Single-cell landscape of immunological responses in patients with COVID-19.

In coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the relationship between disease severity and the host immune response is not fully understood. Here we performed single-cell RNA sequencing in peripheral blood samples of 5 healthy donors and 13 patients with COVID-19, including moderate, severe and convalescent cases. Through determining the transcriptional profiles of immune cells, coupled with assembled T cell receptor and B cell receptor sequences, we analyzed the functional properties of immune cells. Most cell types in patients with COVID-19 showed a strong interferon-α response and an overall acute inflammatory response. Moreover, intensive expansion of highly cytotoxic effector T cell subsets, such as CD4+ effector-GNLY (granulysin), CD8+ effector-GNLY and NKT CD160, was associated with convalescence in moderate patients. In severe patients, the immune landscape featured a deranged interferon response, profound immune exhaustion with skewed T cell receptor repertoire and broad T cell expansion. These findings illustrate the dynamic nature of immune responses during disease progression.

The Tokyo 2020 and Beijing 2022 Olympic Games held during the COVID-19 pandemic: planning, outcomes, and lessons learnt.

The COVID-19 pandemic profoundly affected all mass gatherings for sporting and religious events, causing cancellation, postponement, or downsizing. On March 24, 2020, the Japanese Government, the Tokyo Organising Committee of the Olympic and Paralympic Games, and the International Olympic Committee decided to postpone the Tokyo 2020 Olympic and Paralympic Games until the summer of 2021. With the emergence of SARS-CoV-2, the potential creation of a superspreading event that would overwhelm the Tokyo health system was perceived as a risk. Even with a delayed start date, an extensive scale of resources, planning, risk assessment, communication, and SARS-CoV-2 testing were required for the Games to be held during the COVID-19 pandemic. The effectiveness of various mitigation and control measures, including the availability of vaccines and the expansion of effective testing options, allowed event organisers and the Japanese Government to successfully host the rescheduled 2020 Tokyo Olympic Games from July 23 to Aug 8, 2021 with robust safety plans in place. In February and March, 2022, Beijing hosted the 2022 Winter Olympic Games as scheduled, built on the lessons learnt from the Tokyo Games, and developed specific COVID-19 countermeasure plans in the context of China's national framework for the plan called Zero COVID. Results from the testing programmes at both the Tokyo and Beijing Games show that the measures put in place were effective at preventing the spread of COVID-19 within the Games, and ensured that neither event became a COVID-19-spreading event. The extensive experience from the Tokyo and Beijing Olympic Games highlights that it is possible to organise mass gatherings during a pandemic, provided that appropriate risk assessment, risk mitigation, and risk communication arrangements are in place, leaving legacies for future mass gatherings, public health, epidemic preparedness, and wider pandemic response.

Advancing One human-animal-environment Health for global health security: what does the evidence say?

In this Series paper, we review the contributions of One Health approaches (ie, at the human-animal-environment interface) to improve global health security across a range of health hazards and we summarise contemporary evidence of incremental benefits of a One Health approach. We assessed how One Health approaches were reported to the Food and Agricultural Organization of the UN, the World Organisation for Animal Health (WOAH, formerly OIE), and WHO, within the monitoring and assessment frameworks, including WHO International Health Regulations (2005) and WOAH Performance of Veterinary Services. We reviewed One Health theoretical foundations, methods, and case studies. Examples from joint health services and infrastructure, surveillance-response systems, surveillance of antimicrobial resistance, food safety and security, environmental hazards, water and sanitation, and zoonoses control clearly show incremental benefits of One Health approaches. One Health approaches appear to be most effective and sustainable in the prevention, preparedness, and early detection and investigation of evolving risks and hazards; the evidence base for their application is strongest in the control of endemic and neglected tropical diseases. For benefits to be maximised and extended, improved One Health operationalisation is needed by strengthening multisectoral coordination mechanisms at national, regional, and global levels.

Global and regional governance of One Health and implications for global health security.

The apparent failure of global health security to prevent or prepare for the COVID-19 pandemic has highlighted the need for closer cooperation between human, animal (domestic and wildlife), and environmental health sectors. However, the many institutions, processes, regulatory frameworks, and legal instruments with direct and indirect roles in the global governance of One Health have led to a fragmented, global, multilateral health security architecture. We explore four challenges: first, the sectoral, professional, and institutional silos and tensions existing between human, animal, and environmental health; second, the challenge that the international legal system, state sovereignty, and existing legal instruments pose for the governance of One Health; third, the power dynamics and asymmetry in power between countries represented in multilateral institutions and their impact on priority setting; and finally, the current financing mechanisms that predominantly focus on response to crises, and the chronic underinvestment for epidemic and emergency prevention, mitigation, and preparedness activities. We illustrate the global and regional dimensions to these four challenges and how they relate to national needs and priorities through three case studies on compulsory licensing, the governance of water resources in the Lake Chad Basin, and the desert locust infestation in east Africa. Finally, we propose 12 recommendations for the global community to address these challenges. Despite its broad and holistic agenda, One Health continues to be dominated by human and domestic animal health experts. Substantial efforts should be made to address the social-ecological drivers of health emergencies including outbreaks of emerging, re-emerging, and endemic infectious diseases. These drivers include climate change, biodiversity loss, and land-use change, and therefore require effective and enforceable legislation, investment, capacity building, and integration of other sectors and professionals beyond health.

A global analysis of One Health Networks and the proliferation of One Health collaborations.

There has been a renewed focus on threats to the human-animal-environment interface as a result of the COVID-19 pandemic, and investments in One Health collaborations are expected to increase. Efforts to monitor the development of One Health Networks (OHNs) are essential to avoid duplication or misalignment of investments. This Series paper shows the global distribution of existing OHNs and assesses their collective characteristics to identify potential deficits in the ways OHNs have formed and to help increase the effectiveness of investments. We searched PubMed, Google, Google Scholar, and relevant conference websites for potential OHNs and identified 184 worldwide for further analysis. We developed four case studies to show important findings from our research and exemplify best practices in One Health operationalisation. Our findings show that, although more OHNs were formed in the past 10 years than in the preceding decade, investment in OHNs has not been equitably distributed; more OHNs are formed and headquartered in Europe than in any other region, and emerging infections and novel pathogens were the priority focus area for most OHNs, with fewer OHNs focusing on other important hazards and pressing threats to health security. We found substantial deficits in the OHNs collaboration model regarding the diversity of stakeholder and sector representation, which we argue impedes effective and equitable OHN formation and contributes to other imbalances in OHN distribution and priorities. These findings are supported by previous evidence that shows the skewed investment in One Health thus far. The increased attention to One Health after the COVID-19 pandemic is an opportunity to focus efforts and resources to areas that need them most. Analyses, such as this Series paper, should be used to establish databases and repositories of OHNs worldwide. Increased attention should then be given to understanding existing resource allocation and distribution patterns, establish more egalitarian networks that encompass the breadth of One Health issues, and serve communities most affected by emerging, re-emerging, or endemic threats at the human-animal-environment interface.

How prepared is the world? Identifying weaknesses in existing assessment frameworks for global health security through a One Health approach.

The COVID-19 pandemic has exposed faults in the way we assess preparedness and response capacities for public health emergencies. Existing frameworks are limited in scope, and do not sufficiently consider complex social, economic, political, regulatory, and ecological factors. One Health, through its focus on the links among humans, animals, and ecosystems, is a valuable approach through which existing assessment frameworks can be analysed and new ways forward proposed. Although in the past few years advances have been made in assessment tools such as the International Health Regulations Joint External Evaluation, a rapid and radical increase in ambition is required. To sufficiently account for the range of complex systems in which health emergencies occur, assessments should consider how problems are defined across stakeholders and the wider sociopolitical environments in which structures and institutions operate. Current frameworks do little to consider anthropogenic factors in disease emergence or address the full array of health security hazards across the social-ecological system. A complex and interdependent set of challenges threaten human, animal, and ecosystem health, and we cannot afford to overlook important contextual factors, or the determinants of these shared threats. Health security assessment frameworks should therefore ensure that the process undertaken to prioritise and build capacity adheres to core One Health principles and that interventions and outcomes are assessed in terms of added value, trade-offs, and cobenefits across human, animal, and environmental health systems.

SARS-CoV-2-specific immunoglobulin Y antibodies are protective in infected mice.

Safe, passive immunization methods are required against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its variants. Immunization of chickens with antigen is known to induce specific IgY antibodies concentrated in the egg yolk and has a good safety profile, high yield of IgY per egg, can be topically applied, not requiring parenteral delivery. Our data provide the first evidence of the prophylactic efficacy of Immunoglobulin Y antibodies against SARS-CoV-2 in mice. Lohmann hens were injected with recombinant SARS-CoV-2 RBD protein; IgY-Abs were extracted from the eggs and characterized using SDS-PAGE. Antiviral activity was evaluated using plaque reduction neutralization tests. In additional experiments, IgY-RBD efficacy was examined in mice sensitized to SARS-CoV-2 infection by transduction with Ad5-hACE2 (mild disease) or by using mouse-adapted virus (severe disease). In both cases, prophylactic intranasal administration of IgY-Abs reduced SARS-CoV-2 replication, and reduced morbidity, inflammatory cell infiltration, hemorrhage, and edema in the lungs and increased survival compared to control groups that received non-specific IgY-Abs. These results indicate that further evaluation of IgY-RBD antibodies in humans is warranted.

Acetic Acid Enables Molecular Enumeration of Mycobacterium tuberculosis from Sputum and Eliminates the Need for a Biosafety Level 3 Laboratory.

BACKGROUND: Improved monitoring of Mycobacterium tuberculosis response to treatment is urgently required. We previously developed the molecular bacterial load assay (MBLA), but it is challenging to integrate into the clinical diagnostic laboratory due to a labor-intensive protocol required at biosafety level 3 (BSL-3). A modified assay was needed. METHODS: The rapid enumeration and diagnostic for tuberculosis (READ-TB) assay was developed. Acetic acid was tested and compared to 4 M guanidine thiocyanate to be simultaneously bactericidal and preserve mycobacterial RNA. The extraction was based on silica column technology and incorporated low-cost reagents: 3 M sodium acetate and ethanol for the RNA extraction to replace phenol-chloroform. READ-TB was fully validated and compared directly to the MBLA using sputa collected from individuals with tuberculosis. RESULTS: Acetic acid was bactericidal to M. tuberculosis with no significant loss in 16S rRNA or an unprotected mRNA fragment when sputum was stored in acetic acid at 25°C for 2 weeks or -20°C for 1 year. This novel use of acetic acid allows processing of sputum for READ-TB at biosafety level 2 (BSL-2) on sample receipt. READ-TB is semiautomated and rapid. READ-TB correlated with the MBLA when 85 human sputum samples were directly compared (R2 = 0.74). CONCLUSIONS: READ-TB is an improved version of the MBLA and is available to be adopted by clinical microbiology laboratories as a tool for tuberculosis treatment monitoring. READ-TB will have a particular impact in low- and middle-income countries (LMICs) for laboratories with no BSL-3 laboratory and for clinical trials testing new combinations of anti-tuberculosis drugs.

Mass gathering events and transmission of respiratory tract infections: updates pre and post COVID-19 lockdown.

PURPOSE OF REVIEW: This article reviews the epidemiology and transmission of respiratory tract infections (RTIs) during mass gathering events (MGEs) before and during the COVID-19 pandemic. RECENT FINDINGS: RTIs of viral cause such as influenza, rhinovirus and coronaviruses (229E, HKU1, OC43) are common in MGEs. No cases of MERS-CoV have yet been identified in pilgrims during Hajj, despite the fact that MERS-CoV continues to circulate in the Middle East. Due to the COVID-19 pandemic, organizers of mass gathering religious and sporting events have implemented risk-based infection control measures and lockdowns that limited transmission of RTIs. SUMMARY: Large-scale RTI outbreaks at MGEs are uncommon due to more robust public health planning, prevention, risk assessment and improved health infrastructures in host countries during the COVID-19 pandemic.

Advances in development of new tuberculosis vaccines.

PURPOSE OF REVIEW: Tuberculosis (TB) remains a global public health emergency and caused 1.6 million deaths in 2021. The aim of this review is to provide recent updates on advances in TB vaccine development for prevention and adjunct therapy. RECENT FINDINGS: Targets use indications guiding late stage TB vaccine development have been established, namely: (i) Prevention of disease (PoD), (ii) Prevention of recurrent disease (PoR), (iii) Prevention of established infection in previously uninfected patients (PoI), and (iv) Adjunctive immunotherapy. Novel approaches include vaccines designed to induce immune responses beyond established CD4+, Th1-biased T cell immunity, novel animal models for use in challenge/protection studies, and controlled human infection models to generate vaccine efficacy data. SUMMARY: Recent efforts at developing effective TB vaccines for prevention and adjunct treatment utilising new targets and technologies have yielded 16 candidate vaccines demonstrating proof of concept for inducing potentially protective immune responses to TB which is currently under evaluation in different stages of clinical trials.

A pandemic within a pandemic? Admission to COVID-19 wards in hospitals is associated with increased prevalence of antimicrobial resistance in two African settings.

BACKGROUND: Patients who develop severe illness due to COVID-19 are more likely to be admitted to hospital and acquire bacterial co-infections, therefore the WHO recommends empiric treatment with antibiotics. Few reports have addressed the impact of COVID-19 management on emergence of nosocomial antimicrobial resistance (AMR) in resource constrained settings. This study aimed to ascertain whether being admitted to a COVID-19 ward (with COVID-19 infection) compared to a non-COVID-19 ward (as a COVID-19 negative patient) was associated with a change in the prevalence of bacterial hospital acquired infection (HAI) species or resistance patterns, and whether there were differences in antimicrobial stewardship (AMS) and infection prevention and control (IPC) guidelines between COVID-19 and non-COVID-19 wards. The study was conducted in Sudan and Zambia, two resource constrained settings with differing country-wide responses to COVID-19. METHODS: Patients suspected of having hospital acquired infections were recruited from COVID-19 wards and non-COVID-19 wards. Bacteria were isolated from clinical samples using culture and molecular methods and species identified. Phenotypic and genotypic resistance patterns were determined by antibiotic disc diffusion and whole genome sequencing. Infection prevention and control guidelines were analysed for COVID-19 and non-COVID-19 wards to identify potential differences. RESULTS: 109 and 66 isolates were collected from Sudan and Zambia respectively. Phenotypic testing revealed significantly more multi-drug resistant isolates on COVID-19 wards in both countries (Sudan p = 0.0087, Zambia p = 0.0154). The total number of patients with hospital acquired infections (both susceptible and resistant) increased significantly on COVID-19 wards in Sudan, but the opposite was observed in Zambia (both p = ≤ 0.0001). Genotypic analysis showed significantly more ß-lactam genes per isolate on COVID-19 wards (Sudan p = 0.0192, Zambia p = ≤ 0.0001). CONCLUSIONS: Changes in hospital acquired infections and AMR patterns were seen in COVID-19 patients on COVID-19 wards compared to COVID-19 negative patients on non-COVID-19 wards in Sudan and Zambia. These are likely due to a potentially complex combination of causes, including patient factors, but differing emphases on infection prevention and control, and antimicrobial stewardship policies on COVID-19 wards were highlighted.

Mesenchymal Stromal Cells: an Antimicrobial and Host-Directed Therapy for Complex Infectious Diseases.

There is an urgent need for new antimicrobial strategies for treating complex infections and emerging pathogens. Human mesenchymal stromal cells (MSCs) are adult multipotent cells with antimicrobial properties, mediated through direct bactericidal activity and modulation of host innate and adaptive immune cells. More than 30 in vivo studies have reported on the use of human MSCs for the treatment of infectious diseases, with many more studies of animal MSCs in same-species models of infection. MSCs demonstrate potent antimicrobial effects against the major classes of human pathogens (bacteria, viruses, fungi, and parasites) across a wide range of infection models. Mechanistic studies have yielded important insight into their immunomodulatory and bactericidal activity, which can be enhanced through various forms of preconditioning. MSCs are being investigated in over 80 clinical trials for difficult-to-treat infectious diseases, including sepsis and pulmonary, intra-abdominal, cutaneous, and viral infections. Completed trials consistently report MSCs to be safe and well tolerated, with signals of efficacy against some infectious diseases. Although significant obstacles must be overcome to produce a standardized, affordable, clinical-grade cell therapy, these studies suggest that MSCs may have particular potential as an adjunct therapy in complex or resistant infections.

Examining the microbial composition of natural springs in Bhaderwah, Jammu and Kashmir, India.

Natural springs are the main source of water supply for domestic and agricultural use for humans living in the mountainous regions of Asia. Increasing anthropogenic activities with associated waste load, coupled with inadequate sanitation, and contamination of natural water resources and the environment are emerging as important public health issues. We performed a prospective microbiological and physicochemical investigation of water samples from seven distinct natural springs situated at an altitude of 1615 m in the Bhaderwah region of Jammu and Kashmir, India. Bacterial groups belonging to opportunistic pathogens such as members of Moraxellaceae (Acinetobacter), Arcobacteraceae (Pseudoarcobacter), Pseudomonadaceae (Pseudomonas), Oxalobacteraceae (Massilia), and Flavobacteriaceae (Flavobacterium) were observed. The total coliform test indicated an intermediate level of risk of fecal contamination of the springs, except for one site. Through a questionnaire-based survey of the local population, we discovered that around 40% of participants had suffered from waterborne diseases including typhoid (~14%) and diarrhea (~11%). Our data suggests that increased surveillance of fecal contamination and heterotrophic opportunistic pathogens is needed to enhance water quality and reduce health risks for people living in mountainous regions.

Prioritizing Pregnant Women for Coronavirus Disease 2019 Vaccination in African Countries.

Coronavirus disease 2019 (COVID-19) in pregnancy is associated with excess maternal and infant morbidity and mortality in both African and higher-resource settings. Furthermore, mounting evidence demonstrates the safety and efficacy of COVID-19 vaccination for pregnant women and infants. However, national guidelines in many African countries are equivocal or lack recommendations on COVID-19 vaccine in pregnancy. We summarize key data on COVID-19 epidemiology and vaccination among pregnant African women to highlight major barriers to vaccination and recommend 4 interventions. First, policymakers should prioritize pregnant women for COVID-19 vaccination, with a target of 100% coverage. Second, empirically supported public health campaigns should be sustainably implemented to inform and support pregnant women and their healthcare providers in overcoming vaccine hesitancy. Third, COVID-19 vaccination for pregnant women should be expanded to include antenatal care, obstetrics/gynecology, and targeted mass vaccination campaigns. Fourth, national monitoring and evaluation of COVID-19 vaccine uptake, safety, surveillance, and prospective outcomes assessment should be conducted.

Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Pregnancy in Sub-Saharan Africa: A 6-Country Retrospective Cohort Analysis.

BACKGROUND: Few data are available on COVID-19 outcomes among pregnant women in sub-Saharan Africa (SSA), where high-risk comorbidities are prevalent. We investigated the impact of pregnancy on SARS-CoV-2 infection and of SARS-CoV-2 infection on pregnancy to generate evidence for health policy and clinical practice. METHODS: We conducted a 6-country retrospective cohort study among hospitalized women of childbearing age between 1 March 2020 and 31 March 2021. Exposures were (1) pregnancy and (2) a positive SARS-CoV-2 RT-PCR test. The primary outcome for both analyses was intensive care unit (ICU) admission. Secondary outcomes included supplemental oxygen requirement, mechanical ventilation, adverse birth outcomes, and in-hospital mortality. We used log-binomial regression to estimate the effect between pregnancy and SARS-CoV-2 infection. Factors associated with mortality were evaluated using competing-risk proportional subdistribution hazards models. RESULTS: Our analyses included 1315 hospitalized women: 510 pregnant women with SARS-CoV-2, 403 nonpregnant women with SARS-CoV-2, and 402 pregnant women without SARS-CoV-2 infection. Among women with SARS-CoV-2 infection, pregnancy was associated with increased risk for ICU admission (adjusted risk ratio [aRR]: 2.38; 95% CI: 1.42-4.01), oxygen supplementation (aRR: 1.86; 95% CI: 1.44-2.42), and hazard of in-hospital death (adjusted sub-hazard ratio [aSHR]: 2.00; 95% CI: 1.08-3.70). Among pregnant women, SARS-CoV-2 infection increased the risk of ICU admission (aRR: 2.0; 95% CI: 1.20-3.35), oxygen supplementation (aRR: 1.57; 95% CI: 1.17-2.11), and hazard of in-hospital death (aSHR: 5.03; 95% CI: 1.79-14.13). CONCLUSIONS: Among hospitalized women in SSA, both SARS-CoV-2 infection and pregnancy independently increased risks of ICU admission, oxygen supplementation, and death. These data support international recommendations to prioritize COVID-19 vaccination among pregnant women.

Advances in the epidemiology, clinical features, diagnosis, clinical management and prevention of coronavirus disease 2019.

PURPOSE OF REVIEW: The current article reviews the latest information on the epidemiology, clinical features, diagnostics, clinical management and prevention of coronavirus disease 2019 (COVID-19). RECENT FINDINGS: Atypical pneumonia due to severe acute respiratory syndrome coronavirus-2 emerged in December 2019 in a market in Wuhan, China and rapidly evolved into a pandemic in March 2020. Viral loads of patients with COVID-19 peak in the first week of illness around day 2-4 and hence there is very high-transmission potential causing community outbreaks. Asymptomatic and presymptomatic transmission is a hallmark of COVID-19. Several variants of concern (VOC) have emerged over the last 2 years and Omicron is the predominant variant in many countries. PCR is the standard diagnostic test while rapid antigen test is a useful supplementary test. Serology tests provide indirect evidence of infection 1 -2 weeks after the onset of symptoms. Molnupiravir and nirmatrelvir are oral antiviral agents that may reduce the risk of hospitalization and deaths if administered early to high-risk subjects. Remdesivir, baricitinib, anti-IL-6 tocilizumab and dexamethasone are frequently used for treatment of patients with respiratory failure. SUMMARY: COVID-19 pandemic progresses relentlessly with substantial morbidity and mortality especially in unvaccinated subjects. Mass COVID-19 vaccinations are the most important measure for control of the COVID-19 pandemic.

Monkeypox: another test for PCR.

Monkeypox was declared a public health emergency of international concern by the World Health Organization (WHO) on 23 July 2022. Between 1 January and 23 July 2022, 16,016 laboratory confirmed cases of monkeypox and five deaths were reported to WHO from 75 countries on all continents. Public health authorities are proactively identifying cases and tracing their contacts to contain its spread. As with COVID-19, PCR is the only method capable of being deployed at sufficient speed to provide timely feedback on any public health interventions. However, at this point, there is little information on how those PCR assays are being standardised between laboratories. A likely reason is that testing is still limited on a global scale and that detection, not quantification, of monkeypox virus DNA is the main clinical requirement. Yet we should not be complacent about PCR performance. As testing requirements increase rapidly and specimens become more diverse, it would be prudent to ensure PCR accuracy from the outset to support harmonisation and ease regulatory conformance. Lessons from COVID-19 should aid implementation with appropriate material, documentary and methodological standards offering dynamic mechanisms to ensure testing that most accurately guides public health decisions.

From Easing Lockdowns to Scaling Up Community-based Coronavirus Disease 2019 Screening, Testing, and Contact Tracing in Africa-Shared Approaches, Innovations, and Challenges to Minimize Morbidity and Mortality.

The arrival of coronavirus disease 2019 (COVID-19) on the African continent resulted in a range of lockdown measures that curtailed the spread of the infection but caused economic hardship. African countries now face difficult choices regarding easing of lockdowns and sustaining effective public health control measures and surveillance. Pandemic control will require efficient community screening, testing, and contact tracing; behavioral change interventions; adequate resources; and well-supported, community-based teams of trained, protected personnel. We discuss COVID-19 control approaches in selected African countries and the need for shared, affordable, innovative methods to overcome challenges and minimize mortality. This crisis presents a unique opportunity to align COVID-19 services with those already in place for human immunodeficiency virus, tuberculosis, malaria, and non communicable diseases through mobilization of Africa's interprofessional healthcare workforce. By addressing the challenges, the detrimental effect of the COVID-19 pandemic on African citizens can be minimized.

The Critical Need for Pooled Data on Coronavirus Disease 2019 in African Children: An AFREhealth Call for Action Through Multicountry Research Collaboration.

Globally, there are prevailing knowledge gaps in the epidemiology, clinical manifestations, and outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among children and adolescents; and these gaps are especially wide in African countries. The availability of robust age-disaggregated data is a critical first step in improving knowledge on disease burden and manifestations of coronavirus disease 2019 (COVID-19) among children. Furthermore, it is essential to improve understanding of SARS-CoV-2 interactions with comorbidities and coinfections such as human immunodeficiency virus (HIV), tuberculosis, malaria, sickle cell disease, and malnutrition, which are highly prevalent among children in sub-Saharan Africa. The African Forum for Research and Education in Health (AFREhealth) COVID-19 Research Collaboration on Children and Adolescents is conducting studies across Western, Central, Eastern, and Southern Africa to address existing knowledge gaps. This consortium is expected to generate key evidence to inform clinical practice and public health policy-making for COVID-19 while concurrently addressing other major diseases affecting children in African countries.

Middle East respiratory syndrome.

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.