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1.
Sci Rep ; 11(1): 13780, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215811

RESUMO

Most patients infected with SARS-CoV-2 are asymptomatic or mildly symptomatic. However, the early and late antibody kinetics, and the association between antibody levels, clinical symptoms, and disease phase in these patients have not yet been fully defined. Confirmed SARS-CoV-2 patients and their household contacts were evaluated over a period four months. The evaluation procedure included symptom monitoring, viral load and serology analysis every ten days. A total of 1334 serum samples were collected from 135 patients and analyzed using three assays for IgG-N, IgG-S and IgM antibodies. Of the study participants, 97% were seropositive during the study, and two distinct clusters were identified. These clusters were significantly different in their inflammatory related symptoms. Peak IgG-S was 40.0 AU/ml for the non-inflammatory cluster and 71.5 AU/ml for the inflammatory cluster (P = 0.006), whereas IgG-N peaks were 4.3 and 5.87 (P = 0.023) respectively. Finally, a decision tree model was designed to predict the disease phase based on the serological titer levels, and had an overall accuracy of 80.7%. The specific profile of seroconversion and decay of serum antibodies can be used to predict the time-course from the acute infection.


Assuntos
Anticorpos Antivirais/imunologia , COVID-19/imunologia , SARS-CoV-2/imunologia , Adulto , Idoso , Anticorpos Antivirais/sangue , COVID-19/sangue , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade , Carga Viral
2.
Elife ; 102021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-34250907

RESUMO

Background: Information on SARS-CoV-2 in representative community surveillance is limited, particularly cycle threshold (Ct) values (a proxy for viral load). Methods: We included all positive nose and throat swabs 26 April 2020 to 13 March 2021 from the UK's national COVID-19 Infection Survey, tested by RT-PCR for the N, S, and ORF1ab genes. We investigated predictors of median Ct value using quantile regression. Results: Of 3,312,159 nose and throat swabs, 27,902 (0.83%) were RT-PCR-positive, 10,317 (37%), 11,012 (40%), and 6550 (23%) for 3, 2, or 1 of the N, S, and ORF1ab genes, respectively, with median Ct = 29.2 (~215 copies/ml; IQR Ct = 21.9-32.8, 14-56,400 copies/ml). Independent predictors of lower Cts (i.e. higher viral load) included self-reported symptoms and more genes detected, with at most small effects of sex, ethnicity, and age. Single-gene positives almost invariably had Ct > 30, but Cts varied widely in triple-gene positives, including without symptoms. Population-level Cts changed over time, with declining Ct preceding increasing SARS-CoV-2 positivity. Of 6189 participants with IgG S-antibody tests post-first RT-PCR-positive, 4808 (78%) were ever antibody-positive; Cts were significantly higher in those remaining antibody negative. Conclusions: Marked variation in community SARS-CoV-2 Ct values suggests that they could be a useful epidemiological early-warning indicator. Funding: Department of Health and Social Care, National Institutes of Health Research, Huo Family Foundation, Medical Research Council UK; Wellcome Trust.


Assuntos
Teste para COVID-19 , COVID-19/virologia , SARS-CoV-2 , Carga Viral , Humanos
3.
PLoS One ; 16(7): e0254640, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34255796

RESUMO

BACKGROUND: This study aimed to clarify how SARS-CoV-2 RNAemia is related to COVID-19 critical condition development and mortality in comparison with other predictive markers and scoring systems. METHODS: This is a retrospective cohort study conducted at Yokohama Municipal Citizen's Hospital and National Institute of Infectious Diseases. We recruited adult patients with COVID-19 admitted between March 2020 and January 2021. We compared RNAemia with clinical status on admission including scoring systems such as the 4C Mortality, CURB-65, and A-DROP, as well as the Ct value of the nasopharyngeal PCR, in predicting COVID-19 mortality and critical condition development. RESULTS: Of the 92 recruited patients (median age, 58; interquartile range, 45-71 years), 14 (14.9%) had RNAemia. These patients had an older age (median, 68 years vs. 55.5 years; p = 0.011), higher values of lactated dehydrogenase (median, 381 U/L vs. 256.5 U/L, p < 0.001), C-reactive protein (median, 10.9 mg/dL vs. 3.8 mg/dL; p < 0.001), D-dimer (median, 2.07 µg/mL vs. 1.28 µg/mL; p = 0.015), lower values of lymphocyte (median, 802/µL vs. 1007/µL, p = 0.025) and Ct of the nasopharyngeal PCR assay (median, 20.59 vs. 25.54; p = 0.021) than those without RNAemia. Univariate analysis showed RNAemia was associated with mortality (odds ratio [OR], 18.75; 95% confidence interval [CI], 3.92-89.76; area under the receiver operating characteristic curve [AUC], 0.7851; p = 0.002) and critical condition (OR, 72.00; 95% CI, 12.98-399.29; AUC, 0.8198; p < 0.001). Plus, multivariate analysis also revealed the association of RNAemia with critical condition (adjusted OR, 125.71; 95% CI, 11.47-1377.32; p < 0.001). CONCLUSION: On-admission SARS-CoV-2 RNAemia is a potent predictive marker of COVID-19 critical condition and mortality. The adjusted OR for critical condition was as high as 125.71.


Assuntos
Teste de Ácido Nucleico para COVID-19/normas , COVID-19/diagnóstico , RNA Viral/análise , Idoso , Biomarcadores/análise , COVID-19/mortalidade , Teste de Ácido Nucleico para COVID-19/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/virologia , Admissão do Paciente , Prognóstico , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/patogenicidade , Carga Viral
5.
BMC Infect Dis ; 21(1): 694, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34281502

RESUMO

BACKGROUND: Support groups for people living with HIV (PLWH) may improve HIV care adherence and outcomes. We assessed the impact of support group attendance on antiretroviral therapy (ART) adherence and viral suppression in four African countries. METHODS: The ongoing African Cohort Study (AFRICOS) enrolls participants at 12 clinics in Kenya, Uganda, Tanzania, and Nigeria. Self-reported attendance of any support group meetings, self-reported ART adherence, and HIV RNA are assessed every 6 months. Logistic regression models with generalized estimating equations were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) for support group attendance and other factors potentially associated with ART adherence and viral suppression. RESULTS: From January 2013 to December 1, 2019, 1959 ART-experienced PLWH were enrolled and 320 (16.3%) reported any support group attendance prior to enrollment. Complete ART adherence, with no missed doses in the last 30 days, was reported by 87.8% while 92.4% had viral suppression <1000copies/mL across all available visits. There was no association between support group attendance and ART adherence in unadjusted (OR 1.01, 95% CI 0.99-1.03) or adjusted analyses (aOR 1.00, 95% CI 0.98-1.02). Compared to PLWH who did not report support group attendance, those who did had similar odds of viral suppression in unadjusted (OR 0.99, 95% CI 0.978-1.01) and adjusted analyses (aOR 0.99, 95% CI 0.97-1.01). CONCLUSION: Support group attendance was not associated with significantly improved ART adherence or viral suppression, although low support group uptake may have limited our ability to detect a statistically significant impact.


Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Adesão à Medicação , Grupos de Autoajuda , Adulto , África Oriental , Estudos de Coortes , Feminino , Infecções por HIV/psicologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Autorrelato , Carga Viral
6.
Molecules ; 26(11)2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34198721

RESUMO

There is no approved antiviral therapy for adenovirus (HAdV) ocular infections. Astodrimer sodium (SPL7013) is a polyanionic dendrimer with antiviral activity. The current study evaluated the ocular tolerability and anti-adenoviral efficacy of topical SPL7013 in rabbit ocular models. In a tolerability study, rabbits were treated with 3% SPL7013, vehicle, or 0.5% cidofovir. Their eyes were graded using the Draize scale. In antiviral efficacy studies, HAdV5 inoculated eyes were treated with 3% SPL7013, vehicle, or 0.5% cidofovir. Eyes were cultured for the virus on days 0, 1, 3, 4, 5, 7, 9, 11, and 14. Viral titers were determined. There were no differences in Draize scores between 3% SPL7013 and vehicle on any day. Cidofovir produced significantly higher Draize scores on day 12 than SPL7013 and vehicle. The 3% SPL7013 and 0.5% cidofovir significantly reduced daily viral titers and positive cultures per total compared with vehicle on several different days. The 3% SPL7013 and 0.5% cidofovir significantly reduced the duration of HAdV5 shedding compared to vehicle. The 3% SPL7013 demonstrated significantly more antiviral activity compared with vehicle in the Ad5/NZW rabbit ocular model. The 3% SPL7013 induced "minimal" to "practically non-irritating" Draize scores in the ocular tolerability study. Further development of astodrimer sodium as a topical antiviral therapy for adenoviral ocular infections is indicated.


Assuntos
Infecções por Adenoviridae/tratamento farmacológico , Cidofovir/administração & dosagem , Dendrímeros/administração & dosagem , Infecções Oculares Virais/tratamento farmacológico , Polilisina/administração & dosagem , Células A549 , Adenovírus Humanos/efeitos dos fármacos , Adenovírus Humanos/fisiologia , Administração Tópica , Animais , Cidofovir/farmacologia , Dendrímeros/farmacologia , Modelos Animais de Doenças , Feminino , Humanos , Polilisina/farmacologia , Coelhos , Resultado do Tratamento , Carga Viral/efeitos dos fármacos
7.
PLoS One ; 16(7): e0254167, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34214123

RESUMO

Dexamethasone provides benefits in patients with coronavirus disease 2019 (COVID-19), although data regarding immunological profiles and viral clearance are limited. This study aimed to evaluate for differences in biomarkers among patients with severe COVID-19 who did and did not receive dexamethasone. We measured plasma biomarkers of lung epithelial/endothelial injury and inflammation in 31 patients with severe COVID-19 and in 13 controls. Changes in biomarkers and clinical parameters were compared during the 7-day period among COVID-19 patients, and also according to dexamethasone use. Thirty-two patients with severe COVID-19 who received mechanical ventilation (n = 6), high-flow nasal cannula (n = 11), and supplemental oxygen (n = 15) were analyzed. Relative to controls, patients with severe COVID-19 had significantly higher concentrations of biomarkers related to glycocalyx shedding (endocan and syndecan-1), endothelial injury (von Willebrand factor), and inflammation (soluble receptor for advanced glycation end-products [sRAGE] and interleukin-6). The 7-day decreases in biomarkers of endothelial injury (angiopoietin-2 [Ang-2] and intercellular adhesion molecule-1 [ICAM-1]) and sRAGE, but not in the biomarker of lung epithelial injury (surfactant protein D), were correlated with decreases in C-reactive protein and radiologic score at day 7. Twenty patients (63%) received dexamethasone, and the dexamethasone and non-dexamethasone groups differed in terms of disease severity. However, dexamethasone was associated marginally with increased SpO2/FiO2 and significantly with decreases in C-reactive protein and radiologic score after adjusting for baseline imbalances. Furthermore, the dexamethasone group exhibited a significant decrease in the concentrations of Ang-2, ICAM-1, soluble form of the Tie2 receptor (a biomarker of glycocalyx shedding), and sRAGE. Both groups exhibited a clinically insignificant increase in the cycle threshold value. Severe COVID-19 may be characterized by more severe endothelial injury and inflammation, and less severe lung epithelial injury. There is a possibility that dexamethasone improved severe COVID-19 and related endothelial injury without delaying viral clearance.


Assuntos
Anti-Inflamatórios/uso terapêutico , COVID-19/tratamento farmacológico , Dexametasona/uso terapêutico , Endotélio Vascular/efeitos dos fármacos , Inflamação/prevenção & controle , SARS-CoV-2 , Viremia/tratamento farmacológico , Adulto , Idoso , Anti-Inflamatórios/farmacologia , Biomarcadores , COVID-19/sangue , COVID-19/diagnóstico por imagem , Dexametasona/farmacologia , Endotélio Vascular/patologia , Feminino , Humanos , Inflamação/sangue , Inflamação/etiologia , Lesão Pulmonar/sangue , Lesão Pulmonar/diagnóstico por imagem , Lesão Pulmonar/etiologia , Masculino , Oxigênio/sangue , Projetos Piloto , Carga Viral , Viremia/sangue
8.
BMC Infect Dis ; 21(1): 665, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34238234

RESUMO

BACKGROUND: As SARS-CoV-2 testing expands, particularly to widespread asymptomatic testing, high sensitivity point-of-care PCR platforms may optimise potential benefits from pooling multiple patients' samples. METHOD: We tested patients and asymptomatic citizens for SARS-CoV-2, exploring the efficiency and utility of CovidNudge (i) for detection in individuals' sputum (compared to nasopharyngeal swabs), (ii) for detection in pooled sputum samples, and (iii) by modelling roll out scenarios for pooled sputum testing. RESULTS: Across 295 paired samples, we find no difference (p = 0.1236) in signal strength for sputum (mean amplified replicates (MAR) 25.2, standard deviation (SD) 14.2, range 0-60) compared to nasopharyngeal swabs (MAR 27.8, SD 12.4, range 6-56). At 10-sample pool size we find some drop in absolute strength of signal (individual sputum MAR 42.1, SD 11.8, range 13-60 vs. pooled sputum MAR 25.3, SD 14.6, range 1-54; p < 0.0001), but only marginal drop in sensitivity (51/53,96%). We determine a limit of detection of 250 copies/ml for an individual test, rising only four-fold to 1000copies/ml for a 10-sample pool. We find optimal pooled testing efficiency to be a 12-3-1-sample model, yet as prevalence increases, pool size should decrease; at 5% prevalence to maintain a 75% probability of negative first test, 5-sample pools are optimal. CONCLUSION: We describe for the first time the use of sequentially dipped sputum samples for rapid pooled point of care SARS-CoV-2 PCR testing. The potential to screen asymptomatic cohorts rapidly, at the point-of-care, with PCR, offers the potential to quickly identify and isolate positive individuals within a population "bubble".


Assuntos
Teste para COVID-19/métodos , COVID-19/diagnóstico , COVID-19/virologia , Testes Imediatos , SARS-CoV-2/isolamento & purificação , Escarro/virologia , Testes Diagnósticos de Rotina , Humanos , Limite de Detecção , Nasofaringe/virologia , Sensibilidade e Especificidade , Carga Viral
9.
Artigo em Inglês | MEDLINE | ID: mdl-34281149

RESUMO

Mild to moderate COVID-19 can be found in about 80% of patients. Although mortality is low, mild to moderate COVID-19 may progress to severe or even critical stages in about one week. This poses a substantial burden on the health care system, and ultimately culminates in death or incapacitation and hospitalization. Therefore, pharmacological treatment is paramount for patients with this condition, especially those with recognized risk factors to disease progression. We conducted a comprehensive review in the medical literature searching for randomized studies carried out in patients with mild to moderate COVID-19. A total of 14 randomized studies were identified, enrolling a total of 6848 patients. Nine studies (64%) were randomized, placebo-controlled trials, whereas five were open-label randomized trials (35%). We observed that Bamlanivimab and nitazoxanide reduced viral load, whereas ivermectin may have shortened time to viral clearance; Interferon Beta-1 reduced time to viral clearance and vitamin D reduced viral load; Favirapir, peginterferon, and levamisole improved clinical symptoms, whereas fluvoxamine halted disease progression; inhaled budesonide reduced the number of hospitalizations and visits to emergency departments; colchicine reduced the number of deaths and hospitalizations. Collectively, therefore, these findings show that treatment of early COVID-19 may be associated with reduced viral load, thus potentially decreasing disease spread in the community. Moreover, treatment of patients with mild to moderate COVID-19 may also be associated with improved clinical symptoms, hospitalization, and disease progression. We suggest that colchicine, inhaled budesonide, and nitazoxanide, along with nonpharmacological measures, based on efficacy and costs, may be used to mitigate the effects of the COVID-19 pandemic in middle-income countries.


Assuntos
COVID-19 , Hospitalização , Humanos , Pandemias , SARS-CoV-2 , Resultado do Tratamento , Carga Viral
10.
Sci Immunol ; 6(61)2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34266981

RESUMO

Ongoing SARS-CoV-2 vaccine development is focused on identifying stable, cost-effective, and accessible candidates for global use, specifically in low and middle-income countries. Here, we report the efficacy of a rapidly scalable, novel yeast expressed SARS-CoV-2 specific receptor-binding domain (RBD) based vaccine in rhesus macaques. We formulated the RBD immunogen in alum, a licensed and an emerging alum adsorbed TLR-7/8 targeted, 3M-052-alum adjuvants. The RBD+3M-052-alum adjuvanted vaccine promoted better RBD binding and effector antibodies, higher CoV-2 neutralizing antibodies, improved Th1 biased CD4+T cell reactions, and increased CD8+ T cell responses when compared to the alum-alone adjuvanted vaccine. RBD+3M-052-alum induced a significant reduction of SARS-CoV-2 virus in respiratory tract upon challenge, accompanied by reduced lung inflammation when compared with unvaccinated controls. Anti-RBD antibody responses in vaccinated animals inversely correlated with viral load in nasal secretions and BAL. RBD+3M-052-alum blocked a post SARS-CoV-2 challenge increase in CD14+CD16++ intermediate blood monocytes, and Fractalkine, MCP-1, and TRAIL in the plasma. Decreased plasma analytes and intermediate monocyte frequencies correlated with reduced nasal and BAL viral loads. Lastly, RBD-specific plasma cells accumulated in the draining lymph nodes and not in the bone marrow, contrary to previous findings. Together, these data show that a yeast expressed, RBD-based vaccine+3M-052-alum provides robust immune responses and protection against SARS-CoV-2, making it a strong and scalable vaccine candidate.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Compostos de Alúmen/administração & dosagem , Vacinas contra COVID-19 , COVID-19/prevenção & controle , SARS-CoV-2 , Saccharomycetales/genética , Glicoproteína da Espícula de Coronavírus/genética , Administração por Inalação , Administração Intranasal , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , COVID-19/imunologia , COVID-19/patologia , COVID-19/virologia , Linhagem Celular , Citocinas/imunologia , Humanos , Imunoglobulina G/imunologia , Pulmão/patologia , Macaca mulatta , Masculino , Ligação Proteica , Domínios Proteicos , Glicoproteína da Espícula de Coronavírus/imunologia , Carga Viral
11.
Int J Mol Sci ; 22(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209576

RESUMO

Neurotropic viruses target the brain and contribute to neurologic diseases. Caspase recruitment domain containing family member 9 (CARD9) controls protective immunity in a variety of infectious disorders. To investigate the effect of CARD9 in neurotropic virus infection, CARD9-/- and corresponding C57BL/6 wild-type control mice were infected with Theiler's murine encephalomyelitis virus (TMEV). Brain tissue was analyzed by histology, immunohistochemistry and molecular analyses, and spleens by flow cytometry. To determine the impact of CARD9 deficiency on T cell responses in vitro, antigen presentation assays were utilized. Genetic ablation of CARD9 enhanced early pro-inflammatory cytokine responses and accelerated infiltration of T and B cells in the brain, together with a transient increase in TMEV-infected cells in the hippocampus. CARD9-/- mice showed an increased loss of neuronal nuclear protein+ mature neurons and doublecortin+ neuronal precursor cells and an increase in ß-amyloid precursor protein+ damaged axons in the hippocampus. No effect of CARD9 deficiency was found on the initiation of CD8+ T cell responses by flow cytometry and co-culture experiments using virus-exposed dendritic cells or microglia-enriched glial cell mixtures, respectively. The present study indicates that CARD9 is dispensable for the initiation of early antiviral responses and TMEV elimination but may contribute to the modulation of neuroinflammation, thereby reducing hippocampal injury following neurotropic virus infection.


Assuntos
Proteínas Adaptadoras de Sinalização CARD/deficiência , Suscetibilidade a Doenças , Encefalite Viral/etiologia , Hipocampo/virologia , Infecções por Picornaviridae/etiologia , Picornaviridae/fisiologia , Animais , Biomarcadores , Modelos Animais de Doenças , Encefalite Viral/patologia , Predisposição Genética para Doença , Hipocampo/metabolismo , Hipocampo/patologia , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Imuno-Histoquímica , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , Camundongos , Camundongos Knockout , Infecções por Picornaviridae/patologia , Carga Viral
13.
Pediatr Infect Dis J ; 40(8): e300-e304, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34250969

RESUMO

BACKGROUND: Saliva reverse transcriptase-Polymerase chain reaction (RT-PCR) is an attractive alternative for the detection of severe acute respiratory syndrome coronavirus 2 in adults with less known in children. METHODS: Children with coronavirus disease 2019 symptoms were prospectively enrolled in a 1-month comparative clinical trial of saliva and nasopharyngeal (NP) RT-PCR. Detection rates and sensitivities of saliva and NP RT-PCR were compared as well as discordant NP and saliva RT-PCR findings including viral loads (VLs). RESULTS: Of 405 patients enrolled, 397 patients had 2 tests performed. Mean age was 12.7 years (range, 1.2-17.9). Sensitivity of saliva was 85.2% (95% confidence interval: 78.2%-92.1%) when using NP as the standard; sensitivity of NP was 94.5% (89.8%-99.2%) when saliva was considered as the standard. For a NP RT-PCR VL threshold of ≥103 and ≥104 copies/mL, sensitivity of saliva increases to 88.7% and 95.2%, respectively. Sensitivity of saliva and NP swabs was, respectively, 89.5% and 95.3% in patient with symptoms less than 4 days (P = 0.249) and 70.0% and 95.0% in those with symptoms ≥4-7 days (P = 0.096). The 15 patients who had an isolated positive NP RT-PCR were younger (P = 0.034), had lower NP VL (median 5.6 × 103 vs. 3.9 × 107, P < 0.001), and could not drool saliva at the end of the sampling (P = 0.002). VLs were lower with saliva than with NP RT-PCR (median 8.7 cp/mL × 104; interquartile range 1.2 × 104-5.2 × 105; vs. median 4.0 × 107 cp/mL; interquartile range, 8.6 × 105-1 × 108; P < 0.001). CONCLUSIONS: While RT-PCR testing on saliva performed more poorly in younger children and likely after longer duration of symptoms, saliva remains an attractive alternative to NP swabs in children.


Assuntos
Teste para COVID-19 , COVID-19/diagnóstico , COVID-19/virologia , Nasofaringe/virologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2/isolamento & purificação , Saliva/virologia , Criança , Pré-Escolar , Testes Diagnósticos de Rotina , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos , SARS-CoV-2/genética , Sensibilidade e Especificidade , Manejo de Espécimes , Carga Viral
14.
BMC Infect Dis ; 21(1): 688, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34271860

RESUMO

BACKGROUND: Being able to use COVID-19 RT-PCR Ct values as simple clinical markers of disease outcome or prognosis would allow for the easy and proactive identification and triaging of high-risk cases. This study's objective was thus to explore whether a correlation exists between COVID-19 viral loads, as indicated by RT-PCR Ct values, and disease severity, as indicated by respiratory indices. RESULTS: A multi-centre cross-sectional retrospective study was conducted, using data obtained from Bahrain's National COVID-19 Task force's centralised database. The study period ranged from May 2, 2020 to July 31, 2020. A multivariable logistic regression was used to assess for a correlation using data from a total of 1057 admitted COVID-19 cases. The covariates adjusted for included sex, age, presentation, and comorbidities. In our cohort, Ct value showed no statistical significance for an association with requirement for oxygenation on admission (Odds ratio 1.046; 95%CI 0.999 to 1.096, p = 0.054). CONCLUSION: Viral load, as indicated by Ct values, did not seem to be associated with requirement for oxygenation on admission in our cohort. We postulate however that time since onset of symptom may have acted as an unaccounted-for confounder. As such, RT-PCR Ct values may not be a useful prognostic clinical tool in isolation.


Assuntos
COVID-19/diagnóstico , COVID-19/patologia , SARS-CoV-2/fisiologia , Carga Viral/fisiologia , Adulto , Idoso , Barein/epidemiologia , COVID-19/epidemiologia , COVID-19/virologia , Estudos de Coortes , Comorbidade , Estudos Transversais , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Pulmão/patologia , Pulmão/virologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Testes Sorológicos , Índice de Gravidade de Doença , Carga Viral/estatística & dados numéricos
15.
N Engl J Med ; 385(4): 330-341, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34289276

RESUMO

BACKGROUND: The World Health Organization recommends dolutegravir with two nucleoside reverse-transcriptase inhibitors (NRTIs) for second-line treatment of human immunodeficiency virus type 1 (HIV-1) infection. Evidence is limited for the efficacy of this regimen when NRTIs are predicted to lack activity because of drug resistance, as well as for the recommended switch of an NRTI from tenofovir to zidovudine. METHODS: In a two-by-two factorial, open-label, noninferiority trial, we randomly assigned patients for whom first-line therapy was failing (HIV-1 viral load, ≥1000 copies per milliliter) to receive dolutegravir or ritonavir-boosted darunavir and to receive tenofovir or zidovudine; all patients received lamivudine. The primary outcome was a week 48 viral load of less than 400 copies per milliliter, assessed with the Food and Drug Administration snapshot algorithm (noninferiority margin for the between-group difference in the percentage of patients with the primary outcome, 12 percentage points). RESULTS: We enrolled 464 patients at seven sub-Saharan African sites. A week 48 viral load of less than 400 copies per milliliter was observed in 90.2% of the patients in the dolutegravir group (212 of 235) and in 91.7% of those in the darunavir group (210 of 229) (difference, -1.5 percentage points; 95% confidence interval [CI], -6.7 to 3.7; P = 0.58; indicating noninferiority of dolutegravir, without superiority) and in 92.3% of the patients in the tenofovir group (215 of 233) and in 89.6% of those in the zidovudine group (207 of 231) (difference, 2.7 percentage points; 95% CI, -2.6 to 7.9; P = 0.32; indicating noninferiority of tenofovir, without superiority). In the subgroup of patients with no NRTIs that were predicted to have activity, a viral load of less than 400 copies per milliliter was observed in more than 90% of the patients in the dolutegravir group and the darunavir group. The incidence of adverse events did not differ substantially between the groups in either factorial comparison. CONCLUSIONS: Dolutegravir in combination with NRTIs was effective in treating patients with HIV-1 infection, including those with extensive NRTI resistance in whom no NRTIs were predicted to have activity. Tenofovir was noninferior to zidovudine as second-line therapy. (Funded by Janssen; NADIA ClinicalTrials.gov number, NCT03988452.).


Assuntos
Fármacos Anti-HIV/administração & dosagem , Darunavir/administração & dosagem , Infecções por HIV/tratamento farmacológico , HIV-1 , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Oxazinas/administração & dosagem , Piperazinas/administração & dosagem , Piridonas/administração & dosagem , Inibidores da Transcriptase Reversa/administração & dosagem , Tenofovir/administração & dosagem , Zidovudina/administração & dosagem , Adolescente , Adulto , Fármacos Anti-HIV/efeitos adversos , Criança , Darunavir/efeitos adversos , Resistência a Medicamentos , Quimioterapia Combinada , Feminino , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Oxazinas/efeitos adversos , Piperazinas/efeitos adversos , Piridonas/efeitos adversos , Inibidores da Transcriptase Reversa/efeitos adversos , Carga Viral , Adulto Jovem
16.
PLoS Pathog ; 17(7): e1009381, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34197564

RESUMO

Clearance of viral infections, such as SARS-CoV-2 and influenza A virus (IAV), must be fine-tuned to eliminate the pathogen without causing immunopathology. As such, an aggressive initial innate immune response favors the host in contrast to a detrimental prolonged inflammation. The complement pathway bridges innate and adaptive immune system and contributes to the response by directly clearing pathogens or infected cells, as well as recruiting proinflammatory immune cells and regulating inflammation. However, the impact of modulating complement activation in viral infections is still unclear. In this work, we targeted the complement decay-accelerating factor (DAF/CD55), a surface protein that protects cells from non-specific complement attack, and analyzed its role in IAV infections. We found that DAF modulates IAV infection in vivo, via an interplay with the antigenic viral proteins hemagglutinin (HA) and neuraminidase (NA), in a strain specific manner. Our results reveal that, contrary to what could be expected, DAF potentiates complement activation, increasing the recruitment of neutrophils, monocytes and T cells. We also show that viral NA acts on the heavily sialylated DAF and propose that the NA-dependent DAF removal of sialic acids exacerbates complement activation, leading to lung immunopathology. Remarkably, this mechanism has no impact on viral loads, but rather on the host resilience to infection, and may have direct implications in zoonotic influenza transmissions.


Assuntos
Antígenos CD55/fisiologia , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Pulmão/imunologia , Viremia/imunologia , Animais , Líquido da Lavagem Broncoalveolar/imunologia , Antígenos CD55/química , Antígenos CD55/deficiência , Quimiotaxia de Leucócito , Ativação do Complemento , Glicoproteínas de Hemaglutininação de Vírus da Influenza/fisiologia , Adaptação ao Hospedeiro , Especificidade de Hospedeiro , Interações Hospedeiro-Patógeno , Vírus da Influenza A Subtipo H1N1/enzimologia , Vírus da Influenza A Subtipo H1N1/patogenicidade , Vírus da Influenza A Subtipo H1N1/fisiologia , Interferon gama/análise , Pulmão/patologia , Pulmão/virologia , Camundongos , Camundongos Endogâmicos C57BL , Ácido N-Acetilneuramínico , Neuraminidase/fisiologia , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/patologia , Carga Viral , Proteínas Virais/fisiologia , Virulência , Replicação Viral , Perda de Peso
17.
BMC Health Serv Res ; 21(1): 625, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193138

RESUMO

BACKGROUND: Syphilis infections have been on the rise, affecting men living with HIV in urban centres disproportionately. Since individuals in HIV care undergo routine blood testing, HIV clinics provide practical opportunities to conduct regular and frequent syphilis testing. Following the implementation of a routine syphilis testing intervention in HIV outpatient clinics, we conducted a qualitative process evaluation of patient experiences to measure patient acceptability, barriers to implementation, and facilitators of successful uptake. METHODS: Upon completion of the trial, which took place at four HIV outpatient clinics in Toronto and Ottawa, Canada, we recruited male patients attending these clinics from November 2017 to April 2018. Interviews were conducted on-site and were audio-recorded and transcribed verbatim. All participants provided written informed consent. Interview data were analyzed using grounded theory, assessing qualitative modulators of effective uptake of routinised syphilis testing. RESULTS: A total of 21 male patients were interviewed. Overall, interviewees found the clinical intervention acceptable, endorsing the practice of routinising syphilis testing alongside regular viral load bloodwork. Some men preferred, based on their self-assessment of syphilis risk, to opt out of testing; we considered this as a potential barrier to uptake of population-wide routinised syphilis testing. Interviewees also identified multiple facilitators of successful uptake, including the de-stigmatising of STI testing as a consequence of the universal nature of routinised testing. Participants recommended a routinised syphilis screening intervention to give patients peace of mind surrounding their sexual health. Participants identified HIV care clinics as comfortable and efficient locations to offer testing. CONCLUSIONS: Overall, most men were in support of implementing routinised syphilis testing as part of standard HIV care. From the patient perspective, HIV care clinics are convenient places to be tested for syphilis, and the routine approach was viewed to have a de-stigmatisng effect on syphilis testing. TRIAL REGISTRATION: ClinicalTrials.gov NCT02019043; registered December 23, 2013.


Assuntos
Infecções por HIV , Sífilis , Canadá , Infecções por HIV/diagnóstico , Homossexualidade Masculina , Humanos , Masculino , Programas de Rastreamento , Sífilis/diagnóstico , Carga Viral
18.
Adv Exp Med Biol ; 1327: 169-189, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34279838

RESUMO

With the largest viral loads in both symptomatic and asymptomatic patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) present in the oral and nasal cavities, agents that act on these two areas have the potential for large therapeutic and prophylactic benefit. A literature review was conducted to elucidate the possible agents useful in treatment of SARS-CoV-2. These agents were evaluated for their current applications, adverse reactions, their current state of study, and any future considerations in their management of coronavirus disease 2019 (COVID-2019). Our review has found that, while there are many promising agents with proven efficacy in their in-vitro efficacy against SARS-CoV-2, more clinical trials and in-vivo studies, as well as safety trials, must be conducted before these agents can be effectively implemented.


Assuntos
COVID-19 , Antivirais/uso terapêutico , Humanos , SARS-CoV-2 , Carga Viral
19.
Front Cell Infect Microbiol ; 11: 656393, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34307188

RESUMO

Sustained virologic response (SVR) in chronic hepatitis C (CHC) treatment denotes that the host genetics controls the immune response and unequivocally contribute to viral clearance or disease severity. In this context, single nucleotide polymorphisms (SNPs) in the locus of interferon lambda 3 and 4 genes (IFNL3/4) have been important genetic markers of responsiveness to CHC as prognostic markers for the pegylated-Interferon-alpha/ribavirin (Peg-IFN-α/RBV). Here, we analyzed 12 SNPs at the IFNL3/4 region in 740 treatment-naïve patients with CHC infected with hepatitis C virus (HCV) genotypes 1, 2, or 3 treated with Peg-IFN-α/RBV. Individually, rs12979860-CC, rs8109886-CC, or rs8099917-TT were predictive markers of SVR, while rs12979860-CC demonstrated the stronger effect. Besides, the genotypic combination of these three predictors' genotypes, CC/CC/TT, increased the rate of SVR. Serum levels of cytokines and gene expression analysis on the genes IFNL3, IFNL4, IFNA1, and some of the IFN-stimulated genes (ISGs) were measured in a subgroup of 24 treated patients and 24 healthy volunteers. An antagonist effect was highlighted between the expression of IFNL3/4 and IFNA1 mRNA among patients. Besides, a prominent production of the pro-inflammatory chemokines CCL4 and CXCL10 was observed at a 12-week treatment follow-up. Lower serum levels of these chemokines were detected in patients with an rs12979860-CC genotype associated with the better treatment outcome. Also, lower expression levels of the IFI6, IFI16, IRF9 genes were observed among rs12979860-CC individuals. In conclusion, a combination of the genotypes at the IFNL3/4 locus can act as a better marker for the prognosis for virological responses in an admixed Brazilian population presenting the modulating effect over innate immunity and inflammation that are controlling the outcome of the viral infection, but also other infectious diseases. This study is registered on the ClinicalTrials.gov platform (accession number NCT01889849 and NCT01623336).


Assuntos
Antivirais , Interleucinas , Antivirais/uso terapêutico , Brasil , Quimioterapia Combinada , Genótipo , Humanos , Imunidade Inata , Interferon-alfa/uso terapêutico , Interferons , Interleucinas/genética , Polietilenoglicóis/uso terapêutico , Polimorfismo de Nucleotídeo Único , Proteínas Recombinantes , Resposta Viral Sustentada , Resultado do Tratamento , Carga Viral
20.
PLoS One ; 16(7): e0254540, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34260643

RESUMO

Coronaviruses (CoVs) are a family of viruses that are best known as the causative agents of human diseases like the common cold, Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS) and COVID-19. CoVs spread by human-to-human transmission via droplets or direct contact. There is, however, concern about potential waterborne transmission of SARS-CoV-2, the virus responsible for COVID-19, as it has been found in wastewater facilities and rivers. To date, little is known about the stability of SARS-CoV-2 or any other free coronavirus in aquatic environments. The inactivation of terrestrial CoVs in seawater is rarely studied. Here, we use a porcine respiratory coronavirus (PRCV) that is commonly found in animal husbandry as a surrogate to study the stability of CoVs in natural water. A series of experiments were conducted in which PRCV (strain 91V44) was added to filtered and unfiltered fresh- and saltwater taken from the river Scheldt and the North Sea. Virus titres were then measured by TCID50-assays using swine testicle cell cultures after various incubation times. The results show that viral inactivation of PRCV in filtered seawater can be rapid, with an observed 99% decline in the viral load after just two days, which may depend on temperature and the total suspended matter concentration. PRCV degraded much slower in filtered water from the river Scheldt, taking over 15 days to decline by 99%, which was somewhat faster than the PBS control treatment (T99 = 19.2 days). Overall, the results suggest that terrestrial CoVs are not likely to accumulate in marine environments. Studies into potential interactions with exudates (proteases, nucleases) from the microbial food web are, however, recommended.


Assuntos
Infecções por Coronavirus/transmissão , Coronavirus Respiratório Porcino/isolamento & purificação , Testículo/citologia , Águas Residuárias/virologia , Animais , Células Cultivadas , Filtração , Masculino , Projetos Piloto , Coronavirus Respiratório Porcino/patogenicidade , Rios/virologia , Suínos , Testículo/virologia , Fatores de Tempo , Carga Viral , Microbiologia da Água
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