients positive for SARS-CoV-2 were identified, with 52/70 being positive in NOP and 55/70 in saliva. This corresponds to sensitivities of 74.2% (95% CI; 63.7% to 83.1%) for NOP and 78.6% (95% CI; 67.6% to 86.6%) for saliva. Conclusion: Our data show the feasibility of using at-home self-collected samples (especially saliva), as an adequate alternative for SARS-CoV-2 detection. This new approach of testing can be useful to develop strategies for COVID-19 surveillance and for guiding public health decisions. [ABSTRACT FROM AUTHOR]

Background: Managing SARS‐CoV‐2 infection in frail and immunosuppressed patients still represents an open challenge, but, starting from the phase 3 PROVENT study, prophylaxis with tixagevimab‐cilgavimab has improved the approach in this category of patients, guaranteeing a better outcome and inferior mortality. Real‐life data in a heterogeneous cohort are few. Methods: The aim of this study is to evaluate the benefit of prophylaxis with tixagevimab‐cilgavimab in a cohort of 202 patients affected by different hematological diseases (lymphoproliferative, myeloproliferative, autoimmune, patients recently receiving a bone marrow transplant), active (with ongoing treatment), or in watch‐and‐wait strategy, followed in our center, during a median follow‐up of 249 (45‐325) days. Results: An incidence of 44 breakthrough infections (21.8%) is reported, with no treatment‐related adverse effects. Age ≥70 years, ongoing treatment (above all with monoclonal antibodies), baseline lymphoproliferative disorders, and prior virus exposure are identified as risk factors related to subsequent infection (p < 0.05). Moreover, the incidence is higher in low/nonresponse to prior vaccination (p =.002). Patients treated with tixagevimab‐cilgavimab had a mild course of the infection and a reduction of the duration compared with preprophylaxis infection (11 vs. 15 days, p <.001). The concurrent treatment with anti‐CD20 monoclonal antibodies and B–non‐Hodgkin lymphoma still confers a higher duration of infection despite prophylaxis. No deaths attributable to the infection occurred. Conclusion: Prophylaxis treatment seems to be a valid and safe strategy, although not preventing breakthrough infection, but the severe complications associated with the infection and the possible delays in administering lifesaving therapies from long positivity. The use of tixagevimab‐cilgavimab improved the management of immunocompromised patients with a high risk of severe SARS‐CoV‐2 disease. In a real‐world setting, it confirmed its role not only in preventing the occurrence of breakthrough infection, but also, above all, avoiding the severe complications associated and reducing the total days of positivity. [ABSTRACT FROM AUTHOR]

Objective: To verify the COVID-19 clinical characteristics, associated comorbidities, and outcomes in adolescents. Data source: This is a systematic review study based on articles published between 2020 and 2022 in the United States National Library of Medicine - PubMed (MedLine), Virtual Health Library – VHL (LILACS), Science Direct, Web of Science, and Scopus (Elsevier) databases. The study was registered in the International Prospective Register of Systematic Reviews, under No. CRD42022309108. Data synthesis: A total of 1188 studies were identified. After applying the selection criteria, 13 articles were included. Prevalence was 25%; mild cases were predominant; and fever, cough, headache, anosmia, nasal congestion, and ageusia were frequent. Fever and cough were proportionally higher in hospitalized cases: 81 and 68%, respectively. Dyspnea (odds ratio [OR] 6.3; confidence interval 95%[CI] 2.8–14.3), fever (OR 3.8; 95%CI 2.0–7.4), and cough (OR 3.4; 95%CI 2.0–6.0) were associated with severe cases. Up to 28% required intensive care and 38% required mechanical ventilation. Pre-existing comorbidities increased the risk of hospitalization and death. Severe cases were associated with the risk of death (relative risk [RR] 4.6; 95%CI 2.8–7.5). The black, mixed, and indigenous races/skin colors represented risk groups, as well as residents of poorer regions. Conclusions: The review provided a better understanding of the disease profile and may favor the development of public policies, in addition to contributing to the current literature in the field of adolescent health. [ABSTRACT FROM AUTHOR]

Since the beginning of the COVID-19 pandemic, a decrease in physical activity (PA) related to home confinement has been reported worldwide. However, some individuals were able to engage in physical activities at home. Thus, in a perspective of public health, it may be useful to analyse the available evidence regarding PA adopted during home restrictions, in order to identify possible strategies to help people stay active even during emergency situations. The aim of this review was to analyse how healthy individuals spontaneously exercised at home in the course of the pandemic, in order to detect possible factors associated with this behaviour. A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The protocol was registered in PROSPERO, an international prospective register of systematic reviews, with the registration number CRD42023394673. A literature search was conducted in PubMed, Scopus, and Web of Science. Cross-sectional studies published in English from the inception of each database to February 06th 2023 and focused on healthy individuals practicing spontaneous PA/exercise at home during the pandemic were considered eligible. The quality assessment was performed using the adapted Newcastle–Ottawa Quality Assessment Scale. Bibliographic information, sample size, study paricipant/population with age, gender, ethnicity, socioeconomic status, education, smart workers or not, anthropometric parameters, characteristics of at home exercises, athletic status and sedentariness, associated health-related effects, and main findings were synthetised. From 504 articles, 19 were included. Notwithstanding the differences in the studies examined, the majority of them reported that previous PA level was associated with exercise in such challenging conditions. Furthermore, technologies aimed at supporting exercise were shown to be a useful resource. Being habitually active and using digital supports may be associated with a positive attitude towards exercise at home during isolation. This suggests that in emergency situations, exercise should be promoted, also through digital media, especially among those groups who are usually less engaged in PA. Further analyses of longitudinal studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Autoantibodies (auto-Abs) neutralizing type I interferons (IFNs) are found in the blood of at least 15% of unvaccinated patients with life-threatening COVID-19 pneumonia. We report here the presence of auto-Abs neutralizing type I IFNs in the bronchoalveolar lavage (BAL) of 54 of the 415 unvaccinated patients (13%) with life-threatening COVID-19 pneumonia tested. The 54 individuals with neutralizing auto-Abs in the BAL included 45 (11%) with auto-Abs against IFN-α2, 37 (9%) with auto-Abs against IFN-ω, 54 (13%) with auto-Abs against IFN-α2 and/or ω, and five (1%) with auto-Abs against IFN-β, including three (0.7%) with auto-Abs neutralizing IFN-α2, IFN-ω, and IFN-β, and two (0.5%) with auto-Abs neutralizing IFN-α2 and IFN-β. Auto-Abs against IFN-α2 also neutralize the other 12 subtypes of IFN-α. Paired plasma samples were available for 95 patients. All seven patients with paired samples who had detectable auto-Abs in BAL also had detectable auto-Abs in plasma, and one patient had auto-Abs detectable only in blood. Auto-Abs neutralizing type I IFNs are, therefore, present in the alveolar space of at least 10% of patients with life-threatening COVID-19 pneumonia. These findings suggest that these auto-Abs impair type I IFN immunity in the lower respiratory tract, thereby contributing to hypoxemic COVID-19 pneumonia. [ABSTRACT FROM AUTHOR]

Introduction: SARS-CoV-2 is a highly contagious virus, and despite professionals' best efforts, nosocomial COVID-19 (NC) infections have been reported. This work aimed to describe differences in symptoms and outcomes between patients with NC and community-acquired COVID-19 (CAC) and to identify risk factors for severe outcomes among NC patients. Methods: This is a nationwide, retrospective, multicenter, observational study that analyzed patients hospitalized with confirmed COVID-19 in 150 Spanish hospitals (SEMI-COVID-19 Registry) from March 1, 2020, to April 30, 2021. NC was defined as patients admitted for non-COVID-19 diseases with a positive SARS-CoV-2 test on the fifth day of hospitalization or later. The primary outcome was 30-day in-hospital mortality (IHM). The secondary outcome was other COVID-19-related complications. A multivariable logistic regression analysis was performed. Results: Of the 23,219 patients hospitalized with COVID-19, 1,104 (4.8%) were NC. Compared to CAC patients, NC patients were older (median 76 vs. 69 years; p < 0.001), had more comorbidities (median Charlson Comorbidity Index 5 vs. 3; p < 0.001), were less symptomatic (p < 0.001), and had normal chest X-rays more frequently (30.8% vs. 12.5%, p < 0.001). After adjusting for sex, age, dependence, COVID-19 wave, and comorbidities, NC was associated with lower risk of moderate/severe acute respiratory distress syndrome (ARDS) (adjusted odds ratio [aOR]: 0.72; 95% confidence interval [CI]: 0.59–0.87; p < 0.001) and higher risk of acute heart failure (aOR: 1.40; 1.12–1.72; p = 0.003), sepsis (aOR: 1.73; 1.33–2.54; p < 0.001), and readmission (aOR: 1.35; 1.03–1.83; p = 0.028). NC was associated with a higher case fatality rate (39.1% vs. 19.2%) in all age groups. IHM was significantly higher among NC patients (aOR: 2.07; 1.81–2.68; p < 0.001). Risk factors for increased IHM in NC patients were age, moderate/severe dependence, malignancy, dyspnea, moderate/severe ARDS, multiple organ dysfunction syndrome, and shock; odynophagia was associated with lower IHM. Conclusions: NC is associated with greater mortality and complications compared to CAC. Hospital strategies to prevent NC must be strengthened. [ABSTRACT FROM AUTHOR]

Introduction—The dynamics of SARS-CoV-2 shedding and replication in humans remain incompletely understood. Methods—We analyzed SARS-CoV-2 shedding from multiple sites in individuals with an acute COVID-19 infection by weekly sampling for five weeks in 98 immunocompetent and 25 immunosuppressed individuals. Samples and culture supernatants were tested via RT-PCR for SARS-CoV-2 to determine viral clearance rates and in vitro replication. Results—A total of 2447 clinical specimens were evaluated, including 557 nasopharyngeal swabs, 527 saliva samples, 464 urine specimens, 437 anal swabs and 462 blood samples. The SARS-CoV-2 genome sequences at each site were classified as belonging to the B.1.128 (ancestral strain) or Gamma lineage. SARS-CoV-2 detection was highest in nasopharyngeal swabs regardless of the virus strain involved or the immune status of infected individuals. The duration of viral shedding varied between clinical specimens and individual patients. Prolonged shedding of potentially infectious virus varied from 10 days up to 191 days, and primarily occurred in immunosuppressed individuals. Virus was isolated in culture from 18 nasal swab or saliva samples collected 10 or more days after onset of disease. Conclusions—Our findings indicate that persistent SARS-CoV-2 shedding may occur in both competent or immunosuppressed individuals, at multiple clinical sites and in a minority of subjects is capable of in vitro replication. [ABSTRACT FROM AUTHOR]

Summary: Little is known of the course of COVID‐19 and the antibody response to infection or vaccination in patients with hairy‐cell leukaemia (HCL). Among a total of 58 HCL cases we studied in these regards, 37 unvaccinated patients, mostly enjoying a relatively long period free from anti‐leukaemic treatment, developed COVID‐19 between March 2020 and December 2021 with a usually favourable outcome (fatality rate: 5/37, 14%); however, active leukaemia, older age and more comorbidities were associated with a worse course. Postinfection (n = 11 cases) and postvaccination (n = 28) seroconversion consistently developed, except after recent anti‐CD20 or venetoclax therapy, correlating with perivaccine B‐cell count. Vaccination appeared to protect from severe COVID‐19 in 11 patients with breakthrough infection. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 life cycle is strictly dependent on the environmental redox state that influences both virus entry and replication. A reducing environment impairs the binding of the spike protein (S) to the angiotensin-converting enzyme 2 receptor (ACE2), while a highly oxidizing environment is thought to favor S interaction with ACE2. Moreover, SARS-CoV-2 interferes with redox homeostasis in infected cells to promote the oxidative folding of its own proteins. Here we demonstrate that synthetic low molecular weight (LMW) monothiol and dithiol compounds induce a redox switch in the S protein receptor binding domain (RBD) toward a more reduced state. Reactive cysteine residue profiling revealed that all the disulfides present in RBD are targets of the thiol compounds. The reduction of disulfides in RBD decreases the binding to ACE2 in a cell-free system as demonstrated by enzyme-linked immunosorbent and surface plasmon resonance (SPR) assays. Moreover, LMW thiols interfere with protein oxidative folding and the production of newly synthesized polypeptides in HEK293 cells expressing the S1 and RBD domain, respectively. Based on these results, we hypothesize that these thiol compounds impair both the binding of S protein to its cellular receptor during the early stage of viral infection, as well as viral protein folding/maturation and thus the formation of new viral mature particles. Indeed, all the tested molecules, although at different concentrations, efficiently inhibit both SARS-CoV-2 entry and replication in Vero E6 cells. LMW thiols may represent innovative anti-SARS-CoV-2 therapeutics acting directly on viral targets and indirectly by inhibiting cellular functions mandatory for viral replication. [ABSTRACT FROM AUTHOR]

Around the world, the 2019 Coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has raised serious public health problems and major medical challenges. The Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) published several papers on the impact of COVID-19 on the current management, diagnosis, and treatment of acute and chronic gastrointestinal, hepatic, immune-mediated, and functional disorders. The present article summarizes the most relevant SIGENP reports and consensus during and after the peak of the COVID-19 outbreak, including the diagnosis and treatment of inflammatory bowel disease (IBD), indications and timing of digestive endoscopy, and insights into the novel hepatitis. [ABSTRACT FROM AUTHOR]

Background: Although most children may experience mild to moderate symptoms and do not require hospitalization, there are little data on cardiac involvement in COVID-19. However, cardiac involvement is accurately demonstrated in children with MISC. The objective of this study was to evaluate cardiac mechanics in previously healthy children who recovered from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in a long-term follow-up by means of two-dimensional speckle-tracking echocardiography (STE). Methods: We analyzed a cohort of 157 paediatric patients, mean age 7.7 ± 4.5 years (age range 0.3–18 years), who had a laboratory-confirmed diagnosis of SARS-CoV-2 infection and were asymptomatic or mildly symptomatic for COVID-19. Patients underwent a standard transthoracic echocardiogram and STE at an average time of 148 ± 68 days after diagnosis and were divided in three follow-up groups (<180 days, 180–240 days, >240 days). Patients were compared with 107 (41 females—38%) age- and BSA-comparable healthy controls (CTRL). Results: Left ventricular (LV) global longitudinal strain (post-COVID-19: −20.5 ± 2.9%; CTRL: −21.8 ± 1.7%; p < 0.001) was significantly reduced in cases compared with CTRLs. No significant differences were seen among the three follow-up groups (p = NS). Moreover, regional longitudinal strain was significantly reduced in LV apical-wall segments of children with disease onset during the second wave of the COVID-19 pandemic compared to the first wave (second wave: −20.2 ± 2.6%; first wave: −21.2 ± 3.4%; p = 0.048). Finally, peak left atrial systolic strain was within the normal range in the post-COVID-19 group with no significant differences compared to CTRLs. Conclusions: Our study demonstrated for the first time the persistence of LV myocardial deformation abnormalities in previously healthy children with an asymptomatic or mildly symptomatic (WHO stages 0 or 1) COVID-19 course after an average follow-up of 148 ± 68 days. A more significant involvement was found in children affected during the second wave. These findings imply that subclinical LV dysfunction may also be a typical characteristic of COVID-19 infection in children and are concerning given the predictive value of LV longitudinal strain in the general population. [ABSTRACT FROM AUTHOR]

Summary: To optimise management of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection identifying high‐risk patients and maintaining treatment dose intensity is an important issue in patients with aggressive lymphomas. In the present study, we report on the presentation, management, and outcome of an international series of 91 patients with primary central nervous system lymphoma and SARS‐CoV‐2 infection. SARS‐CoV‐2 was diagnosed before/during first‐line treatment in 64 patients, during follow‐up in 21, and during salvage therapy in six. Among the 64 patients infected before/during first‐line chemotherapy, 38 (59%) developed pneumonia and 26 (41%) did not clear the virus. Prolonged exposure to steroids before viral infection and/or treatment with high‐dose cytarabine favoured pneumonia development and virus persistence and were associated with poorer survival; 81% of patients who did not clear virus died early from coronavirus disease 2019 (COVID‐19). Vaccination was associated with lower pneumonia incidence and in‐hospital mortality. Chemotherapy was initiated/resumed in 43 (67%) patients, more commonly among patients who did not develop pneumonia, cleared the virus, or did not receive steroids during infection. Chemotherapy resumption in patients with viral persistence should be indicated cautiously as it was associated with a poorer survival (6‐month, 70% and 87%, p = 0.07). None of the 21 patients infected during follow‐up died from COVID‐19, requiring similar measures as infected subjects in the general population. [ABSTRACT FROM AUTHOR]

VOC Omicron induce "common cold symptoms" and sore throat more often than wild-type and VOC Delta infections (Figures 2 and 3). Presentation of airway and general symptoms in COVID-19 caused by dominant SARS-CoV-2 variants: A follow-up on ARIA consensus GLO:1X5/01nov22:all15416-fig-0001.jpg PHOTO (COLOR): 1 Expected symptom intensity on analogue scale (0: no symptom and 10: strongest symptoms) for wild-type and virus variants of SARS-CoV-2, rated by ARIA specialists. Symptom groups A/B/C/D are explained in the main text and referred to Figure 2 gl Significantly differing symptoms were grouped concerning common cold and sore throat, chemosensory, bronchial and pulmonary, as well as systemic (Figure 2). [Extracted from the article]

We aimed to assess the feasibility of TESTA'T COVID strategy among healthcare and education professionals.in Spain during the peak of the 6th wave caused by Omicron variant. Kits were ordered online and sent by mail, participants answered an online acceptability/usability survey and uploaded the picture of results. 492 participants ordered a test, 304 uploaded the picture (61.8%). Eighteen positive cases were detected (5.9%). 92.2% were satisfied/very satisfied with the intervention; and 92.5% found performing the test easy/very easy. We demonstrated that implementing online COVID-19 self-testing in schools and healthcare settings in Spain is feasible. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the coronavirus disease 2019 (COVID-19), has provoked more than six million deaths worldwide and continues to pose a major threat to global health. Enormous efforts have been made by researchers around the world to elucidate COVID-19 pathophysiology, design efficacious therapy and develop new vaccines to control the pandemic. To this end, experimental models are essential. While animal models and conventional cell cultures have been widely utilized during these research endeavors, they often do not adequately reflect the human responses to SARS-CoV-2 infection. Therefore, models that emulate with high fidelity the SARS-CoV-2 infection in human organs are needed for discovering new antiviral drugs and vaccines against COVID-19. Three-dimensional (3D) cell cultures, such as lung organoids and bioengineered organs-on-chips, are emerging as crucial tools for research on respiratory diseases. The lung airway, small airway and alveolus organ chips have been successfully used for studies on lung response to infection by various pathogens, including corona and influenza A viruses. In this review, we provide an overview of these new tools and their use in studies on COVID-19 pathogenesis and drug testing. We also discuss the limitations of the existing models and indicate some improvements for their use in research against COVID-19 as well as future emerging epidemics. [ABSTRACT FROM AUTHOR]

Vaccination against SARS-CoV2 represents a key weapon to prevent COVID-19, but lower response rates to vaccination have frequently been reported in solid organ transplant recipients. The aim of our study was to evaluate the rate of seroconversion to SARS-CoV-2 mRNA vaccines in a cohort of kidney transplant recipients and the potential role of the different immunosuppressive regimens. We conducted an observational retrospective cohort study in kidney transplant patients vaccinated for COVID-19. For each patient, we evaluated IgG anti-S-RBD SARS-CoV-2 titers immediately before the administration of first COVID-19 vaccination dose, 20 days after the first dose and 40 days after the second dose. Moreover, we evaluated the type of immunosuppressive treatment and the incidence of vaccine breakthrough SARS-CoV-2 infection. We enrolled 121 kidney transplant patients vaccinated for COVID-19. At the time of administration of the first vaccine dose, all patients had a negative antibody titer; only 4.1% had positive antibody titers 20 days after the first dose. More than half patients 62 (51%) had protective antibody titers 40 days after the second dose. A total of 18 Solid Organ Transplant Recipients (SOTRs) (14.9%) got a SARS-CoV-2 breakthrough infection during the study period. With regard to immunosuppressive regimen, patients on mycophenolate-based regimen (48.7%) showed the lowest antibody response rates (27.5%) compared to other regimens. Our study confirms that kidney transplant patients show a poor response to two doses of COVID-19 vaccination. Moreover, in our study the use of mycophenolate is significantly associated with a non-response to COVID-19 m-RNA vaccines. [ABSTRACT FROM AUTHOR]

This study sets up to test the hypothesis that when age, comorbidities, and pathophysiological conditions are considered, vaccines are effective to prevent deaths in patients requiring ICU admission for breakthrough infection. In vaccinated patients, observed hospital mortality was lower than expected hospital mortality (Fig. [Extracted from the article]

People with cystic fibrosis should be considered at increased risk of developing severe symptoms of COVID-19. Strikingly, a broad array of evidence shows reduced spread of SARS-CoV-2 in these subjects, suggesting a potential role for CFTR in the regulation of SARS-CoV-2 infection/replication. Here, we analyzed SARS-CoV-2 replication in wild-type and CFTR-modified human bronchial epithelial cell lines and primary cells to investigate SARS-CoV-2 infection in people with cystic fibrosis. Both immortalized and primary human bronchial epithelial cells expressing wt or F508del-CFTR along with CRISPR/Cas9 CFTR-ablated clones were infected with SARS-CoV-2 and samples were harvested before and from 24 to 72 h post-infection. CFTR function was also inhibited in wt-CFTR cells with the CFTR-specific inhibitor IOWH-032 and partially restored in F508del-CFTR cells with a combination of CFTR modulators (VX-661+VX-445). Viral load was evaluated by real-time RT-PCR in both supernatant and cell extracts, and ACE-2 expression was analyzed by both western blotting and flow cytometry. SARS-CoV-2 replication was reduced in CFTR-modified bronchial cells compared with wild-type cell lines. No major difference in ACE-2 expression was detected before infection between wild-type and CFTR-modified cells, while a higher expression in wild-type compared to CFTR-modified cells was detectable at 72 h post-infection. Furthermore, inhibition of CFTR channel function elicited significant inhibition of viral replication in cells with wt-CFTR, and correction of CFTR function in F508del-CFTR cells increased the release of SARS-CoV-2 viral particles. Our study provides evidence that CFTR expression/function is involved in the regulation of SARS-CoV-2 replication, thus providing novel insights into the role of CFTR in SARS-CoV-2 infection and the development of therapeutic strategies for COVID-19. [ABSTRACT FROM AUTHOR]

Introduction Coronavirus disease 2019 (COVID-19) has claimed millions of lives. Adequate protection of the professionals involved in patient care is essential in the battle against this disease. However, there is much uncertainty involving safety-relarted topics that are of particular interest to the rhinologist in the context of COVID-19. Objective To evaluate the current evidence regarding three safety-related topics: mask and respirator use, performance of nasal endoscopic procedures, and use of topical nasal and intranasal medications (saline irrigation and nasal corticosteroids). Methods A literature review was performed on the PubMed, Scopus, and Cochrane databases, with standardized search queries for each of the three topics of interest. Results In total, 13 articles on mask use, 6 articles on the safety of nasal corticosteroids, 6 articles on the safety of nasal endoscopic procedures, and 1 article on nasal irrigation with saline solution were included in the final analysis. Conclusion N95 respirators are essential for the adequate protection of otolaryngologists. If reuse is necessary, physical methods of sterilization must be employed. No evidence was found to contraindicate the use of nasal corticosteroids, whether acute (in the management of sinonasal inflammatory conditions) or continued (in patients who use them chronically). Nasal irrigation with saline solution apparently does not increase the risk in the context of COVID-19. Nasal endoscopic procedures should only be performed after testing the patient for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the surgical team must wear full personal protective equipment to prevent aerosol exposure. [ABSTRACT FROM AUTHOR]

Background: SARS‐CoV‐2 caused one of the most devastating pandemics in the recent history of mankind. Due to various countermeasures, including lock‐downs, wearing masks, and increased hygiene, the virus has been controlled in some parts of the world. More recently, the availability of vaccines, based on RNA or adenoviruses, has greatly added to our ability to keep the virus at bay; again, however, in some parts of the world only. While available vaccines are effective, it would be desirable to also have more classical vaccines at hand for the future. Key feature of vaccines for long‐term control of SARS‐CoV‐2 would be inexpensive production at large scale, ability to make multiple booster injections, and long‐term stability at 4℃. Methods: Here, we describe such a vaccine candidate, consisting of the SARS‐CoV‐2 receptor‐binding motif (RBM) grafted genetically onto the surface of the immunologically optimized cucumber mosaic virus, called CuMVTT‐RBM. Results: Using bacterial fermentation and continuous flow centrifugation for purification, the yield of the production process is estimated to be >2.5 million doses per 1000‐litre fermenter run. We demonstrate that the candidate vaccine is highly immunogenic in mice and rabbits and induces more high avidity antibodies compared to convalescent human sera. The induced antibodies are more cross‐reactive to mutant RBDs of variants of concern (VoC). Furthermore, antibody responses are neutralizing and long‐lived. In addition, the vaccine candidate was stable for at least 14 months at 4℃. Conclusion: Thus, the here presented VLP‐based vaccine may be a good candidate for use as conventional vaccine in the long term. [ABSTRACT FROM AUTHOR]

Background: Improving the availability and usability of data and analytical tools is a critical precondition for further advancing modern biological and biomedical research. For instance, one of the many ramifications of the COVID-19 global pandemic has been to make even more evident the importance of having bioinformatics tools and data readily actionable by researchers through convenient access points and supported by adequate IT infrastructures. One of the most successful efforts in improving the availability and usability of bioinformatics tools and data is represented by the Galaxy workflow manager and its thriving community. In 2020 we introduced Laniakea, a software platform conceived to streamline the configuration and deployment of "on-demand" Galaxy instances over the cloud. By facilitating the set-up and configuration of Galaxy web servers, Laniakea provides researchers with a powerful and highly customisable platform for executing complex bioinformatics analyses. The system can be accessed through a dedicated and user-friendly web interface that allows the Galaxy web server's initial configuration and deployment. Results: "Laniakea@ReCaS", the first instance of a Laniakea-based service, is managed by ELIXIR-IT and was officially launched in February 2020, after about one year of development and testing that involved several users. Researchers can request access to Laniakea@ReCaS through an open-ended call for use-cases. Ten project proposals have been accepted since then, totalling 18 Galaxy on-demand virtual servers that employ ~ 100 CPUs, ~ 250 GB of RAM and ~ 5 TB of storage and serve several different communities and purposes. Herein, we present eight use cases demonstrating the versatility of the platform. Conclusions: During this first year of activity, the Laniakea-based service emerged as a flexible platform that facilitated the rapid development of bioinformatics tools, the efficient delivery of training activities, and the provision of public bioinformatics services in different settings, including food safety and clinical research. Laniakea@ReCaS provides a proof of concept of how enabling access to appropriate, reliable IT resources and ready-to-use bioinformatics tools can considerably streamline researchers' work. [ABSTRACT FROM AUTHOR]

Background: Multisystem inflammatory syndrome in children (MIS-C) has recently been described in children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This report describes 2 children with MIS-C who were initially diagnosed with toxic shock syndrome but who tested positive for SARS-CoV-2 infection on reverse transcription-polymerase chain reaction, supporting the diagnosis of MIS-C. Case Reports: Case 1. A 7-year-old boy with fever, cough, and dyspnea was treated with oxygen, intravenous immunoglobulin (IVIG) infusion, and methylprednisolone and showed a worsening of clinical conditions, persistent fever, hypotension, and hematological parameters compatible with macrophage activation syndrome (MAS). Three intravenous boluses of methylprednisolone (30 mg/kg/day) were followed by a progressive resolution. Case 2. A 14-year-old girl with syncope, fever, diarrhea, oliguria, and increased creatinine levels required fluid infusion and correction of electrolyte imbalance. The increase of creatine phosphokinase (CPK), myoglobin, troponin, and creatine kinase-MB (CK-MB) was associated with grade I atrioventricular block and pericardial effusion. The patient showed myositis and severe muscular weakness, with hematological parameters compatible with MIS-C. She started IVIG and 3 intravenous boluses of methylprednisolone. However, bradycardia, tachypnea, severe hypotension, loss of consciousness, oliguria, bilateral ground-glass pneumonia, bilateral pleural, and peritoneal effusion, in the absence of thromboembolism, required treatment with furosemide, albumin, and enoxaparin, and was followed by a prompt resolution. Conclusions: These 2 pediatric cases highlight the importance of SARS-CoV-2 testing in all patients with acute symptoms and signs of infection during the COVID-19 pandemic. As new variants of SARS-CoV-2 emerge, cases of MIS-C can become more prevalent, and pediatricians should be aware of diagnostic and management guidelines. [ABSTRACT FROM AUTHOR]

Background: SARS-CoV-2 has been detected in stool samples of COVID-19 patients, with potential implications for faecal-oral transmission. Compared to nasopharyngeal swab samples, the complexity of the stool matrix poses a challenge in the detection of the virus that has not yet been solved. However, robust and reliable methods are needed to estimate the prevalence and persistence of SARS-CoV-2 in the gut and to ensure the safety of microbiome-based procedures such as faecal microbiota transplant (FMT). The aim of this study was to establish a sensitive and reliable method for detecting SARS-CoV-2 in stool samples. Results: Stool samples from individuals free of SARS-CoV-2 were homogenised in saline buffer and spiked with a known titre of inactivated virus ranging from 50 to 750 viral particles per 100 mg stool. Viral particles were concentrated by ultrafiltration, RNA was extracted, and SARS-CoV-2 was detected via real-time reverse-transcription polymerase chain reaction (RT-qPCR) using the CDC primers and probes. The RNA extraction procedure we used allowed for the detection of SARS-CoV-2 via RT-qPCR in most of the stool samples tested. We could detect as few as 50 viral particles per 100 mg of stool. However, high variability was observed across samples at low viral titres. The primer set targeting the N1 region provided more reliable and precise results and for this primer set our method had a limit of detection of 1 viral particle per mg of stool. Conclusions: Here we describe a sensitive method for detecting SARS-CoV-2 in stool samples. This method can be used to establish the persistence of SARS-CoV-2 in stool and ensure the safety of clinical practices such as FMT. [ABSTRACT FROM AUTHOR]

During COVID-19 pandemic, older adults are the segment of the population at higher health risk. Given the important role the risk perception has in influencing both the behaviors and psychological well-being, it appears useful exploring this factor in this segment of the population. Despite different studies already described the factors influencing the risk perception, few focused on older adults. For this reason, we investigated risk perception in 514 people over 60 years during the lockdown. We administered a structured interview collecting socio-demographic information, sources of information used, actions undertaken to avoid contagion, and risk perception. Risk perception related to COVID-19 was significantly lower than the perceived risk associated with other threats, and it was correlated to the number of sources of information used but not to the actions undertaken. Furthermore, we found higher risk perception in who knew infected persons, and a negative correlation between the risk perception and age, with the over 75 perceiving a lower risk of getting infected compared to the younger participants. Our results should be taken as informative for future studies. Indeed, further studies on the older adults and the risk perception during emergencies are needed to better orient both communication and supporting strategies. [ABSTRACT FROM AUTHOR]

Torquetenovirus (TTV) is present in biological fluids from healthy individuals and measurement of its titer is used to assess immune status in individuals with chronic infections and after transplants. We assessed if the titer of TTV in saliva varied with the presence of SARS-CoV-2 in the nasopharynx and could be a marker of COVID-19 status. Saliva from 91 individuals positive for SARS-CoV-2 in nasal-oropharyngeal samples, and from 126 individuals who were SARS-CoV-2-negative, all with mild respiratory symptoms, were analyzed. Both groups were similar in age, gender, symptom duration and time after symptom initiation when saliva was collected. Titers of TTV and SARS-CoV-2 were assessed by gene amplification. Loss of smell (p = 0.0001) and fever (p = 0.0186) were more prevalent in SARS-CoV-2-positive individuals, while sore throat (p = 0.0001), fatigue (p = 0.0037) and diarrhea (p = 0.0475) were more frequent in the SARS-CoV-2 negative group. The saliva TTV and nasal-oropharyngeal SARS-CoV-2 titers were correlated (p = 0.0085). The TTV level decreased as symptoms resolved in the SARS-CoV-2 infected group (p = 0.0285) but remained unchanged in the SARS-CoV-2 negative controls. In SARS-CoV-2 positive subjects who provided 2–4 saliva samples and in which TTV was initially present, the TTV titer always decreased over time as symptoms resolved. We propose that sequential TTV measurement in saliva is potentially useful to assess the likelihood of symptom resolution in SARS-CoV-2-positive individuals and to predict prognosis. [ABSTRACT FROM AUTHOR]

Compared to RT-PCR, lower performance of antigen detection assays, including the Lumipulse G SARS-CoV-2 Ag assay, may depend on specific testing scenarios. We tested 594 nasopharyngeal swab samples from individuals with COVID-19 (RT-PCR cycle threshold [Ct] values ≤ 40) or non-COVID-19 (Ct values >40) diagnoses. RT-PCR positive samples were assigned to diagnostic, screening, or monitoring groups of testing. With a limit of detection of 1.2 × 104 SARS-CoV-2 RNA copies/mL, Lumipulse showed positive percent agreement (PPA) of 79.9% (155/194) and negative percent agreement of 99.3% (397/400), whereas PPAs were 100% for samples with Ct values of <18 or 18–<25 and 92.5% for samples with Ct values of 25–<30. By three groups, Lumipulse showed PPA of 87.0% (60/69), 81.1% (43/53), or 72.2% (52/72), respectively, whereas PPA was 100% for samples with Ct values of <18 or 18–<25, and was 94.4, 80.0, or 100% for samples with Ct values of 25–<30, respectively. Additional testing of RT-PCR positive samples for SARS-CoV-2 subgenomic RNA showed that, by three groups, PPA was 63.8% (44/69), 62.3% (33/53), or 33.3% (24/72), respectively. PPAs dropped to 55.6, 20.0, or 41.7% for samples with Ct values of 25–<30, respectively. All 101 samples with a subgenomic RNA positive result had a Lumipulse assay's antigen positive result, whereas only 54 (58.1%) of remaining 93 samples had a Lumipulse assay's antigen positive result. Lumipulse assay was highly sensitive in samples with low RT-PCR Ct values, implying repeated testing to reduce consequences of false-negative results. [ABSTRACT FROM AUTHOR]

Background: COVID-19 can occur asymptomatically, as influenza-like illness, or as more severe forms, which characterize severe acute respiratory syndrome (SARS). Its mortality rate is higher in individuals over 80 years of age and in people with comorbidities, so these constitute the risk group for severe forms of the disease. We analyzed the factors associated with death in confirmed cases of COVID-19 in the state of Rio de Janeiro. This cross-sectional study evaluated the association between individual demographic, clinical, and epidemiological variables and the outcome (death) using data from the Unified Health System information systems.Methods: We used the extreme boosting gradient (XGBoost) model to analyze the data, which uses decision trees weighted by the estimation difficulty. To evaluate the relevance of each independent variable, we used the SHapley Additive exPlanations (SHAP) metric. From the probabilities generated by the XGBoost model, we transformed the data to the logarithm of odds to estimate the odds ratio for each independent variable.Results: This study showed that older individuals of black race/skin color with heart disease or diabetes who had dyspnea or fever were more likely to die.Conclusions: The early identification of patients who may progress to a more severe form of the disease can help improve the clinical management of patients with COVID-19 and is thus essential to reduce the lethality of the disease. [ABSTRACT FROM AUTHOR]

Keywords: Pfizer COVID-19 vaccine; SARS-CoV-2; S-RBD-specific; immunoglobulins; seroconversion; decreasing immunity; neutralizing antibodies EN Pfizer COVID-19 vaccine SARS-CoV-2 S-RBD-specific immunoglobulins seroconversion decreasing immunity neutralizing antibodies 1 3 3 01/05/22 20211201 NES 211201 Research letter Emerging evidence is offering significant insights into the effectiveness and safety of the vaccination against the Coronavirus Disease 2019 (COVID-19), but another crucial aspect of the current global vaccination campaign is the time trend of the antibody response to COVID-19 vaccines over a longer period and the resulting duration of the protection offered.1 Here, we present data on the dynamics of antibodies that bind SARS-CoV-2 spike (S) protein receptor binding domain (RBD) - the most critical target for SARS-CoV-2-specific antibodies within the S1 sub-unit2 - after 6 months from the administration with BNT162b2 vaccine. Pfizer COVID-19 vaccine, SARS-CoV-2, S-RBD-specific, immunoglobulins, seroconversion, decreasing immunity, neutralizing antibodies Complete methods of the VASCO project have been presented elsewhere.3 In this survey, HCWs who were administered the two-dose BNT162b2 mRNA vaccine 21 days apart between December 2020 and January 2021 were invited to undertake a quantitative serology test for the research of SARS-CoV-2 S-RBD-specific immunoglobulins G (IgG). [Extracted from the article]

Herein, we describe three patients, with no history of SARS-CoV-2 infection, who developed skin reactions after receiving Pfizer-BioNTech (New York, NY, USA) COVID-19 vaccine. The patients in this manuscript have given written informed consent to the publication of their case details Conflict of interest The authors have no financial obligations or conflict of interest to declare. Purpuric lesions on the eyelids developed after BNT162b2 mRNA COVID-19 vaccine: another piece of SARS-CoV-2 skin puzzle?. [Extracted from the article]

• Molnupiravir and nirmatrelvir/ritonavir are administered to patients with mild COVID-19 to prevent worsening of disease. • Hospitalisation and mortality rates with molnupiravir vs. nirmatrelvir/ritonavir were compared in patients with leukaemia or lymphoma. • No statistically significant differences between treatments for hospitalisation, mortality rates or survival probability. • Results support the use of molnupiravir in patients with haematological malignancies in Europe. • Patients with nirmatrelvir/ritonavir-related contraindications and drug-drug interactions may benefit from molnupiravir treatment. Molnupiravir and nirmatrelvir/ritonavir are antivirals used to prevent progression to severe SARS-CoV-2 infections and decrease hospitalisation and mortality rates. Nirmatrelvir/ritonavir was authorised in Europe in December 2021, whereas molnupiravir is not yet licensed in Europe as of February 2022. Molnupiravir may be an alternative to nirmatrelvir/ritonavir because it is associated with fewer drug-drug interactions and contraindications. A caveat for molnupiravir is the mode of action induces viral mutations. Mortality rate reduction with molnupiravir was less pronounced than that with nirmatrelvir/ritonavir in patients without haematological malignancy. Little is known about the comparative efficacy of the two drugs in patients with haematological malignancy at high-risk of severe COVID-19. Thus, molnupiravir and nirmatrelvir/ritonavir were compared in a cohort of patients with haematological malignancies. Clinical data from patients treated with molnupiravir or nirmatrelvir/ritonavir monotherapy for COVID-19 were retrieved from the EPICOVIDEHA registry. Patients treated with molnupiravir were matched by sex, age (±10 years), and severity of baseline haematological malignancy to controls treated with nirmatrelvir/ritonavir. A total of 116 patients receiving molnupiravir for the clinical management of COVID-19 were matched to an equal number of controls receiving nirmatrelvir/ritonavir. In each of the groups, 68 (59%) patients were male; with a median age of 64 years (interquartile range [IQR] 53-74) for molnupiravir recipients and 64 years (IQR 54-73) for nirmatrelvir/ritonavir recipients; 56.9% (n=66) of the patients had controlled baseline haematological malignancy, 12.9% (n=15) had stable disease, and 30.2% (n=35) had active disease at COVID-19 onset in each group. During COVID-19 infection, one third of patients from each group were admitted to hospital. Although a similar proportion of patients in the two groups were vaccinated (molnupiravir n=77, 66% vs. nirmatrelvir/ritonavir n=87, 75%), more of those treated with nirmatrelvir/ritonavir had received four vaccine doses (n=27, 23%) compared with those treated with molnupiravir (n=5, 4%) (P <0.001). No differences were detected in COVID-19 severity (P =0.39) or hospitalisation (P =1.0). No statistically significant differences were identified in overall mortality rate (P =0.78) or survival probability (d30 P =0.19, d60 P =0.67, d90 P =0.68, last day of follow up P =0.68). Deaths were either attributed to COVID-19, or the infection was judged by the treating physician to have contributed to death. Hospitalisation and mortality rates with molnupiravir were comparable to those with nirmatrelvir/ritonavir in high-risk patients with haematological malignancies and COVID-19. Molnupiravir is a plausible alternative to nirmatrelvir/ritonavir for COVID-19 treatment in patients with haematological malignancy. [ABSTRACT FROM AUTHOR]

The risk of pre-term delivery, pre-eclampsia (PE), cesarean section, severe neonatal/perinatal morbidity and mortality was significantly increased in COVID-19 pregnant women (2). The infection of host cells by SARS-CoV-2 requires the presence of two receptors: the transmembrane receptor Angiotensin-Converting Enzyme 2 (ACE2) and the Type II Transmembrane Serine Protease (TMPRSS2) (3,4). Moreover, SARS-CoV-2 may bind to a third alternative receptor, the cluster of differentiation 147 (CD147)/EMMPRIN (5). There is therefore a lack of information on how maternal infection with SARS-CoV-2 impacts the expression of ACE2 and TMPRSS2 in the placenta, at both transcript and protein level. Here, we investigated term placentae collected before the SARS-CoV-2 pandemic and COVID-19+ placentae, analyzing the expression of the three main COVID-19 receptors, namely ACE2, TMPRSS2 and CD147. We performed RT-qPCR, Western blot and cytofluorimetric analysis on placental tissues and on isolated placental cells, both in resting conditions and after stimulation with Spike protein. Finally, we evaluated the SARS-CoV-2 capability to infect placental cells in vitro. We observed very low expression of the canonical SARS-CoV-2 entry receptors on syncytio- and cytotrophoblast cells, as well as on human umbilical vein endothelial cells (HUVECs), but the infection by the virus resulted into an up-regulation of their expression. In order to try to understand the mechanisms underlying the resistance to Sars-CoV-2 infection of placental cells, we performed transfection tests with the Spike protein to see the formation of cellular syncytia. The simultaneous presence of Spike and functional receptors (ACE2, TMPRSS2) on the cell surface, in fact, leads to the activation of fusogenic mechanisms, which manifest with the formation of syncytia. Our results lead us to affirm that in healthy placentas there are elevated levels of CD147 expression and variable levels of ACE2, while TMPRSS2 is not present, identifying placenta as a non-preferential tissue for Sars-CoV-2 infection in normal conditions. The COVID-19 syndrome and the presence of circulating virus could determine an up-regulation of TMPRSS2 facilitating the virus to enter the syncytiotrophoblast and cytototrophoblast cells. We have demonstrated that endothelial cells are not permissive for virus entry, but the systemic effect linked to endothelitiis and therefore to the preeclamptic-like syndrome, could be due to the induced direct activation of the Spike protein (with its shedding and release) on placental cells, in terms of increased expression of proinflammatory cytokines, increased vascular permeability and induced syncytiotrophoblasts apoptosis. Finally, because the transfection of placental cells with Spike protein and the simultaneous overexpression of ACE2 did not lead to cell fusion, an intrinsic mechanism of cell fusion resistance expressed by placental cells, is proposed. [ABSTRACT FROM AUTHOR]

Butyrate is a major gut microbiome metabolite that regulates several defense mechanisms against infectious diseases. Alterations in the gut microbiome, leading to reduced butyrate production, have been reported in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A new butyrate releaser, useful for all the known applications of butyrate, presenting physiochemical characteristics suitable for easy oral administration, (N-(1-carbamoyl-2-phenyl-ethyl) butyramide (FBA), has been recently developed. We investigated the protective action of FBA against SARS-CoV-2 infection in the human small intestine and enterocytes. Relevant aspects of SARS-CoV-2 infection were assessed: infectivity, host functional receptor angiotensin-converting enzyme-2 (ACE2), transmembrane protease serine 2 (TMPRSS2), neuropilin-1 (NRP1), pro-inflammatory cytokines expression, genes involved in the antiviral response and the activation of Nf-kB nuclear factor (erythroid-derived 2-like) 2 (Nfr2) pathways. We found that FBA positively modulates the crucial aspects of the infection in small intestinal biopsies and human enterocytes, reducing the expression of ACE2, TMPRSS2 and NRP1, pro-inflammatory cytokines interleukin (IL)-15, monocyte chemoattractant protein-1 (MCP-1) and TNF-α, and regulating several genes involved in antiviral pathways. FBA was also able to reduce the number of SARS-CoV-2-infected cells, and ACE2, TMPRSS2 and NRP1 expression. Lastly, through the inhibition of Nf-kB and the up-regulation of Nfr2, it was also able to reduce the expression of pro-inflammatory cytokines IL-15, MCP-1 and TNF-α in human enterocytes. The new butyrate releaser, FBA, exerts a preventive action against SARS-CoV-2 infection. It could be considered as an innovative strategy to limit COVID-19. [ABSTRACT FROM AUTHOR]