Clozapine Therapy and COVID-19: A Systematic Review of the Prevalence Rates, Health Outcomes, Hematological Markers, and Patient Perspectives.

BACKGROUND/OBJECTIVES: There have been concerns that clozapine treatment may undermine the capacity of the body to fight infection and increase the vulnerability to contracting COVID-19. This review of recent cohort studies investigated (1) whether people with a severe psychiatric disorder are at increased risk of COVID-19 and complications, (2) the immunological response of clozapine-users who contract COVID-19, and (3) patients' perspectives on COVID-19 and the pandemic response. METHODS: A systematic search of EMBASE, Medline, Pubmed, and PsycINFO databases using PRISMA guidelines using "COVID-19", "clozapine", and "vaccination" terms. RESULTS: 18 studies (out of 330 identified) met all criteria (N = 119 054 including 8045 on clozapine). There was no strong evidence that clozapine users may be at increased risk of contracting COVID-19 or developing complications after adjusting for medical comorbidities. Hematological studies showed temporary reductions in neutrophils in COVID-19-positive patients and vaccination suggesting a clozapine effect in defence against infection. Vaccination studies did not report major adverse effects. Increased plasma levels of clozapine and neutropenia however point to COVID-19-related interference of clozapine metabolism. Patient surveys reported limited impact on mental health and positive attitudes regarding pandemic response. CONCLUSION: This review did not find compelling evidence that the immune system of clozapine users put them at risk of COVID-19 and further complications. Evidence of drug-infection interactions however points to the importance of adhering to consensus guidelines about clozapine therapy during the pandemic. More evidence using longitudinal designs is required to examine the longer-term effects of COVID-19 and vaccination in this vulnerable population.

Distinguishing immune activation and inflammatory signatures of multisystem inflammatory syndrome in children (MIS-C) versus hemophagocytic lymphohistiocytosis (HLH).

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a potentially life-threatening sequela of severe acute respiratory syndrome coronavirus 2 infection characterized by hyperinflammation and multiorgan dysfunction. Although hyperinflammation is a prominent manifestation of MIS-C, there is limited understanding of how the inflammatory state of MIS-C differs from that of well-characterized hyperinflammatory syndromes such as hemophagocytic lymphohistiocytosis (HLH). OBJECTIVES: We sought to compare the qualitative and quantitative inflammatory profile differences between patients with MIS-C, coronavirus disease 2019, and HLH. METHODS: Clinical data abstraction from patient charts, T-cell immunophenotyping, and multiplex cytokine and chemokine profiling were performed for patients with MIS-C, patients with coronavirus disease 2019, and patients with HLH. RESULTS: We found that both patients with MIS-C and patients with HLH showed robust T-cell activation, markers of senescence, and exhaustion along with elevated TH1 and proinflammatory cytokines such as IFN-γ, C-X-C motif chemokine ligand 9, and C-X-C motif chemokine ligand 10. In comparison, the amplitude of T-cell activation and the levels of cytokines/chemokines were higher in patients with HLH when compared with patients with MIS-C. Distinguishing inflammatory features of MIS-C included elevation in TH2 inflammatory cytokines such as IL-4 and IL-13 and cytokine mediators of angiogenesis, vascular injury, and tissue repair such as vascular endothelial growth factor A and platelet-derived growth factor. Immune activation and hypercytokinemia in MIS-C resolved at follow-up. In addition, when these immune parameters were correlated with clinical parameters, CD8+ T-cell activation correlated with cardiac dysfunction parameters such as B-type natriuretic peptide and troponin and inversely correlated with platelet count. CONCLUSIONS: Overall, this study characterizes unique and overlapping immunologic features that help to define the hyperinflammation associated with MIS-C versus HLH.

Healthcare Workers' Emotions, Stressor Experiences and Coping Strategies During the COVID-19 Pandemic in Vietnam.

PURPOSE: Healthcare workers (HCWs) are a crucial resource in the battle against the COVID-19 pandemic but are vulnerable to both SARS-CoV-2 infection and negative psychological consequences. This study evaluated HCWs' emotions, stressor experiences and coping strategies during the pandemic. METHODS: A cross-sectional study was conducted among HCWs at the University Medical Center in Ho Chi Minh City. The questionnaire was adapted from the MERS-CoV Staff Questionnaire to measure HCWs' emotions, stressor experiences and coping strategies during the COVID-19 pandemic. RESULTS: Among the 1423 participants eligible in the data analysis, the majority were female (71.1%) with a mean age of 34.2 (standard deviation 7.8) years. While most participants reported that they did their job because of their professionalism and duty as HCWs (87.4%), a high number reported feeling nervous and scared (86.0%). Most participants reported worry about transmitting SARS-CoV-2 to their families or friends (76.6%) and concern that a small mistake or lapse in concentration could infect themselves and others (76.7%). The most common coping strategies were following strict personal protective measures (95.3%), avoiding going out (92.5%) and reading about SARS-CoV-2 (92.3%). Females who had a higher educational level and less than 5-years work experience and those who worked at clinical departments and subclinical departments were more vulnerable. CONCLUSION: This study indicates an urgent need for psychological support for HCWs, especially for those at high risk of having stress. Interventions and support should utilize psychological resources and approaches effectively to adapt to the new situation during the COVID-19 pandemic.

Genome-wide analysis of SARS-CoV-2 strains circulating in Vietnam: Understanding the nature of the epidemic and role of the D614G mutation.

Genome-wide analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains is essential to better understand infectivity and virulence and to track coronavirus disease 2019 (COVID-19) cases and outbreaks. We performed whole-genome sequencing of 27 SARS-CoV-2 strains isolated between January 2020 and April 2020. A total of 54 mutations in different genomic regions was found. The D614G mutation, first detected in March 2020, was identified in 18 strains and was more likely associated with a lower cycle threshold (<25) in real-time reverse-transcription polymerase chain reaction diagnostic tests than the original D614 (prevalence ratio = 2.75; 95% confidence interval, 1.19-6.38). The integration of sequencing and epidemiological data suggests that SARS-CoV-2 transmission in both quarantine areas and in the community in Vietnam occur at the beginning of the epidemic although the country implemented strict quarantine quite early, with strict contact tracing, and testing. These findings provide insights into the nature of the epidemic, as well as shape strategies for COVID-19 prevention and control in Vietnam.

In the interest of public safety: rapid response to the COVID-19 epidemic in Vietnam.

We describe the status of the COVID-19 epidemic in Vietnam, major response successes, factors that prompted implementation of certain public health actions, and the impact of these actions. In addition, information for three case studies is reported, with crucial learnings to inform future response. Findings from this study suggest that as early as 20 January 2020, Vietnam held a national risk assessment, established a national COVID-19 Response Plan and Technical Treatment and Care Guidelines, and prepared public health laboratories to accurately diagnose cases and hospitals to effectively treat patients. The first COVID-19 case was detected on 23 January. As of 30 September, there had been three waves of the COVID-19 epidemic totalling 1095 cases, and resulting in 35 deaths all among people with underlying health conditions. Evidence of potential transmission of SARS-CoV-2 from a commercial passenger flight inbound to Vietnam was reported. This study also highlights the importance of early technical preparedness, strong political commitment, multisectoral and multilevel efforts, increased resourcing and coordination towards an effective COVID-19 response. Controlling outbreaks in settings, such as crowded public places (bars and hospitals), within certain villages and over cities, required early detection, aggressive trace-test-quarantine efforts, a geographically extensive lockdown area and an adoption of several non-pharmaceutical interventions. Many low-income and middle-income countries have experienced their second or third wave of the COVID-19 epidemic, and they can learn from Vietnam's response across the three epidemic waves. Swift governmental action, strict border control measures, effective communication of health promotion measures, widespread community engagement, expanded testing capacity and effective social measures to slow the spread of SARS-CoV-2, are highly important in these locations.

Clinical features, isolation, and complete genome sequence of severe acute respiratory syndrome coronavirus 2 from the first two patients in Vietnam.

In January 2020, we identified two severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients in a familial cluster with one person coming from Wuhan, China. The complete genome sequences of two SARS-CoV-2 strains isolated from these patients were identical and 99.98% similar to strains isolated in Wuhan. This is genetically suggestive of human-to-human transmission of SARS-CoV-2 and indicates Wuhan as the most plausible origin of the early outbreak in Vietnam. The younger patient had a mild upper respiratory illness and a brief viral shedding, whereas the elderly with multi-morbidity had pneumonia, prolonged viral shedding, and residual lung damage. The evidence of nonsynonymous substitutions in the ORF1ab region of the viral sequence warrants further studies.