Persistence of a Frameshifting Deletion in SARS-CoV-2 ORF7a for the Duration of a Major Outbreak.

Australia experienced widespread COVID-19 outbreaks from infection with the SARS-CoV-2 Delta variant between June 2021 and February 2022. A 17-nucleotide frameshift-inducing deletion in ORF7a rapidly became represented at the consensus level (Delta-ORF7aΔ17del) in most Australian outbreak cases. Studies from early in the COVID-19 pandemic suggest that frameshift-inducing deletions in ORF7a do not persist for long in the population; therefore, Delta-ORF7aΔ17del genomes should have disappeared early in the Australian outbreak. In this study, we conducted a retrospective analysis of global Delta genomes to characterise the dynamics of Delta-ORF7aΔ17del over time, determined the frequency of all ORF7a deletions worldwide, and compared global trends with those of the Australian Delta outbreak. We downloaded all GISAID clade GK Delta genomes and scanned them for deletions in ORF7a. For each deletion we identified, we characterised its frequency, the number of countries it was found in, and how long it persisted. Of the 4,018,216 Delta genomes identified globally, 134,751 (~3.35%) possessed an ORF7a deletion, and ORF7aΔ17del was the most common. ORF7aΔ17del was the sole deletion in 28,014 genomes, of which 27,912 (~99.6%) originated from the Australian outbreak. During the outbreak, ~87% of genomes were Delta-ORF7aΔ17del, and genomes with this deletion were sampled until the outbreak's end. These data demonstrate that, contrary to suggestions early in the COVID-19 pandemic, genomes with frameshifting deletions in ORF7a can persist over long time periods. We suggest that the proliferation of Delta-ORF7aΔ17del genomes was likely a chance founder effect. Nonetheless, the frequency of ORF7a deletions in SARS-CoV-2 genomes worldwide suggests they might have some benefit for virus transmission.

Longitudinal Characterization of Phagocytic and Neutralization Functions of Anti-Spike Antibodies in Plasma of Patients after Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

Phagocytic responses by effector cells to opsonized viruses have been recognized to play a key role in antiviral immunity. Limited data on coronavirus disease 2019 suggest that the role of Ab-dependent and -independent phagocytosis may contribute to the observed immunological and inflammatory responses; however, their development, duration, and role remain to be fully elucidated. In this study of 62 acute and convalescent patients, we found that patients with acute coronavirus disease 2019 can mount a phagocytic response to autologous plasma-opsonized Spike protein-coated microbeads as early as 10 d after symptom onset, while heat inactivation of this plasma caused 77-95% abrogation of the phagocytic response and preblocking of Fc receptors showed variable 18-60% inhibition. In convalescent patients, phagocytic response significantly correlated with anti-Spike IgG titers and older patients, while patients with severe disease had significantly higher phagocytosis and neutralization functions compared with patients with asymptomatic, mild, or moderate disease. A longitudinal subset of the convalescent patients over 12 mo showed an increase in plasma Ab affinity toward Spike Ag and preservation of phagocytic and neutralization functions, despite a decline in the anti-Spike IgG titers by >90%. Our data suggest that early phagocytosis is primarily driven by heat-liable components of the plasma, such as activated complements, while anti-Spike IgG titers account for the majority of observed phagocytosis at convalescence. Longitudinally, a significant increase in the affinity of the anti-Spike Abs was observed that correlated with the maintenance of both the phagocytic and neutralization functions, suggesting an improvement in the quality of the Abs.

Prevalence and Contributing Factors of Gender-based Violence in SAARC Territories from 2010 to 2020: A Systematic Review and Meta-analysis.

BACKGROUND: Gender-based violence is a key global concern due to the high prevalence and increased socio-economic burden for survivors. However, estimation of the prevalence of gender-based violence is difficult due to differences in study design and underreporting of abuse, especially in developing nations. Therefore, we conducted this study to estimate the prevalence of Gender-based violence among women living in the SAARC region. METHODS: The review protocol was registered in PROSPERO (CRD42020219577). Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed throughout the review. A thorough database search was conducted to identify studies done in the SAARC region. Title and abstract screening were done in Covidence, followed by a full-text review. Data were extracted and pooled for analysis using the inclusion and exclusion criteria. Subgroup analysis was done where possible. RESULTS: A total of 76 studies were included in the systematic review and metaanalysis. The community prevalence of domestic violence (DV) was 43.8% (95% CI, 35.1% - 52.9%), GBV prevalence was 34.9% (95% CI, 30.2% - 39.9%) and IPV prevalence was 39.8% (95% CI, 30.7% - 49.6%). GBV prevalence was highest in illiterate women [54.2% (95% CI, 46.8% - 61.5%)] and lowest among women with higher than secondary level education [23.1% (95% CI, 16.2% - 32.0%)]. The prevalence of GBV among women in pregnancy or postpartum period was 32.3% (95% CI, 25.1% - 40.4%, I2: 98.64), while among female sexual workers, the prevalence of Gender-based violence was 42.1% (95% CI, 28.1% - 57.5%, I2: 99.25). CONCLUSIONS: There is a high prevalence of Gender-based violence in the SAARC region. Higher socioeconomic status and educational status are protective factors for Gender-based violence. However, more studies using validated tools are needed to understand the true extent of the problem.

Participatory Approach to Develop Evidence-Based Clinical Ethics Guidelines for the Care of COVID-19 Patients: A Mixed Method Study From Nepal.

During health emergencies such as the COVID-19 pandemic, healthcare workers face numerous ethical challenges while catering to the needs of patients in healthcare settings. Although the data recapitulating high-income countries ethics frameworks are available, the challenges faced by clinicians in resource-limited settings of low- and middle-income countries are not discussed widely due to a lack of baseline data or evidence. The Nepali healthcare system, which is chronically understaffed and underequipped, was severely affected by the COVID-19 pandemic in its capacity to manage health services and resources for needy patients, leading to ethical dilemmas and challenges during clinical practice. This study aimed to develop a standard guideline that would address syndemic ethical dilemmas during clinical care of COVID-19 patients who are unable to afford standard-of-care. A mixed method study was conducted between February and June of 2021 in 12 government designated COVID-19 treatment hospitals in central Nepal. The draft guideline was discussed among the key stakeholders in the pandemic response in Nepal. The major ethical dilemmas confronted by the study participants (50 healthcare professionals providing patient care at COVID-19 treatment hospitals) could be grouped into five major pillars of ethical clinical practice: rational allocation of medical resources, updated treatment protocols that guide clinical decisions, standard-of-care regardless of patient's economic status, effective communication among stakeholders for prompt patient care, and external factors such as political and bureaucratic interference affecting ethical practice. This living clinical ethics guideline, which has been developed based on the local evidence and case stories of frontline responders, is expected to inform the policymakers as well as the decision-makers positioned at the concerned government units. These ethics guidelines could be endorsed with revisions by the concerned regulatory authorities for the use during consequent waves of COVID-19 and other epidemics that may occur in the future. Other countries affected by the pandemic could conduct similar studies to explore ethical practices in the local clinical and public health context.

N-acetyl cysteine versus standard of care for non-acetaminophen induced acute liver injury: a systematic review and meta-analysis.

The role of N-acetylcysteine (NAC) in the treatment of acetaminophen induced acute liver injury (ALI) is well established but its role in non-acetaminophen induced ALI is still elusive. We conducted this meta-analysis to evaluate the role of NAC in non-acetaminophen induced ALI. We searched electronic databases for studies published till Oct 25, 2020. We used RevMan v5.4 software to analyze the data extracted from selected studies by using Covidence systematic review software. Outcome estimation was done using Odds Ratio (OR) with 95% confidence interval (CI). The heterogeneity in various studies was determined using the I2 test. A total of 11 studies were included in quantitative analysis. Use of NAC in non-acetaminophen induced ALI showed 53% reduction in mortality compared to standard of care (OR, 0.47; CI, 0.29-0.75) and reduced mean duration of hospital stay by 6.52 days (95% CI, -12.91 to -0.13). Similarly, the rate of encephalopathy was 59% lower in the treatment group (OR, 0.41; CI, 0.20-0.83). However, the risk of developing nausea and vomiting (OR, 3.99; CI, 1.42-11.19), and the need for mechanical ventilation (OR 3.88; CI, 1.14-13.29) were significantly higher in the treatment group. These findings conclude use of NAC decreases mortality and hepatic encephalopathy compared to standard of care in patients with non-acetaminophen induced ALI. Although there is an increased risk of nausea and vomiting with the use of NAC, the majority of adverse events are transient and minor.

COVID Stress among Nepal Police Officers.

BACKGROUND: In Nepal, the stress factor is exacerbated by a large number of police officers working away from home with less family contact, a hectic work schedule in a pandemic situation, companions suffering from illness and updates on additional cases with rising mortality rates, and a lack of access to Personal Protection Equipment. The main aim of this study was to identify the prevalence of COVID stress among Nepal police officers working during pandemic. METHODS: We conducted a cross-sectional study among police officers (n=1526) working during pandemic in Province X Nepal. Semi-structured questionnaire was administered using google form. COVID Stress Scale -36 (CSS-36) was used to assess the stress in officers. Data collection was done after obtaining ethical approval. Data cleaning was done using a python script and then was exported to Ms. Excel for graph analysis. RESULTS: The highest percentage was seen in the xenophobia subscale (24.63%), followed by contamination (20.10 %) and compulsive checking (19.21%). Comparing socio-demographic variables, 18-27 aged groups including male officers and unmarried groups had experienced high COVID stress. CONCLUSIONS: Most of the officers feared from the foreigners perceiving them the main source of COVID-19. Fears about getting contaminated related to COVID-19 was also seen high. There is a need to assess psychological issues and provide social support to police officers during this pandemic situation.

Use of Tocilizumab May Avoid the Need of Invasive Ventilation.

Coronavirus disease 2019 (COVID-19) is an illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Increased pro-inflammatory cytokines including interleukin 6 (IL-6) are associated with severe forms of illnesses. The severe cases of COVID-19 require a high amount of oxygen supplementation and might even require endotracheal intubation with ventilator support. A blockade of inflammatory cascade with the use of tocilizumab has been shown to decrease the need for intubation and ventilator requirement.

D-dimer as a biomarker for assessment of COVID-19 prognosis: D-dimer levels on admission and its role in predicting disease outcome in hospitalized patients with COVID-19.

INTRODUCTION: Coronavirus Disease 2019 is a primarily respiratory illness that can cause thrombotic disorders. Elevation of D-dimer is a potential biomarker for poor prognosis in COVID-19, though optimal cutoff value for D-dimer to predict mortality has not yet been established. This study aims to assess the accuracy of admission D-dimer in the prognosis of COVID-19 and to establish the optimal cutoff D-dimer value to predict hospital mortality. METHODS: Clinical and laboratory parameters and outcomes of confirmed COVID-19 cases admitted to four hospitals in Kathmandu were retrospectively analyzed. Admitted COVID-19 cases with recorded D-dimer and definitive outcomes were included consecutively. D-dimer was measured using immunofluorescence assay and reported in Fibrinogen Equivalent Unit (µg/ml). The receiver operating characteristic curve was used to determine the accuracy of D-dimer in predicting mortality, and to calculate the optimal cutoff value, based on which patients were divided into two groups and predictive value of D-dimer for mortality was measured. RESULTS: 182 patients were included in the study out of which 34(18.7%) died during the hospital stay. The mean admission D-dimer among surviving patients was 1.067 µg/ml (±1.705 µg/ml), whereas that among patients who died was 3.208 µg/ml (±2.613 µg/ml). ROC curve for D-dimer and mortality gave an area under the curve of 0.807 (95% CI 0.728-0.886, p<0.001). Optimal cutoff value for D-dimer was 1.5 µg/ml (sensitivity 70.6%, specificity 78.4%). On Cox proportional hazards regression analysis, the unadjusted hazard ratio for high D-dimer was 6.809 (95% CI 3.249-14.268, p<0.001), and 5.862 (95% CI 2.751-12.489, p<0.001) when adjusted for age. CONCLUSION: D-dimer value on admission is an accurate biomarker for predicting mortality in patients with COVID-19. 1.5 µg/ml is the optimal cutoff value of admission D-dimer for predicting mortality in COVID-19 patients.

Recurrent Pneumothorax in an Adult Male With Bilateral COVID-19 Pneumonia.

Pneumothorax is defined as the condition in which air is collected between the visceral and parietal pleura. Pneumothorax as a complication of coronavirus disease 2019 (COVID-19) infection has been reported in relatively few cases and recurrent pneumothorax is even rarer. We present a case of a 50-year-old critically ill patient who required mechanical ventilation for 55 days and developed recurrent bilateral pneumothorax. The patient initially presented with shortness of breath and cough. He was found to be COVID-19 positive on the polymerase chain reaction (PCR) test. Subsequently, his oxygen demand increased, and he ultimately needed mechanical ventilation. He developed four episodes of pneumothorax. The patient was managed in all four episodes with intercostal tube insertion. To prevent subsequent episodes, pleurodesis was performed after the fourth episode of pneumothorax.