We documented 4 cases of severe acute respiratory syndrome coronavirus 2 reinfection by non-variant of concern strains among healthcare workers in Campinas, Brazil. We isolated infectious particles ...from nasopharyngeal secretions during both infection episodes. Improved and continued protection measures are necessary to mitigate the risk for reinfection among healthcare workers.
Sickle cell disease (SCD) is a well-studied monogenetic disease with an established chronic inflammatory component
.
The paradigm shift towards inflammation has made the pathophysiology of SCD even ...more complex. Studies have shown that an imbalance between the pro-inflammatory and anti-inflammatory cytokines in SCD exists; however, the reports are skewed toward the pro-inflammatory mediators. We enumerate recent in vitro and in vivo studies on anti-inflammatory cytokines in SCD patients, and discuss the biology of anti-inflammatory cytokines including the already reported IL-2, TGF-β, and IL-10 as well as the recently discovered IL-27, IL-35 and IL-37. This review will improve the understanding of the pathophysiology of SCD and aid in the search of new therapeutic options for patients with SCD.
Sickle cell anemia (SCA) pathophysiology is characterized by the activation of sickle red blood cells, reticulocytes, leukocytes, platelets, and endothelial cells, and with the expression of several ...inflammatory molecules. Therefore, it is conceivable that variations in levels of proinflammatory cytokines may act as a signaling of differential clinical course in SCA. Here, we evaluated the clinical impact of proinflammatory cytokines interleukin 1-β (IL-1β), interleukin 6 (IL-6), and interleukin 8 (IL-8) in 79 patients with SCA, followed in a single reference center from northeastern Brazil. The main clinical/laboratory data were obtained from patient interview and medical records. The proinflammatory markers IL-1β, IL-6, and IL-8 were evaluated by using commercially available enzyme-linked immunosorbent assay kits. According to levels of the proinflammatory markers, we observed that patients who had a higher frequency of VOC per year (
P
= 0.0236), acute chest syndrome (
P
= 0.01), leg ulcers (
P
= 0.0001), osteonecrosis (
P
= 0.0006), stroke (
P
= 0.0486), and priapism (
P
= 0.0347) had higher IL-6 levels compared with patients without these clinical complications. Furthermore, increased levels of IL-8 were found in patients who presented leg ulcers (
P
= 0.0184). No significant difference was found for IL-1β levels (
P
> 0.05). In summary, the present study emphasizes the role of inflammation in SCA pathophysiology, reveals an association of IL-8 levels and leg ulcer occurrence, and indicates that IL-6 levels can be used as a useful predictor for poor outcomes in SCA.
Mutations accrued by SARS-CoV-2 lineage P.1—first detected in Brazil in early January, 2021—include amino acid changes in the receptor-binding domain of the viral spike protein that also are reported ...in other variants of concern, including B.1.1.7 and B.1.351. We aimed to investigate whether isolates of wild-type P.1 lineage SARS-CoV-2 can escape from neutralising antibodies generated by a polyclonal immune response.
We did an immunological study to assess the neutralising effects of antibodies on lineage P.1 and lineage B isolates of SARS-CoV-2, using plasma samples from patients previously infected with or vaccinated against SARS-CoV-2. Two specimens (P.1/28 and P.1/30) containing SARS-CoV-2 lineage P.1 (as confirmed by viral genome sequencing) were obtained from nasopharyngeal and bronchoalveolar lavage samples collected from patients in Manaus, Brazil, and compared against an isolate of SARS-CoV-2 lineage B (SARS.CoV2/SP02.2020) recovered from a patient in Brazil in February, 2020. Isolates were incubated with plasma samples from 21 blood donors who had previously had COVID-19 and from a total of 53 recipients of the chemically inactivated SARS-CoV-2 vaccine CoronaVac: 18 individuals after receipt of a single dose and an additional 20 individuals (38 in total) after receipt of two doses (collected 17–38 days after the most recent dose); and 15 individuals who received two doses during the phase 3 trial of the vaccine (collected 134–230 days after the second dose). Antibody neutralisation of P.1/28, P.1/30, and B isolates by plasma samples were compared in terms of median virus neutralisation titre (VNT50, defined as the reciprocal value of the sample dilution that showed 50% protection against cytopathic effects).
In terms of VNT50, plasma from individuals previously infected with SARS-CoV-2 had an 8·6 times lower neutralising capacity against the P.1 isolates (median VNT50 30 IQR <20–45 for P.1/28 and 30 <20–40 for P.1/30) than against the lineage B isolate (260 160–400), with a binominal model showing significant reductions in lineage P.1 isolates compared with the lineage B isolate (p≤0·0001). Efficient neutralisation of P.1 isolates was not seen with plasma samples collected from individuals vaccinated with a first dose of CoronaVac 20–23 days earlier (VNT50s below the limit of detection <20 for most plasma samples), a second dose 17–38 days earlier (median VNT50 24 IQR <20–25 for P.1/28 and 28 <20–25 for P.1/30), or a second dose 134–260 days earlier (all VNT50s below limit of detection). Median VNT50s against the lineage B isolate were 20 (IQR 20–30) after a first dose of CoronaVac 20–23 days earlier, 75 (<20–263) after a second dose 17–38 days earlier, and 20 (<20–30) after a second dose 134–260 days earlier. In plasma collected 17–38 days after a second dose of CoronaVac, neutralising capacity against both P.1 isolates was significantly decreased (p=0·0051 for P.1/28 and p=0·0336 for P.1/30) compared with that against the lineage B isolate. All data were corroborated by results obtained through plaque reduction neutralisation tests.
SARS-CoV-2 lineage P.1 might escape neutralisation by antibodies generated in response to polyclonal stimulation against previously circulating variants of SARS-CoV-2. Continuous genomic surveillance of SARS-CoV-2 combined with antibody neutralisation assays could help to guide national immunisation programmes.
São Paulo Research Foundation, Brazilian Ministry of Science, Technology and Innovation and Funding Authority for Studies, Medical Research Council, National Council for Scientific and Technological Development, National Institutes of Health.
For the Portuguese translation of the abstract see Supplementary Materials section.
Hemoglobin (Hb) Zürich‐Albisrieden (ZA) α2 59(E8) Gly > Arg; HBA2:c.178G > C is a rare and highly unstable α‐chain variant. A few simple and compound heterozygotes (αZAα/αα and –/αZAα, respectively) ...have been described so far in Switzerland and China. We describe here a case of homozygosity for the Hb ZA mutation (αZAα/αZAα) in a Brazilian child with severe congenital hemolytic anemia and ineffective erythropoiesis.
We present a new approach to the validation of a fractional mathematical model that describes erythrocyte sedimentation rates using a diffusion equation with a Caputo fractional derivative. We ...discuss the experimental data obtained and plot their graphs. We analyze the graphs to validate our model.
Alpha-thalassemias are among the most common genetic diseases in the world. They are characterized by hypochromic and microcytic anemia and great clinical variability, ranging from a practically ...asymptomatic phenotype to severe anemia, which can lead to intrauterine or early neonatal death. Deletions affecting the α-globin genes, located on chromosome 16p13.3, are the main causes of α-thalassemia. Multiplex ligation-dependent probe amplification (MLPA) can be used to detect rearrangements that cause α-thalassemia, particularly large deletions involving the whole α cluster and/or deletions in the HS-40 region. Here, MLPA was used to investigate the molecular basis of α-thalassemia in five unrelated patients, three of whom had Hb H disease. In addition to the -α3.7 deletion identified in the patients with Hb H disease, four different α0 deletions removing 15 to 225 kb DNA segments were found: two of them remove both the α genes, one affects only the regulatory element (HS-40) region, and another one extends over the entire α cluster and the HS-40 region. These results illustrate the diversity of α-thalassemia deletions in the Brazilian population and highlight the importance of molecular investigation in cases that present with microcytosis and hypochromia without iron deficiency and normal or reduced Hb A2 levels..
Hyperbilirubinemia in patients with sickle cell anemia (SCA) as a result of enhanced erythrocyte destruction, lead to cholelithiasis development in a subset of patients. Evidence suggests that ...hyperbilirubinemia may be related to genetic variations, such as the
UGT1A1
gene promoter polymorphism, which causes Gilbert syndrome (GS). Here, we aimed to determine the frequencies of
UGT1A1
promoter alleles, alpha thalassemia, and β
S
haplotypes and analyze their association with cholelithiasis and bilirubin levels. The
UGT1A1
alleles, −3.7 kb alpha thalassemia deletion and β
S
haplotypes were determined using DNA sequencing and PCR-based assays in 913 patients with SCA. The mean of total and unconjugated bilirubin and the frequency of cholelithiasis in GS patients were higher when compared to those without this condition, regardless of age (
P
< 0.05). Cumulative analysis demonstrated an early age-at-onset for cholelithiasis in GS genotypes (
P
< 0.05). Low fetal hemoglobin (HbF) levels and normal alpha thalassemia genotype were related to cholelithiasis development (
P
> 0.05). However, not cholelithiasis but total and unconjugated bilirubin levels were associated with β
S
haplotype. These findings confirm in a large cohort that the
UGT1A1
polymorphism influences cholelithiasis and hyperbilirubinemia in SCA. HbF and alpha thalassemia also appear as modulators for cholelithiasis risk.
Hb Bristol-Alesha HBB: c.202G>A; β 67 Val>Met is a rare structural variant of hemoglobin (Hb) resulting from a GTG>ATG substitution at codon 67 of the β-globin gene that leads to the replacement of ...valine by methionine in the corresponding position of the β-globin chain. The methionine residue is subsequently modified to aspartic acid β67(E11)Val-Met→Asp, possibly by autoxidation mechanisms. This substitution prevents normal non-polar binding of Val67 to the heme group, resulting in molecular instability and severe hemolysis. We identified Hb Bristol-Alesha (in the heterozygous state), as the cause of severe congenital hemolytic anemia in an 11-month-old girl of mixed (native Indian and European) ethnic origin from the Midwestern region of Brazil, whose parents were clinically and hematologically normal. The mutation on the β-globin gene was found to have been coinherited with the α212 patchwork allele.
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