Increased prevalence of autoimmune thyroid disease after COVID-19: A single-center, prospective study.

Introduction: Thyroid dysfunctions associated with SARS-CoV-2 acute infection have been extensively described since the beginning of COVID-19 pandemics. Conversely, few data are available on the occurrence of thyroid autoimmunity after COVID-19 resolution. We assessed the prevalence of autoimmune thyroid disease (ATD) and thyroid dysfunctions in COVID-19 survivors three months after hospital admission. Design and methods: Single-center, prospective, observational, cohort study performed at ASST Papa Giovanni XXIII Hospital, Bergamo, Italy. 599 COVID-19 survivors were prospectively evaluated for thyroid function and autoimmunity thyroperoxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb). When a positive antibody concentration was detected, thyroid ultrasound was performed. Multiple logistic regression model was used to estimate the association between autoimmunity and demographic characteristics, respiratory support, and comorbidities. Autoimmunity results were compared to a cohort of 498 controls referred to our Institution for non-thyroid diseases before the pandemic onset. A sensitivity analysis comparing 330 COVID-19 patients with 330 age and sex-matched controls was performed. Results: Univariate and multivariate analysis found that female sex was positively associated (OR 2.01, SE 0.48, p = 0.003), and type 2 diabetes (T2DM) was negatively associated (OR 0.36, SE 0.16, p = 0.025) with thyroid autoimmunity; hospitalization, ICU admission, respiratory support, or COVID-19 treatment were not associated with thyroid autoimmunity (p > 0.05). TPOAb prevalence was greater in COVID-19 survivors than in controls: 15.7% vs 7.7%, p = 0.002. Ultrasonographic features of thyroiditis were present in 94.9% of the evaluated patients with positive antibodies. TSH was within the normal range in 95% of patients. Conclusions: Autoimmune thyroid disease prevalence in COVID-19 survivors was doubled as compared to age and sex-matched controls, suggesting a role of SARS-CoV-2 in eliciting thyroid autoimmunity.

SARS-CoV-2 infection clinical picture and outcomes in adults living with HIV: a cohort analysis.

Existing evidence about HIV and SARS-CoV-2 co-infection has, so far, yield conflicting results. Methods: This is a cohort, single center, clinical study aimed at identifying possible characteristics of PLWH that could correlate with the risk of acquiring SARS-CoV-2 and would influence the outcome. 155 cases of SARS-CoV-2 infection were compared with 307 PLWH who tested negative. No variable was associated with an increased risk of infection. SARS-CoV-2 PLWH were completely asymptomatic in 20.6% of cases. Factors associated with severe COVID-19 were age (P=0.001), diabetes (P=0.009) hypertension (P=0.004), cardiovascular disease (P=0.001) or an increasing number of chronic co-morbidities (P=0.002); only the first two variables retained statistical significance in a multivariable model. Only older age and a lower CD4 count were statistically associated with death in the multivariate model. Sixteen PLWH not included in the analysis were infected by SARS-Cov-2 after vaccination. In 4 cases the infection was completely asymptomatic, while in the remaining 12 cases the infection was mild and resembled a flu-like syndrome. Conclusions: No baseline characteristic defines patients at greater risk of SARS-CoV-2 infection. Older age and the presence of multi-comorbidities are risk factors for a severe clinical course. Lower CD4 counts correlate with a fatal outcome.

One-year mortality in COVID-19 is associated with patients' comorbidities rather than pneumonia severity.

BACKGROUND: In patients with pneumonia or acute respiratory distress syndrome who survived hospitalization, one-year mortality can affect up to one third of discharged patients. Therefore, significant long-term mortality after COVID-19 respiratory failure could be expected. The primary outcome of the present study was one-year all-cause mortality in hospitalized COVID-19 patients. METHODS: Observational study of COVID-19 patients hospitalized at Papa Giovanni XXIII Hospital (Bergamo, Italy), during the first pandemic wave. RESULTS: A total of 1326 COVID-19 patients were hospitalized. Overall one-year mortality was 33.6% (N 446/1326), with the majority of deaths occurring during hospitalization (N=412, 92.4%). Thirty-four patients amongst the 914 discharged (3.7%) subsequentely died within one year. A third of these patients died for advanced cancer, while death without a cause other than COVID-19 was uncommon (8.8% of the overall post-discharge mortality). In-hospital late mortality (i.e. after 28 days of admission) interested a population with a lower age, and fewer comorbidities, more frequentely admitted in ICU. Independent predictors of post-discharge mortality were age over 65 years (HR 3.19; 95% CI 1.28-7.96, p-value=0.013), presence of chronic obstructive pulmonary disease (COPD) (HR 2.52; 95% CI 1.09-5.83, p-value=0.031) or proxy of cardiovascular disease (HR 4.93; 95% CI 1.45-16.75, p-value=0.010), and presence of active cancer (HR 3.64; 95% CI 1.50-8.84, p-value=0.004), but not pneumonia severity. CONCLUSIONS: One-year post-discharge mortality depends on underlying patients' comorbidities rather than COVID-19 pneumonia severity per se. Awareness among physicians of predictors of post-discharge mortality might be helpful in structuring a follow-up program for discharged patients.

Frequency, characteristics, and outcome of patients with COVID-19 pneumonia and "silent hypoxemia" at admission: a severity-matched analysis.

BACKGROUND: An aspect of COVID-19 baffling physicians is the presentation of patients with acute respiratory failure, but normal mental faculties and no perception of dyspnea (i.e. "silent hypoxemia"). The aim of this study was to investigate the frequency, characteristics, and outcome of COVID-19 patients with silent hypoxemic status and comparing them with a symptomatic severity-matched group. METHODS: This is a retrospective monocentric observational study involving all patients with PCR confirmed SARS-CoV-2 pneumonia, admitted at Papa Giovanni XXIII Hospital, Bergamo (Italy) from Emergency Department due to acute respiratory failure, during the first Italian pandemic peak (February-April 2020). RESULTS: Overall 28-day mortality in 1,316 patients was 26.9%. Patients who did not report dyspnea at admission (N 469, 35.6%) had a lower 28-day mortality (22.6 vs. 29.3%, p=0.009). The severity matching analysis (i.e. PaO2/FiO2 and imaging) led to the identification of two groups of 254 patients that did not differ for sex prevalence, age, BMI, smoking history, comorbidities, and PaCO2 at admission. The use of CPAP during the first 24 hours, such as the need of endotracheal intubation (ETI) during the overall admission were significantly lower in matched patients with silent hypoxemia, whereas 28-day mortality resulted similar (p=0.21). CONCLUSIONS: Lack of dyspnea is common in patients suffering from severe COVID-19 pneumonia leading to respiratory failure, since up to a third of them could be asymptomatic on admission. Dyspnea per se correlates with pneumonia severity, and prognosis. However, dyspnea loses its predictive relevance once other findings to evaluate pneumonia severity are available such as PaO2/FiO2 and imaging. Silent hypoxemic patients are less likely to receive CPAP during the first 24 hours and ETI during the hospitalization, in spite of a comparable mortality to the dyspneic ones.

COVID-19 vaccine Mandates: An Australian attitudinal study.

BACKGROUND: The rollout of vaccines against COVID-19 is prompting governments and the private sector to adopt mandates. However, there has been little conceptual analysis of the types of mandates available, nor empirical analysis of how the public thinks about different mandates and why. Our conceptual study examines available instruments, how they have been implemented pre-COVID, and their use for COVID-19 globally. Then, our qualitative study reports the acceptability of such measures in Western Australia, which has experienced very limited community transmission, posing an interesting scenario for vaccine acceptance and acceptability of measures to enforce it. METHOD: Our conceptual study developed categories of mandates from extant work, news reports, and legislative interventions globally. Then, our empirical study asked 44 West Australians about their attitudes towards potential mandatory policies, with data analysed using NVivo 12. RESULTS: Our novel studies contribute richness and depth to emerging literature on the types and varying acceptability of vaccine requirements. Participants demonstrated tensions and confusion about whether instruments were incentives or punishments, and many supported strong consequences for non-vaccination even if they ostensibly opposed mandates. Those attached to restrictions for disease prevention were most popular. There were similar degrees of support for mandates imposed by employers or businesses, with participants showing little concern for potential issues of accountability linked to public health decisions delegated to the private sector. Participants mostly supported tightly regulated medical exemptions granted by specialists, with little interest in religious or personal belief exemptions. CONCLUSION: Our participants are used to being governed by vaccine mandates, and now by rigorous lockdown and travel restrictions that have ensured limited local COVID-19 disease and transmission. These factors appear influential in their general openness to COVID-19 vaccine mandates, especially when linked explicitly to the prevention of disease in high-risk settings.

Consolidating a research agenda for vaccine mandates.

A workshop on mandatory vaccination was pitched to the World Public Health Congress in 2019 and the resultant special issue was pitched to Vaccine in 2020. During this project, the COVID-19 pandemic pushed vaccine policy to the forefront of global public health policy, and the imposition of vaccine mandates prompted a new wave of scholarship in the field. This introductory article employs the heuristic of Lasswell's (1956) policy cycle to synthesise the findings of the articles in the special issue. It considers the temporal lifetime of mandates and highlights findings regarding: the emergence of mandates as a policy option, public support and policy instrument design, what matters in the implementation of mandates, and what we can learn from evaluating them. The second half of the paper categorizes the included papers in terms of what aspects of mandates they study and the methods they employ to do so, in order to formulate a guide for future researchers of vaccine mandates. Scholars study either speculative or existing mandates - research can address several stages of the policy cycle or just one of them, ranging from attitudinal research to implementation studies and impact studies. Historical and contextual studies that take deep dives into a particular mandate are a much needed resource for studying emerging mandates, too, and scoping and framework- building work will undoubtedly be valuable in understanding and appreciating the wealth of knowledge production in this growing field. This special issue can serve as a roadmap for a consolidation of this interdisciplinary research agenda, and provide a helpful resource for decisionmakers at this historical juncture.

What is the impact of SARS-CoV-2 pandemic on antimicrobial stewardship programs (ASPs)? The results of a survey among a regional network of infectious disease centres.

Discontinuation of antimicrobial stewardship programs (ASPs) and increased antibiotic use were described during SARS-CoV-2 pandemic. In order to measure COVID-19 impact on ASPs in a setting of high multidrug resistance organisms (MDRO) prevalence, a qualitative survey was designed. In July 2021, eighteen ID Units were asked to answer a questionnaire about their hospital characteristics, ASPs implementation status before the pandemic and impact of SARS-CoV-2 pandemic on ASPs after the 1st and 2nd pandemic waves in Italy. Nine ID centres (50%) reported a reduction of ASPs and in 7 cases (38.9%) these were suspended. After the early pandemic waves, the proportion of centres that restarted their ASPs was higher among the ID centres where antimicrobial stewardship was formally identified as a priority objective (9/11, 82%, vs 2/7, 28%). SARS-CoV-2 pandemic had a severe impact in ASPs in a region highly affected by COVID-19 and antimicrobial resistance but weaknesses related to the pre-existent ASPs might have played a role.

Population Pharmacokinetic and Pharmacodynamic Analysis of Dalbavancin for Long-Term Treatment of Subacute and/or Chronic Infectious Diseases: The Major Role of Therapeutic Drug Monitoring.

A population pharmacokinetic analysis of dalbavancin was conducted in patients with different infection sites. Non-linear mixed effect modeling was used for pharmacokinetic analysis and covariate evaluation. Monte Carlo simulations assessed the probability of target attainment (PTA) of total dalbavancin concentration ≥ 8.04 mg/L over time (associated with ≥90% probability of optimal pharmacodynamic target attainment of fAUC24h/MIC > 111.1 against S. aureus) associated with a single or double dosage, one week apart, of 1000 or 1500 mg in patients with different classes of renal function. Sixty-nine patients with 289 concentrations were included. Most of them (53/69, 76.8%) had bone and joint infections. A two-compartment model adequately fitted dalbavancin concentration-time data. Creatinine clearance (CLCR) was the only covariate associated with dalbavancin clearance. Monte Carlo simulations showed that, in patients with severe renal dysfunction, the 1000 mg single or double one week apart dosage may ensure optimal PTAs of 2 and 5 weeks, respectively. In patients with preserved renal function, the 1500 mg single or double one-week apart dosage may ensure optimal PTAs of 2 and 4 to 6 weeks, respectively. Therapeutic drug monitoring should be considered mandatory for managing inter-individual variability and for supporting clinicians in long-term treatments of subacute and chronic infections.

Fibrinolytic Proteins and Factor XIII as Predictors of Thrombotic and Hemorrhagic Complications in Hospitalized COVID-19 Patients.

Introduction: In a prospective cohort of hospitalized COVID-19 patients, an extensive characterization of hemostatic alterations by both global and specific assays was performed to clarify mechanisms underlying the coagulopathy and identify predictive factors for thrombotic and hemorrhagic events during hospitalization. Materials and Methods: Intensive care unit (ICU; n = 46) and non-ICU (n = 55) patients were enrolled, and the occurrence of thrombotic and hemorrhagic events was prospectively monitored. At study inclusion, thromboelastometry together with the measurement of specific coagulation proteins and hypercoagulation markers was performed. Results: Patients (median age 67 years) showed significantly shorter clot formation time together with greater maximum clot firmness by thromboelastometry, increased levels of F1 + 2 and D-dimer, as biomarkers of hypercoagulability, and of procoagulant factors V, VIII, IX, XI, and fibrinogen, while FXIII was significantly reduced. The concentration of fibrinolytic proteins, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were elevated in the overall cohort of patients. Many of these hemostatic alterations were significantly greater in ICU compared to non-ICU subjects and, furthermore, they were associated with inflammatory biomarker elevation [i.e., interleukin 6 (IL-6), C-reactive protein (CRP), neutrophil to lymphocyte ratio (NLR), and procalcitonin]. After enrollment, 7 thrombosis and 14 major bleedings occurred. Analysis of clinical and biological data identified increased t-PA, PAI-1, and NLR values as independent predictive factors for thrombosis, while lower FXIII levels were associated with bleeding. Conclusion: This study demonstrates alterations in all different hemostatic compartments analyzed, particularly in severe COVID-19 conditions, that strongly correlated with the inflammatory status. A potential role of fibrinolytic proteins together with NLR and of FXIII as predictors of thrombotic and hemorrhagic complications, respectively, is highlighted.

The changing pattern of bacterial and fungal respiratory isolates in patients with and without COVID-19 admitted to intensive care unit.

OBJECTIVES: Severe acute respiratory syndrome 2 (SARS-CoV-2) pandemic has had a heavy impact on national health system, especially in the first wave. That impact hit principally the intensive care units (ICUs). The large number of patients requiring hospitalization in ICUs lead to a complete upheaval of intensive wards. The increase in bed, the fewer number of nurses per patient, the constant use of personal protective equipment, the new antimicrobial surveillance protocols could have had deeply effects on microbiological flora of these wards. Moreover, the overconsumption of antimicrobial therapy in COVID-19 patients, like several studies report, could have impact of this aspect. Aim of this study is to evaluate the changing pattern of microbiological respiratory isolates during and before COVID-19 pandemic in a tertiary hospital ICUs. METHODS: A retrospective, observational study was conducted in ICUs of "ASST Papa Giovanni XXIII", a large tertiary referral hospital in Northern Italy. We have retrospectively collected the microbiological data from bronchoalveolar lavage (BAL) and tracheal aspirate (TA) of patients with COVID-19, hospitalized in ICUs from 22nd February 2020 to 31st May 2020 (Period 1), and without COVID-19, from 22nd February 2019 to 31st May 2019 (Period 2). We compared the prevalence and the antibiotic profile of bacterial and fungal species in the two time periods. RESULTS: The prevalence of Pseudomonas spp. shows a statistically significant increase from patients without COVID-19 compared to COVID-19 positive as well as the prevalence of Enterococcus spp. On the contrary, the prevalence of Gram negative non fermenting bacteria (GN-NFB), Haemophilus influenzae and Streptococcus pneumoniae showed a significant reduction between two periods. There was a statistically significant increase in resistance of Pseudomonas spp. to carbapenems and piperacillin/tazobactam and Enterobacterales spp. for piperacillin/tazobactam, in COVID-19 positive patients compared to patients without COVID-19. We did not observe significant changing in fungal respiratory isolates. CONCLUSIONS: A changing pattern in prevalence and resistance profiles of bacterial and fungal species was observed during COVID-19 pandemic.

Preparing for future waves and pandemics: a global hospital survey on infection control measures and infection rates in COVID-19.

A survey of hospitals on three continents was performed to assess their infection control preparedness and measures, and their infection rate in hospital health care workers during the COVID-19 pandemic. All surveyed hospitals used similar PPE but differences in preparedness, PPE shortages, and infection rates were reported.

Endothelium Activation Markers in Severe Hospitalized COVID-19 Patients: Role in Mortality Risk Prediction.

Introduction Endothelial damage and hypercoagulability are major players behind the hemostatic derangement of SARS-CoV-2 infection. Aim In this prospective study we assessed endothelial and inflammatory biomarkers in a cohort of COVID-19 patients, aiming to identify predictive factors of in-hospital mortality. Methods COVID-19 patients hospitalized in intensive care (ICU) and non-ICU units at 2 Bergamo (Italy) hospitals from March 23 to May 30, 2020, were enrolled. Markers of endothelium activation including von-Willebrand factor (vWF), soluble thrombomodulin (sTM), and fibrinolytic proteins (t-PA and PAI-1) were measured. Additionally, D-dimer, Fibrinogen, FVIII, nucleosomes, C reactive protein (CRP) and procalcitonin were assessed. Results Sixty-three (45 ICU, and 18 non-ICU) patients, with a median age of 62 years were analyzed. Increased plasma levels of D-dimer, FVIII, fibrinogen, nucleosomes, CRP, and procalcitonin were observed in the whole cohort. Extremely elevated vWF levels characterized all patients (highest values in ICU-subjects). After a median time of 30 days, death occurred in 13 (21%) patients. By multivariable analysis, vWF-activity, neutrophil-count and PaO2/FiO2 were significantly associated with death. Using these variables, a linear score with 3-risk groups was generated that provided a cumulative incidence of death of 0% in the low-, 32% in the intermediate-, and 78% in the high-risk group. Conclusions COVID-19-induced hemostatic abnormalities are exacerbated by the severity of the disease and strongly correlate with the inflammatory status, underlying the link between coagulation, endothelial activation, and inflammation. Our study provides evidence for a role of vWF, together with neutrophils and PaO2/FiO2, as a significant predictor of in-hospital mortality by SARSCoV-2 infection.

Coronavax: preparing community and government for COVID-19 vaccination: a research protocol for a mixed methods social research project.

INTRODUCTION: Ahead of the implementation of a COVID-19 vaccination programme, the interdisciplinary Coronavax research team developed a multicomponent mixed methods project to support successful roll-out of the COVID-19 vaccine in Western Australia. This project seeks to analyse community attitudes about COVID-19 vaccination, vaccine access and information needs. We also study how government incorporates research findings into the vaccination programme. METHODS AND ANALYSIS: The Coronavax protocol employs an analytical social media study, and a qualitative study using in-depth interviews with purposively selected community groups. Participant groups currently include healthcare workers, aged care workers, first responders, adults aged 65+ years, adults aged 30-64 years, young adults aged 18-29 years, education workers, parents/guardians of infants and young children (<5 years), parents/guardians of children aged 5-18 years with comorbidities and parents/guardians who are hesitant about routine childhood vaccines. The project also includes two studies that track how Australian state and Commonwealth (federal) governments use the study findings. These are functional dialogues (translation and discussion exercises that are recorded and analysed) and evidence mapping of networks within government (which track how study findings are used). ETHICS AND DISSEMINATION: Ethics approval has been granted by the Child and Adolescent Health Service Human Research Ethics Committee (HREC) and the University of Western Australia HREC. Study findings will be disseminated by a series of journal articles, reports to funders and stakeholders, and invited and peer-reviewed presentations.

Inaction, under-reaction action and incapacity: communication breakdown in Italy's vaccination governance.

This article explores why governments do not respond to public compliance problems in a timely manner with appropriate instruments, and the consequences of their failure to do so. Utilising a case study of Italian vaccination policy, the article considers counterfactuals and the challenges of governing health policy in an age of disinformation. It counterposes two methods of governing vaccination compliance: discipline, which uses public institutions to inculcate the population with favourable attitudes and practices, and modulation, which uses access to public institutions as a form of control. The Italian government ineffectively employed discipline for a number of years. Epistemological and organisational constraints stymied its efforts to tackle a significant childhood vaccination compliance problem. With a loss of control over the information environment, vaccinations were not served well by exogenous crises, the sensationalism of the news cycle and online misinformation. Hampered by austerity, lack of capacity and epistemic shortcomings, the Italian government did not protect the public legitimacy of the vaccination programme. Instead of employing communications to reassure a hesitant population, they focused on systemic and delivery issues, until it was too late to do anything except make vaccinations mandatory (using modulation). The apparent short-term success of this measure in generating population compliance does not foreclose the need for ongoing governance of vaccine confidence through effective discipline. This is evident for the COVID-19 vaccination campaign, with many Italians still indicating that they would not accept a vaccine despite the devastation that the disease has wrought throughout their country.