SARS-CoV-2 B.1.214.1, B.1.214.2 and B.1.620 are predominant lineages between December 2020 and July 2021 in the Republic of Congo.

Background: : SARS-CoV-2 variants have been emerging and are shown to increase transmissibility, pathogenicity, and decreased vaccine efficacies. The objective of this study was to determine the distribution, prevalence, and dynamics of SARS-CoV-2 variants circulating in Brazzaville, the Republic of Congo (ROC). Methods: : Between December 2020 and July 2021, a total of n=600 oropharyngeal specimens collected in the community were tested for COVID-19. Of the samples tested, 317 (53%) were SARS-CoV-2 positive. All samples that had a threshold of Ct <30 (n=182) were sequenced by next-generation sequencing (NGS), and all complete sequenced genomes were submitted to GISAID; lineages were assigned using pangolin nomenclature and a phylogenetic tree was reconstructed. In addition, the global prevalence of the predominant lineages was analysed using data from GISAID and Outbreak databases. Results: : A total of 15 lineages circulated with B.1.214.2 (26%), B.1.214.1 (19%) and B.1.620 (18%) being predominant. The variants of concern (VOC) alpha (B.1.1.7) (6%) and for the first time in June delta (B.1.617.2) (4%) were observed. In addition, the B.1.214.1 lineage first reported from ROC was observed to be spreading locally and regionally. Phylogenetic analysis suggests that the B.1.620 variant (VUM) under observation may have originated from either Cameroon or the Central African Republic. SARS-CoV-2 lineages were heterogeneous, with the densely populated districts of Poto-Poto and Moungali likely the epicenter of spread. Conclusion: : Longitudinal monitoring and molecular surveillance across time and space are critical to understanding viral phylodynamics, which could have important implications for transmissibility and impact infection prevention and control measures.

Multi-omics approach to COVID-19: a domain-based literature review.

BACKGROUND: Omics data, driven by rapid advances in laboratory techniques, have been generated very quickly during the COVID-19 pandemic. Our aim is to use omics data to highlight the involvement of specific pathways, as well as that of cell types and organs, in the pathophysiology of COVID-19, and to highlight their links with clinical phenotypes of SARS-CoV-2 infection. METHODS: The analysis was based on the domain model, where for domain it is intended a conceptual repository, useful to summarize multiple biological pathways involved at different levels. The relevant domains considered in the analysis were: virus, pathways and phenotypes. An interdisciplinary expert working group was defined for each domain, to carry out an independent literature scoping review. RESULTS: The analysis revealed that dysregulated pathways of innate immune responses, (i.e., complement activation, inflammatory responses, neutrophil activation and degranulation, platelet degranulation) can affect COVID-19 progression and outcomes. These results are consistent with several clinical studies. CONCLUSIONS: Multi-omics approach may help to further investigate unknown aspects of the disease. However, the disease mechanisms are too complex to be explained by a single molecular signature and it is necessary to consider an integrated approach to identify hallmarks of severity.

Rationale and Criteria for a COVID-19 Model Framework.

Complex systems are inherently multilevel and multiscale systems. The infectious disease system is considered a complex system resulting from the interaction between three sub-systems (host, pathogen, and environment) organized into a hierarchical structure, ranging from the cellular to the macro-ecosystem level, with multiscales. Therefore, to describe infectious disease phenomena that change through time and space and at different scales, we built a model framework where infectious disease must be considered the set of biological responses of human hosts to pathogens, with biological pathways shared with other pathologies in an ecological interaction context. In this paper, we aimed to design a framework for building a disease model for COVID-19 based on current literature evidence. The model was set up by identifying the molecular pathophysiology related to the COVID-19 phenotypes, collecting the mechanistic knowledge scattered across scientific literature and bioinformatic databases, and integrating it using a logical/conceptual model systems biology. The model framework building process began from the results of a domain-based literature review regarding a multiomics approach to COVID-19. This evidence allowed us to define a framework of COVID-19 conceptual model and to report all concepts in a multilevel and multiscale structure. The same interdisciplinary working groups that carried out the scoping review were involved. The conclusive result is a conceptual method to design multiscale models of infectious diseases. The methodology, applied in this paper, is a set of partially ordered research and development activities that result in a COVID-19 multiscale model.

Looking for pathways related to COVID-19: confirmation of pathogenic mechanisms by SARS-CoV-2-host interactome.

In the last months, many studies have clearly described several mechanisms of SARS-CoV-2 infection at cell and tissue level, but the mechanisms of interaction between host and SARS-CoV-2, determining the grade of COVID-19 severity, are still unknown. We provide a network analysis on protein-protein interactions (PPI) between viral and host proteins to better identify host biological responses, induced by both whole proteome of SARS-CoV-2 and specific viral proteins. A host-virus interactome was inferred, applying an explorative algorithm (Random Walk with Restart, RWR) triggered by 28 proteins of SARS-CoV-2. The analysis of PPI allowed to estimate the distribution of SARS-CoV-2 proteins in the host cell. Interactome built around one single viral protein allowed to define a different response, underlining as ORF8 and ORF3a modulated cardiovascular diseases and pro-inflammatory pathways, respectively. Finally, the network-based approach highlighted a possible direct action of ORF3a and NS7b to enhancing Bradykinin Storm. This network-based representation of SARS-CoV-2 infection could be a framework for pathogenic evaluation of specific clinical outcomes. We identified possible host responses induced by specific proteins of SARS-CoV-2, underlining the important role of specific viral accessory proteins in pathogenic phenotypes of severe COVID-19 patients.

COVID-19 welbeing study: a protocol examining perceived coercion and psychological well-being during the COVID-19 pandemic by means of an online survey, asynchronous virtual focus groups and individual interviews.

INTRODUCTION: The COVID-19 pandemic has resulted in many countries applying restrictive measures, such as lockdown, to contain and prevent further spread. The psychological impact of lockdown and working as a healthcare worker on the frontline has been chronicled in studies pertaining to previous infectious disease pandemics that have reported the presence of depressive symptoms, anxiety, insomnia, and post-traumatic stress symptoms. Potentially linked to psychological well-being and not yet studied is the possibility that lockdown and working on the frontline of the pandemic are associated with perceptions of coercion. METHODS AND ANALYSIS: The present study aimed to examine perceived coercion in those who have experienced COVID-19-related lockdown and/or worked as a frontline healthcare worker across three European countries. It aimed to describe how such perceptions may impact on psychological well-being, coping and post-traumatic growth. It will employ an explanatory mixed-methods research methodology consisting of an online survey and online asynchronous virtual focus groups (AVFGs) and individual interviews. χ2 tests and analyses of variance will be used to examine whether participants from different countries differ according to demographic factors, whether there are differences between cohorts on perceived coercion, depression, anxiety and post-traumatic growth scores. The relationship between coercion and symptoms of distress will be assessed using multiple regression. Both the AVFGs and the narrative interviews will be analysed using thematic narrative analysis. ETHICS AND DISSEMINATION: The study has been approved by University College London's Research Ethics Committee under Project ID Number 7335/004. Results will be disseminated by means of peer-reviewed publications and at national and/or international conferences.

COVID-19 disease-Temporal analyses of complete blood count parameters over course of illness, and relationship to patient demographics and management outcomes in survivors and non-survivors: A longitudinal descriptive cohort study.

BACKGROUND: Detailed temporal analyses of complete (full) blood count (CBC) parameters, their evolution and relationship to patient age, gender, co-morbidities and management outcomes in survivors and non-survivors with COVID-19 disease, could identify prognostic clinical biomarkers. METHODS: From 29 January 2020 until 28 March 2020, we performed a longitudinal cohort study of COVID-19 inpatients at the Italian National Institute for Infectious Diseases, Rome, Italy. 9 CBC parameters were studied as continuous variables [neutrophils, lymphocytes, monocytes, platelets, mean platelet volume, red blood cell count, haemoglobin concentration, mean red blood cell volume and red blood cell distribution width (RDW %)]. Model-based punctual estimates, as average of all patients' values, and differences between survivors and non-survivors, overall, and by co-morbidities, at specific times after symptoms, with relative 95% CI and P-values, were obtained by marginal prediction and ANOVA- style joint tests. All analyses were carried out by STATA 15 statistical package. MAIN FINDINGS: 379 COVID-19 patients [273 (72% were male; mean age was 61.67 (SD 15.60)] were enrolled and 1,805 measures per parameter were analysed. Neutrophils' counts were on average significantly higher in non-survivors than in survivors (P<0.001) and lymphocytes were on average higher in survivors (P<0.001). These differences were time dependent. Average platelets' counts (P<0.001) and median platelets' volume (P<0.001) were significantly different in survivors and non-survivors. The differences were time dependent and consistent with acute inflammation followed either by recovery or by death. Anaemia with anisocytosis was observed in the later phase of COVID-19 disease in non-survivors only. Mortality was significantly higher in patients with diabetes (OR = 3.28; 95%CI 1.51-7.13; p = 0.005), obesity (OR = 3.89; 95%CI 1.51-10.04; p = 0.010), chronic renal failure (OR = 9.23; 95%CI 3.49-24.36; p = 0.001), COPD (OR = 2.47; 95% IC 1.13-5.43; p = 0.033), cardiovascular diseases (OR = 4.46; 95%CI 2.25-8.86; p = 0.001), and those >60 years (OR = 4.21; 95%CI 1.82-9.77; p = 0.001). Age (OR = 2.59; 95%CI 1.04-6.45; p = 0.042), obesity (OR = 5.13; 95%CI 1.81-14.50; p = 0.002), renal chronic failure (OR = 5.20; 95%CI 1.80-14.97; p = 0.002) and cardiovascular diseases (OR 2.79; 95%CI 1.29-6.03; p = 0.009) were independently associated with poor clinical outcome at 30 days after symptoms' onset. INTERPRETATION: Increased neutrophil counts, reduced lymphocyte counts, increased median platelet volume and anaemia with anisocytosis, are poor prognostic indicators for COVID19, after adjusting for the confounding effect of obesity, chronic renal failure, COPD, cardiovascular diseases and age >60 years.

Chikungunya Outbreak in the Republic of the Congo, 2019-Epidemiological, Virological and Entomological Findings of a South-North Multidisciplinary Taskforce Investigation.

The Republic of Congo (RoC) declared a chikungunya (CHIK) outbreak on 9 February 2019. We conducted a ONE-Human-Animal HEALTH epidemiological, virological and entomological investigation. Methods: We collected national surveillance and epidemiological data. CHIK diagnosis was based on RT-PCR and CHIKV-specific antibodies. Full CHIKV genome sequences were obtained by Sanger and MinION approaches and Bayesian tree phylogenetic analysis was performed. Mosquito larvae and 215 adult mosquitoes were collected in different villages of Kouilou and Pointe-Noire districts and estimates of Aedes (Ae.) mosquitos' CHIKV-infectious bites obtained. We found two new CHIKV sequences of the East/Central/South African (ECSA) lineage, clustering with the recent enzootic sub-clade 2, showing the A226V mutation. The RoC 2019 CHIKV strain has two novel mutations, E2-T126M and E2-H351N. Phylogenetic suggests a common origin from 2016 Angola strain, from which it diverged around 1989 (95% HPD 1985-1994). The infectious bite pattern was similar for 2017, 2018 and early 2019. One Ae. albopictus pool was RT-PCR positive. The 2019 RoC CHIKV strain seems to be recently introduced or be endemic in sylvatic cycle. Distinct from the contemporary Indian CHIKV isolates and in contrast to the original Central-African strains (transmitted by Ae. aegypti), it carries the A226V mutation, indicating an independent adaptive mutation in response to vector replacement (Ae. albopictus vs Ae. aegypti).

Antimicrobial resistance preparedness in sub-Saharan African countries.

BACKGROUND: Antimicrobial resistance (AMR) is of growing concern globally and AMR status in sub-Saharan Africa (SSA) is undefined due to a lack of real-time data recording, surveillance and regulation. World Health Organization (WHO) Joint External Evaluation (JEE) reports are voluntary, collaborative processes to assess country capacities and preparedness to prevent, detect and rapidly respond to public health risks, including AMR. The data from SSA JEE reports were analysed to gain an overview of how SSA is working towards AMR preparedness and where strengths and weaknesses lie. METHODS: SSA country JEE AMR preparedness scores were analysed. A cumulative mean of all the SSA country AMR preparedness scores was calculated and compared to the overall mean SSA JEE score. AMR preparedness indicators were analysed, and data were weighted by region. FINDINGS: The mean SSA AMR preparedness score was 53% less than the overall mean SSA JEE score. East Africa had the highest percentage of countries reporting having AMR National Action Plans in place, as well as human and animal pathogen AMR surveillance programmes. Southern Africa reported the highest percentage of countries with training programmes and antimicrobial stewardship. CONCLUSIONS: The low mean AMR preparedness score compared to overall JEE score, along with the majority of countries lacking implemented National Action Plans, suggests that until now AMR has not been a priority for most SSA countries. By identifying regional and One Health strengths, AMR preparedness can be fortified across SSA with a multisectoral approach.

Ebola Virus Disease: Epidemiology, Clinical Features, Management, and Prevention.

Ebola virus disease (EVD) is a deadly zoonotic disease caused by the Ebola virus. There is no specific treatment approved for EVD. Supportive care and management of complications are mainstays of treatment. Effective outbreak control requires a multidisciplinary team effort applying case management, infection prevention and control practices, surveillance and contact tracing, a good laboratory service, safe and dignified burials, and social and community mobilization. This article highlights the epidemiology, clinical features, diagnosis, management, and prevention of EVD. The emerging diagnostic technologies, rapid viral characterization, geospatial mapping of EVD transmission, and new treatments and vaccines are discussed.

Early improvement of glycaemic control after virus clearance in patients with chronic hepatitis C and severe liver fibrosis: a cohort study.

HCV has been recognized as the cause of chronic hepatitis C (CHC) since 1990. CHC is associated with progressive liver damage and extrahepatic conditions. Direct antiviral agents (DAAs), approved in 2014, have shown effectiveness in eradicating HCV in most patients. However, little is known about the effect of viral eradication on hepatic and extra-hepatic damage. We performed a historical cohort study of patients with HCV-related liver diseases who achieved SVR from March 2015 to October 2016 at INMI Lazzaro Spallanzani liver Unit in Rome (Italy). Repeated measures of glycaemia were analysed through a multilevel analysis framework to assess short time kinetics of blood glucose level at different times after therapy and for different levels of HCV viremia. The analysis included 205 patients. A model assessing temporal kinetics and variation of glycaemia according to HCV viremia provided evidence that blood glucose levels significantly dropped in patients with diabetes achieving SVR. Most of the variations occurred at 3-5 weeks of therapy (-17.96 mg/dL; p<0.001) and in coincidence with HCV clearance (-13.92 mg/dL; p<0.001). A weak, non-statistically significant reduction was observed in normoglycemic patients. Our study provides evidence that DAAs therapy may significantly improve glycaemic control in patients with CHC achieving SVR even when liver diseases are already established.

Dangerous crossing: demographic and clinical features of rescued sea migrants seen in 2014 at an outpatient clinic at Augusta Harbor, Italy.

BACKGROUND: In recent years Europe has received an increasing influx of migrants, many of whom risked their lives crossing the Mediterranean Sea. In October 2013, Italy launched a search and rescue operation at sea in response to migrant deaths during the sea crossing. In August 2014, Médecins sans Frontières and the local Ministry of Health established an outpatient clinic at Augusta harbor, in Sicily, which received 26 % of total sea migrants arrived in Italy in 2014, to provide immediate medical assessment and care. METHODS: This is a descriptive study of demographic and clinical data of sea migrants seen at the port clinic in Augusta from August to December 2014. We compared migrants from Near Eastern, war-torn regions (Group 1) and the others, mostly African (Group 2), as there were significant differences in terms of demographic and morbidity profiles. RESULTS: There were 2593 migrants consulting the clinic (17 % af all rescued migrants) with 5 % being referred to hospital. Most were young males. The overall burden of vulnerability (pregnant women, children ≤5 years, unaccompanied minors, single parents with children of minor age, disabled and elderly persons) was 24 %. There were more small children, pregnant women, elderly, disabled, and persons with chronic diseases in Group 1, as compared to Group 2. Group 2 had more unaccompanied minors. Morbitidies in common were respiratory, dermatological, trauma-related and gastrointestinal conditions. However, acute and chronic cardiovascular disease, as well as diabetes, were more frequent in Group 1; chronic diseases affected 19 % of this group. Group 2 had more patients with skin diseases. Most migrants attributed their presenting symptoms to the perils of their journey. No risks for public health were detected. CONCLUSION: Among sea migrants, we identified two groups with different demographic and clinical characteristics, as well as vulnerability patterns. Overall morbidity suggested that the dangerous journey affected migrants' health. Medical activities at reception sites should include screening for vulnerability and chronic disease management. Ensuring medical care to migrants on arrival can address European humanitarian obligations and provide support to local medical facilities.

Ambulatory multi-drug resistant tuberculosis treatment outcomes in a cohort of HIV-infected patients in a slum setting in Mumbai, India.

BACKGROUND: India carries one quarter of the global burden of multi-drug resistant TB (MDR-TB) and has an estimated 2.5 million people living with HIV. Despite this reality, provision of treatment for MDR-TB is extremely limited, particularly for HIV-infected individuals. Médecins Sans Frontières (MSF) has been treating HIV-infected MDR-TB patients in Mumbai since May 2007. This is the first report of treatment outcomes among HIV-infected MDR-TB patients in India. METHODS: HIV-infected patients with suspected MDR-TB were referred to the MSF-clinic by public Antiretroviral Therapy (ART) Centers or by a network of community non-governmental organizations. Patients were initiated on either empiric or individualized second-line TB-treatment as per WHO recommendations. MDR-TB treatment was given on an ambulatory basis and under directly observed therapy using a decentralized network of providers. Patients not already receiving ART were started on treatment within two months of initiating MDR-TB treatment. RESULTS: Between May 2007 and May 2011, 71 HIV-infected patients were suspected to have MDR-TB, and 58 were initiated on treatment. MDR-TB was confirmed in 45 (78%), of which 18 (40%) were resistant to ofloxacin. Final treatment outcomes were available for 23 patients; 11 (48%) were successfully treated, 4 (17%) died, 6 (26%) defaulted, and 2 (9%) failed treatment. Overall, among 58 patients on treatment, 13 (22%) were successfully treated, 13 (22%) died, 7 (12%) defaulted, two (3%) failed treatment, and 23 (40%) were alive and still on treatment at the end of the observation period. Twenty-six patients (45%) experienced moderate to severe adverse events, requiring modification of the regimen in 12 (20%). Overall, 20 (28%) of the 71 patients with MDR-TB died, including 7 not initiated on treatment. CONCLUSIONS: Despite high fluoroquinolone resistance and extensive prior second-line treatment, encouraging results are being achieved in an ambulatory MDR-T- program in a slum setting in India. Rapid scale-up of both ART and second-line treatment for MDR-TB is needed to ensure survival of co-infected patients and mitigate this growing epidemic.

Kaposi's sarcoma in an HIV-positive person successfully treated with paclitaxel.

Epidemic Kaposi's sarcoma is one of the malignant neoplasms, which can develop in HIV-infected patients. Although the prevalence of HIV infection is reported to be high in Asian countries, Kaposi's sarcoma is rarely reported. We report a case of Kaposi's sarcoma involving the skin and oral mucosa along with extensive bilateral lymphedema of lower extremities, treated successfully with paclitaxel and antiretrovirals.