Directions of change in intrinsic case severity across successive SARS-CoV-2 variant waves have been inconsistent.

OBJECTIVES: To determine how the intrinsic severity of successively dominant SARS-CoV-2 variants changed over the course of the pandemic. METHODS: A retrospective cohort analysis in the NHS Greater Glasgow and Clyde (NHS GGC) Health Board. All sequenced non-nosocomial adult COVID-19 cases in NHS GGC with relevant SARS-CoV-2 lineages (B.1.177/Alpha, Alpha/Delta, AY.4.2 Delta/non-AY.4.2 Delta, non-AY.4.2 Delta/Omicron, and BA.1 Omicron/BA.2 Omicron) during analysis periods were included. Outcome measures were hospital admission, ICU admission, or death within 28 days of positive COVID-19 test. We report the cumulative odds ratio; the ratio of the odds that an individual experiences a severity event of a given level vs all lower severity levels for the resident and the replacement variant after adjustment. RESULTS: After adjustment for covariates, the cumulative odds ratio was 1.51 (95% CI: 1.08-2.11) for Alpha versus B.1.177, 2.09 (95% CI: 1.42-3.08) for Delta versus Alpha, 0.99 (95% CI: 0.76-1.27) for AY.4.2 Delta versus non-AY.4.2 Delta, 0.49 (95% CI: 0.22-1.06) for Omicron versus non-AY.4.2 Delta, and 0.86 (95% CI: 0.68-1.09) for BA.2 Omicron versus BA.1 Omicron. CONCLUSIONS: The direction of change in intrinsic severity between successively emerging SARS-CoV-2 variants was inconsistent, reminding us that the intrinsic severity of future SARS-CoV-2 variants remains uncertain.

Predicting Parent Trust Based on Professionals' Communication Skills

Trust is critical to the establishment and maintenance of working relationships between the parents of children with disabilities and their child's professional. Knowledge of the specific communication skills needed to secure trust is unclear. The current study investigated the relationship between parent evaluation of professionals' communication skills and parent trust of professionals. A total of 165 parents responded to an online survey during the COVID-19 pandemic. The results indicated that professionals' communication skills had a significant and moderately positive relationship with the parent trust of professionals. Hierarchical multiple regression analyses indicated that parents' ratings of professionals' communication competence, and professionals' use of in-person communication were the only predictors of parent trust of special education professionals, even when other factors were considered. This study's findings draw attention to the importance communication skills may have in establishing and maintaining trusting relationships with parents.

The SARS-CoV-2 Alpha variant was associated with increased clinical severity of COVID-19 in Scotland: A genomics-based retrospective cohort analysis.

OBJECTIVES: The SARS-CoV-2 Alpha variant was associated with increased transmission relative to other variants present at the time of its emergence and several studies have shown an association between Alpha variant infection and increased hospitalisation and 28-day mortality. However, none have addressed the impact on maximum severity of illness in the general population classified by the level of respiratory support required, or death. We aimed to do this. METHODS: In this retrospective multi-centre clinical cohort sub-study of the COG-UK consortium, 1475 samples from Scottish hospitalised and community cases collected between 1st November 2020 and 30th January 2021 were sequenced. We matched sequence data to clinical outcomes as the Alpha variant became dominant in Scotland and modelled the association between Alpha variant infection and severe disease using a 4-point scale of maximum severity by 28 days: 1. no respiratory support, 2. supplemental oxygen, 3. ventilation and 4. death. RESULTS: Our cumulative generalised linear mixed model analyses found evidence (cumulative odds ratio: 1.40, 95% CI: 1.02, 1.93) of a positive association between increased clinical severity and lineage (Alpha variant versus pre-Alpha variants). CONCLUSIONS: The Alpha variant was associated with more severe clinical disease in the Scottish population than co-circulating lineages.

Non-invasive respiratory support in the management of COVID-19: a synthesis of systematic reviews

Hospitalised patients with COVID-19 often require oxygen because of the increased risk of hypoxia, and one of the main treatment goals is to avoid mechanical ventilation where possible. Non-invasive respiratory support such as high-flow nasal oxygen, bi-level positive airway pressure and continuous positive airway pressure appear to be clinical alternatives. However, further research is needed to assess the effectiveness of non-invasive respiratory support and its varying modes as a treatment for COVID-19 within a diverse population. This commentary aims to critically appraise three reviews concerning the use of non-invasive respiratory support in patients with COVID-19 and expand upon the findings with regards to clinical practice.

Dementia and the risk of poor outcomes as a result of the COVID-19 pandemic

People with dementia belong to some of the most vulnerable groups of people, and their vulnerability has been augmented by the Covid-19 pandemic. This article critically appraises and evaluates a systematic review that investigated the relationship between dementia and COVID-19 related outcomes.

THE IMPACT OF COVID-19 ON PERINATAL MENTAL HEALTH - PART 1

The perinatal period is a high risk for onset and relapse of mental health problems. The COVID-19 pandemic is a particularly stressful occurrence with reported negative impacts on perinatal mental health, hence the need to understand these impacts on pregnant and post-partum childbearing women and people, and prioritise interventions to alleviate them. This is the first of two articles.

A potent virucidal activity of functionalized TiO2 nanoparticles adsorbed with flavonoids against SARS-CoV-2.

The coronavirus SARS-CoV-2 has caused a pandemic with > 550 millions of cases and > 6 millions of deaths worldwide. Medical management of COVID-19 relies on supportive care as no specific targeted therapies are available yet. Given its devastating effects on the economy and mental health, it is imperative to develop novel antivirals. An ideal candidate will be an agent that blocks the early events of viral attachment and cell entry, thereby preventing viral infection and spread. This work reports functionalized titanium dioxide (TiO2)-based nanoparticles adsorbed with flavonoids that block SARS-CoV-2 entry and fusion. Using molecular docking analysis, two flavonoids were chosen for their specific binding to critical regions of the SARS-CoV-2 spike glycoprotein that interacts with the host cell angiotensin-converting enzyme-2 (ACE-2) receptor. These flavonoids were adsorbed onto TiO2 functionalized nanoparticles (FTNP). This new nanoparticulate compound was assayed in vitro against two different coronaviruses; HCoV 229E and SARS-CoV-2, in both cases a clear antiviral effect was observed. Furthermore, using a reporter-based cell culture model, a potent antiviral activity is demonstrated. The adsorption of flavonoids to functionalized TiO2 nanoparticles induces a ~ threefold increase of that activity. These studies also indicate that FTNP interferes with the SARS-CoV-2 spike, impairing the cell fusion mechanism. KEY POINTS/HIGHLIGHTS: • Unique TiO2 nanoparticles displaying flavonoid showed potent anti-SARS-CoV-2 activity. • The nanoparticles precisely targeting SARS-CoV-2 were quantitatively verified by cell infectivity in vitro. • Flavonoids on nanoparticles impair the interactions between the spike glycoprotein and ACE-2 receptor.

Obstetric services in the UK during the COVID-19 pandemic: A national survey.

BACKGROUND: The management of obstetric patients with coronavirus disease 2019 (COVID-19) due to human-to-human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires unique considerations. Many aspects of labour and delivery practice required adaptation in response to the global pandemic and were supported by guidelines from the Royal College of Obstetrics and Gynaecologists. The adoption and adherence to these guidelines is unknown. METHODS: Participating centres in "Quality of Recovery in Obstetric Anaesthesia study-a multicentre study" (ObsQoR) completed an electronic survey based on the provision of services and care related to COVID-19 in October 2021. The survey was designed against the Royal College of Obstetricians and Gynaecologists COVID-19 guidelines. RESULTS: One hundred and five of the 107 participating centres completed the survey (98% response rate representing 54% of all UK obstetric units). The median [IQR] annual number of deliveries among the included sites was 4389 [3000-5325]. Ninety-nine of the 103 (94.3%) sites had guidelines for the management of peripartum women with COVID-19. Sixty-one of 105 (58.1%) sites had specific guidance for venous thromboembolism (VTE) prophylaxis. Thirty-seven of 104 (35.6%) centres restricted parturient birthing plans if a positive diagnosis of COVID-19 was made. A COVID-19 vaccination referral pathway encouraging full vaccination for all pregnant women was present in 63/103 centres (61.2%). CONCLUSION: We found variability in care delivered and adherence to guidelines related to COVID-19. The clinical implications for this related to quality of peripartum care is unclear, however there remains scope to improve pathways for immunisation, birth plans and VTE prophylaxis.

Faecal immunochemical testing (FIT) in patients with signs or symptoms of suspected colorectal cancer (CRC): a joint guideline from the Association of Coloproctology of Great Britain and Ireland (ACPGBI) and the British Society of Gastroenterology (BSG).

Faecal immunochemical testing (FIT) has a high sensitivity for the detection of colorectal cancer (CRC). In a symptomatic population FIT may identify those patients who require colorectal investigation with the highest priority. FIT offers considerable advantages over the use of symptoms alone, as an objective measure of risk with a vastly superior positive predictive value for CRC, while conversely identifying a truly low risk cohort of patients. The aim of this guideline was to provide a clear strategy for the use of FIT in the diagnostic pathway of people with signs or symptoms of a suspected diagnosis of CRC. The guideline was jointly developed by the Association of Coloproctology of Great Britain and Ireland/British Society of Gastroenterology, specifically by a 21-member multidisciplinary guideline development group (GDG). A systematic review of 13 535 publications was undertaken to develop 23 evidence and expert opinion-based recommendations for the triage of people with symptoms of a suspected CRC diagnosis in primary care. In order to achieve consensus among a broad group of key stakeholders, we completed an extended Delphi of the GDG, and also 61 other individuals across the UK and Ireland, including by members of the public, charities and primary and secondary care. Seventeen research recommendations were also prioritised to inform clinical management.

The currency and completeness of specialized databases of COVID-19 publications.

OBJECTIVE: Several specialized collections of COVID-19 literature have been developed during the global health emergency. These include the WHO COVID-19 Global Literature Database, Cochrane COVID-19 Study Register, CAMARADES COVID-19 SOLES, Epistemonikos' COVID-19 L-OVE, and LitCovid. Our objective was to evaluate the completeness of these collections and to measure the time from when COVID-19 articles are posted to when they appear in the collections. STUDY DESIGN AND SETTING: We tested each selected collection for the presence of 440 included studies from 25 COVID-19 systematic reviews. We sampled 112 journals and prospectively monitored their websites until a new COVID-19 article appeared. We then monitored for 2 weeks to see when the new articles appeared in each collection. PubMed served as a comparator. RESULTS: Every collection provided at least one record not found in PubMed. Four records (1%) were not in any of the sources studied. Collections contained between 83% and 93% of the primary studies with the WHO database being the most complete. By 2 weeks, between 60% and 78% of tracked articles had appeared. CONCLUSION: Our findings support the use of the best performing COVID-19 collections by systematic reviews to replace paywalled databases.

Infection Prevention and Control in Three Tertiary Healthcare Facilities in Freetown, Sierra Leone during the COVID-19 Pandemic: More Needs to Be Done!

Infection Prevention and Control (IPC) measures are critical to the reduction in healthcare-associated infections, especially during pandemics, such as that of COVID-19. We conducted a hospital-based cross-sectional study in August 2021 at Connaught Hospital, Princess Christian Maternity Hospital and Ola During Children's Hospital located in Freetown, Sierra Leone. We used the World Health Organization's Infection Prevention and Control Assessment Framework Tool to assess the level of IPC compliance at these healthcare facilities. The overall IPC compliance score at Connaught Hospital was 323.5 of 800 points, 313.5 of 800 at Ola During Children's Hospital, 281 of 800 at Princess Christian Maternity Hospital, implying a 'Basic' IPC compliance grade. These facilities had an IPC program, IPC committees and dedicated IPC focal persons. However, there were several challenges, including access to safe and clean water and insufficient quantities of face masks, examination gloves and aprons. Furthermore, there was no dedicated budget or no healthcare-associated infection (HAI) surveillance, and monitoring/audit of IPC practices were weak. These findings are of concern during the COVID-19 era, and there is an urgent need for both financial and technical support to address the gaps and challenges identified.

The prevalence of mental health conditions in healthcare workers during and after a pandemic: Systematic review and meta-analysis.

AIMS: This review aims to explore the prevalence and incidence rates of mental health conditions in healthcare workers during and after a pandemic outbreak and which factors influence rates. BACKGROUND: Pandemics place considerable burden on care services, impacting on workers' health and their ability to deliver services. We systematically reviewed the prevalence and incidence of mental health conditions in care workers during pandemics. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Searches of MEDLINE, Embase, Cochrane Library and PsychINFO for cohort, cross-sectional and case-control studies were undertaken on the 31 March 2020 (from inception to 31 March 2020). REVIEW METHODS: Only prevalence or incidence rates for mental health conditions from validated tools were included. Study selection, data extraction and quality assessment were carried out by two reviewers. Meta-analyses and subgroup analyses were produced for pandemic period (pre- and post), age, country income, country, clinical setting for major depression disorder (MDD), anxiety disorder and post-traumatic stress disorder (PTSD). RESULTS: No studies of incidence were found. Prevalence estimates showed that the most common mental health condition was PTSD (21.7%) followed by anxiety disorder (16.1%), MDD (13.4%) and acute stress disorder (7.4%) (low risk of bias). For symptoms of these conditions there was substantial variation in the prevalence estimates for depression (95% confidence interval [CI]:31.8%; 60.5%), anxiety (95% CI:34.2%; 57.7%) and PTSD symptoms (95% CI,21.4%; 65.4%) (moderate risk of bias). Age, level of exposure and type of care professional were identified as important moderating factors. CONCLUSION: Mental disorders affect healthcare workers during and after infectious disease pandemics, with higher proportions experiencing symptoms. IMPACT: This review provides prevalence estimates of mental health conditions during and after a pandemic which could be used to inform service staffing impact and formulation of preventative strategies, by identifying clinical populations who may be at high risk of developing mental health symptoms and conditions.

Viral E Protein Neutralizes BET Protein-Mediated Post-Entry Antagonism of SARS-CoV-2 (preprint)

Inhibitors of Bromodomain and Extra-terminal domain (BET) proteins are possible anti-SARS-CoV-2 prophylactics as they downregulate angiotensin-converting enzyme 2 (ACE2). Here, we show that BET proteins should not be inactivated therapeutically as they are critical antiviral factors at the post-entry level. Knockouts of BRD3 or BRD4 in cells overexpressing ACE2 exacerbate SARS-CoV-2 infection; the same is observed when cells with endogenous ACE2 expression are treated with BET inhibitors during infection, and not before. Viral replication and mortality are also enhanced in BET inhibitor-treated mice overexpressing ACE2. BET inactivation suppresses interferon production induced by SARS-CoV-2, a process phenocopied by the envelope (E) protein previously identified as a possible "histone mimetic." E protein, in an acetylated form, directly binds the second bromodomain of BRD4. Our data support a model where SARS-CoV-2 E protein evolved to antagonize interferon responses via BET protein inhibition; this neutralization should not be further enhanced with BET inhibitor treatment.

Viral load and disease severity in COVID-19.

The relationship between COVID-19 severity and viral load is unknown. Our objective was to assess the association between viral load and disease severity in COVID-19. In this single center observational study of adults with laboratory confirmed SARS-CoV-2, the first positive in-hospital nasopharyngeal swab was used to calculate the log10 copies/ml [log10 copy number (CN)] of SARS-CoV-2. Four categories based on level of care and modified sequential organ failure assessment score (mSOFA) at time of swab were determined. Median log10CN was compared between different levels of care and mSOFA quartiles. Median log10CN was compared in patients who did and did not receive influenza vaccine, and the correlation between log10CN and D-dimer was examined. We found that of 396 patients, 54.3% were male, and 25% had no major comorbidity. Hospital mortality was 15.7%. Median mSOFA was 2 (IQR 0-3). Median log10CN was 5.5 (IQR 3.3-8.0). Median log10CN was highest in non-intubated ICU patients [6.4 (IQR 4.4-8.1)] and lowest in intubated ICU patients [3.6 (IQR 2.6-6.9)] (p value < 0.01). In adjusted analyses, this difference remained significant [mean difference 1.16 (95% CI 0.18-2.14)]. There was no significant difference in log10CN between other groups in the remaining pairwise comparisons. There was no association between median log10CN and mSOFA in either unadjusted or adjusted analyses or between median log10CN in patients with and without influenza immunization. There was no correlation between log10CN and D-dimer. We conclude, in our cohort, we did not find a clear association between viral load and disease severity in COVID-19 patients. Though viral load was higher in non-intubated ICU patients than in intubated ICU patients there were no other significant differences in viral load by disease severity.

Austrian syndrome, ceftriaxone-induced agranulocytosis and COVID-19.

We present a case of a 75-year-old woman with Austrian syndrome: pneumonia, meningitis and endocarditis all due to Streptococcus pneumoniae Transoesophageal echocardiogram demonstrated a large mitral valve vegetation with severe mitral regurgitation. She was treated with intravenous ceftriaxone and listed for surgical repair of her mitral valve. Preoperatively, she developed an idiosyncratic drug-induced agranulocytosis secondary to ceftriaxone, which resolved on cessation of the medication. However, while awaiting neutrophil recovery, she developed an acute deterioration, becoming critically unwell. This deterioration was multifactorial, with acute decompensated heart failure alongside COVID-19. After multidisciplinary discussion, she was considered too unwell for surgery and palliated.

Genomic epidemiology reveals multiple introductions of SARS-CoV-2 from mainland Europe into Scotland.

Coronavirus disease 2019 (COVID-19) was first diagnosed in Scotland on 1 March 2020. During the first month of the outbreak, 2,641 cases of COVID-19 led to 1,832 hospital admissions, 207 intensive care admissions and 126 deaths. We aimed to identify the source and number of introductions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into Scotland using a combined phylogenetic and epidemiological approach. Sequencing of 1,314 SARS-CoV-2 viral genomes from available patient samples enabled us to estimate that SARS-CoV-2 was introduced to Scotland on at least 283 occasions during February and March 2020. Epidemiological analysis confirmed that early introductions of SARS-CoV-2 originated from mainland Europe (the majority from Italy and Spain). We identified subsequent early outbreaks in the community, within healthcare facilities and at an international conference. Community transmission occurred after 2 March, 3 weeks before control measures were introduced. Earlier travel restrictions or quarantine measures, both locally and internationally, would have reduced the number of COVID-19 cases in Scotland. The risk of multiple reintroduction events in future waves of infection remains high in the absence of population immunity.