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1.
Biologicals ; 2022 Sep 02.
Article in English | MEDLINE | ID: covidwho-2007466

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in Wuhan, China, is the causative agent of the coronavirus disease 2019 (COVID-19). Since its first notification in São Paulo state (SP) on 26th February 2020, more than 22,300,000 cases and 619,000 deaths were reported in Brazil. In early pandemic, SARS-CoV-2 spread locally, however, over time, this virus was disseminated to other regions of the country. Herein, we performed genomic sequencing and phylogenetic analysis of SARS-CoV-2 using 20 clinical samples of COVID-19 confirmed cases from 9 cities of Minas Gerais state (MG), in order to evaluate the molecular properties of circulating viral strains in this locality from March to May 2020. Our analyses demonstrated the circulation of B.1 lineage isolates in the investigated locations and nucleotide substitutions were observed into the genomic regions related to important viral structures. Additionally, sequences generated in this study clustered with isolates from SP, suggesting a dissemination route between these two states. Alternatively, monophyletic groups of sequences from MG and other states or country were observed, indicating independent events of virus introduction. These results reinforce the need of genomic surveillance for understand the ongoing spread of emerging viral pathogens.

2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329915

ABSTRACT

SARS-CoV-2 virus genomes are currently being sequenced at an unprecedented pace. The choice of viral sequences used in genetic and epidemiological analysis is important as it can induce biases that detract from the value of these rich datasets. This raises questions about how a set of sequences should be chosen for analysis, and which epidemiological parameters derived from genomic data are sensitive or robust to changes in sampling. We provide initial insights on these largely understudied problems using SARS-CoV-2 genomic sequences from Hong Kong and the Amazonas State, Brazil. We consider sampling schemes that select sequences uniformly, in proportion or reciprocally with case incidence and which simply use all available sequences (unsampled). We apply Birth-Death Skyline and Skygrowth methods to estimate the time-varying reproduction number ( R t ) and growth rate ( r t ) under these strategies as well as related R 0 and date of origin parameters. We compare these to estimates from case data derived from EpiFilter , which we use as a reference for assessing bias. We find that both R t and r t are sensitive to changes in sampling whilst R 0 and the date of origin are relatively robust. Moreover, we find that the unsampled datasets, which reflect an opportunistic sampling scheme, engender the most biased R t and r t estimates for both our Hong Kong and Amazonas case studies. We highlight that sampling strategy choices may be an influential yet neglected component of sequencing analysis pipelines. More targeted attempts at genomic surveillance and epidemic analyses, particularly in resource-poor settings with limited sequencing capabilities, are necessary to maximise the informativeness of virus genomic datasets.

3.
Immun Ageing ; 19(1): 12, 2022 Mar 05.
Article in English | MEDLINE | ID: covidwho-1724508

ABSTRACT

BACKGROUND: COVID-19 patients may experience "cytokine storm" when human immune system produces excessive cytokines/chemokines. However, it remains unclear whether early responses of inflammatory cytokines would lead to high or low titers of anti-SARS-CoV-2 antibodies. METHODS: This retrospective study enrolled a cohort of 272 hospitalized patients with laboratory-confirmed SARS-CoV-2. Laboratory assessments of serum cytokines (IL-2R, IL-6, IL-8, IL-10, TNF-α), anti-SARS-CoV-2 IgG/IgM antibodies, and peripheral blood biomarkers were conducted during hospitalization. RESULTS: At hospital admission, 36.4% patients were severely ill, 51.5% patients were ≥ 65 years, and 60.3% patients had comorbidities. Higher levels of IL-2R and IL-6 were observed in older patients (≥65 years). Significant differences of IL-2R (week 2 to week ≥5 from symptom onset), IL-6 (week 1 to week ≥5), IL-8 (week 2 to week ≥5), and IL-10 (week 1 to week 3) were observed between moderately-ill and severely ill patients. Anti-SARS-CoV-2 IgG titers were significantly higher in severely ill patients than in moderately ill patients, but such difference was not observed for IgM. High titers of early-stage IL-6, IL-8, and TNF-α (≤2 weeks after symptom onset) were positively correlated with high titers of late-stage IgG (≥5 weeks after symptom onset). Deaths were mostly observed in severely ill older patients (45.9%). Survival analyses revealed risk factors of patient age, baseline COVID-19 severity, and baseline IL-6 that affected survival time, especially in severely ill older patients. CONCLUSION: Early responses of elevated cytokines such as IL-6 reflect the active immune responses, leading to high titers of IgG antibodies against COVID-19.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-308600

ABSTRACT

Emerging and re-emerging viruses are a global health concern. Genome sequencing as an approach for monitoring circulating viruses is currently hampered by complex and expensive methods. Untargeted, metagenomic nanopore sequencing can provide genomic information to identify pathogens, prepare for or even prevent outbreaks. SMART (Switching Mechanism at the 5′ end of RNA Template) is a popular method for RNA-Seq but most current methods rely on oligo-dT priming to target polyadenylated mRNA molecules. We have developed two random primed SMART-Seq approaches, ‘SMART-9N’, and a version compatible with barcoded PCR primers available from Oxford Nanopore Technologies, ‘Rapid SMART-9N’, for the detection, characterization, and whole-genome sequencing of RNA viruses. The methods were developed using viral isolates, clinical samples, and compared to a gold-standard amplicon-based method. From a Zika virus isolate the SMART-9N approach recovered 10kb of the 10.8kb RNA genome in a single nanopore read. We also obtained full genome coverage at a high depth coverage using the Rapid SMART-9N, which takes only 10 minutes and costs up to 45% less than other methods. We found the limits of detection of these methods to be 6e00 focus forming units (FFU)/mL with 99.02% and 87.58% genome coverage for SMART-9N and Rapid SMART-9N respectively. Yellow fever virus plasma samples and SARS-CoV-2 nasopharyngeal samples previously confirmed by RT-qPCR with a broad range of Ct-values were selected for validation. Both methods produced greater genome coverage when compared to the multiplex PCR approach and we obtained the longest single read of this study (18.5 kb) with a SARS-CoV-2 clinical sample, 60% of the virus genome using the Rapid SMART-9N method. This work demonstrates that SMART-9N and Rapid SMART-9N are sensitive, low input, and long-read compatible alternatives for RNA virus detection and genome sequencing and Rapid SMART-9N improves the cost, time, and complexity of laboratory work.

5.
Rev Inst Med Trop Sao Paulo ; 63: e36, 2021.
Article in English | MEDLINE | ID: covidwho-1288733

ABSTRACT

Reinfection by the severe acute respiratory syndrome coronavirus type 2 (SARS-COV-2) has been reported in many countries, suggesting that the virus may continue to circulate among humans despite the possibility of local herd immunity due to massive previous infections. The emergence of variants of concern (VOC) that are more transmissible than the previous circulating ones has raised particular concerns on the vaccines effectiveness and reinfection rates. The P.1 lineage was first identified in December 2020 in Manaus city and is now globally spread. We report the first case of reinfection of SARS-CoV-2 caused by the P.1 variant outside of Manaus. The potential of these new variants to escape naturally and vaccine- induced immunity highlights the need for a global vigilance.


Subject(s)
COVID-19 , Reinfection , SARS-CoV-2 , Brazil/epidemiology , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/virology , Humans , Reinfection/virology , SARS-CoV-2/isolation & purification
6.
Aging (Albany NY) ; 13(1): 27-60, 2020 12 31.
Article in English | MEDLINE | ID: covidwho-1068117

ABSTRACT

The COVID-19 pandemic causes severe morbidity and mortality. This multi-country study aimed to explore risk factors that drive mortality in COVID-19 patients who received neither dexamethasone nor remdesivir. We analyzed a cohort of 568 survivors and 507 non-survivors from China, European regions, and North America. Elderly males ≥70 years accounted for only 25% of survivors, but this rate was significantly higher in non-survivors from China (55%), European regions (63%), and North America (47%). Compared with survivors, non-survivors had more incidences of comorbidities such as cerebrovascular disease and chronic obstructive pulmonary disease (COPD, p-values<0.05). Survival analyses revealed age, male gender, shortness of breath, cerebrovascular disease, and COPD as mortality-associated factors. Survival time from symptom onset was significantly shorter in elderly versus young patients (median: 29 versus 62 days), males versus females (median: 46 versus 59 days), and patients with versus without comorbidities (mean: 41 versus 61 days). Mortality risk was higher in elderly males with comorbidities than in young females without comorbidities (p-value<0.01). Elderly male survivors with comorbidities also had longer hospital stays than other survivors (25 versus 18.5 days, p-value<0.01). Overall, the high mortality risk in elderly males with COVID-19-associated comorbidities supports early prevention and critical care for elderly populations.


Subject(s)
Aging , COVID-19/complications , COVID-19/mortality , Cardiovascular Diseases/complications , SARS-CoV-2 , Tuberculosis/complications , Adolescent , Adult , Aged , COVID-19/epidemiology , Cerebrovascular Disorders/complications , Child , Child, Preschool , Cohort Studies , Comorbidity , Female , Global Health , Humans , Infant , Liver Diseases/complications , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/complications , Respiratory Tract Diseases/complications , Risk Factors , Young Adult
7.
Emerg Infect Dis ; 27(3): 970-972, 2021 03.
Article in English | MEDLINE | ID: covidwho-1048946

ABSTRACT

In December 2020, research surveillance detected the B.1.1.7 lineage of severe acute respiratory syndrome coronavirus 2 in São Paulo, Brazil. Rapid genomic sequencing and phylogenetic analysis revealed 2 distinct introductions of the lineage. One patient reported no international travel. There may be more infections with this lineage in Brazil than reported.


Subject(s)
COVID-19 , Phylogeny , SARS-CoV-2/isolation & purification , Travel , Adult , Brazil , COVID-19/epidemiology , COVID-19/virology , Female , Genome, Viral , Humans , Male , Young Adult
9.
Clin Transl Immunology ; 9(9): e1182, 2020.
Article in English | MEDLINE | ID: covidwho-796073

ABSTRACT

OBJECTIVES: Asymptomatic and symptomatic patients may transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but their clinical features and immune responses remain largely unclear. We aimed to characterise the clinical features and immune responses of asymptomatic and symptomatic patients infected with SARS-CoV-2. METHODS: We collected clinical, laboratory and epidemiological records of patients hospitalised in a coronavirus field hospital in Wuhan. We performed qualitative detection of anti-SARS-CoV-2 immunoglobulin M (IgM) and immunoglobulin G (IgG) using archived blood samples. RESULTS: Of 214 patients with SARS-CoV-2, 26 (12%) were asymptomatic at hospital admission and during hospitalisation. Most asymptomatic patients were ≤ 60 years (96%) and females (65%) and had few comorbidities (< 16%). Serum levels of white and red blood cells were higher in asymptomatic than in symptomatic patients (P-values < 0.05). During hospitalisation, IgG seroconversion was commonly observed in both asymptomatic and symptomatic patients (85% versus 94%, P-value = 0.07); in contrast, IgM seroconversion was less common in asymptomatic than in symptomatic patients (31% versus 74%, P-value < 0.001). The median time from the first virus-positive screening to IgG or IgM seroconversion was significantly shorter in asymptomatic than in symptomatic patients (median: 7 versus 14 days, P-value < 0.01). Furthermore, IgG/IgM seroconversion rates increased concomitantly with the clearance of SARS-CoV-2 in both asymptomatic and symptomatic patients. At the time of virus clearance, IgG/IgM titres and plasma neutralisation capacity were significantly lower in recovered asymptomatic than in recovered symptomatic patients (P-values < 0.01). CONCLUSION: Asymptomatic and symptomatic patients exhibited different kinetics of IgG/IgM responses to SARS-CoV-2. Asymptomatic patients may transmit SARS-CoV-2, highlighting the importance of early diagnosis and treatment.

10.
Nat Hum Behav ; 4(8): 856-865, 2020 08.
Article in English | MEDLINE | ID: covidwho-690410

ABSTRACT

The first case of COVID-19 was detected in Brazil on 25 February 2020. We report and contextualize epidemiological, demographic and clinical findings for COVID-19 cases during the first 3 months of the epidemic. By 31 May 2020, 514,200 COVID-19 cases, including 29,314 deaths, had been reported in 75.3% (4,196 of 5,570) of municipalities across all five administrative regions of Brazil. The R0 value for Brazil was estimated at 3.1 (95% Bayesian credible interval = 2.4-5.5), with a higher median but overlapping credible intervals compared with some other seriously affected countries. A positive association between higher per-capita income and COVID-19 diagnosis was identified. Furthermore, the severe acute respiratory infection cases with unknown aetiology were associated with lower per-capita income. Co-circulation of six respiratory viruses was detected but at very low levels. These findings provide a comprehensive description of the ongoing COVID-19 epidemic in Brazil and may help to guide subsequent measures to control virus transmission.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections , Disease Transmission, Infectious , Influenza, Human , Pandemics , Pneumonia, Viral , Adult , Aged , Brazil/epidemiology , COVID-19 , COVID-19 Testing , Child , Clinical Laboratory Techniques/methods , Clinical Laboratory Techniques/statistics & numerical data , Coinfection/epidemiology , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/mortality , Coronavirus Infections/therapy , Coronavirus Infections/transmission , Disease Transmission, Infectious/prevention & control , Disease Transmission, Infectious/statistics & numerical data , Female , Hospitalization/statistics & numerical data , Humans , Infant , Influenza, Human/diagnosis , Influenza, Human/epidemiology , Influenza, Human/virology , Male , Mortality , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Pneumonia, Viral/therapy , Pneumonia, Viral/transmission , SARS-CoV-2 , Socioeconomic Factors
12.
Rev Inst Med Trop Sao Paulo ; 62: e30, 2020.
Article in English | MEDLINE | ID: covidwho-246727

ABSTRACT

We conducted the genome sequencing and analysis of the first confirmed COVID-19 infections in Brazil. Rapid sequencing coupled with phylogenetic analyses in the context of travel history corroborate multiple independent importations from Italy and local spread during the initial stage of COVID-19 transmission in Brazil.


Subject(s)
Betacoronavirus/genetics , Communicable Diseases, Imported/transmission , Coronavirus Infections/transmission , Pandemics , Pneumonia, Viral/transmission , Aged , Brazil/epidemiology , COVID-19 , Communicable Diseases, Imported/epidemiology , Communicable Diseases, Imported/virology , Coronavirus Infections/epidemiology , Humans , Middle Aged , Phylogeny , Pneumonia, Viral/epidemiology , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2
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