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1.
BMC Microbiol ; 21(1): 136, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33947325

RESUMO

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-ß-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.

2.
Am J Trop Med Hyg ; 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33882025

RESUMO

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.

3.
Int J Mol Sci ; 22(9)2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33926110

RESUMO

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.

4.
Pathogens ; 10(3)2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33800223

RESUMO

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 M. pneumoniae 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.

5.
Int J Infect Dis ; 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33794380

RESUMO

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.

7.
Int J Infect Dis ; 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33757874

RESUMO

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.

8.
Curr Opin Pulm Med ; 27(3): 146-154, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33660619

RESUMO

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.


Assuntos
Controle de Doenças Transmissíveis , Infecções por Coronavirus , Síndrome Respiratória Aguda Grave , Animais , /prevenção & controle , Quirópteros/virologia , Controle de Doenças Transmissíveis/métodos , Controle de Doenças Transmissíveis/organização & administração , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Humanos , Filogenia , /patogenicidade , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/prevenção & controle , Síndrome Respiratória Aguda Grave/transmissão , /prevenção & controle , /transmissão
10.
Int J Infect Dis ; 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33713812

RESUMO

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.

13.
Int J Infect Dis ; 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33716198

RESUMO

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.

14.
Int J Infect Dis ; 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33713815

RESUMO

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.

15.
Int J Infect Dis ; 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33716195

RESUMO

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.

16.
Cell Death Dis ; 12(3): 263, 2021 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-33712574

RESUMO

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.


Assuntos
Gotículas Lipídicas , Metabolismo dos Lipídeos , Pulmão , /metabolismo , Animais , /patologia , Chlorocebus aethiops , Efeito Citopatogênico Viral , Humanos , Gotículas Lipídicas/ultraestrutura , Gotículas Lipídicas/virologia , Pulmão/metabolismo , Pulmão/ultraestrutura , Pulmão/virologia , Vírus da SARS/metabolismo , Vírus da SARS/ultraestrutura , Síndrome Respiratória Aguda Grave/metabolismo , Síndrome Respiratória Aguda Grave/patologia , Células Vero
17.
Int J Infect Dis ; 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33716197

RESUMO

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 1st 2019 and January 31st 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.

18.
Curr Opin Pulm Med ; 27(3): 205-209, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33629969

RESUMO

PURPOSE OF REVIEW: Severe acute respiratory syndrome coronavirus-2-induced hyperinflammation is a major cause of death or end-organ dysfunction in COVID-19 patients. We review adjunct host-directed therapies (HDTs) for COVID-19 management. RECENT FINDINGS: The use of umbilical cord-derived mesenchymal stem cells as HDT for COVID-19 has been shown to be safe in phase 1 and 2 trials. Trials of anti-interleukin-6 receptor antibodies show promising mortality benefit in hospitalized COVID-19 patients. Repurposed drugs and monoclonal antibodies targeting specific cytokines acting on different aspects of the pro- and anti-inflammatory cascades are under evaluation. SUMMARY: A range of HDTs shows promise for reducing mortality and improving long term disability in patients with severe COVID-19, and require evaluation in randomized, controlled trials.


Assuntos
Fatores Imunológicos/farmacologia , Transplante de Células-Tronco Mesenquimais/métodos , Terapia de Alvo Molecular/métodos , /imunologia , Humanos , Inflamação/imunologia , Inflamação/terapia
19.
Am J Trop Med Hyg ; 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33571138

RESUMO

Most African countries have recorded relatively lower COVID-19 burdens than Western countries. This has been attributed to early and strong political commitment and robust implementation of public health measures, such as nationwide lockdowns, travel restrictions, face mask wearing, testing, contact tracing, and isolation, along with community education and engagement. Other factors include the younger population age strata and hypothesized but yet-to-be confirmed partially protective cross-immunity from parasitic diseases and/or other circulating coronaviruses. However, the true burden may also be underestimated due to operational and resource issues for COVID-19 case identification and reporting. In this perspective article, we discuss selected best practices and challenges with COVID-19 contact tracing in Nigeria, Rwanda, South Africa, and Uganda. Best practices from these country case studies include sustained, multi-platform public communications; leveraging of technology innovations; applied public health expertise; deployment of community health workers; and robust community engagement. Challenges include an overwhelming workload of contact tracing and case detection for healthcare workers, misinformation and stigma, and poorly sustained adherence to isolation and quarantine. Important lessons learned include the need for decentralization of contact tracing to the lowest geographic levels of surveillance, rigorous use of data and technology to improve decision-making, and sustainment of both community sensitization and political commitment. Further research is needed to understand the role and importance of contact tracing in controlling community transmission dynamics in African countries, including among children. Also, implementation science will be critically needed to evaluate innovative, accessible, and cost-effective digital solutions to accommodate the contact tracing workload.

20.
Int J Infect Dis ; 105: 49-53, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33578018

RESUMO

BACKGROUND/OBJECTIVES: A dysregulated inflammatory profile plays an important role in coronavirus disease-2019 (COVID-19) pathogenesis. Moreover, the depletion of lymphocytes is typically associated with an unfavourable disease course. We studied the role and impact of p53 and deacetylase Sirtuin 1 (SIRT1) on lymph-monocyte homeostasis and their possible effect on T and B cell signalling. METHODS: Gene expression analysis and flow cytometry were performed on peripheral blood mononuclear cells (PBMC) of 35 COVID-19 patients and 10 healthy donors (HD). Inflammatory cytokines, the frequency of Annexin+ cells among CD3+ T cells and CD19+ B cell subsets were quantified. RESULTS: PBMC from COVID-19 patients had a higher p53 expression, and higher concentrations of plasma proinflammatory cytokines (IL1ß, TNF-α, IL8, and IL6) than HD. Deacetylase Sirtuin 1 (SIRT1) expression was significantly decreased in COVID-19 patients and was negatively correlated with p53 (p = 0.003 and r = -0.48). A lower expression of IL-7R and B Cell linker (BLNK), key genes for lymphocyte homeostasis and function, was observed in COVID-19 than in HD. The reduction of IgK and IgL chains was seen in lymphopenic COVID-19 patients. A significant increase in both apoptotic B and T cells were observed. Inflammatory cytokines correlated positively with p53 (IL-1ß: r = 0.5 and p = 0.05; IL-8: r = 0.5 and p = 0.05) and negatively with SIRT1 (IL1-ß: r = -0.5 and p = 0.04; TNF-α: r = -0.4 and p = 0.04). CONCLUSIONS: Collectively, our data indicate that the inflammatory environment, the dysregulated p53/SIRT1 axis and low expression of IL7R and BLNK may impact cell survival, B cell signalling and antibody production in COVID-19 patients. Further studies are required to define the functional impact of low BLNK/IL7R expression during severe acute respiratory syndrome coronavirus-2 infection.

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