Identifying the Next Mutation of Concern - Exploiting Genomics for Tracking Sars-Cov-2 Mutations and Their Biological Impact in Canada

Intro: Viruses, including SARS-CoV-2, which causes COVID-19, are constantly changing. These genetic changes (aka mutations) occur over time and can lead to the emergence of new variants that may have different characteristics. After the first SARS-CoV-2 genome was published in early 2020, scientists all over the world soon realized the immediate need to obtain as much genetic information from as many strains as possible. However, understanding the functional significance of the mutations harbored by a variant is important to assess its impact on transmissibility, disease severity, immune escape, and the effectiveness of vaccines and therapeutics. Method(s): Here in Canada, we have developed an interactive framework for visualizing and reporting mutations in SARS-CoV-2 variants. This framework is composed of three stand-alone yet connected components;an interactive visualization (COVID-MVP), a manually curated functional annotation database (pokay), and a genomic analysis workflow (nf-ncov-voc). Finding(s): COVID-MVP provides (i) an interactive heatmap to visualize and compare mutations in SARS-CoV-2 lineages classified across different VOCs, VOIs, and VUMs;(ii) mutation profiles including the type, impact, and contextual information;(iii) annotation of biological impacts for mutations where functional data is available in the literature;(iv) summarized information for each variant and/or lineage in the form of a surveillance report;and (v) the ability to upload raw genomic sequence(s) for rapid processing and annotating for real-time classification. Discussion(s): This comprehensive comparison allows microbiologists and public health practitioners to better predict how the mutations in emerging variants will impact factors such as infection severity, vaccine resistance, hospitalization rates, etc. Conclusion(s): This framework is cloud-compatible & standalone, which makes it easier to integrate into other genomic surveillance tools as well. COVID-MVP is integrated into the Canadian VirusSeq data portal (https://virusseqdataportal.ca) - a national data hub for SARS-COV-2 genomic data. COVID-MVP is also used by the CanCOGeN and CoVaRR networks in national COVID-19 genomic surveillance.Copyright © 2023

COVID-19: The Unprecedented Malady-A Holistic Review

Background: Coronavirus disease (COVID-19) is spreading rapidly at an unprecedented scale across continents and has emerged as the single biggest risk the world has faced in modern times. Some scientists are comparing it to Spanish flu that created havoc around a century ago. The fear of death by COVID-19 looms large in the world today. The disease has reached devastating proportions since its first reports in December 2019. Doctors are having a difficult time dealing with this challenge and the microbiologists are having sleepless nights to bring about an effective vaccine for this disease. Method(s): A number of research and review articles have been exhaustively reviewed. The collected data has been meticulously analyzed and documented. Conclusion(s): This paper reviews the different types of coronaviruses, the structure of SARS-CoV-2 re-sponsible for COVID-19, its transmission, and virulence. Further, the article discusses the diagnosis, signs and symptoms like fever, breathlessness, cough, potential loss of taste or smell, sneezing, runny nose, fatigue, headache, sore throat and different treatment approaches including drug repurposing being tried by doctors around the globe that may come handy in the management of disease symptoms. The article describes the use of remdesivir, ribavarin, lopinavir, favipiravir, hydoxychloroquine, chloroquine, and tocilizumab among others in treating COVID-19.Copyright © 2021 Bentham Science Publishers.

Deep learning-based hybrid clinical decision support system algorithm for COVID-19 diagnosis via PCR graphics and Thorax CT images, preliminary data

Introduction: The limited sensitivity of microbiological testing, challenges in radiological differential diagnosis, and expectations of quick and accurate diagnosis required developing clinical decision support systems (CDSS). We propose a new deep learning-based hybrid CDSS that combines the advantageous aspects of thorax computed tomography(CT) and reverse transcriptase-polymerase chain reaction(PCR) to overcome the weakness of each one. Method(s): We retrospectively constructed a database that contains CT images of healthy subjects and patients with COVID-19 pneumonia(CP), bacterial/viral pneumonia(BVP), interstitial lung diseases(ILD), and PCR data of patients who were tested positive and negative for SARS-CoV-2. A new 3D-convolutional neural network (3D-CNN) and long short-term memory network(LSTM) based CDSS is developed to perform accurate and robust detection of COVID19 using CT images and PCR data. Result(s): Performance results of the proposed models (Fig1) provide highly reliable diagnosis of COVID-19 with 93.2% and 99.7% AUC for CT and PCR data, respectively. Conclusion(s): Proposed CDSS with state-of-the-art deep learning methods provides similar performance compared to both radiologists in CT evaluation and microbiologists in PCR evaluation and can be safely used. We plan to develop a hybrid CDSS algorithm further, combining laboratory data with CT and PCR models.

A rare fungi, Candida Krusei implicated in Ludwig's angina and deep neck necrotising infection- a case report and review of literature

Introduction/Aim: Ludwig's angina is potentially life-threatening, polymicrobial infection of bilateral submandibular and sublingual spaces. Most common organisms isolated from deep neck infections are viridans streptococci, streptococcus anginosus group of oral flora. We describe a previously un-reported case of Ludwig's angina associated with an unusual fungus, Candida Krusei. Case Description: 35-year-old, fit and healthy, non-smoking male patient presented with ludwig's angina and sepsis, previously diagnosed with parotitis following telephone consultation with his GP due to the COVID-19 pandemic. CT scan showed periapical pathology of both carious lower third molars with involvement of deep neck tissue spaces including the prevertebral space. The patient underwent multiple theatre visits for neck exploration and had prolonged hospital stay and subsequently recovered and discharged. Tissue samples grew Candida Krusei on multiple occasions. Discussion(s): This is a rare and previously unreported case of Ludwig's angina related to Candida Krusei. Literature search was carried out using MeSH terms Candida krusei, dental infection, neck infection, cervicofacial infection and Ludwig's angina using EMBASE, Medline, PubMed and Google Scholar. Candida Krusei has low disease-causing potential when compared to commonly found candida, with poor adhesive properties to oral cavity. It is not well-studied with regards to its virulence but has high resistance to azoles and other antifungal medications. Conclusion/Clinical Relevance: This report emphasises keeping an open mind when considering potential pathogens in cervico-dentofacial infections, to test tissue for fungi as well as bacteria, and to seek timely advice from microbiologists. The authors also counsel caution when carrying out telephone consultations during the ongoing COVID-19 pandemic. Copyright © 2022

Implementing a E-Health Tool for COVID-19 Care in West and Central Africa

Introduction/ Background: Limited access to Covid-19 guidelines may have led to patient mismanagement and antibiotic overuse. E-health tools can improve access to Covid-19 guidelines. This qualitative study supported by ANRS, Expertise France aims to identify the implementation challenges of a CDSS and aims to improve the management of Covid-19 and common infections. Methods: By videoconference, 21 qualitative, semi structured interviews were conducted with health care practitioners (57%), health care actors trained in engineering (9%), project managers (14%), biologists (5%), microbiologists/antimicrobial resistance experts (10%), and anthropologists (5%). Once transcribed by an external firm, the data were analyzed by the same researchers following a thematic analysis. Identified site visits were conducted in Abidjan and an acceptability questionnaire completed by the practitioners and the responses have been analyzed. Results: This analysis revealed limited access to Covid-19 clinical guidelines and infections in general, which were identified as structural challenges for nonspecialist practitioners depending on the country. The clinical decision support system (CDSS) <<Antibioclic Afrique>> was deployed on a pilot basis in Abidjan (Côte d'Ivoire). Out of 1380 practitioners who visited the website in 2390 sessions from February to October 2021, 62.5% had never had access to such a tool and 53.8% found it very relevant. These results formed the basis for a pilot CDSS for antimicrobial prescribing in Africa. (https://www.antibioclic-afrique.com) available as an IOS and Android mobile application. Impact: According to WHO, the diffusion of digital health tools is still very limited in Africa . This CDSS aims at improving the management of Covid-19 by strengthening prescribers' capacities and their adherence to clinical guidelines. Considering the weight of socio-economic factors in the misuse of antibiotics, qualitative multi-dimensional studies are needed. Conclusion: These results confirm the relevance of the CDSS for better access to Covid-19 clinical guidelines and demonstrate that digital tools can help practitioners in their diagnostic and therapeutic decisions. The survey continues and the feedback from users will allow us to improve it.

The State of Hospital Infection Services in the UK: National Workforce Survey 2021

Introduction: With the evolution of centralised ‘hub and spoke’ microbiology services, the expansion of infectious diseases as a medical specialty and the advent of joint infection training pathways, the infection services within the United Kingdom (UK) are experiencing a period of rapid change. Despite this, to date there has been no comprehensive description of the distribution of specialty staffing and service provision across the country. To this end, the British Infection Association (BIA), in conjunction with the Royal College of Pathologists (RCPath), has undertaken a national survey of National Health Service (NHS) infection services. Methods: Questions were compiled following consultation with an expert panel including BIA Council members. An online survey was distributed to clinical leads at all UK NHS acute trusts or health boards with inpatient beds and data were collected between April and August 2021. Results: The overall response rate was 72% (108 respondents). The median number of infection consultant full time equivalents (FTE) per service was 6.1 overall (5.6 per 1000 acute beds) although this varied between the devolved nations and was lowest in centres with microbiology specialists only. Forty-three services had three or fewer FTE medically qualified infection specialists. Overall, 17.5% of all funded FTE consultant-level posts were vacant, although this was markedly higher for microbiology-accredited posts (20.3%) than for infectious diseases (ID) (9.3%) or medical virology (14.6%). There were fewer vacancies in centres with ID-accredited consultants;median 1.0 (IQR 0–2.2) versus those with microbiology only;1.8 (IQR 0–2.9). Distribution of non-consultant staff was extremely heterogenous with 44 services having none and 25 having one or less FTE (most of which employed microbiology-only accredited consultants). 30% of organisations reported at least one vacant training post. Half of the responding organisations reported at least one consultant accredited in ID but only 28 provided inpatient care with a total of 520 ‘dedicated’ ID beds, of which 235 were negative pressure side-rooms. Geographically, several large areas of the country lacked inpatient ID capacity and/or ID-accredited consultant expertise. The burden of laboratory-related and reporting work in relation to staffing levels is disproportionately greater at smaller centres;there are a median 7.7 (IQR 5.9–9.5) hours/person/week at centres with three or fewer consultants and 4.0 (IQR 2.1–6.3) at larger centres. Conclusion: Microbiology specialists continue to provide the bulk of infection services across the UK and there is marked geographical variation in staffing with regards to other specialities. With Core Infection Training now producing dual-accredited consultants, there is an untapped potential to expand inpatient ID service provision although the requirement for placements on an existing inpatient ID unit may be limiting this currently. There are extremely high vacancies rates across the country but smaller, microbiology-only centres are hardest-hit with many barely attaining the consultant numbers required to staff a safe on-call rota. Workforce planning with utilisation of the valuable expertise of non-medically-trained staff, such as Clinical Scientists, is urgently needed. The results of this survey, in conjunction with Best Practice Standards recently published by the BIA, RCPath and Royal College of Physicians can inform commissioning and delivery of infection expertise in the context of the aftermath of the COVID-19 pandemic.

Urinary antigen testing for respiratory infection during COVID-19: The microbiologist as a diagnostic steward

The use of antimicrobials in the management of community-acquired COVID-19 is commonplace but evidence for coinfection with common bacterial pathogens to justify their use is lacking. We undertook a retrospective review of all respiratory cultures, blood cultures and urinary antigen tests in COVID-19 patients looking for co-infection with Streptococcus pneumoniae and Legionella pneumophila, and specifically to judge the utility of urinary antigen testing. 2674 GSTT patients were included who had a positive RT-PCR test for SARS-CoV-2 performed at GSTT between 03-March-2020 and 31-Jan-2021 and who had at least one other microbiology sample for review.

Impact of an Antimicrobial Stewardship Program in the First Year of Pandemic 2020 in a Large,Academic, Public Network Hospitals in Bogotá,Colombia

Background. Antimicrobial resistance is a major public health threat internationally but, particularly in Colombia. High and increasing rates of carbapenemases are challenging. Implementing antimicrobial stewardship programs (AMSs) in a large, academic, public network hospitals in Bogotá, Colombia.will help curb inappropriate antibiotic use. Methods. AMS was established in April 2020 consisting of an administrative champion, Infectious Diseases staff, nurse, General Physician, microbiologist, and pharmacists. Antimicrobial stewardship program interventions included postprescriptive audit and establishment of institutional guidelines. The AMS tracked appropriate drug selection including loading dose, maintenance dose, frequency, route, duration of therapy, de-escalation, and compliance with AMS recommendations. Defined daily dose (DDD) of drugs and health economics evaluations of antimicrobials (April-December 2020). Recommendations are placed in the electronic medical record as a progress note. Results. From April to December 2020, 1013 patients were evaluated by means of a prospective methodology. Unnecessary 689 days of hospitalization and 4420 days of antibiotic therapy were avoided. Among the top antibiotics discontinued were piperacillin tazobactam for the months of July, August, November and December, while for September and October was meropenem. The intensive care unit was the most frequently intervened service (52%), followed by hospitalization (43%) and the emergency department (5%).Over the course of the year, there was significant adherence to the program, with 100% in July, followed by 93.3% in April, 87% in December, 86.6% in May and June, 83% in November, 80% in September, 73.3% in August and 57% in October. The AMS program was able to save $47.409US in antibiotics and $55.529US in hospitalization, and 11% decrease in nephrotoxicity events (14 renal failures were avoided), which also saved additionally $ 23.503 US for a total of an estimated cost saving for the network public hospitals of $ 126.441 US by 2020. Conclusion. Implementation of a multidisciplinary antibiotic stewardship program in this academic, large, academic, public network hospitals in Bogotá, Colombia demonstrated feasibility and economic benefits even in a Covid19 pandemic situation.

Melioidosis: A Neglected Infection in Bangladesh

Bangladesh is an example of a highly populous, agricultural country where melioidosis may be a significantly under diagnosed cause of infection and death. A recent regression model predicted 16,931 cases annually in Bangladesh with a mortality rate of 56%. However, we only manage to confirm (culture) around 80 cases in last 60 years. A lack of awareness among microbiologists and clinicians and a lack of diagnostic microbiology infrastructure are factors that are likely to lead to the underreporting of melioidosis. Melioidosis transmits through inoculation, inhalation and ingestion. Diabetes mellitus is the most common risk factor (12 times higher chance of getting the infection) predisposing individuals to melioidosis and is present in >50% of all patients. The clinical presentation is widely varied and can be mistaken for other diseases such as tuberculosis or more common forms of pneumonia giving rise to its nickname as the “great mimicker”. Disease manifestations vary from pneumonia or localized abscess to acute septicemias, or may present as a chronic infection. Culture is considered the current gold-standard for diagnosis and culture-confirmation should always be sought in patients where disease is suspected. It is strongly recommended that any non–Pseudomonas aeruginosa, oxidase-positive, Gram-negative bacillus isolated from any clinical specimen from a patient in an endemic area should be suspected to be Burkholderia pseudomallei (BP). In addition, based on antibiogram, any Gramnegative bacilli that are oxidase-positive, typically resistant to aminoglycosides (e.g., gentamicin), colistin, and polymyxin but sensitive to amoxicillin/clavulanic acid should be considered as BP. This bacteria is inherently resistant to penicillin, ampicillin, first generation and second-generation cephalosporins, gentamicin, tobramycin, streptomycin, and polymyxin. For intensive phase (10 to 14 days), ceftazidime or carbapenem is the drug of choice. For eradication phase (3 to 6 months), oral trimethoprim/ sulfamethoxazole is the drug of choice. Surgery (drainage of abscess) has an important role in the management of melioidosis. Preventive measures through protective gears could be useful particularly for the risk groups.