Psychological Distress of Healthcare Workers in 4 Hospitals Compared to General Population During the First Italian Wave of COVID-19 Pandemic.

COVID-19 caused important consequences on public health, economy, physical, and mental health of people. The aim of this study was to evaluate the impact of COVID-19 on frontline workers, comparing them with their colleagues who had no contact with the patients and with the general population, by administering an online questionnaire based on the Distress Questionnaire-5 (DQ5). The study was carried out during the first Italian wave of COVID-19 pandemic from 1st to 30th of April. Participants were divided in 3 groups: group 1 is general population group that includes the general population which are quarantined but not isolated, group health care staff not working in COVID-19 hospitals, and group 3 healthcare staff group working in COVID-19 hospitals. The survey was carried with the Distress Questionnaire-5 (DQ5) as a tool to detect the psychological distress and mental health problems. A total of 2983 people participated in this survey. Seven hundred and twenty four out of 1123 (64%) were employers of the 4 hospitals included in this study. Particularly among the respondents, 2259 (75.7%) were general population, 502 (16.8%) were health care staff not working in COVID-19 hospitals, while 222 (7.4%) were health care staff working in covid-19 hospitals. Health care personnel working in COVID-19 hospitals (DQ-5 = 13, 10-16) had less psychological distress compared with health care staff not working in COVID-19 hospitals (DQ-5 = 14, 11-16) and general population (DQ-5 = 14, 11-17; P = .04). The regression model showed that people aged 26 to 35 (OR: 2.06, 95% CI: 1.21-3.48) and female (OR: 2.35, 95% CI: 1.95-2.83) were significantly at risk to develop a DQ-5 ≥ 11. During the first Italian wave of COVID-19 pandemic, healthcare personnel working in COVID-19 hospitals had less psychological distress compared with health care staff not working in COVID-19 hospitals and general population, probably because they were prepared to face situations like outbreak or emergencies.

Preoperative anxiety during COVID-19 pandemic: A single-center observational study and comparison with a historical cohort.

Background: Preoperative anxiety is a common sensation experienced by patients undergoing surgical interventions. It can influence intraoperative and postoperative management through the activation of the neuroendocrine system, leading to tachycardia, hypertension, pulmonary complications, higher consumption of anesthetic drugs, and increased postoperative pain. Our aim was to investigate the level of preoperative anxiety during the COVID-19 pandemic; we also compared it to the preoperative anxiety of a historical cohort before the outbreak. Methods: This is a single-center observational study. We enrolled 314 patients during the pandemic from May 2021 to November 2021, and our historical cohort consisted of 122 patients enrolled from July 2015 to May 2016 in the university hospital "Federico II" of Naples. The Amsterdam Preoperative Anxiety and Information Scale (APAIS) and the State-Trait Anxiety Inventory (STAI) were used to evaluate preoperative anxiety. In particular, APAIS measures preoperative anxiety and the need for information, and STAI assesses state and trait anxiety through STAI-Y1 and STAI-Y2, respectively. We analyzed APAIS and STAI scores in our population stratified on the basis of age, gender, marital status, previous surgical experiences, and type of surgery, and we compared them to our historical cohort. Statistical analysis was performed through a t-test and ANOVA for parametric data, and the Mann-Whitney and Kruskal-Wallis tests for non-parametric data. Linear regression was used to investigate the correlation between demographic data and the scores of STAI and APAIS in both groups. Results: Our results showed that state and preoperative anxiety remained stable, whereas trait anxiety increased in all the subgroups analyzed. Discussion: Even if state anxiety is considered a variable characteristic of the emotional sphere and trait anxiety a stable element, our findings suggested that COVID-19 deeply influenced trait anxiety, thus altering the patients' psychological foundations.

Implementations and strategies of telehealth during COVID-19 outbreak: a systematic review.

BACKGROUND: Telehealth is an effective option to fight the outbreak of COVID-19. This review aims to systematically characterize the utilization and applications of telehealth during the COVID-19 pandemic focusing mainly on technology implementations. METHODS: This study was conducted in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). The literature search was conducted in Science Direct, IEEE XPLORE, Scopus, and Web of Science databases from January 2020 until July 2021, with an English language restriction. A quality assessment was based on the Critical Appraisal Skills Programs checklist. RESULTS: The included studies focused on the implementation of technology for telehealth, multidisciplinary approach, service satisfaction, guidelines, and medical training. They provided illustrative insight into the strategy of telehealth in different medical specialties, such as pediatric gastroenterology, oncology, ophthalmology, and laryngology. Nonsurgical specialties had the greatest number of telehealth visits. Clinicians showed positive attitudes toward the implementation of video telehealth visits; patients report high levels of satisfaction with this care and strong interest in continuing this modality as a significant portion of clinical practice. CONCLUSIONS: This systematic review provided an illustrative insight into the strategy of telehealth for different purposes. According to our findings, telehealth may be used in different medical area with a clear strategy of intervention according to patients' and doctors' needs.

Germline rare variants of lectin pathway genes predispose to asymptomatic SARS-CoV-2 infection in elderly individuals.

PURPOSE: Emerging evidence suggest that infection-dependent hyperactivation of complement system (CS) may worsen COVID-19 outcome. We investigated the role of predicted high impact rare variants - referred as qualifying variants (QVs) - of CS genes in predisposing asymptomatic COVID-19 in elderly individuals, known to be more susceptible to severe disease. METHODS: Exploiting exome sequencing data and 56 CS genes, we performed a gene-based collapsing test between 164 asymptomatic subjects (aged ≥60 years) and 56,885 European individuals from the Genome Aggregation Database. We replicated this test comparing the same asymptomatic individuals with 147 hospitalized patients with COVID-19. RESULTS: We found an enrichment of QVs in 3 genes (MASP1, COLEC11, and COLEC10), which belong to the lectin pathway, in the asymptomatic cohort. Analyses of complement activity in serum showed decreased activity of lectin pathway in asymptomatic individuals with QVs. Finally, we found allelic variants associated with asymptomatic COVID-19 phenotype and with a decreased expression of MASP1, COLEC11, and COLEC10 in lung tissue. CONCLUSION: This study suggests that genetic rare variants can protect from severe COVID-19 by mitigating the activity of lectin pathway and prothrombin. The genetic data obtained through ES of 786 asymptomatic and 147 hospitalized individuals are publicly available at http://espocovid.ceinge.unina.it/.

Protocols of Anesthesia Management in Parturients with SARS-CoV-2 Infection.

BACKGROUND: Our hospital became a referral center for COVID-19-positive obstetric patients from 1 May 2020. The aim of our study is to illustrate our management protocols for COVID-19-positive obstetric patients, to maintain safety standards for patients and healthcare workers. METHODS: Women who underwent vaginal or operative delivery and induced or spontaneous abortion with a SARS-CoV-2-positive nasopharyngeal swab using real-time PCR (RT-PCR) were included in the study. Severity and onset of new symptoms were carefully monitored in the postoperative period. All the healthcare workers received a nasopharyngeal swab for SARS-CoV-2 using RT-PCR serially every five days. RESULTS: We included 152 parturients with COVID-19 infection. None of the included women had general anesthesia, an increase of severe symptoms or onset of new symptoms. The RT-PCR test was "negative" for the healthcare workers. CONCLUSIONS: In our study, neuraxial anesthesia for parturients' management with SARS-CoV-2 infection has been proven to be safe for patients and healthcare workers. Neuraxial anesthesia decreases aerosolization during preoxygenation, face-mask ventilation, endotracheal intubation, oral or tracheal suctioning and extubation. This anesthesia management protocol can be generalizable.

Loss of Detection of sgN Precedes Viral Abridged Replication in COVID-19-Affected Patients-A Target for SARS-CoV-2 Propagation.

The development of prophylactic agents against the SARS-CoV-2 virus is a public health priority in the search for new surrogate markers of active virus replication. Early detection markers are needed to follow disease progression and foresee patient negativization. Subgenomic RNA transcripts (with a focus on sgN) were evaluated in oro/nasopharyngeal swabs from COVID-19-affected patients with an analysis of 315 positive samples using qPCR technology. Cut-off Cq values for sgN (Cq < 33.15) and sgE (Cq < 34.06) showed correlations to high viral loads. The specific loss of sgN in home-isolated and hospitalized COVID-19-positive patients indicated negativization of patient condition, 3-7 days from the first swab, respectively. A new detection kit for sgN, gene E, gene ORF1ab, and gene RNAse P was developed recently. In addition, in vitro studies have shown that 2'-O-methyl antisense RNA (related to the sgN sequence) can impair SARS-CoV-2 N protein synthesis, viral replication, and syncytia formation in human cells (i.e., HEK-293T cells overexpressing ACE2) upon infection with VOC Alpha (B.1.1.7)-SARS-CoV-2 variant, defining the use that this procedure might have for future therapeutic actions against SARS-CoV-2.

COVID-19 pandemic and mental distress in multiple sclerosis: Implications for clinical management.

BACKGROUND AND PURPOSE: In multiple sclerosis (MS), disease-related factors and dysfunctional coping might favor the development of mental distress induced by COVID-19 containment measures. Aim of this study was exploring the relationship between disability, coping strategies, daily life reorganization and neuropsychiatric symptoms in an Italian MS population during the COVID-19 lockdown, in order to identify potentially modifiable factors that could inform clinical management of mental distress in people with MS. METHODS: We explored the relationship between mental distress, disability and coping strategies in the Italian MS population under lockdown. Structural equation modeling was applied to information collected via web survey to identify modifiable factors that could account for mental distress. RESULTS: A total of 845 participants (497 with MS and 348 controls) were included in the study. The MS group had higher scores than the control group for depression (p = 0.005), but not for anxiety, emotional dyscontrol or sleep disturbances. The structural equation modeling explained 74% of the variance observed in depression score. Within the model, three latent factors were characterized from measured variables: motor disability and cognitive dysfunction contributed to disability (ß = 0.509 and ß = 0.836; p < 0.001); positive attitude and exercise contributed to active attitude (ß = 0.386 and ß = 0.297; p < 0.001); and avoidance, social support and watching television contributed to passive attitude (ß = 0.301, ß = 0.243 and ß = 0.212; p < 0.001). With regard to the relationship between latent factors and their influence on depression, disability contributed to passive attitude (ß = 0.855; p < 0.001), while both passive and active attitude significantly influenced depression (ß = 0.729 and ß = -0.456; p < 0.001). CONCLUSION: As a practical implication of our model, favoring exercise would enhance active attitude and its positive impact on mental well-being while, at the same time, reducing the negative impact of disability on depression, representing a valuable tool in facing COVID-19-related mental distress.

Fragility Index and Fragility Quotient in Randomized Controlled Trials on Corticosteroids in ARDS Due to COVID-19 and Non-COVID-19 Etiology.

BACKGROUND: The effectiveness of corticosteroids in acute respiratory distress syndrome (ARDS) and COVID-19 still remains uncertain. Since ARDS is due to a hyperinflammatory response to a direct injury, we decided to perform a meta-analysis and an evaluation of robustness of randomised clinical trials (RCTs) investigating the impact of corticosteroids on mortality in ARDS in both COVID-19 and non-COVID-19 patients. We conducted a systematic search of the literature from inception up to 30 October 2020, using the MEDLINE database and the PubMed interface. We evaluated the fragility index (FI) of the included RCTs using a two-by-two contingency table and the p-value produced by the Fisher exact test; the fragility quotient (FQ) was calculated by dividing the FI score by the total sample size of the trial. RESULTS: Thirteen RCTs were included in the analysis; five of them were conducted in COVID-19 ARDS, including 7692 patients, while 8 RCTS were performed in non-COVID ARDS with 1091 patients evaluated. Three out of eight RCTs in ARDS had a FI > 0 while 2 RCTs out of five in COVID-19 had FI > 0. The median of FI for ARDS was 0.625 (0.47) while the median of FQ was 0.03 (0.014). The median of FI for COVID-19 was 6 (2) while the median of FQ was 0.059 (0.055). In this systematic review, we found that FI and FQ of RCTs evaluating the use of corticosteroids in ARDS and COVID-19 were low.

Venous Thromboembolism in COVID-19 Compared to Non-COVID-19 Cohorts: A Systematic Review with Meta-Analysis.

BACKGROUND: A high incidence of venous thromboembolism (VTE) is reported in hospitalized COVID-19 patients, in particular in patients admitted to the intensive care unit (ICU). In patients with respiratory tract infections, including influenza A (H1N1), many studies have demonstrated an increased incidence of thromboses, but evidence is lacking regarding the risk difference (RD) of the occurrence of VTE between COVID-19 and non-COVID-19 patients. METHODS: In this systematic review with meta-analysis, we evaluated the RD of the occurrence of VTE, pulmonary embolism (PE), and deep venous thrombosis (DVT) between COVID-19 and other pulmonary infection cohorts, in particular H1N1, and in an ICU setting. We searched for all studies comparing COVID-19 vs. non-COVID-19 regarding VTE, PE, and DVT. RESULTS: The systematic review included 12 studies and 1,013,495 patients. The RD for VTE in COVID-19 compared to non-COVID-19 patients was 0.06 (95% CI 0.11-0.25, p = 0.011, I2 = 97%), and 0.16 in ICU (95% CI 0.045-0.27, p = 0.006, I2 = 80%). The RD for PE between COVID-19 and non-COVID-19 patients was 0.03 (95% CI, 0.006-0.045, p = 0.01, I2 = 89%). The RD for PE between COVID-19 and non-COVID-19 patients was 0.021 in retrospective studies (95% CI 0.00-0.04, p = 0.048, I2 = 92%) and 0.11 in ICU studies (95% CI 0.06-0.16, p < 0.001, I2 = 0%). CONCLUSIONS: The growing awareness and understanding of a massive inflammatory response combined with a hypercoagulable state that predisposes patients to thrombosis in COVID-19, in particular in the ICU, may contribute to a more appropriate strategy of prevention and earlier detection of the thrombotic events.

Soluble Urokinase Receptor as a Promising Marker for Early Prediction of Outcome in COVID-19 Hospitalized Patients.

The Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has rapidly spread to become a global pandemic, putting a strain on health care systems. SARS-CoV-2 infection may be associated with mild symptoms or, in severe cases, lead patients to the intensive care unit (ICU) or death. The critically ill patients suffer from acute respiratory distress syndrome (ARDS), sepsis, thrombotic complications and multiple organ failure. For optimization of hospital resources, several molecular markers and algorithms have been evaluated in order to stratify COVID-19 patients, based on the risk of developing a mild, moderate, or severe disease. Here, we propose the soluble urokinase receptor (suPAR) as a serum biomarker of clinical severity and outcome in patients who are hospitalized with COVID-19. In patients with mild disease course, suPAR levels were increased as compared to healthy controls, but they were dramatically higher in severely ill patients. Since early identification of disease progression may facilitate the individual management of COVID-19 symptomatic patients and the time of admission to the ICU, we suggest paying more clinical attention on patients with high suPAR levels.

Low-dose spinal and opioid-free anesthesia in patient with Severe Aortic Stenosis and SARS-CoV-2 infection: Case report.

The best anesthesiologic approach to severe AS patient has not been adequately studied in literature. Although the current guidelines have a cautious attitude in this regard, Combined Spinal-Epidural Anesthesia (CSEA) has proved to be a safe technique. Therefore, we would like to provide our experience with a severe AS and COVID-19 patient.

Spontaneous Muscle Hematoma in Patients with COVID-19: A Systematic Literature Review with Description of an Additional Case Series.

Coagulation abnormalities, thrombosis, and endothelial dysfunction have been described in COVID-19 patients. Spontaneous muscle hematoma (SMH) is a rare complication in COVID-19. The aims of this study are to: (1) perform a systematic review of the literature to better define the clinical SMH characteristics, (2) describe the prevalence and the clinical characteristics of SMH in COVID-19 patients referring to a Department of Internal Medicine (IM) (Federico II University of Naples), a Department of Sub-Intensive Care Medicine (SIM) (Ospedale Del Mare), and a Department of Intensive Care Unit (ICU) (Federico II University). The systematic review was performed according to PRISMA criteria. The local prevalence of SMH in COVID-19 was evaluated retrospectively. The medical records of all COVID-19 patients referring to IM and ICU from March 11th, 2020, to February 28th, 2021 were examined for SMH occurrence. In our retrospective analysis, we describe 10 cases of COVID-19 patients with SMH not previously reported in literature, with a prevalence of 2.1%. The literature review, inclusive of our case series, describes a total of 50 SMHs in COVID-19 patients (57.4% males; mean age 68.8 ± 10.0 years). The SMH sites were ileo-psoas, vastus intermedius, gluteus, sternocleidomastoid, and pectoralis major muscles. Males developed SMH earlier than females (9.5 ± 7.8 vs. 17.1 ± 9.7 days). Ileo-psoas hematoma was more frequent in males (69.2 vs. 30.8%), while pectoralis major hematoma occurred only in females. The in-hospital mortality rate of SMH in COVID-19 patients was 32.4%. SMH is a rare but severe complication in COVID-19 hospitalized patients, associated with high mortality. A gender difference seems to be present in the clinical presentation of the disorder.

B-Type Natriuretic Peptides and High-Sensitive Troponin I as COVID-19 Survival Factors: Which One Is the Best Performer?

Increased concentrations of B-type natriuretic peptide (BNP), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin I (HsTnI) in COVID-19 patients have already been reported. The aim of this study is to evaluate which of these common markers of cardiac disease is the most useful predictor of fatal outcome in COVID-19 patients. One hundred and seventy-four patients affected with COVID-19 were recruited, and markers of cardiac disease and the clinical history of the patients were collected at admission in the infectious disease unit or intensive care unit. NT-proBNP, BNP and HsTnI values were higher in in-hospital non-surviving patients. Receiver operating characteristic (ROC) curve analysis of NT-proBNP, BNP and HsTnI was performed, with NT-proBNP (AUC = 0.951) and HsTnI (AUC = 0.947) being better performers (p = 0.01) than BNP (AUC = 0.777). Logistic regression was performed assessing the relation of HsTnI and NT-proBNP to fatal outcome adjusting for age and gender, with only NT-proBNP being significant. The population was then divided into two groups, one with higher NT-proBNP values at admission than the cut-off resulted from the ROC curve (511 ng/L) and a second one with lower values. The Kaplan-Meier analysis showed an absence of fatal outcome in the group of patients with NT-proBNP values lower than the cut-off (p < 0.001). NT-proBNP proved to be the best prognostic tool for fatal outcome among markers of cardiac disease in COVID-19 patients.

Tracheostomy Timing and Outcome in Severe COVID-19: The WeanTrach Multicenter Study.

BACKGROUND: Tracheostomy can be performed safely in patients with coronavirus disease 2019 (COVID-19). However, little is known about the optimal timing, effects on outcome, and complications. METHODS: A multicenter, retrospective, observational study. This study included 153 tracheostomized COVID-19 patients from 11 intensive care units (ICUs). The primary endpoint was the median time to tracheostomy in critically ill COVID-19 patients. Secondary endpoints were survival rate, length of ICU stay, and post-tracheostomy complications, stratified by tracheostomy timing (early versus late) and technique (surgical versus percutaneous). RESULTS: The median time to tracheostomy was 15 (1-64) days. There was no significant difference in survival between critically ill COVID-19 patients who received tracheostomy before versus after day 15, nor between surgical and percutaneous techniques. ICU length of stay was shorter with early compared to late tracheostomy (p < 0.001) and percutaneous compared to surgical tracheostomy (p = 0.050). The rate of lower respiratory tract infections was higher with surgical versus percutaneous technique (p = 0.007). CONCLUSIONS: Among critically ill patients with COVID-19, neither early nor percutaneous tracheostomy improved outcomes, but did shorten ICU stay. Infectious complications were less frequent with percutaneous than surgical tracheostomy.

The TNFRSF13C H159Y Variant Is Associated with Severe COVID-19: A Retrospective Study of 500 Patients from Southern Italy.

To identify host genetic determinants involved in humoral immunity and associated with the risk of developing severe COVID-19, we analyzed 500 SARS-CoV-2 positive subjects from Southern Italy. We examined the coding sequences of 10 common variable immunodeficiency-associated genes obtained by the whole-exome sequencing of 121 hospitalized patients. These 10 genes showed significant enrichment in predicted pathogenic point mutations in severe patients compared with the non-severe ones. Moreover, in the TNFRSF13C gene, the minor allele of the p.His159Tyr variant, which is known to increase NF-kB activation and B-cell production, was significantly more frequent in the 38 severe cases compared to both the 83 non-severe patients and the 375 asymptomatic subjects further genotyped. This finding identified a potential genetic risk factor of severe COVID-19 that not only may serve to unravel the mechanisms underlying the disease severity but, also, may contribute to build the rationale for individualized management based on B-cell therapy.

Diffuse functional brain disconnection syndrome in critically ill patients with COVID-19.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is most closely related to severe respiratory syndrome; however, recent reports showed that it is capable of causing neurological disease. Here we report a case-series of 4 critically ill COVID-19 patients who recovered from pneumonia but showed serious neurological symptoms and eventually died.

Regulatory Noncoding and Predicted Pathogenic Coding Variants of CCR5 Predispose to Severe COVID-19.

Genome-wide association studies (GWAS) found locus 3p21.31 associated with severe COVID-19. CCR5 resides at the same locus and, given its known biological role in other infection diseases, we investigated if common noncoding and rare coding variants, affecting CCR5, can predispose to severe COVID-19. We combined single nucleotide polymorphisms (SNPs) that met the suggestive significance level (P ≤ 1 × 10-5) at the 3p21.31 locus in public GWAS datasets (6406 COVID-19 hospitalized patients and 902,088 controls) with gene expression data from 208 lung tissues, Hi-C, and Chip-seq data. Through whole exome sequencing (WES), we explored rare coding variants in 147 severe COVID-19 patients. We identified three SNPs (rs9845542, rs12639314, and rs35951367) associated with severe COVID-19 whose risk alleles correlated with low CCR5 expression in lung tissues. The rs35951367 resided in a CTFC binding site that interacts with CCR5 gene in lung tissues and was confirmed to be associated with severe COVID-19 in two independent datasets. We also identified a rare coding variant (rs34418657) associated with the risk of developing severe COVID-19. Our results suggest a biological role of CCR5 in the progression of COVID-19 as common and rare genetic variants can increase the risk of developing severe COVID-19 by affecting the functions of CCR5.