Mutations in SARS-CoV-2 variants of concern link to increased spike cleavage and virus transmission.

SARS-CoV-2 lineages have diverged into highly prevalent variants termed "variants of concern" (VOCs). Here, we characterized emerging SARS-CoV-2 spike polymorphisms in vitro and in vivo to understand their impact on transmissibility and virus pathogenicity and fitness. We demonstrate that the substitution S:655Y, represented in the gamma and omicron VOCs, enhances viral replication and spike protein cleavage. The S:655Y substitution was transmitted more efficiently than its ancestor S:655H in the hamster infection model and was able to outcompete S:655H in the hamster model and in a human primary airway system. Finally, we analyzed a set of emerging SARS-CoV-2 variants to investigate how different sets of mutations may impact spike processing. All VOCs tested exhibited increased spike cleavage and fusogenic capacity. Taken together, our study demonstrates that the spike mutations present in VOCs that become epidemiologically prevalent in humans are linked to an increase in spike processing and virus transmission.

Evolution of enhanced innate immune evasion by SARS-CoV-2.

The emergence of SARS-CoV-2 variants of concern suggests viral adaptation to enhance human-to-human transmission1,2. Although much effort has focused on the characterization of changes in the spike protein in variants of concern, mutations outside of spike are likely to contribute to adaptation. Here, using unbiased abundance proteomics, phosphoproteomics, RNA sequencing and viral replication assays, we show that isolates of the Alpha (B.1.1.7) variant3 suppress innate immune responses in airway epithelial cells more effectively than first-wave isolates. We found that the Alpha variant has markedly increased subgenomic RNA and protein levels of the nucleocapsid protein (N), Orf9b and Orf6-all known innate immune antagonists. Expression of Orf9b alone suppressed the innate immune response through interaction with TOM70, a mitochondrial protein that is required for activation of the RNA-sensing adaptor MAVS. Moreover, the activity of Orf9b and its association with TOM70 was regulated by phosphorylation. We propose that more effective innate immune suppression, through enhanced expression of specific viral antagonist proteins, increases the likelihood of successful transmission of the Alpha variant, and may increase in vivo replication and duration of infection4. The importance of mutations outside the spike coding region in the adaptation of SARS-CoV-2 to humans is underscored by the observation that similar mutations exist in the N and Orf9b regulatory regions of the Delta and Omicron variants.

Reliability and validity of the Diagnostic Scales of the Schedule for Nonadaptive and Adaptive Personality-2 (SNAP-2) in Italian community-dwelling adults and psychiatric patients.

To evaluate the psychometric properties of the Italian translation of the Schedule for Nonadaptive and Adaptive Personality-2 (SNAP-2) diagnostic scales, 837 Italian community-dwelling adults and 429 consecutively admitted Italian psychiatric adults were administered the SNAP-2. The 12 SNAP-2 diagnostic scales yielded reliable scores in both community (median ω value = .90) and psychiatric (median ω value = .92) samples. The 6-month temporal stability was adequate for all SNAP-2 diagnostic scales (median test-retest r-value = .84) in a subsample of the community-dwelling adults (n = 97). When we examined the correlations between the SNAP-2 diagnostic scales and the Five-Factor Model Rating Form trait scales among the community-dwelling adults, the double-entry intraclass correlation values (median ICCDE = .94) indicated a marked similarity between our correlation profiles and the correlation profiles that were reported in Samuel and Widiger (2008) meta-analysis. In our psychiatric-adult sample, the SNAP-2 diagnostic scales showed adequate convergent-validity coefficients (median r-value = .61) with criterion measures of DSM-IV axis II/DSM-5 Section II personality disorders (PDs). Finally, relative-weight analysis results showed that selected Personality Inventory for DSM-5 trait-scale scores explained a substantial amount of variance in SNAP-2 antisocial, avoidant, borderline, narcissistic, obsessive-compulsive, and schizotypal PD scale scores (median R 2 value = .55). As a whole, our data suggest that the Italian SNAP-2 diagnostic scales have adequate reliability and construct validity in the Italian culture. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

A nine-month study on the course of COVID-19 related perceived post-traumatic stress disorder among Italian community-dwelling adults.

The present study aimed to evaluate base rate estimates, course of, and psychopathology and personality risk factors for COVID-19-related post-traumatic stress disorder (PTSD) in community-dwelling adults during the pandemic. 203 participants from a sample of 811 Italian community-dwelling adults agreed to participate in a nine-month, three-wave (Wave 1: March 2020; Wave 2: June 2020; Wave 3: December 2020) longitudinal study. Participants in the longitudinal study did not differ from the cross-sectional original sample on age, gender, civil status, educational level, occupation, and Italian area of residence. At each wave, participants were administered the PTSD scale of the International Trauma Questionnaire (ITQ), DSM-5 measures of acute stress, dissociation, depression and anxiety, as well as a maladaptive personality domain measure at Wave 1. Participants were instructed to answer to the ITQ items based only on COVID-19 pandemic and related containment measures. The point prevalence estimates of COVID-19 related PTSD at each wave ranged from 11% to 13%; however, up to roughly 23% of our participants experienced clinically relevant PTSD features during nine months of the COVID-19 pandemic in Italy. Multiple logistic regression results showed that experiencing internalizing symptoms (i.e., mostly acute stress) and selected personality features (i.e., Negative Affectivity and Psychoticism) at Wave 1 represent risk factors for PTSD symptoms at later waves. These findings extend previous knowledge on COVID-19 related PTSD and support the need for preventive and treatment interventions for PTSD during the COVID-19 pandemic.

A longitudinal study on clinically relevant self-reported depression, anxiety and acute stress features among Italian community-dwelling adults during the COVID-19 related lockdown: Evidence of a predictive role for baseline dysfunctional personality dimensions.

BACKGROUND: Although necessary for public health, quarantine has been documented to cause post-traumatic stress symptoms, anxiety, and depression. We designed the present longitudinal study to evaluate the psychological impact of quarantine in Italian community-dwelling adult participants. METHODS: A sample of 304 Italian community-dwelling adult participants (75.7% female; mean age = 35.28 years) was administered self-reported measures of depression, anxiety and acute stress symptoms at the beginning and at the end of the lockdown. Potential predictors of clinically relevant symptoms at the end of the lockdown were assessed. Specifically, data on gender, civil status, education level, occupation, and area of residence, as well as maladaptive personality domains were collected. RESULTS: More than 43% of participants suffered from the early impact of the lockdown; at the end of the lockdown roughly 32% of participants still reported any clinically relevant depression anxiety, and/or acute stress disorder condition. Clinically relevant acute stress reaction at the beginning of lockdown was a particularly important risk factor for experiencing clinically relevant acute stress, depression, and anxiety at the end of the lockdown. Maladaptive personality domains represent non-trivial predictors of participants' self-reports of clinically relevant depression, anxiety, and acute stress conditions at the end of the lockdown. LIMITATIONS: Excess of female participants and the impossibility of evaluating if participants suffered from any internalizing disorder before the COVID-19 quarantine represent major limitations of our study. CONCLUSIONS: Our findings suggest assessment of internalizing disorder symptoms during quarantine may be helpful in identifying people who may benefit from early treatment interventions.

COVID-19 pandemic preventive behaviors and causal beliefs among Italian community dwelling adults.

In an online sample of 1054 Italian community-dwelling adults, we assessed the relationships between the frequency of implementation of practices intended to prevent COVID-19 infection, degree of agreement with theories about the origin of the infections, and the frequency of use of different sources of information concerning the COVID-19 pandemic. The results showed that participants' COVID-19-related preventive behaviors and causal beliefs were significantly associated with selected demographic variables and frequency of use of specific sources of information (e.g. scientific journals vs social media).

Impact of COVID-19 lockdown on sleep quality in university students and administration staff.

INTRODUCTION: In Italy, lockdown due to COVID-19 health emergency started on March 10 and partially ended on May 3rd, 2020. There was a significant increase of psychological distress and symptoms of mental illness, and worsening of quality of sleep in the general population. METHODS: Participants completed an anonymous web-based survey that include questionnaires about sleep and anxiety and depression symptoms. Our sample included 400 subjects: 307 students (mean age 22.84 ± 2.68) and 93 university administration staff workers (mean age 37.02 ± 12.46). RESULTS: we found an increase in Bed Time hour, Sleep Latency, and Wake-Up time between before and during COVID-19 emergency and a worsening of sleep quality and of insomnia symptoms. In particular, during the lockdown, the impact of the delay in Bed Time and in Wake-Up was more pronounced in students. In workers, we observed a prevalence of maintenance insomnia before COVID-19 of 24% that significantly increase during COVID-19 reaching 40%, while workers with difficulties in sleep initiation were only 15% that increased to 42%. In our sample, 27.8% showed depressive symptoms, while 34.3% showed anxious symptoms, in particular in students. CONCLUSION: The impact of lockdown was greater in students than in workers, and in females than in males. Concerning the psycho-emotional aspects, about one-third of our sample showed depressive or anxious symptoms. The results of our study may provide support for the implementation of some interventions for well-being in pandemic condition.

Dysfunctional personality features, non-scientifically supported causal beliefs, and emotional problems during the first month of the COVID-19 pandemic in Italy.

The present study aimed at assessing the impact of demographic characteristics, maladaptive personality traits and causal beliefs about COVID-19 on perceived emotional problems in a sample of Italian community-dwelling adults (N = 1043) in the first month of the social distancing period due to the COVID-19 pandemic in Italy. Hierarchical logistic regression analysis results showed that dysfunctional personality domains and non-scientifically supported causal beliefs explained all the variance that was originally explained by demographic variables (i.e., age and gender). In particular, negative affectivity and detachment represented relevant risk factors for reduced emotional well-being in our sample. A significant positive association was observed also between emotional problems and supernatural causal beliefs on the COVID-19 infection. Our data supported the importance of considering the impact of quarantine measures on psychological well-being, while suggesting possible risk factors related to individual differences in personality and causal beliefs.