World Tuberculosis Day 2023 theme "Yes! We Can End TB!"

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. METHODS: 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). Findings: 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: 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: 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.

Historical perspective: other human coronavirus infectious diseases, SARS and MERS

Alphacoronaviruses (HCoV-229E and HCoV-NL63) and betacoronaviruses (HCoV-OC43 and HCoV-HKU1) are common causes of upper respiratory tract infection in humans. SARS-CoV-1 and MERS-CoV emerged in 2002 and 2012, respectively, with the potential of causing severe and lethal disease in humans, termed SARS and MERS, respectively. Bats appear to be the common natural source of SARS-like coronaviruses including SARS-CoV-1, but their role in MERS-CoV is less clear. Civet cats and dromedary camels are the intermediary animal sources for SARS-CoV-1 and MERS-CoV, respectively. Nosocomial outbreaks are hallmarks of SARS and MERS. MERS patients with comorbidities or immunosuppression tend to progress more rapidly to respiratory failure and have a higher case fatality rate than SARS patients. SARS has disappeared since 2004, while there are still sporadic cases of MERS in the Middle East. Continued global surveillance is essential for SARS-like coronaviruses and MERS-CoV to monitor changing epidemiology due to viral variants.Copyright © ERS 2021.

Advancing detection and response capacities for emerging and re-emerging pathogens in Africa

Recurrent disease outbreaks caused by a range of emerging and resurging pathogens over the past decade reveal major gaps in public health preparedness, detection, and response systems in Africa. Underlying causes of recurrent disease outbreaks include inadequacies in the detection of new infectious disease outbreaks in the community, in rapid pathogen identification, and in proactive surveillance systems. In sub-Saharan Africa, where 70% of zoonotic outbreaks occur, there remains the perennial risk of outbreaks of new or re-emerging pathogens for which no vaccines or treatments are available. As the Ebola virus disease, COVID-19, and mpox (formerly known as monkeypox) outbreaks highlight, a major paradigm shift is required to establish an effective infrastructure and common frameworks for preparedness and to prompt national and regional public health responses to mitigate the effects of future pandemics in Africa.Copyright © 2022 Elsevier Ltd

Human Coronavirus Infections—Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and SARS-CoV-2

Three novel coronaviruses have emerged as new lethal zoonotic pathogens of humans during the past 17 years: The Severe Acute Respiratory Syndrome (SARS) coronavirus (SARS-CoV), the Middle East Respiratory Syndrome (MERS) coronavirus (MERS-CoV), and most recently SARS-CoV-2. SARS-CoV first surfaced as a human pathogen in Guangdong, China in November 2002 and rapidly spread worldwide with 8098 cases and 774 deaths before the end of the epidemic. SARS-like CoVs have been detected in horseshoe bats with high sequence homology with human or civet isolates, suggesting that bats could be a natural reservoir of a close ancestor of SARS-CoV. No cases of SARS have been reported since January 2004. MERS-CoV was first reported in September 2012, after it was isolated from respiratory samples from a patient in Jeddah, Saudi Arabia who died in June 2012. How humans acquire MERS-CoV infection is not yet known although bats and dromedary camels are intermediary reservoirs. MERS-CoV continues to circulate in the Middle East. As of May 22, 2019, 2428 cases of laboratory-confirmed MERS-CoV cases reported to the World Health Organization, including 838 deaths (34.5% mortality) have been reported from 27 countries. While the majority of MERS cases occur in the Middle East, travel related MERS cases have been reported from all continents. Large health care associated outbreaks of MERS-CoV have occurred in Saudi Arabia, United Arab Emirates, and the Republic of Korea. SARS-CoV-2 emerged from Wuhan, China in December 2019, and by March 2020 had established as a pandemic which has caused massive disruption in multiple countries. The eventual mortality caused by this virus remains to be seen. All three viruses cause a similar wide range of nonspecific clinical manifestations from mild upper respiratory tract illness to severe respiratory, gastrointestinal and other extra-pulmonary disease. Early recognition of cases, improved compliance with internationally recommended infection control protocols, and rapid implementation of infection control measures are required to prevent health care facility-associated outbreaks, and in the case of SARS-CoV-2 for control of community spread as well. Treatment is supportive and there are no specific antivirals or vaccines available for both SARS and MERS. © 2022 Elsevier Ltd. All rights reserved

Comparison of patients with severe COVID-19 admitted to an intensive care unit in South Africa during the first and second wave of the COVID-19 pandemic.

Background: The second wave of coronavirus disease 2019 (COVID-19), dominated by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Beta variant, has been reported to be associated with increased severity in South Africa (SA). Objectives: To describe and compare clinical characteristics, management and outcomes of COVID-19 patients admitted to an intensive care unit (ICU) in SA during the first and second waves. Methods: In a prospective, single-centre, descriptive study, we compared all patients with severe COVID-19 admitted to ICU during the first and second waves. The primary outcomes assessed were ICU mortality and ICU length of stay (LOS). Results: In 490 patients with comparable ages and comorbidities, no difference in mortality was demonstrated during the second compared with the first wave (65.9% v. 62.5%, p=0.57). ICU LOS was longer in the second wave (10 v. 6 days, p<0.001). More female admissions (67.1% v. 44.6%, p<0.001) and a greater proportion of patients were managed with invasive mechanical ventilation than with non-invasive respiratory support (39.0% v. 14%, p<0.001) in the second wave. Conclusion: While clinical characteristics were comparable between the two waves, a higher proportion of patients was invasively ventilated and ICU stay was longer in the second. ICU mortality was unchanged.

An inflammatory profile correlates with decreased frequency of cytotoxic cells in coronavirus disease 2019. (COVID special issue #2.)

Increased production of inflammatory cytokines and myeloid-derived suppressor cells occurs in patients with coronavirus disease 2019. These inversely correlated with perforin-expressing natural killer (NK) and CD3⁺ T cells. We observed a lower number of perforin-expressing NK cells in intensive care unit (ICU) patients compared with non-ICU patients, suggesting an impairment of the immune cytotoxic arm as a pathogenic mechanism.

Mass gatherings medicine: public health issues arising from mass gathering religious and sporting events

Mass gathering events are associated with major public health challenges. The 2014 Lancet Series on the new discipline of mass gatherings medicine was launched at the World Health Assembly of Ministers of Health in Geneva in May, 2014. The Series covered the planning and surveillance systems used to monitor public health risks, public health threats, and experiences of health-care providers from mass gathering events in 2012 and 2013. This follow-up Review focuses on the main public health issues arising from planned mass gathering events held between 2013 and 2018. We highlight public health and research data on transmission of infectious diseases and antibiotic-resistant bacteria, mass casualty incidents, and non-communicable diseases, including thermal disorders. In the events discussed in this Review, the combination of a large influx of people, many from countries with outbreak-prone infectious diseases, with a high degree of crowd interactions imposed substantial burdens on host countries' health systems. The detection and transmission of antibiotic-resistant bacteria in pilgrims attending the Kumbh Mela and the Hajj raise concern of possible globalisation from mass-gathering religious events. Priorities for further investments and opportunities for research into prevention, surveillance, and management of these public health issues are discussed.

COVID-19 and renin-angiotensin system inhibition: role of angiotensin converting enzyme 2 (ACE2) - Is there any scientific evidence for controversy?

Renin-angiotensin system (RAS) blockers are extensively used worldwide to treat many cardiovascular disorders, where they are effective in reducing both mortality and morbidity. These drugs are known to induce an increased expression of angiotensin-converting enzyme 2 (ACE2). ACE2 acts as receptor for the novel SARS coronavirus-2 (SARS-CoV-2) which raising the important issue of possible detrimental effects that RAS blockers could exert on the natural history and pathogenesis of the coronavirus disease-19 (COVID-19) and associated excessive inflammation, myocarditis and cardiac arrhythmias. We review the current knowledge on the interaction between SARS-CoV-2 infection and RAS blockers and suggest a scientific rationale for continuing RAS blockers therapy in patients with COVID-19 infection.

Middle East respiratory syndrome [Review]

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal zoonotic pathogen that was first identified in humans in Saudi Arabia and Jordan in 2012. Intermittent sporadic cases, community clusters, and nosocomial outbreaks of MERS-CoV continue to occur. Between April 2012 and December 2019, 2499 laboratory-confirmed cases of MERS-CoV infection, including 858 deaths (34.3% mortality) were reported from 27 countries to WHO, the majority of which were reported by Saudi Arabia (2106 cases, 780 deaths). Large outbreaks of human-to-human transmission have occurred, the largest in Riyadh and Jeddah in 2014 and in South Korea in 2015. MERS-CoV remains a high-threat pathogen identified by WHO as a priority pathogen because it causes severe disease that has a high mortality rate, epidemic potential, and no medical countermeasures. This Seminar provides an update on the current knowledge and perspectives on MERS epidemiology, virology, mode of transmission, pathogenesis, diagnosis, clinical features, management, infection control, development of new therapeutics and vaccines, and highlights unanswered questions and priorities for research, improved management, and prevention.