Analysis of psychological status and effect of psychological intervention in quarantined population during the epidemic of SARS-CoV-2.

ABSTRACT: During outbreaks of the coronavirus disease 2019 (COVID-19), many countries adopted quarantine to slow the spread of the virus of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Quarantine will cause isolation from families, friends, and the public, which consequently leads to serious psychological pressure with potentially long-lasting effects on the quarantined population. Experience of specific practices to improve the psychological status of the mandatory quarantined population was limited. The aim of this study was to investigate the psychological impact of mandatory quarantine, and evaluate the effect of psychological intervention on the quarantined population.We conducted a prospective cohort study to assess and manage the psychological status of a mandatory quarantined population in Beijing, China. A total of 638 individuals completed 2 questionnaires and were enrolled in this study, of which 372 participants accepted designed psychological intervention while other 266 participants refused it. The SCL-90 questionnaire was used to evaluate the psychological status and its change before and after the intervention. The differences of SCL-90 factor scores between participants and the national norm group were assessed by 2 samples t test. While the SCL-90 factor scores before and after intervention were compared with 2 paired samples t test.Compared with the Chinese norms of SCL-90, the participants had higher SCL-90 factor scores in most items of the SCL-90 inventory. The SCL-90 factor scores of participants with psychological intervention significantly decreased in somatization, obsessive-compulsive, depression, anxiety, phobic anxiety, paranoid ideation, and psychoticism. In contrast, most factor scores of the SCL-90 inventory changed little without statistical significance in participants without psychological intervention.Psychological problems should be emphasized in the quarantined individuals and professional psychological intervention was a feasible approach to improve the psychological status of the mandatory quarantined population in the epidemic of SARS-CoV-2.

A new intracellular targeting motif in the cytoplasmic tail of the spike protein may act as a target to inhibit SARS-CoV-2 assembly.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a threat to global public health, underscoring the urgent need for the development of preventive and therapeutic measures. The spike (S) protein of SARS-CoV-2, which mediates receptor binding and subsequent membrane fusion to promote viral entry, is a major target for current drug development and vaccine design. The S protein comprises a large N-terminal extracellular domain, a transmembrane domain, and a short cytoplasmic tail (CT) at the C-terminus. CT truncation of the S protein has been previously reported to promote the infectivity of SARS-CoV and SARS-CoV-2 pseudoviruses. However, the underlying molecular mechanism has not been precisely elucidated. In addition, the CT of various viral membrane glycoproteins play an essential role in the assembly of virions, yet the role of the S protein CT in SARS-CoV-2 infection remains unclear. In this study, through constructing a series of mutations of the CT of the S protein and analyzing their impact on the packaging of the SARS-CoV-2 pseudovirus and live SARS-CoV-2 virus, we identified V1264L1265 as a new intracellular targeting motif in the CT of the S protein, that regulates the transport and subcellular localization of the spike protein through the interactions with cytoskeleton and vesicular transport-related proteins, ARPC3, SCAMP3, and TUBB8, thereby modulating SARS-CoV-2 pseudovirus and live SARS-CoV-2 virion assembly. Either disrupting the V1264L1265 motif or reducing the expression of ARPC3, SCAMP3, and TUBB8 significantly repressed the assembly of the live SARS-CoV-2 virion, raising the possibility that the V1264L1265 motif and the host responsive pathways involved could be new drug targets for the treatment of SARS-CoV-2 infection. Our results extend the understanding of the role played by the S protein CT in the assembly of pseudoviruses and live SARS-CoV-2 virions, which will facilitate the application of pseudoviruses to the study of SARS-CoV-2 and provide potential strategies for the treatment of SARS-CoV-2 infection.

Older age and depressive state are risk factors for re-positivity with SARS-CoV-2 Omicron variant

Background The reinfection rate of SARS-CoV-2 Omicron variant is high;thus, exploring the risk factors for reinfection is important for the effective control of the epidemic. This study aimed to explore the effects of psychological and sleep factors on re-positivity with Omicron. Methods Through a prospective cohort study, 933 adult patients diagnosed with Omicron BA.2.2 infection and testing negative after treatment were included for screening and follow-up. We collected data on patients' demographic characteristics, SARS-CoV-2 Omicron vaccination status, anxiety, depression, and sleep status. Patients underwent nucleic acid testing for SARS-CoV-2 Omicron for 30 days. Regression and Kaplan-Meier analyses were used to determine the risk factors for re-positivity of Omicron. Results Ultimately, 683 patients were included in the analysis. Logistic regression analysis showed that older age (P = 0.006) and depressive status (P = 0.006) were two independent risk factors for Omicron re-positivity. The odds ratios of re-positivity in patients aged ≥60 years and with a Patient Health Questionnaire-9 (PHQ-9) score ≥5 was 1.82 (95% confidence interval:1.18–2.78) and 2.22 (1.27–3.85), respectively. In addition, the time from infection to recovery was significantly longer in patients aged ≥60 years (17.2 ± 4.5 vs. 16.0 ± 4.4, P = 0.003) and in patients with PHQ-9≥5 (17.5 ± 4.2vs. 16.2 ± 4.5, P = 0.026). Kaplan–Meier analysis showed that there was a significantly higher primary re-positivity rate in patients aged ≥60 years (P = 0.004) and PHQ-9 ≥ 5 (P = 0.007). Conclusion This study demonstrated that age of ≥60 years and depressive status were two independent risk factors for re-positivity with Omicron and that these factors could prolong the time from infection to recovery. Thus, it is necessary to pay particular attention to older adults and patients in a depressive state.

The E484K Substitution in a SARS-CoV-2 Spike Protein Subunit Vaccine Resulted in Limited Cross-Reactive Neutralizing Antibody Responses in Mice.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially emerging variants, poses an increased threat to global public health. The significant reduction in neutralization activity against the variants such as B.1.351 in the serum of convalescent patients and vaccinated people calls for the design of new potent vaccines targeting the emerging variant. However, since most vaccines approved and in clinical trials are based on the sequence of the original SARS-CoV-2 strain, the immunogenicity and protective efficacy of vaccines based on the B.1.351 variant remain largely unknown. In this study, we evaluated the immunogenicity, induced neutralization activity, and protective efficacy of wild-type spike protein nanoparticle (S-2P) and mutant spike protein nanoparticle (S-4M-2P) carrying characteristic mutations of B.1.351 variant in mice. Although there was no significant difference in the induction of spike-specific IgG responses in S-2P- and S-4M-2P-immunized mice, neutralizing antibodies elicited by S-4M-2P exhibited noteworthy, narrower breadth of reactivity with SARS-CoV-2 variants compared with neutralizing antibodies elicited by S-2P. Furthermore, the decrease of induced neutralizing antibody breadth at least partly resulted from the amino acid substitution at position 484. Moreover, S-4M-2P vaccination conferred insufficient protection against live SARS-CoV-2 virus infection, while S-2P vaccination gave definite protection against SARS-CoV-2 challenge in mice. Together, our study provides direct evidence that the E484K substitution in a SARS-CoV-2 subunit protein vaccine limited the cross-reactive neutralizing antibody breadth in mice and, more importantly, draws attention to the unfavorable impact of this mutation in spike protein of SARS-CoV-2 variants on the induction of potent neutralizing antibody responses.