Publications by authors named "Alimuddin Zumla"

553 Publications

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

Clin Microbiol Rev 2021 Oct 6:e0006421. Epub 2021 Oct 6.

Wellcome-Wolfson Institute for Experimental Medicine, Queen's University, Belfast, United Kingdom.

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 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/CMR.00064-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510528PMC
October 2021

Antimicrobial Resistance Patterns and Risk Factors Associated with spp. Isolates from Poultry Farms in the East Coast of Peninsular Malaysia: A Cross-Sectional Study.

Pathogens 2021 Sep 9;10(9). Epub 2021 Sep 9.

The Royal Veterinary College, University of London, Hawkshead Lane, North Mymms, Hatfield AL9 7TA, UK.

The burden of antimicrobial use in agricultural settings is one of the greatest challenges facing global health and food security in the modern era. Malaysian poultry operations are a relevant but understudied component of epidemiology of antimicrobial resistance. We aimed to identify the prevalence, resistance patterns, and risk factors associated with isolates from poultry farms in three states of East Coast Peninsular Malaysia. Between 8 February 2019 and 23 February 2020, a total of 371 samples (cloacal swabs = 259; faecal = 84; Sewage = 14, Tap water = 14) was collected from poultry operations. Characteristics of the sampled farms and associated risk factors were obtained using semi-structured questionnaires. Presumptive spp. isolates were identified based on colony morphology with subsequent biochemical and PCR confirmation. Susceptibility of isolates was tested against a panel of 12 antimicrobials using disk diffusion method. Our findings revealed that the proportion of spp.-positive isolates across sample source were as following: cloacal swab (46.3%, 120/259); faecal (59.5%, 50/84); in tap water (14.3%, 2/14); and in sewage sample (35.7%, 5/14). Isolates from faecal (15.5%, 13/84), cloacal (1.2%, 3/259), and sewage (7.1%, 1/14) samples were significantly resistant to at least five classes of antimicrobials. Resistance to Sulfonamides class (52%, 92/177) was predominantly observed followed by tetracycline (39.5%, 70/177) and aminoglycosides (35.6%, 63/177). Multivariate regression analysis identified intensive management system (OR = 1.55, 95% CI = 1.00-2.40) as a leading driver of antimicrobial resistance (AMR) acquisition. A prevalence of resistance to common antimicrobials was recorded for sulfamethoxazole (33.9%), tetracycline (39.5%), and trimethoprim-sulphamethoxazole (37.9%). A close association between different risk factors and the prevalence of AMR of strains suggests a concern over rising misuse of veterinary antimicrobials that may contribute to the emergence and evolution of multidrug-resistant pathogen isolates. One Health approach is recommended to achieve a positive health outcome for all species.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/pathogens10091160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470665PMC
September 2021

Neuropathology and Inflammatory Cell Characterization in 10 Autoptic COVID-19 Brains.

Cells 2021 08 31;10(9). Epub 2021 Aug 31.

Pathology Unit, National Institute for Infectious Diseases "Lazzaro Spallanzani"-IRCCS, 00149 Rome, Italy.

COVID-19 presents with a wide range of clinical neurological manifestations. It has been recognized that SARS-CoV-2 infection affects both the central and peripheral nervous system, leading to smell and taste disturbances; acute ischemic and hemorrhagic cerebrovascular disease; encephalopathies and seizures; and causes most surviving patients to have long lasting neurological symptoms. Despite this, typical neuropathological features associated with the infection have still not been identified. Studies of post-mortem examinations of the cerebral cortex are obtained with difficulty due to laboratory safety concerns. In addition, they represent cases with different neurological symptoms, age or comorbidities, thus a larger number of brain autoptic data from multiple institutions would be crucial. Histopathological findings described here are aimed to increase the current knowledge on neuropathology of COVID-19 patients. We report post-mortem neuropathological findings of ten COVID-19 patients. A wide range of neuropathological lesions were seen. The cerebral cortex of all patients showed vascular changes, hyperemia of the meninges and perivascular inflammation in the cerebral parenchyma with hypoxic neuronal injury. Perivascular lymphocytic inflammation of predominantly CD8-positive T cells mixed with CD68-positive macrophages, targeting the disrupted vascular wall in the cerebral cortex, cerebellum and pons were seen. Our findings support recent reports highlighting a role of microvascular injury in COVID-19 neurological manifestations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cells10092262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469459PMC
August 2021

A comparison of vitamin D and cathelicidin (LL-37) levels between patients with active TB and their healthy contacts in a high HIV prevalence setting: a prospective descriptive study.

Trans R Soc Trop Med Hyg 2021 Aug 16. Epub 2021 Aug 16.

Lusaka Apex Medical University, Faculty of Medicine, Lusaka, Zambia.

Background: Studies from Asia and Europe indicate an association between vitamin D deficiency and susceptibility to TB. We performed an observational case-control study to determine vitamin D and cathelicidin (LL-37) levels and their association with active TB in newly diagnosed and microbiologically confirmed adult TB patients in Zambia, a high HIV prevalence setting.

Methods: Both total vitamin D and LL-37 were measured using ELISA from serum and supernatant isolated from cultured whole blood that was stimulated with heat-killed Mycobacterium tuberculosis. Statistical analysis was performed using STATA statistical software version 12.

Results: The median vitamin D in TB patients and healthy contacts was 28.7 (19.88-38.64) and 40.8 (31.2-49.44) ng/ml, respectively (p<0.001). The median LL-37 in TB patients compared with healthy contacts was 1.87 (2.74-8.93) and 6.73 (5.6-9.58) ng/ml, respectively (p=0.0149). Vitamin D correlation with LL-37 in healthy contacts was R2=0.7 (95% CI 0.566 to 0.944), p<0.0001. Normal vitamin D significantly predicted a healthy status (OR 4.06, p=0.002).

Conclusions: Significantly lower levels of vitamin D and LL-37 are seen in adults with newly diagnosed active TB. Longitudinal studies across various geographical regions are required to accurately define the roles of vitamin D and LL-37 in preventive and TB treatment outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/trstmh/trab126DOI Listing
August 2021

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

Cell Death Dis 2021 08 12;12(8):788. Epub 2021 Aug 12.

National Institute for Infectious Diseases "Lazzaro Spallanzani" IRCCS, Rome, Italy.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-021-03881-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357963PMC
August 2021

COVID-19 and Sudden Unexpected Community Deaths in Lusaka, Zambia, Africa - A Medico-Legal Whole-Body Autopsy Case Series.

Int J Infect Dis 2021 Aug 5;109:160-167. Epub 2021 Jul 5.

Ministry of Home Affairs, Office of the State Forensic Pathologist, Nationalist Road, Lusaka, Zambia; University Teaching Hospitals, Department of Pathology and Microbiology, Nationalist Road, Lusaka, Zambia.

Background: Data from Africa regarding sudden and unexpected COVID-19 community deaths and underlying pathological, demographic, and co-morbidity features require definition.

Methods: We performed a case series of COVID-19-related deaths seen at Forensic Post-Mortem examination of sudden and unexpected Community Deaths in Lusaka, Zambia, Africa. Whole-body Post-Mortem examinations were performed according to Standard Operating Procedures. Patient demographics, history, co-morbidities, pathological gross and microscopic findings, and cause(s) of death were recorded. Variables were grouped as frequencies and percentages. Comparison of data was made with autopsy findings of hospital COVID-19 deaths.

Findings: Of 21 COVID-19 decedents, 14/21 (66.7%) were male; 18/21, (85.7%) were below 55 years of age (mean age, 40 ± 12.3; range, 20-73). The median duration of symptoms was 1 day (range 0-2); 9/21 (42.9%) had co-morbidities, with hypertension and obesity being the most common. Main post-mortem findings were diffuse alveolar damage (DAD) (80.9%), saddle and shower emboli (38.1%, respectively), and pneumonia (14.3%). Pulmonary thromboembolism (76.2%), DAD (14.3%), and SARS-CoV-2 pneumonia (9.5%) were common causes of death.

Conclusions: COVID-19 is an important cause of death to consider in forensic investigations of sudden and unexpected community deaths. Risk factors for the younger age of COVID-19 deaths and thromboembolism need to be identified.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijid.2021.07.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255190PMC
August 2021

Re-infection with a different SARS-CoV-2 clade and prolonged viral shedding in a hematopoietic stem cell transplantation patient.

Int J Infect Dis 2021 Sep 18;110:267-271. Epub 2021 Jul 18.

Special Infectious Agents Unit-BSL3, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia. Electronic address:

Immunocompromised patients who have a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection pose many clinical and public health challenges. We describe the case of a hematopoietic stem cell transplantation patient with lymphoma who had a protracted illness requiring three consecutive hospital admissions. Whole genome sequencing confirmed two different SARS-CoV-2 clades. Clinical management issues and the unanswered questions arising from this case are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijid.2021.07.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286546PMC
September 2021

One and a half years into the COVID-19 pandemic - Exit strategies and efficacy of SARS-CoV-2 vaccines for holistic management and achieving global control.

Turk J Med Sci 2021 Jul 21. Epub 2021 Jul 21.

The pandemic has now unfolded over the past one and a half year and all data show that SARS-CoV-2 has a higher mortality compared to influenza and people with sequelae after infection need to be treated by the health care systems. Evolution of new virus variants is discussed. The global expansion of the delta variant demonstrates that new variants with a higher transmission potential and also being more pathogenic can easily arise. So far, the roll out of vaccines has been the most efficient tool to control the pandemic. With the evolution of new variants vaccine efficacy must be closely monitored. The zoonotic nature of the virus means that it can cross from humans into an animal reservoir and back again, and surveillance of SARS-CoV-2 virus in animals in close contact to humans are needed. There will most certainly be a new wave in the coming year and it is possible that a booster vaccination is needed. To increase population immunity and reduce circulation of SARS-CoV-2 vaccinations most probably have to be expanded to children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3906/sag-2106-236DOI Listing
July 2021

Extended Ecological Restoration of Bacterial Communities in the Godavari River During the COVID-19 Lockdown Period: a Spatiotemporal Meta-analysis.

Microb Ecol 2021 Aug 5;82(2):365-376. Epub 2021 Jul 5.

DBT-National Centre for Cell Science, Pune, India.

The unprecedented COVID-19 pandemic has had major impact on human health worldwide. Whilst national and international COVID-19 lockdown and travel restriction measures have had widespread negative impact on economies and mental health, they may have beneficial effect on the environment, reducing air and water pollution. Mass bathing events (MBE) also known as Kumbh Mela are known to cause perturbations of the ecosystem affecting resilient bacterial populations within water of rivers in India. Lockdowns and travel restrictions provide a unique opportunity to evaluate the impact of minimum anthropogenic activity on the river water ecosystem and changes in bacterial populations including antibiotic-resistant strains. We performed a spatiotemporal meta-analysis of bacterial communities of the Godavari River, India. Targeted metagenomics revealed a 0.87-fold increase in the bacterial diversity during the restricted activity of lockdown. A significant increase in the resilient phyla, viz. Proteobacteria (70.6%), Bacteroidetes (22.5%), Verrucomicrobia (1.8%), Actinobacteria (1.2%) and Cyanobacteria (1.1%), was observed. There was minimal incorporation of allochthonous bacterial communities of human origin. Functional profiling using imputed metagenomics showed reduction in infection and drug resistance genes by - 0.71-fold and - 0.64-fold, respectively. These observations may collectively indicate the positive implications of COVID-19 lockdown measures which restrict MBE, allowing restoration of the river ecosystem and minimise the associated public health risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00248-021-01781-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255117PMC
August 2021

Post-mortem examination of Hospital Inpatient COVID-19 Deaths in Lusaka, Zambia - A Descriptive Whole-body Autopsy Series.

Int J Infect Dis 2021 Jul 17;108:363-369. Epub 2021 Jun 17.

Ministry of Home Affairs, Office of the State Forensic Pathologist, Nationalist Road, Lusaka, Zambia. Electronic address:

Background: Since information on the pathology of COVID-19 from sub-Saharan Africa (SSA) remains scarce, the objective of our study was to define the gross pathology and histological features of COVID-19. We report data from 29 whole-body autopsies of COVID-19 deaths occurring in hospitals in Lusaka, Zambia - the first large autopsy case series from Africa.

Methods: We performed a descriptive post-mortem examination study of inpatient COVID-19 related deaths at two hospitals in Lusaka, Zambia. Whole-body autopsies were conducted according to Standard Operating Procedures. Gross and histopathological examinations of all organs were performed. Patient demographics, history, co-morbidities, autopsy gross and microscopic findings, and cause(s) of death were recorded and analyzed using STATA version 14. Variables were grouped and presented as frequencies and percentages.

Findings: Autopsies were performed on 29 decedents (mean age = 44 ± 15.8years; age range = 19-82; 17/29 [58.8%] males). 22/29 [75.9%] cases were <55 years of age. A spectrum of pathological manifestations of COVID-19 were seen in all organs. The commonest causes of death were pulmonary thromboembolism (13/29, 45%), Diffuse Alveolar Damage (9/29, 31%), and COVID-19 pneumonia (7/29, 25%). 22/29 (76%) had co-morbidities. Common co-morbidities included HIV (8/29, 28%), Hypertension (6/29, 20%) Tuberculosis (3/29, 10%), Diabetes (3/29, 10%).

Conclusions: A spectrum of gross anatomical and histopathological findings are seen in COVID-19 deaths in hospitalized decedents. These appear broadly similar to those reported from China, Europe and USA. Differences include a younger age group, and co-morbidities of HIV and TB co-infection which require further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijid.2021.06.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215884PMC
July 2021

Middle East respiratory syndrome coronavirus - The need for global proactive surveillance, sequencing and modeling.

Travel Med Infect Dis 2021 Sep-Oct;43:102118. Epub 2021 Jun 16.

Department of Infection, Division of Infection and Immunity, University College London and NIHR Biomedical Research Centre, UCL Hospitals NHS Foundation Trust, London, United Kingdom. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tmaid.2021.102118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205546PMC
September 2021

Specific COVID-19 messaging targeting ethnic minority communities.

EClinicalMedicine 2021 May 24;35:100862. Epub 2021 Apr 24.

Mass Gatherings and Global Health Network, London, United Kingdom.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eclinm.2021.100862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099741PMC
May 2021

Detection and characterization of carbapenem resistant Gram-negative bacilli isolates recovered from hospitalized patients at Soba University Hospital, Sudan.

BMC Microbiol 2021 05 4;21(1):136. Epub 2021 May 4.

Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.

Background: Antimicrobial resistance (AMR) poses a complex threat to global health security and universal health coverage. Recently, nosocomial infections with carbapenemase-producing Gram-negative bacilli (GNB) is increasing worldwide. We report the molecular characterization and detection of genes associated with carbapenemase producing Gram negative bacteria isolated from hospitalized patients at Soba University Hospital (SUH) in Khartoum State, Sudan.

Results: Between October 2016 and February 2017, a total of 206 GNB clinical specimens were collected from hospitalized patients in SUH. Of 206 carbapenem resistance isolates, 171 (83 %) were confirmed as phenotypically resistant and 121 (58.7 %) isolates harboured one or more carbapenemase genes. New Delhi metallo-β-lactamase (NDM) types were the most predominant genes, blaNDM 107(52 %), followed by blaIMP 7 (3.4 %), blaOXA-48 5(2.4 %) and blaVIM 2 (0.9 %). Co-resistance genes with NDM producing GNB were detected in 87 (81.3 %) of all blaNDM producing isolates. NDM-1 was the most frequent subtype observed in 75 (70 %) blaNDM producing isolates. The highest percentage of resistance was recorded in ampicillin (98 %), cephalexin (93.5 %) amoxicillin clavulanic acid (90 %), cefotaxime (89.7 %), ceftriaxone (88.4 %), ceftazidime (84.2 %), sulfamethoxazole-trimethoprim (78.4 %) and nitrofurantoin (75.2 %), aztreonam (66 %) and temocillin (64 %). A close correlation between phenotypic and carbapenemase genes detection in all GNB was observed.

Conclusions: The frequency of carbapenemase producing bacilli was found to be high in SUH. NDM was found to be the most prevalent carbapenemase gene among clinical isolates. Close surveillance across all hospitals in Sudan is required. The relative distribution of carbapenemase genes among GNB in nosocomial infections in Africa needs to be defined.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12866-021-02133-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094518PMC
May 2021

Effects of SARS-CoV-2 on Cardiovascular System: The Dual Role of Angiotensin-Converting Enzyme 2 (ACE2) as the Virus Receptor and Homeostasis Regulator-Review.

Int J Mol Sci 2021 Apr 26;22(9). Epub 2021 Apr 26.

Cardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) and Department of Medical Surgical and Health Science, University of Trieste, 34149 Trieste, Italy.

Angiotensin-converting enzyme 2 (ACE2) is the entry receptor for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the cause of Coronavirus Disease-2019 (COVID-19) in humans. ACE-2 is a type I transmembrane metallocarboxypeptidase expressed in vascular endothelial cells, alveolar type 2 lung epithelial cells, renal tubular epithelium, Leydig cells in testes and gastrointestinal tract. ACE2 mediates the interaction between host cells and SARS-CoV-2 spike (S) protein. However, ACE2 is not only a SARS-CoV-2 receptor, but it has also an important homeostatic function regulating renin-angiotensin system (RAS), which is pivotal for both the cardiovascular and immune systems. Therefore, ACE2 is the key link between SARS-CoV-2 infection, cardiovascular diseases (CVDs) and immune response. Susceptibility to SARS-CoV-2 seems to be tightly associated with ACE2 availability, which in turn is determined by genetics, age, gender and comorbidities. Severe COVID-19 is due to an uncontrolled and excessive immune response, which leads to acute respiratory distress syndrome (ARDS) and multi-organ failure. In spite of a lower ACE2 expression on cells surface, patients with CVDs have a higher COVID-19 mortality rate, which is likely driven by the imbalance between ADAM metallopeptidase domain 17 (ADAM17) protein (which is required for cleavage of ACE-2 ectodomain resulting in increased ACE2 shedding), and TMPRSS2 (which is required for spike glycoprotein priming). To date, ACE inhibitors and Angiotensin II Receptor Blockers (ARBs) treatment interruption in patients with chronic comorbidities appears unjustified. The rollout of COVID-19 vaccines provides opportunities to study the effects of different COVID-19 vaccines on ACE2 in patients on treatment with ACEi/ARB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22094526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123609PMC
April 2021

The Global Case-Fatality Rate of COVID-19 Has Been Declining Since May 2020.

Am J Trop Med Hyg 2021 Apr 21. Epub 2021 Apr 21.

1Department of Statistics, Shahjalal University of Science and Technology, Sylhet 3114, Bangladesh.

The objective of this study was to evaluate the trend of reported case fatality rate (rCFR) of COVID-19 over time, using globally reported COVID-19 cases and mortality data. We collected daily COVID-19 diagnoses and mortality data from the WHO's daily situation reports dated January 1 to December 31, 2020. We performed three time-series models [simple exponential smoothing, auto-regressive integrated moving average, and automatic forecasting time-series (Prophet)] to identify the global trend of rCFR for COVID-19. We used beta regression models to investigate the association between the rCFR and potential predictors of each country and reported incidence rate ratios (IRRs) of each variable. The weekly global cumulative COVID-19 rCFR reached a peak at 7.23% during the 17th week (April 22-28, 2020). We found a positive and increasing trend for global daily rCFR values of COVID-19 until the 17th week (pre-peak period) and then a strong declining trend up until the 53rd week (post-peak period) toward 2.2% (December 29-31, 2020). In pre-peak of rCFR, the percentage of people aged 65 and above and the prevalence of obesity were significantly associated with the COVID-19 rCFR. The declining trend of global COVID-19 rCFR was not merely because of increased COVID-19 testing, because COVID-19 tests per 1,000 population had poor predictive value. Decreasing rCFR could be explained by an increased rate of infection in younger people or by the improvement of health care management, shielding from infection, and/or repurposing of several drugs that had shown a beneficial effect on reducing fatality because of COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4269/ajtmh.20-1496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176487PMC
April 2021

Pattern of Respiratory Viruses among Pilgrims during 2019 Hajj Season Who Sought Healthcare Due to Severe Respiratory Symptoms.

Pathogens 2021 Mar 8;10(3). Epub 2021 Mar 8.

Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

The aim of our study was to define the spectrum of viral infections in pilgrims with acute respiratory tract illnesses presenting to healthcare facilities around the holy places in Makkah, Saudi Arabia during the 2019 Hajj pilgrimage. During the five days of Hajj, a total of 185 pilgrims were enrolled in the study. Nasopharyngeal swabs (NPSs) of 126/185 patients (68.11%) tested positive for one or more respiratory viruses by PCR. Among the 126 pilgrims whose NPS were PCR positive: (a) there were 93/126 (74%) with a single virus infection, (b) 33/126 (26%) with coinfection with more than one virus (up to four viruses): of these, 25/33 cases had coinfection with two viruses; 6/33 were infected with three viruses, while the remaining 2/33 patients had infection with four viruses. Human rhinovirus (HRV) was the most common detected viruses with 53 cases (42.06%), followed by 27 (21.43%) cases of influenza A (H1N1), and 23 (18.25%) cases of influenza A other than H1N1. Twenty-five cases of CoV-229E (19.84%) were detected more than other coronavirus members (5 CoV-OC43 (3.97%), 4 CoV-HKU1 (3.17%), and 1 CoV-NL63 (0.79%)). PIV-3 was detected in 8 cases (6.35%). A single case (0.79%) of PIV-1 and PIV-4 were found. HMPV represented 5 (3.97%), RSV and influenza B 4 (3.17%) for each, and Parechovirus 1 (0.79%). Enterovirus, Bocavirus, and were not detected. Whether identification of viral nucleic acid represents nasopharyngeal carriage or specific causal etiology of RTI remains to be defined. Large controlled cohort studies (pre-Hajj, during Hajj, and post-Hajj) are required to define the carriage rates and the specific etiology and causal roles of specific individual viruses or combination of viruses in the pathogenesis of respiratory tract infections in pilgrims participating in the annual Hajj. Studies of the specific microbial etiology of respiratory track infections (RTIs) at mass gathering religious events remain a priority, especially in light of the novel SARS-CoV-2 pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/pathogens10030315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001913PMC
March 2021

Bacille Calmette-Guérin (BCG) vaccine and potential cross-protection against SARS-CoV-2 infection - Assumptions, knowns, unknowns and need for developing an accurate scientific evidence base.

Int J Infect Dis 2021 Mar 29. Epub 2021 Mar 29.

Department of Medicine, Therapeutics, Dermatology and Psychiatry, Kenyatta University, Nairobi, Kenya; Division of Infection and Immunity, University College London, London, UK; NIHR Biomedical Research Centre, University College London Hospitals, London, UK. Electronic address:

After a century of controversies on its usefulness in protection against TB, underlying mechanisms of action, and benefits in various groups and geographical areas, the BCG vaccine is yet again a focus of global attention- this time due to the global COVID-19 pandemic caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Recent studies have shown that human CD4+ and CD8+ T-cells primed with a BCG-derived peptide developed high reactivity to its corresponding SARS-CoV-2-derived peptide. Furthermore, BCG vaccine has been shown to substantially increase interferon-gamma (IFN-g) production and its effects on CD4+ T-cells and these non-specific immune responses through adjuvant effect could be harnessed as cross protection against severe forms of COVID-19.The completion of ongoing BGG trials is important as they may shed light on the mechanisms underlying BCG-mediated immunity and could lead to improved efficacy, increased tolerance of treatment, and identification of other ways of combining BCG with other immunotherapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijid.2021.03.060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006492PMC
March 2021

Scaling Up Covid-19 Vaccination in Africa - Lessons from the HIV Pandemic.

N Engl J Med 2021 Jul 31;385(3):196-198. Epub 2021 Mar 31.

From the Departments of Epidemiology and of Infectious Diseases and Microbiology and the Center for Global Health, University of Pittsburgh Graduate School of Public Health (J.B.N.); and the Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine (J.W.M.) - both in Pittsburgh; the Department of Medicine and the Center for Infectious Diseases, Stellenbosch University, Faculty of Medicine and Health Sciences, Cape Town, South Africa (J.B.N.); the Departments of Epidemiology and International Health, Johns Hopkins Bloomberg School of Public Health (J.B.N.), and the Department of Pediatrics and the Institute of Human Virology, University of Maryland School of Medicine (N.A.S.-A.) - both in Baltimore; the Pediatric/Adolescent HIV Unit and International Research Center of Excellence, Institute of Human Virology Nigeria, Abuja, Nigeria (N.A.S.-A.); the Department of Pediatrics and Child Health, School of Medical Sciences, University of Cape Coast, Cape Coast, Ghana (N.A.S.-A.); the Division of Infection and Immunity, University College London, and the NIHR Biomedical Research Centre, University College London Hospitals - both in London (A.Z.); the African Forum for Research and Education in Health, Kumasi, Ghana (J.B.N., N.A.S.-A., A.Z.); and the Elizabeth Glaser Pediatric AIDS Foundation, Washington, DC (L.M.M.).

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMp2103313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291168PMC
July 2021

Editorial: Coronavirus disease 2019 (COVID-19) - advances in epidemiology, diagnostics, treatments, host-directed therapies, pathogenesis, vaccines, and ongoing challenges.

Curr Opin Pulm Med 2021 05;27(3):141-145

Division of Infection and Immunity, Centre for Clinical Microbiology, University College London.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MCP.0000000000000771DOI Listing
May 2021

Zoonotic disease preparedness in sub-Saharan African countries.

One Health Outlook 2021 22;3(1). Epub 2021 Mar 22.

Centre for Clinical Microbiology, Division of Infection & Immunity, University College London, London, UK.

Background: The emergence of high consequence pathogens such as Ebola and SARS-CoV-2, along with the continued burden of neglected diseases such as rabies, has highlighted the need for preparedness for emerging and endemic infectious diseases of zoonotic origin in sub-Saharan Africa (SSA) using a One Health approach. To identify trends in SSA preparedness, the World Health Organization (WHO) Joint External Evaluation (JEE) reports were analysed. JEEs are voluntary, collaborative processes to assess country's capacities to prevent, detect and rapidly respond to public health risks. This report aimed to analyse the JEE zoonotic disease preparedness data as a whole and identify strengths and weaknesses.

Methods: JEE zoonotic disease preparedness scores for 44 SSA countries who had completed JEEs were analysed. An overall zoonotic disease preparedness score was calculated as an average of the sum of all the SSA country zoonotic disease preparedness scores and compared to the overall mean JEE score. Zoonotic disease preparedness indicators were analysed and data were collated into regions to identify key areas of strength.

Results: The mean 'Zoonotic disease' preparedness score (2.35, range 1.00-4.00) was 7% higher compared to the mean overall JEE preparedness score (2.19, range 1.55-3.30), putting 'Zoonotic Diseases' 5th out of 19 JEE sub-areas for preparedness. The average scores for each 'Zoonotic Disease' category were 2.45 for 'Surveillance Systems', 2.76 for 'Veterinary Workforce' and 1.84 for 'Response Mechanisms'. The Southern African region scored highest across the 'Zoonotic disease' categories (2.87).A multisectoral priority zoonotic pathogens list is in place for 43% of SSA countries and 70% reported undertaking national surveillance on 1-5 zoonotic diseases. 70% of SSA countries reported having public health training courses in place for veterinarians and 30% had veterinarians in all districts (reported as sufficient staffing). A multisectoral action plan for zoonotic outbreaks was in place for 14% countries and 32% reported having an established inter-agency response team for zoonotic outbreaks. The zoonotic diseases that appeared most in reported country priority lists were rabies and Highly Pathogenic Avian Influenza (HPAI) (both 89%), anthrax (83%), and brucellosis (78%).

Conclusions: With 'Zoonotic Diseases' ranking 5th in the JEE sub-areas and a mean SSA score 7% greater than the overall mean JEE score, zoonotic disease preparedness appears to have the attention of most SSA countries. However, the considerable range suggests that some countries have more measures in place than others, which may perhaps reflect the geography and types of pathogens that commonly occur. The category 'Response Mechanisms' had the lowest mean score across SSA, suggesting that implementing a multisectoral action plan and response team could provide the greatest gains.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s42522-021-00037-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982296PMC
March 2021

Minimizing the impact of the triple burden of COVID-19, tuberculosis and HIV on health services in sub-Saharan Africa.

Int J Infect Dis 2021 Mar 20. Epub 2021 Mar 20.

Division of Infection and Immunity, University College London, London, UK; NIHR Biomedical Research Centre, University College London Hospitals, London, UK. Electronic address:

In this perspective, we discuss the impact of COVID-19 on tuberculosis (TB)/HIV health services and approaches to mitigating the growing burden of these three colliding epidemics in sub-Saharan Africa (SSA). SSA countries bear significantly high proportions of TB and HIV cases reported worldwide, compared to countries in the West. Whilst COVID-19 epidemiology appears to vary across Africa, most countries in this region have reported relatively lower-case counts compared to the West. Nevertheless, the COVID-19 pandemic has added an additional burden to already overstretched health systems in SSA, which, among other things, have been focused on the longstanding dual epidemics of TB and HIV. As with these dual epidemics, inadequate resources and poor case identification and reporting may be contributing to underestimations of the COVID-19 case burden in SSA. Modelling studies predict that the pandemic-related disruptions in TB and HIV services will result in significant increases in associated morbidity and mortality over the next five years. Furthermore, limited empirical evidence suggests that SARS-CoV-2 coinfections with TB and HIV are associated with increased mortality risk in SSA. However, predictive models require a better evidence-base to accurately define the impact of COVID-19, not only on communicable diseases such as TB and HIV, but on non-communicable disease comorbidities. Further research is needed to assess morbidity and mortality data among both adults and children across the African continent, paying attention to geographic disparities, as well as the clinical and socio-economic determinants of COVID-19 in the setting of TB and/or HIV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijid.2021.03.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980520PMC
March 2021

Recovering from the Impact of the Covid-19 Pandemic and Accelerating to Achieving the United Nations General Assembly Tuberculosis Targets.

Int J Infect Dis 2021 Mar 11. Epub 2021 Mar 11.

Division of Infection and Immunity, Center for Clinical Microbiology, University College London, London, UK; National Institute for Health Research Biomedical Research Centre, University College London Hospitals, NHS Foundation Trust, London, EC1V 2PD, UK. Electronic address:

In 2020, the novel COVID-19 pandemic replaced TB as the world's top cause of death from an infectious disease. The October 21, 2020 the UN Secretary-General report on progress towards implementation of the UNHLM political declaration on TB stresses that although high-level commitments and targets had galvanized global and national progress towards ending TB, urgent and more ambitious investments and actions were required, especially in lieu of the COVID-19 pandemic where associated public health measures and travel restrictions, have disrupted health services universally. The report sets out 10 priority recommendations to get the world on track to reach agreed targets by 2022. Political commitment is more critical than ever. COVID-19 diagnostic and vaccination health services need to be aligned to TB services with active early case finding in communities, engaging the private sector care providers and mitigation of fear and stigma. Healthcare staff and community workers and leaders need to be provided with COVID-19 vaccination and personal protective equipment. The UNHLM declaration committed to mobilize 15 billion USD per annum for TB, of which 13 billion USD is for TB care and 2 billion USD per annum for TB R&D. The Global Fund needs to increase funding for TB. Learning from the unprecedented speed of COVID-19 vaccine development, fastracking development and evaluation of TB vaccines is essential. World leaders need to urgently address and reverse the socio-economic consequences of the COVID-19 pandemic and these will determine to what extent they will impact on achieving TB targets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijid.2021.02.078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948527PMC
March 2021

Clinical and Imaging Features of Adults with Recurrent Pulmonary Tuberculosis - A Prospective Case-Controlled Study.

Int J Infect Dis 2021 Mar 11. Epub 2021 Mar 11.

School of Medicine, Muhimbili University of Health and Allied Sciences, PO Box 65001, Dar es Salaam, Tanzania; Department of Internal Medicine, Muhimbili National Hospital, Dar es Salaam, Tanzania. Electronic address:

Background: Recurrent pulmonary tuberculosis (RPTB) is a growing, important and neglected problem affecting treated TB patients and TB health services across the world, particularly in sub-Saharan Africa. Analyses and identification of differences in clinical features between recurrent PTB and newly diagnosed PTB may lead to improved management recommendations.

Methods: Between September 1 2019 and January 31 2020, we performed a prospective case controlled study of clinical and imaging features of patients with recurrent pulmonary tuberculosis and compared them with those of newly diagnosed PTB cases. Recurrent PTB was defined as a patient with bacteriologically confirmed active PTB who was previously successfully treated for PTB and was cured. A control was defined as a patient who presents for the first time with bacteriologically confirmed PTB. Clinical and radiological features were assessed and documented. Chi-square and t-test were used to test the difference between proportion and continuous data, respectively. Logistic regression analysis was done to determine factors associated with RPTB using SPSS version 23 software.

Results: A total of 312 patients with PTB were enrolled (104 RPTB cases and 208 newly diagnosed controls). Clinically hemoptysis was more common in RPTB compared to controls 28/104 (26.9%) vs 35/208 (16.8%), P = 0.036. Chest pain was significantly less common among patients with RPTB compared to controls 33 (31.7%) vs 92 (44.2%), P = 0.034. A higher proportion of RPTB presented with cavitation 34/104 (32.7%) compared to control 44/208 (21.2%) P = 0.027. The median score for lung pathology was higher among patients with RPTB (50) compared to controls (30); P = 0.001. Lung function of patients with RPTB at diagnosis of index TB were more likely to show mixed restrictive and obstructive pattern 36/104 (34.6%) compared to controls 31/208 (14.9%). p<0.001. Multivariate analysis showed that patients older than 45 years of age (adjusted odds ratio [aOR]: 3.59, 95% CI: 1.38 - 9.32), those with hemoptysis (aOR 1.96, 95% CI: 1.04 - 3.69) p=0.04) and fibrosis on chest x rays (aOR 2.18, 95% CI: 1.16 - 4.10) were significantly associated with recurrent PTB.

Conclusions: Hemoptysis, lung parenchymal damage, and patients being older than 45 years of age are significant features of RPTB. Management should focus on risk factors for recurrence, and a more holistic model of care to prevent long term lung injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijid.2021.01.071DOI Listing
March 2021

Global Tuberculosis Report 2020 - Reflections on the Global TB burden, treatment and prevention efforts.

Int J Infect Dis 2021 Mar 11. Epub 2021 Mar 11.

Department of Infection, Division of Infection and Immunity, University College London, and NIHR Biomedical Research Centre, University College London Hospitals NHS Foundation Trust, London, United Kingdom. Electronic address:

The October 2020 Global TB report reviews TB control strategies and United Nations (UN) targets set in the political declaration at the September 2018 UN General Assembly high-level meeting on TB held in New York. Progress in TB care and prevention has been very slow. In 2019, TB remained the most common cause of death from a single infectious pathogen. Globally, an estimated 10.0 million people developed TB disease in 2019, and there were an estimated 1.2 million TB deaths among HIV-negative people and an additional 208, 000 deaths among people living with HIV. Adults accounted for 88% and children for 12% of people with TB. The WHO regions of South-East Asia (44%), Africa (25%), and the Western Pacific (18%) had the most people with TB. Eight countries accounted for two thirds of the global total: India (26%), Indonesia (8.5%), China (8.4%), the Philippines (6.0%), Pakistan (5.7%), Nigeria (4.4%), Bangladesh (3.6%) and South Africa (3.6%). Only 30% of the 3.5 million five-year target for children treated for TB was met. Major advances have been development of new all oral regimens for MDRTB and new regimens for preventive therapy. In 2020, the COVID-19 pandemic dislodged TB from the top infectious disease cause of mortality globally. Notably, global TB control efforts were not on track even before the advent of the COVID-19 pandemic. Many challenges remain to improve sub-optimal TB treatment and prevention services. Tuberculosis screening and diagnostic test services need to be ramped up. The major drivers of TB remain undernutrition, poverty, diabetes, tobacco smoking, and household air pollution and these need be addressed to achieve the WHO 2035 TB care and prevention targets. National programs need to include interventions for post-tuberculosis holistic wellbeing. From first detection of COVID-19 global coordination and political will with huge financial investments have led to the development of effective vaccines against SARS-CoV2 infection. The world now needs to similarly focus on development of new vaccines for TB utilizing new technological methods.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijid.2021.02.107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433257PMC
March 2021

Accelerating development of new shorter TB treatment regimens in anticipation of a resurgence of multi-drug resistant TB due to the COVID-19 pandemic.

Int J Infect Dis 2021 Mar 10. Epub 2021 Mar 10.

Division of Infection and Immunity, University College London, UK; NIHR Biomedical Research Centre, UCL Hospitals NHS Foundation Trust, London, UK. Electronic address:

The WHO 2020 global TB Report estimates that in 2019 there were an estimated 500,000 cases of multi-drug resistant TB (MDR-TB) of which only 186,772 MDR-TB cases were diagnosed, and positive treatment outcomes were achieved in 57% of them. These data highlight the need for accelerating and improving MDR-TB screening, diagnostic, treatment and patient follow-up services. The last decade has seen three new TB drugs being licensed; bedaquiline, delamanid and pretomanid, and combinations these new, existing and repurposed drugs are leading to improved cure rates. The all oral six month WHO regimen for MDR-TB is more tolerable, has higher treatment success rates and lower mortality. However, the unprecedented ongoing COVID-19 pandemic is having major direct and indirect negative impacts on health services overall, including national TB programs and TB services. This adds further to longstanding challenges for tackling MDR-TB such as cost, rollout of diagnostics and drugs, and implementation of latest WHO guidelines for MDR-TB. In light of COVID-19 disruption of TB services, it is anticipated the numbers of MDR-TB cases will rise in 2021 and 2022 and will affect treatment outcomes further. Investing more in development of new TB drugs and shorter MDR-TB treatment regimens is required in anticipation of emerging drug resistance to new TB drug regimens. There is an urgent need for protecting current investments in TB services, sustaining gains being made in TB control and accelerating roll out of TB diagnostic and treatment services.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijid.2021.02.067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944856PMC
March 2021

Zoonotic Tuberculosis - The Changing Landscape.

Int J Infect Dis 2021 Mar 10. Epub 2021 Mar 10.

Division of Infection and Immunity, University College London, London, UK; National Institute for Health Research Biomedical Research Centre, University College London Hospitals National Health Service Foundation Trust, London, UK. Electronic address:

Despite slow reductions in the annual burden of active human tuberculosis (TB) cases, zoonotic TB (zTB) remains a poorly monitored and an important unaddressed global problem. There is a higher incidence in some regions and countries, especially where close association exists between growing numbers of cattle (the major source of Mycobacterium bovis) and people, many suffering from poverty, and where dairy products are consumed unpasteurised. More attention needs to be focused on possible increased zTB incidence resulting from growth in dairy production globally and increased demand in low income countries in particular. Evidence of new zoonotic mycobacterial strains in South Asia and Africa (e.g. M. orygis), warrants urgent assessment of prevalence, potential drivers and risk in order to develop appropriate interventions. Control of M. bovis infection in cattle through detect and cull policies remain the mainstay of reducing zTB risk, whilst in certain circumstances animal vaccination is proving beneficial. New point of care diagnostics will help to detect animal infections and human cases. Given the high burden of human tuberculosis (caused by M. tuberculosis) in endemic areas, animals are affected by reverse zoonosis, including multi-drug resistant strains. This, may create drug resistant reservoirs of infection in animals. Like COVID-19, zTB is evolving in an ever-changing global landscape.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijid.2021.02.091DOI Listing
March 2021

Evidences for lipid involvement in SARS-CoV-2 cytopathogenesis.

Cell Death Dis 2021 03 12;12(3):263. Epub 2021 Mar 12.

Laboratory of Electron Microscopy, National Institute for Infectious Diseases "Lazzaro Spallanzani", IRCCS, Rome, Italy.

The pathogenesis of SARS-CoV-2 remains to be completely understood, and detailed SARS-CoV-2 cellular cytopathic effects requires definition. We performed a comparative ultrastructural study of SARS-CoV-1 and SARS-CoV-2 infection in Vero E6 cells and in lungs from deceased COVID-19 patients. SARS-CoV-2 induces rapid death associated with profound ultrastructural changes in Vero cells. Type II pneumocytes in lung tissue showed prominent altered features with numerous vacuoles and swollen mitochondria with presence of abundant lipid droplets. The accumulation of lipids was the most striking finding we observed in SARS-CoV-2 infected cells, both in vitro and in the lungs of patients, suggesting that lipids can be involved in SARS-CoV-2 pathogenesis. Considering that in most cases, COVID-19 patients show alteration of blood cholesterol and lipoprotein homeostasis, our findings highlight a peculiar important topic that can suggest new approaches for pharmacological treatment to contrast the pathogenicity of SARS-CoV-2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-021-03527-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952828PMC
March 2021

Lethal zoonotic coronavirus infections of humans - comparative phylogenetics, epidemiology, transmission, and clinical features of coronavirus disease 2019, The Middle East respiratory syndrome and severe acute respiratory syndrome.

Curr Opin Pulm Med 2021 05;27(3):146-154

Respiratory Sciences, University of Leicester, Leicester, UK.

Purpose Of Review: Severe acute respiratory syndrome-coronaviruses-2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged as a new zoonotic pathogen of humans at the end of 2019 and rapidly developed into a global pandemic. Over 106 million COVID-19 cases including 2.3 million deaths have been reported to the WHO as of February 9, 2021. This review examines the epidemiology, transmission, clinical features, and phylogenetics of three lethal zoonotic coronavirus infections of humans: SARS-CoV-1, SARS-CoV-2, and The Middle East respiratory syndrome coronavirus (MERS-COV).

Recent Findings: Bats appear to be the common natural source of SARS-like CoV including SARS-CoV-1 but their role in SARS-CoV-2 and MERS-CoV remains unclear. Civet cats and dromedary camels are the intermediary animal sources for SARS-CoV-1 and MERS-CoV infection, respectively whereas that of SARS-CoV-2 remains unclear. SARS-CoV-2 viral loads peak early on days 2-4 of symptom onset and thus high transmission occurs in the community, and asymptomatic and presymptomatic transmission occurs commonly. Nosocomial outbreaks are hallmarks of SARS-CoV-1 and MERS-CoV infections whereas these are less common in COVID-19. Several COVID-19 vaccines are now available.

Summary: Of the three lethal zoonotic coronavirus infections of humans, SARS-CoV-2 has caused a devastating global pandemic with over a million deaths. The emergence of genetic variants, such as D614G, N501Y (variants 1 and 2), has led to an increase in transmissibility and raises concern about the possibility of re-infection and impaired vaccine response. Continued global surveillance is essential for both SARS-CoV-2 and MERS-CoV, to monitor changing epidemiology due to viral variants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MCP.0000000000000774DOI Listing
May 2021
-->