Development and external validation of prediction models for critical outcomes of unvaccinated COVID-19 patients based on demographics, medical conditions and dental status.

Background: Multiple prediction models were developed for critical outcomes of COVID-19. However, prediction models using predictors which can be easily obtained in clinical practice and on dental status are scarce. Aim: The study aimed to develop and externally validate prediction models for critical outcomes of COVID-19 for unvaccinated adult patients in hospital settings based on demographics, medical conditions, and dental status. Methods: A total of 285 and 352 patients from two hospitals in the Netherlands were retrospectively included as derivation and validation cohorts. Demographics, medical conditions, and dental status were considered potential predictors. The critical outcomes (death and ICU admission) were considered endpoints. Logistic regression analyses were used to develop two models: for death alone and for critical outcomes. The performance and clinical values of the models were determined in both cohorts. Results: Age, number of teeth, chronic kidney disease, hypertension, diabetes, and chronic obstructive pulmonary diseases were the significant independent predictors. The models showed good to excellent calibration with observed: expected (O:E) ratios of 0.98 (95%CI: 0.76 to 1.25) and 1.00 (95%CI: 0.80 to 1.24), and discrimination with shrunken area under the curve (AUC) values of 0.85 and 0.79, based on the derivation cohort. In the validation cohort, the models showed good to excellent discrimination with AUC values of 0.85 (95%CI: 0.80 to 0.90) and 0.78 (95%CI: 0.73 to 0.83), but an overestimation in calibration with O:E ratios of 0.65 (95%CI: 0.49 to 0.85) and 0.67 (95%CI: 0.52 to 0.84). Conclusion: The performance of the models was acceptable in both derivation and validation cohorts. Number of teeth was an additive important predictor of critical outcomes of COVID-19. It is an easy-to-apply tool in hospitals for risk stratification of COVID-19 prognosis.

Hyper-inflammation and complement in COVID-19.

COVID-19 is a complex disease manifesting in a broad severity spectrum and involving distinct organs and systems. Hyperinflammation, including complement over-activation, has a pivotal role in severe COVID-19 pathobiology, stimulating the inflammatory response, causing microangiopathy, platelet-neutrophil activation, and hypercoagulability. SARS-CoV-2 can directly activate the complement system by the classic, alternative, and lectin pathways, and infected cells can produce intracellular complement (the complesome). COVID-19 severity appears to be associated with the degree of complement activation, and it has been hypothesized that patients with COVID-19 may benefit from therapeutic complement inhibition. Different complement cascade molecules may be targeted with potential advantages and disadvantages. Which target(s) is the most effective and when is the best timing for intervention remain open questions. Early phase I and phase II clinical trials have shown promising but conflicting results, warranting phase III controlled randomized trials. Upstream complement inhibition appears to better and more effectively block hyperinflammation with potential clinical significance. Understanding how SARS-CoV-2 exploits the complement system can add precious information about the pathogenesis of other infections, inflammatory, and autoimmune diseases beyond COVID-19.

Late diagnosis of HIV before and during the COVID-19 pandemic: preliminary insights from an Infectious Diseases Unit in Apulia.

Abstract: During the COVID-19 pandemic, many HIV outpatient clinics were temporarily closed or their activities were reduced. Similarly, many infectious disease wards were converted into COVID-19 Units. Thus, an increase in late HIV diagnoses was expected due to reduced access to testing, screening services and consultation with HIV infection specialists. A higher rate of late HIV diagnoses was reported during the COVID-19 pandemic compared with the period before COVID-19. We analyzed all consecutive individuals newly diagnosed with HIV in our Center between January 1, 2017 and September 30, 2022. We did not observe differences in terms of late HIV diagnoses and AIDS between the two periods.

Characterization of SARS-CoV-2 Spike mutations important for infection of mice and escape from human immune sera.

Due to differences in human and murine angiotensin converting enzyme 2 (ACE-2) receptor, initially available SARS-CoV-2 isolates could not infect mice. Here we show that serial passaging of USA-WA1/2020 strain in mouse lungs results in "mouse-adapted" SARS-CoV-2 (MA-SARS-CoV-2) with mutations in S, M, and N genes, and a twelve-nucleotide insertion in the S gene. MA-SARS-CoV-2 infection causes mild disease, with more pronounced morbidity depending on genetic background and in aged and obese mice. Two mutations in the S gene associated with mouse adaptation (N501Y, H655Y) are present in SARS-CoV-2 variants of concern (VoCs). N501Y in the receptor binding domain of viruses of the B.1.1.7, B.1.351, P.1 and B.1.1.529 lineages (Alpha, Beta, Gamma and Omicron variants) is associated with high transmissibility and allows VoCs to infect wild type mice. We further show that S protein mutations of MA-SARS-CoV-2 do not affect neutralization efficiency by human convalescent and post vaccination sera.

Post-Operative Bleeding Complications in a Periodontitis Patient Testing Positive for COVID-19.

Recent scientific evidence states that a subset of COVID-19 patients may have a risk of increased bleeding tendency. This case report presents a healthy 38-year-old woman with generalized stage III, grade C periodontitis with an abnormal post-operative blood clot formation who tested positive for COVID-19 after a standard periodontal surgery. Previously, two periodontal surgeries proceeded without any complications and were considered standard. On day one after the third periodontal surgery the patient had no complaints. On day two the patient reported excess bleeding in the oral cavity from the operated area simultaneously with fever and loss of taste. On day three the patient was seen in our clinic; general malaise symptoms and bleeding tendency had started to decline and the patient received a COVID-19 PCR test. At day four the test resulted positive, and she reported no further complaints of intraoral bleeding. Six months later the taste of the patient was still distorted. For this patient with free medical anamnesis, we suggest that the patient had increased plasma levels of tissue plasminogen activator during the crucial postoperative period due to an acute COVID-19 infection. This led to increased plasmin levels with a hyper-fibrinolytic state as a consequence.

The role of respiratory microbiota in the protection against viral diseases: respiratory commensal bacteria as next-generation probiotics for COVID-19.

On March 11, 2020, the World Health Organization declared a pandemic of coronavirus infectious disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and imposed the biggest public health challenge for our civilization, with unforeseen impacts in the subsequent years. Similar to other respiratory infections, COVID-19 is associated with significant changes in the composition of the upper respiratory tract microbiome. Studies have pointed to a significant reduction of diversity and richness of the respiratory microbiota in COVID-19 patients. Furthermore, it has been suggested that Prevotella, Staphylococcus, and Streptococcus are associated with severe COVID-19 cases, while Dolosigranulum and Corynebacterium are significantly more abundant in asymptomatic subjects or with mild disease. These results have stimulated the search for new microorganisms from the respiratory microbiota with probiotic properties that could alleviate symptoms and even help in the fight against COVID-19. To date, the potential positive effects of probiotics in the context of SARS-CoV-2 infection and COVID-19 pandemics have been extrapolated from studies carried out with other viral pathogens, such as influenza virus and respiratory syncytial virus. However, scientific evidence has started to emerge demonstrating the capacity of immunomodulatory bacteria to beneficially influence the resistance against SARS-CoV-2 infection. Here we review the scientific knowledge regarding the role of the respiratory microbiota in viral infections in general and in the infection caused by SARS-CoV-2 in particular. In addition, the scientific work that supports the use of immunomodulatory probiotic microorganisms as beneficial tools to reduce the severity of respiratory viral infections is also reviewed. In particular, our recent studies that evaluated the role of immunomodulatory Dolosigranulum pigrum strains in the context of SARS-CoV-2 infection are highlighted.

Effective recommendations towards healthy routines to preserve mental health during the COVID-19 pandemic.

OBJECTIVE: To assess the adherence to a set of evidence-based recommendations to support mental health during the coronavirus disease 2019 (COVID-19) pandemic and its association with depressive and anxiety symptoms. METHODS: A team of health workers and researchers prepared the recommendations, formatted into three volumes (1: COVID-19 prevention; 2: Healthy habits; 3: Biological clock and sleep). Participants were randomized to receive only Volume 1 (control), Volumes 1 and 2, Volumes 1 and 3, or all volumes. We used a convenience sample of Portuguese-speaking participants over age 18 years. An online survey consisting of sociodemographic and behavioral questionnaires and mental health instruments (Patient Health Questionnaire-9 [PHQ-9] and Generalized Anxiety Disorder-7 [GAD-7]) was administered. At 14 and 28 days later, participants were invited to complete follow-up surveys, which also included questions regarding adherence to the recommendations. A total of 409 participants completed the study - mostly young adult women holding university degrees. RESULTS: The set of recommendations contained in Volumes 2 and 3 was effective in protecting mental health, as suggested by significant associations of adherence with PHQ-9 and GAD-7 scores (reflecting anxiety and depression symptoms, respectively). CONCLUSION: The recommendations developed in this study could be useful to prevent negative mental health effects in the context of the pandemic and beyond.

A MEMS-CMOS Microsystem for Contact-Less Temperature Measurements

This paper presents a microsystem suitable for contact-less human body temperature measurements, as well as for presence, motion and proximity detection. It consists of a 130-nm CMOS-SOI MEMS (Micro-Electro Mechanical System) thermal sensor, referred to as ``TMOS'', and its 130-nm CMOS interface circuit. The TMOS, based on a micromachined transistor, being an active device, features advantages in terms of internal gain: with optimal biasing, indeed, the TMOS achieves 274-mu V/degrees C input-referred sensitivity at 3-cm distance and 50.33 degrees field-of-view (FOV), outperforming thermopile detectors. The sensor and the interface circuit, featuring a chopper-stabilized-based analog readout with a 12-bit SAR ADC (Successive Approximation Register Analog-to-Digital Converter), were mounted in the same package and extensively measured: the microsystem achieves repeatability and +/- 0.17 degrees C precision, thus satisfying the requirements for contact-less human body temperature measurements;furthermore, its performance as presence, motion and proximity detector was also verified.

Learning Sentence-to-Hashtags Semantic Mapping for Hashtag Recommendation on Microblogs

The growing use of microblogging platforms is generating a huge amount of posts that need effective methods to be classified and searched. In Twitter and other social media platforms, hashtags are exploited by users to facilitate the search, categorization, and spread of posts. Choosing the appropriate hashtags for a post is not always easy for users, and therefore posts are often published without hashtags or with hashtags not well defined. To deal with this issue, we propose a new model, called HASHET (HAshtag recommendation using Sentence-to-Hashtag Embedding Translation), aimed at suggesting a relevant set of hashtags for a given post. HASHET is based on two independent latent spaces for embedding the text of a post and the hashtags it contains. A mapping process based on a multi-layer perceptron is then used for learning a translation from the semantic features of the text to the latent representation of its hashtags. We evaluated the effectiveness of two language representation models for sentence embedding and tested different search strategies for semantic expansion, finding out that the combined use of BERT (Bidirectional Encoder Representation from Transformer) and a global expansion strategy leads to the best recommendation results. HASHET has been evaluated on two real-world case studies related to the 2016 United States presidential election and COVID-19 pandemic. The results reveal the effectiveness of HASHET in predicting one or more correct hashtags, with an average F-score up to 0.82 and a recommendation hit-rate up to 0.92. Our approach has been compared to the most relevant techniques used in the literature (generative models, unsupervised models, and attention-based supervised models) by achieving up to 15% improvement in F-score for the hashtag recommendation task and 9% for the topic discovery task. © 2021 Association for Computing Machinery.

Immunobiotic Lactobacilli Improve Resistance of Respiratory Epithelial Cells to SARS-CoV-2 Infection.

Previously, we reported that immunomodulatory lactobacilli, nasally administered, beneficially regulated the lung antiviral innate immune response induced by Toll-like receptor 3 (TLR3) activation and improved protection against the respiratory pathogens, influenza virus and respiratory syncytial virus in mice. Here, we assessed the immunomodulatory effects of viable and non-viable Lactiplantibacillus plantarum strains in human respiratory epithelial cells (Calu-3 cells) and the capacity of these immunobiotic lactobacilli to reduce their susceptibility to the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Immunobiotic L. plantarum MPL16 and CRL1506 differentially modulated IFN-ß, IL-6, CXCL8, CCL5 and CXCL10 production and IFNAR2, DDX58, Mx1 and OAS1 expression in Calu-3 cells stimulated with the TLR3 agonist poly(I:C). Furthermore, the MPL16 and CRL1506 strains increased the resistance of Calu-3 cells to the challenge with SARS-CoV-2. L. plantarum MPL16 induced these beneficial effects more efficiently than the CRL1506 strain. Of note, neither non-viable MPL16 and CRL1506 strains nor the non-immunomodulatory strains L. plantarum CRL1905 and MPL18 could modify the resistance of Calu-3 cells to SARS-CoV-2 infection or the immune response to poly(I:C) challenge. To date, the potential beneficial effects of immunomodulatory probiotics on SARS-CoV-2 infection and COVID-19 outcome have been extrapolated from studies carried out in the context of other viral pathogens. To the best of our knowledge, this is the first demonstration of the ability of immunomodulatory lactobacilli to positively influence the replication of the new coronavirus. Further mechanistic studies and in vivo experiments in animal models of SARS-CoV-2 infection are necessary to identify specific strains of beneficial immunobiotic lactobacilli like L. plantarum MPL16 or CRL1506 for the prevention or treatment of the COVID-19.

COVID-19 outbreak perception in Italian dentists

The aim of this study is an evaluation of the Italian dentists' knowledge regarding COVID-19 and their perception of the risks associated with COVID-19, their attitude in resuming their activities, and how they judge the institutional intervention on a health and economic basis.

A Brief Research Report on the Perception and Satisfaction of Italian University Students With Disabilities and Specific Learning Disabilities at the Emergency Remote Teaching During the COVID-19 Lockdown

Introduction: The COVID-19 pandemic has inevitably transformed face-to-face teaching to remote teaching (e-learning or blended) which has had psychological and social impacts on the mental health of university students. Object: In this study, we surveyed university students with disabilities and specific learning disabilities (SLDs) on their perceptions of and satisfaction with emergency remote teaching (ERT) during the lockdown phase (March–April 2020) and following restrictions due to the COVID-19 pandemic. We compared the responses of students with disabilities and SLDs with those of normotypical students. Methodology: A questionnaire was completed remotely: five items on the ERT were designed as ad hoc questions and five items were taken from the Short Form 12 Health Survey (SF-12) to evaluate physical and mental self-perceived health. There was a total of 163 students surveyed, 67 students with disabilities and/or SLDs and 96 normotypical students. Results and Conclusion: Students with disabilities and SLDs were more satisfied with remote teaching than the normotypical students. In fact, only 22% of the students with disabilities or SLDs indicated that they were dissatisfied with the teaching method used due to difficulties encountered, including those related to a weak technological infrastructure. We found that among all the students, important social and emotional aspects emerged as a consequence of the absence of interactions and relationships with both faculty and peer groups. © Copyright © 2021 Carpinelli, Bruno and Savarese.

Ongoing COVID-19 vaccination in Italy. Online survey of gender- and age-related side effects

Background: Evidences suggest that gender may influence the response to various vaccines in terms of immune response and side effects. Whether similar differences also occur with COVID-19 vaccine, is still uncertain. Materials and Methods: In March 2021, we advertised a short anonymous questionnaire (Google forms) to medical doctors, nurses, postgraduates, students and general public, consisting of 30 questions exploring 16 possible side effects (local pain or hardness, swelling, redness, allergic reaction, tiredness, headache, sleep disorders, myalgia, fever, enlarged lymph nodes, irritability, diarrhea, urticaria, vomiting, anaphylaxis). We recorded side effects after 1st dose, and within one week after 2nd dose. Data were analyzed according to gender and seven age groups. Results: We received 1,034 questionnaires from all over Italy (369 males, 665 females, age range 20-83 years). Injected vaccines were Pfizer-BioNTech (96.9%), Astra-Zeneca (2.4%), Moderna (0.7%). Major adverse events were absent. Minor adverse events occurred with both 1st dose (76.0%) and 2nd dose (78.0%) and were invariably higher in females than in males (1st dose: 79.4% vs 69.9% p = 0.0006;2nd dose: 81.8% vs 70.7%, p = 0.00004). The significant cluster of adverse events were local pain, redness, hardness at the injection site, fever, sleep disturbances, headache, lymph nodes enlargement following both doses (0.00001 < p < 0.02). Effects disappeared within 48hrs in 80% of cases (range 1-7 days). The gender difference was confirmed in the age class 30-39 after 1st dose (85.8% vs 70%, in females and males, respectively p = 0.03), and in the age classes 30-39 (84.6% vs 75.5%, in females and males, respectively p = 0.03) and 40-49 (74.8% vs 57.9%, in females and males, respectively p = 0.02) after 2nd dose. Fever tended to be more frequent in females after the 1st dose (6.5% vs 3.8%) and became significantly higher after the 2nd dose (32.9% vs 17.3%, p = 0.00001). After 50 years of age, the rate of all the recorded adverse events was similar between genders. Conclusions: COVID-19 vaccines generate frequent, although mild side effects with a gender (female) prevalence, especially in the age range 30-49 years. The gender difference disappears after 50 years of age, thus pointing to possible involvement of sex hormones and attenuated immune response.

Dolosigranulum pigrum Modulates Immunity against SARS-CoV-2 in Respiratory Epithelial Cells.

In a previous work, we demonstrated that nasally administered Dolosigranulum pigrum 040417 beneficially modulated the respiratory innate immune response triggered by the activation of Toll-like receptor 3 (TLR3) and improved protection against Respiratory Syncytial Virus (RSV) in mice. In this work, we aimed to evaluate the immunomodulatory effects of D. pigrum 040417 in human respiratory epithelial cells and the potential ability of this immunobiotic bacterium to increase the protection against Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The respiratory commensal bacterium D. pigrum 040417 differentially modulated the production of IFN-ß, IL-6, CXCL8, CCL5 and CXCL10 in the culture supernatants of Calu-3 cells stimulated with poly(I:C) or challenged with SARS-CoV-2. The differential cytokine profile induced by the 040417 strain was associated with a significant reduction in viral replication and cellular damage after coronavirus infection. Of note, D. pigrum 030918 was not able to modify the resistance of Calu-3 cells to SARS-CoV-2 infection, indicating a strain-specific immunomodulatory effect for respiratory commensal bacteria. The findings of this work improve our understanding of the immunological mechanisms involved in the modulation of respiratory immunity induced by respiratory commensal bacteria, by demonstrating their specific effect on respiratory epithelial cells. In addition, the results suggest that particular strains such as D. pigrum 040417 could be used as a promising alternative for combating SARS-CoV-2 and reducing the severity of COVID-19.

Nasopharyngeal Microbial Communities of Patients Infected With SARS-CoV-2 That Developed COVID-19.

BACKGROUND: SARS-CoV-2 is an RNA virus causing COVID-19. The clinical characteristics and epidemiology of COVID-19 have been extensively investigated, however, only one study so far focused on the patient's nasopharynx microbiota. In this study we investigated the nasopharynx microbial community of patients that developed different severity levels of COVID-19. We performed 16S ribosomal DNA sequencing from nasopharyngeal swab samples obtained from SARS-CoV-2 positive (56) and negative (18) patients in the province of Alicante (Spain) in their first visit to the hospital. Positive SARS-CoV-2 patients were observed and later categorized in mild (symptomatic without hospitalization), moderate (hospitalization), and severe (admission to ICU). We compared the microbiota diversity and OTU composition among severity groups and built bacterial co-abundance networks for each group. RESULTS: Statistical analysis indicated differences in the nasopharyngeal microbiome of COVID19 patients. 62 OTUs were found exclusively in SARS-CoV-2 positive patients, mostly classified as members of the phylum Bacteroidota (18) and Firmicutes (25). OTUs classified as Prevotella were found to be significantly more abundant in patients that developed more severe COVID-19. Furthermore, co-abundance analysis indicated a loss of network complexity among samples from patients that later developed more severe symptoms. CONCLUSION: Our study shows that the nasopharyngeal microbiome of COVID-19 patients showed differences in the composition of specific OTUs and complexity of co-abundance networks. Taxa with differential abundances among groups could serve as biomarkers for COVID-19 severity. Nevertheless, further studies with larger sample sizes should be conducted to validate these results.

Peculiar clinical presentation of COVID-19 and predictors of mortality in the elderly: A multicentre retrospective cohort study.

BACKGROUND: The spectrum of COVID-19 clinical manifestations is not yet known. In the elderly, mortality and extrapulmonary involvement appears more frequent than expected. METHODS: A multicentre-retrospective-case-series study of COVID-19 patients, aged ≥65 years, hospitalised between March 1 and June 15, 2020. Patients were classified at admission into 3 groups based on their Clinical Frailty Scale (CFS) score: 1-3 (group A), 4-6 (group B) and 7-9 (group C). RESULTS: Of the 206 patients in the study, 60 (29%) were assigned to group A, 60 (29%) to B and 86 (42%) to C. Significantly more frequent in group C than in B or A were: mental confusion (respectively 65%, 33%, 7%; P < 0.001), kidney failure (39%, 22%, 20%; P = 0.019), dehydration syndrome (55%, 27%, 13%; P < 0.001), electrolyte imbalance (54%, 32%, 25%; P = 0.001), and diabetic decompensation (22%, 12%, 7%; P = 0.026). Crude mortality was 27%. By multivariate logistic regression model independent predictors of death were male sex (adjusted odds ratio (aOR) = 2.87,95%CI = 1.15-7.18), CFS 7-9 (aOR = 9.97,95%CI = 1.82-52.99), dehydration at admission (aOR = 4.27,95%CI = 1.72-10.57) and non-invasive/invasive ventilation (aOR = 4.88,95%CI = 1.94-12.26). CONCLUSIONS: Elderly patients with a high CFS showed frequent extrapulmonary signs at admission, even in the absence of lung involvement. These findings, along with a high CFS, predicted a significant risk of mortality.

Tocilizumab and corticosteroids for covid-19 treatment in elderly patients

Background. The mortality rate for coronavirus disease-19 (COVID-19) increases with age. Some anti-inflammatory drugs such as tocilizumab or steroids have been proposed for the treatment of severe disease;however, few data are available in the elderly. Methods. A retrospective case-series of patients hospitalized between March 1st and June 15th, 2020 with confirmed COVID-19 by RT-PCR testing on throat/nasopharyngeal swabs and age ≥ 65 years was analysed. Patients were retrospectively divided into three groups according to the chosen treatment [standard of care (SOC), tocilizumab or corticosteroids] and patient characteristics and occurrence of adverse events were compared among groups. Results. Overall, 206 patients were included, 148 treated with standard of care, 42 with steroids and 16 with tocilizumab. Patients treated with steroids or Tocilizumab presented more frequently with fever (p =.003), dyspnea (p <.001), bilateral opacities/infiltrates at chest X-ray (p =.026) or CT-scan (p =.020), and more frequently required non-invasive/invasive ventilation (p <.001). Crude mortality was 27%, without differences among groups (p =.074). No specific adverse events were observed during/after the administration of steroids or tocilizumab;however, a trend towards an increased risk of secondary infections was described compared to SOC (p =.097). At multivariate logistic regression, only tocilizumab administration was an independent predictor of secondary infections (aOR = 6.72, 95% CI = 1.43-31.39, p =.015). Conclusions. Tocilizumab and corticosteroid could have a possible role for severe form of pneumonia in course of COVID-19 also in elderly patients, even if great attention to the monitoring of infectious complications should be paid in this special population.