Value of Verbal Autopsy in a Fragile Setting: Reported versus Estimated Community Deaths Associated with COVID-19, Banadir, Somalia.

BACKGROUND: Accurate mortality data associated with infectious diseases such as coronavirus disease 2019 (COVID-19) are often unavailable in countries with fragile health systems such as Somalia. We compared officially reported COVID-19 deaths in Somalia with COVID-19 deaths estimated using verbal autopsy. METHODS: We interviewed relatives of deceased persons to collect information on symptoms, cause, and place of death. We compared these data with officially reported data and estimated the positive and negative predictive values of verbal autopsy. RESULTS: We identified 530 deaths during March-October 2020. We classified 176 (33.2%) as probable COVID-19 deaths. Most deaths (78.5%; 416/530) occurred at home and 144 (34.6%) of these were attributed to COVID-19. The positive predictive value of verbal autopsy was lower for home deaths (22.3%; 95% CI: 15.7-30.1%) than for hospital deaths (32.3%; 95% CI: 16.7-51.4%). The negative predictive value was higher: 97.8% (95% CI: 95.0-99.3%) for home deaths and 98.4% (95% CI: 91.5-100%) for hospital deaths. Conclusions Verbal autopsy has acceptable predictive value to estimate COVID-19 deaths where disease prevalence is high and can provide data on the COVID-19 burden in countries with low testing and weak mortality surveillance where home deaths may be missed.

Impact of the COVID-19 pandemic on opioid overdose and other adverse events in the USA and Canada: a systematic review.

IMPORTANCE: The COVID-19 pandemic impacted healthcare beyond COVID-19 infections. A better understanding of how COVID-19 worsened the opioid crisis has potential to inform future response efforts. OBJECTIVE: To summarize changes from the COVID-19 pandemic on outcomes regarding opioid use and misuse in the USA and Canada. EVIDENCE REVIEW: We searched MEDLINE via PubMed, EMBASE, and CENTRAL for peer-reviewed articles published between March 2020 and December 2021 that examined outcomes relevant to patients with opioid use, misuse, and opioid use disorder by comparing the period before vs after COVID-19 onset in the USA and Canada. Two reviewers independently screened studies, extracted data, assessed methodological quality and bias via Newcastle-Ottawa Scale, and synthesized results. FINDINGS: Among 20 included studies, 13 (65%) analyzed service utilization, 6 (30%) analyzed urine drug testing results, and 2 (10%) analyzed naloxone dispensation. Opioid-related emergency medicine utilization increased in most studies (85%, 11/13) for both service calls (17% to 61%) and emergency department visits (42% to 122%). Urine drug testing positivity results increased in all studies (100%, 6/6) for fentanyl (34% to 138%), most (80%, 4/5) studies for heroin (-12% to 62%), and most (75%, 3/4) studies for oxycodone (0% to 44%). Naloxone dispensation was unchanged and decreased in one study each. INTERPRETATION: Significant increases in surrogate measures of the opioid crisis coincided with the onset of COVID-19. These findings serve as a call to action to redouble prevention, treatment, and harm reduction efforts for the opioid crisis as the pandemic evolves. PROSPERO REGISTRATION NUMBER: CRD42021236464.

The Nigerian Military Public Health Response to COVID-19: A 14-Month Appraisal.

The COVID-19 pandemic has caused significant morbidity and mortality since its emergence in December 2019. In Nigeria, the government inaugurated the Presidential Task Force on COVID-19 to coordinate resources while the Nigeria Centre for Disease Control led the public health response. The Nigeria Ministry of Defence Health Implementation Programme (MODHIP), in partnership with the US Army Medical Research Directorate - Africa/Nigeria, responded immediately to the pandemic by establishing a public health emergency operations center to coordinate the military response in support of national efforts. MODHIP has 5 functional units and 6 pillars that coordinate testing, surveillance, case management, risk communication, logistics, research, and infection prevention and control. It developed an incident action plan and each pillar had its own terms of reference to guide specific response activities while preventing duplication of efforts within the military and the Nigeria Centre for Disease Control. In addition, awareness and sensitization sessions were conducted on preventive practices for COVID-19 and infrastructure was provided for hand hygiene and screening at all military facilities. Military laboratories were configured for SARS-CoV-2 testing while selected military health facilities were equipped and designated as COVID-19 treatment centers. Research proposals aimed at better understanding the disease and controlling it were also developed. The traditional combat role of the military was redirected to complement this public health emergency response. In this article, we highlight gaps, opportunities, and lessons to improve military participation in public health emergency response in the future. More funding and multisectoral collaboration with civilian institutions are key to strengthening military public health emergency preparedness and response capabilities.

Conducting mass gathering events during the COVID-19 pandemic: a case study of Kumbh Mela 2021 as a potential 'super spreader event'.

BACKGROUND: With the emergence of novel pathogens, there is a worldwide debate on the cancellation or conduction of mass gathering events. METHODS: In the current coronavirus disease-2019 (COVID-19) pandemic situation, this study assesses the challenges in the conduction of the recently held Kumbh Mela mass gathering (MG), which took place from 14th January 2021 to 29th April 2021 at Haridwar, the capital city of the state of Uttarakhand, India. The correlation between increased cases of COVID-19 and the Kumbh Mela MG has been highlighted through statistical analysis and growth curves using the available data. RESULTS: The Kumbh Mela-2021 emerged as a potential super spreader event with an increase of 37 cases per day to 144 cases per day (276%) in the COVID-19 cases in Haridwar. An increase from 138 to 480 cases per day (236%) and from 45 600 to 92 754 cases per day (92%) was noted in Uttarakhand and India respectively during this MG. A very strong correlation of 'more than 0.99' was seen between the number of cumulative cases of COVID-19 in Uttarakhand and Haridwar, and Haridwar and India during the Kumbh Mela in the third wave of the pandemic. CONCLUSIONS: The direct influence of Kumbh Mela on the increase in the overall number of COVID-19 cases is observed. Although, the socio-cultural, psychological and economical advantages of MGs are considerable in a developing nation like India, but organization of such events can be a huge health hazard. The lack of efficient implementation and observance of COVID-19 guidelines elevates the necessity of cancellation of such MGs to prevent the outbreak of diseases. Thus, a well-conducted risk assessment prior to the hosting of a MG event during a pandemic is required with strict application of precautionary measures towards prevention of super-spreader events.

Global research priorities for COVID-19 in maternal, reproductive and child health: Results of an international survey.

BACKGROUND: The World Health Organization's "Coordinated Global Research Roadmap: 2019 Novel Coronavirus" outlined the need for research that focuses on the impact of COVID-19 on pregnant women and children. More than one year after the first reported case significant knowledge gaps remain, highlighting the need for a coordinated approach. To address this need, the Maternal, Newborn and Child Health Working Group (MNCH WG) of the COVID-19 Clinical Research Coalition conducted an international survey to identify global research priorities for COVID-19 in maternal, reproductive and child health. METHOD: This project was undertaken using a modified Delphi method. An electronic questionnaire was disseminated to clinicians and researchers in three different languages (English, French and Spanish) via MNCH WG affiliated networks. Respondents were asked to select the five most urgent research priorities among a list of 17 identified by the MNCH WG. Analysis of questionnaire data was undertaken to identify key similarities and differences among respondents according to questionnaire language, location and specialty. Following elimination of the seven lowest ranking priorities, the questionnaire was recirculated to the original pool of respondents. Thematic analysis of final questionnaire data was undertaken by the MNCH WG from which four priority research themes emerged. RESULTS: Questionnaire 1 was completed by 225 respondents from 29 countries. Questionnaire 2 was returned by 49 respondents. The four priority research themes which emerged from the analysis were 1) access to healthcare during the COVID-19 pandemic, 2) the direct and 3) indirect effects of COVID-19 on pregnant and breastfeeding women and children and 4) the transmission of COVID-19 and protection from infection. CONCLUSION: The results of these questionnaires indicated a high level of concordance among continents and specialties regarding priority research themes. This prioritized list of research uncertainties, developed to specifically highlight the most urgent clinical needs as perceived by healthcare professionals and researchers, could help funding organizations and researchers to answer the most pressing questions for clinicians and public health professionals during the pandemic. It is hoped that these identified priority research themes can help focus the discussion regarding the allocation of limited resources to enhance COVID-19 research in MNCH globally.

Delirium and neuropsychological outcomes in critically Ill patients with COVID-19: a cohort study.

OBJECTIVE: To characterise the clinical course of delirium for patients with COVID-19 in the intensive care unit, including postdischarge neuropsychological outcomes. DESIGN: Retrospective chart review and prospective survey study. SETTING: Intensive care units, large academic tertiary-care centre (USA). PARTICIPANTS: Patients (n=148) with COVID-19 admitted to an intensive care unit at Michigan Medicine between 1 March 2020 and 31 May 2020 were eligible for inclusion. PRIMARY AND SECONDARY OUTCOME MEASURES: Delirium was the primary outcome, assessed via validated chart review method. Secondary outcomes included measures related to delirium, such as delirium duration, antipsychotic use, length of hospital and intensive care unit stay, inflammatory markers and final disposition. Neuroimaging data were also collected. Finally, a telephone survey was conducted between 1 and 2 months after discharge to determine neuropsychological function via the following tests: Family Confusion Assessment Method, Short Blessed Test, Patient-Reported Outcomes Measurement Information System Cognitive Abilities 4a and Patient-Health Questionnaire-9. RESULTS: Delirium was identified in 108/148 (73%) patients, with median (IQR) duration lasting 10 (4-17) days. In the delirium cohort, 50% (54/108) of patients were African American and delirious patients were more likely to be female (76/108, 70%) (absolute standardised differences >0.30). Sedation regimens, inflammation, delirium prevention protocol deviations and hypoxic-ischaemic injury were likely contributing factors, and the most common disposition for delirious patients was a skilled care facility (41/108, 38%). Among patients who were delirious during hospitalisation, 4/17 (24%) later screened positive for delirium at home based on caretaker assessment, 5/22 (23%) demonstrated signs of questionable cognitive impairment or cognitive impairment consistent with dementia and 3/25 (12%) screened positive for depression within 2 months after discharge. CONCLUSION: Patients with COVID-19 commonly experience a prolonged course of delirium in the intensive care unit, likely with multiple contributing factors. Furthermore, neuropsychological impairment may persist after discharge.

Analysis of SARS-CoV-2 infection associated cell entry proteins ACE2, CD147, PPIA, and PPIB in datasets from non SARS-CoV-2 infected neuroblastoma patients, as potential prognostic and infection biomarkers in neuroblastoma.

SARS-CoV-2 viral contagion has given rise to a worldwide pandemic. Although most children experience minor symptoms from SARS-CoV-2 infection, some have severe complications including Multisystem Inflammatory Syndrome in Children. Neuroblastoma patients may be at higher risk of severe infection as treatment requires immunocompromising chemotherapy and SARS-CoV-2 has demonstrated tropism for nervous cells. To date, there is no sufficient epidemiological data on neuroblastoma patients with SARS-CoV-2. Therefore, we evaluated datasets of non-SARS-CoV-2 infected neuroblastoma patients to assess for key genes involved with SARS-CoV-2 infection as possible neuroblastoma prognostic and infection biomarkers. We hypothesized that ACE2, CD147, PPIA and PPIB, which are associated with viral-cell entry, are potential biomarkers for poor prognosis neuroblastoma and SARS-CoV-2 infection. We have analysed three publicly available neuroblastoma gene expression datasets to understand the specific molecular susceptibilities that high-risk neuroblastoma patients have to the virus. Gene Expression Omnibus (GEO) GSE49711 and GEO GSE62564 are the microarray and RNA-Seq data, respectively, from 498 neuroblastoma samples published as part of the Sequencing Quality Control initiative. TARGET, contains microarray data from 249 samples and is part of the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative. ACE2, CD147, PPIA and PPIB were identified through their involvement in both SARS-CoV-2 infection and cancer pathogenesis. In-depth statistical analysis using Kaplan-Meier, differential gene expression, and Cox multivariate regression analysis, demonstrated that overexpression of ACE2, CD147, PPIA and PPIB is significantly associated with poor-prognosis neuroblastoma samples. These results were seen in the presence of amplified MYCN, unfavourable tumour histology and in patients older than 18 months of age. Previously, we have shown that high levels of the nerve growth factor receptor NTRK1 together with low levels of the phosphatase PTPN6 and TP53 are associated with increased relapse-free survival of neuroblastoma patients. Interestingly, low levels of expression of ACE2, CD147, PPIA and PPIB are associated with this NTRK1-PTPN6-TP53 module, suggesting that low expression levels of these genes are associated with good prognosis. These findings have implications for clinical care and therapeutic treatment. The upregulation of ACE2, CD147, PPIA and PPIB in poor-prognosis neuroblastoma samples suggests that these patients may be at higher risk of severe SARS-CoV-2 infection. Importantly, our findings reveal ACE2, CD147, PPIA and PPIB as potential biomarkers and therapeutic targets for neuroblastoma.

COVID-19 in the least developed, fragile, and conflict-affected countries - How can the most vulnerable be protected?

The relentless spread of coronavirus disease 2019 (COVID-19) and its penetration into the least developed, fragile, and conflict-affected countries (LDFCAC) is a certainty. Expansion of the pandemic will be expedited by factors such as an abundance of at-risk populations, inadequate COVID-19 mitigation efforts, sheer inability to comply with community mitigation strategies, and constrained national preparedness. This situation will reduce the benefits achieved through decades of disease control and health promotion measures, and the economic progress made during periods of global development. Without interventions, and as soon as international travel and trade resume, reservoirs of COVID-19 and other vaccine-preventable diseases in LDFCAC will continue 'feeding' developed countries with repeated infection seeds. Assuring LDFCAC equity in access to medical countermeasures, funds to mitigate the pandemic, and a paradigm change in the global development agenda, similar to the post-World War II Marshall Plan for Europe, are urgently needed. We argue for a paradigm change in strategy, including a new global pandemic financing mechanism for COVID-19 and other future pandemics. This approach should assist LDFCAC in gaining access to and membership of a global interdisciplinary pandemic taskforce to enable in-country plans to train, leverage, and maintain essential functioning and also to utilize and enhance surveillance and early detection capabilities. Such a task force will be able to build on and expand research into the management of pandemics, protect vulnerable populations through international laws/treaties, and reinforce and align the development agenda to prevent and mitigate future pandemics. Lifting LDFCAC from COVID-related failure will offer the global community the best economic dividends of the century.

All Hands on Deck: A synchronized whole-of-world approach for COVID-19 mitigation.

The COVID-19 pandemic can no longer be mitigated by a nationwide approach of individual nations alone. Given its scale and accelerating expansion, COVID-19 requires a coordinated and simultaneous Whole- of-World approach that galvanizes clear global leadership and solidarity from all governments of the world. Considering an 'all hands-on deck' concept, we present a comprehensive list of tools and entities responsible for enabling them, as well a conceptual framework to achieve the maximum impact. The list is drawn from pandemic mitigation tools developed in response to past outbreaks including influenza, coronaviruses, and Ebola, and includes tools to minimize transmission in various settings including person-to-person, crowd, funerals, travel, workplace, and events and gatherings including business, social and religious venues. Included are the roles of individuals, communities, government and other sectors such as school systems, health, institutions, and business. While individuals and communities have significant responsibilities to prevent person-to-person transmission, other entities can play a significant role to enable individuals and communities to make use of the tools. Historic and current data indicate the role of political will, whole-of-government approach, and the role of early introduction of mitigation measures. There is also an urgent need to further elucidate the immunologic mechanisms underlying the epidemiological characteristics such as the low disease burden among women, and the role of COVID-19 in inducing Kawasaki-like syndromes in children. Understanding the role of and development of anti-inflammatory strategies based on our understanding of pro-inflammatory cytokines (IL1, IL-6) is also critical. Similarly, the role of oxygen therapy as an anti-inflammatory strategy is evident and access to oxygen therapy should be prioritized to avoid the aggravation of COVID-19 infection. We highlight the need for global solidarity to share both mitigation commodities and infrastructure between countries. Given the global reach of COVID-19 and potential for repeat waves of outbreaks, we call on all countries and communities to act synergistically and emphasize the need for synchronized pan-global mitigation efforts to minimize everyone's risk, to maximize collaboration, and to commit to shared progress.