Cytokines, chemokines, and cells growth factors in patients with mild to moderate SARS-CoV-2 infection: A case-control study.

Several biomarkers have been evaluated as predictors of severity or in directing the treatment of COVID-19, however there are no conclusive results. In this study, we evaluated serum levels of cytokines, chemokines, and cell growth factors in association with the pathobiology of mild to moderate SARS-CoV-2 infection. Serum levels of SARS-CoV-2 infected patients (n = 113) and flu symptoms individuals negative for SARS-CoV-2 (n = 58), tested by the RT-qPCR test-nasal swab were compared to healthy controls (n = 53). Results showed that the proinflammatory cytokines IL-1ß, MCP-3, TNF-α, and G-CSF were increased in symptomatic patients and the cytokines IL-6 and IL-10 were associated with patients positive for SARS-CoV-2 when compared to healthy controls. Symptoms associated with COVID-19 were fever, anosmia, ageusia, and myalgia. For patients without SARS-CoV-2 infection, their major symptom was sore throat. The pathobiology of mild to moderate SARS-CoV-2 infection was associated with increasing proinflammatory cytokines and a pleiotropic IL-6 and anti-inflammatory IL-10 cytokines compared to healthy controls. Thus, knowledge about the pathophysiology and the involvement of biomarkers in the mild to moderate profile of the disease should be evaluated. Monitoring these biomarkers in patients with mild to moderate disease can help establish adequate treatment and prevention strategies for long-term COVID-19.

SARS-CoV-2 antibody dynamics in blood donors and COVID-19 epidemiology in eight Brazilian state capitals: A serial cross-sectional study.

Background: The COVID-19 situation in Brazil is complex due to large differences in the shape and size of regional epidemics. Understanding these patterns is crucial to understand future outbreaks of SARS-CoV-2 or other respiratory pathogens in the country. Methods: We tested 97,950 blood donation samples for IgG antibodies from March 2020 to March 2021 in 8 of Brazil's most populous cities. Residential postal codes were used to obtain representative samples. Weekly age- and sex-specific seroprevalence were estimated by correcting the crude seroprevalence by test sensitivity, specificity, and antibody waning. Results: The inferred attack rate of SARS-CoV-2 in December 2020, before the Gamma variant of concern (VOC) was dominant, ranged from 19.3% (95% credible interval [CrI] 17.5-21.2%) in Curitiba to 75.0% (95% CrI 70.8-80.3%) in Manaus. Seroprevalence was consistently smaller in women and donors older than 55 years. The age-specific infection fatality rate (IFR) differed between cities and consistently increased with age. The infection hospitalisation rate increased significantly during the Gamma-dominated second wave in Manaus, suggesting increased morbidity of the Gamma VOC compared to previous variants circulating in Manaus. The higher disease penetrance associated with the health system's collapse increased the overall IFR by a minimum factor of 2.91 (95% CrI 2.43-3.53). Conclusions: These results highlight the utility of blood donor serosurveillance to track epidemic maturity and demonstrate demographic and spatial heterogeneity in SARS-CoV-2 spread. Funding: This work was supported by Itaú Unibanco 'Todos pela Saude' program; FAPESP (grants 18/14389-0, 2019/21585-0); Wellcome Trust and Royal Society Sir Henry Dale Fellowship 204311/Z/16/Z; the Gates Foundation (INV- 034540 and INV-034652); REDS-IV-P (grant HHSN268201100007I); the UK Medical Research Council (MR/S0195/1, MR/V038109/1); CAPES; CNPq (304714/2018-6); Fundação Faculdade de Medicina; Programa Inova Fiocruz-CE/Funcap - Edital 01/2020 Number: FIO-0167-00065.01.00/20 SPU N°06531047/2020; JBS - Fazer o bem faz bem.

Predicting SARS-CoV-2 Variant Spread in a Completely Seropositive Population Using Semi-Quantitative Antibody Measurements in Blood Donors.

SARS-CoV-2 serologic surveys estimate the proportion of the population with antibodies against historical variants, which nears 100% in many settings. New approaches are required to fully exploit serosurvey data. Using a SARS-CoV-2 anti-Spike (S) protein chemiluminescent microparticle assay, we attained a semi-quantitative measurement of population IgG titers in serial cross-sectional monthly samples of blood donations across seven Brazilian state capitals (March 2021−November 2021). Using an ecological analysis, we assessed the contributions of prior attack rate and vaccination to antibody titer. We compared anti-S titer across the seven cities during the growth phase of the Delta variant and used this to predict the resulting age-standardized incidence of severe COVID-19 cases. We tested ~780 samples per month, per location. Seroprevalence rose to >95% across all seven capitals by November 2021. Driven by vaccination, mean antibody titer increased 16-fold over the study, with the greatest increases occurring in cities with the highest prior attack rates. Mean anti-S IgG was strongly correlated (adjusted R2 = 0.89) with the number of severe cases caused by Delta. Semi-quantitative anti-S antibody titers are informative about prior exposure and vaccination coverage and may also indicate the potential impact of future SARS-CoV-2 variants.

Efeito da bomba de infusão de soluções sobre o grau de hemólise em concentrados de hemácias / Effect of the infusion pumps of solutions on the degree of hemolysis

A lise das hemácias, de causa imune ou não imune, pode provocar a elevação da hemoglobina plasmática induzindo efeitos deletérios principalmente nos rins e no sistema cardiovascular. Este trabalho objetiva evidenciar o possível efeito hemolítico induzido pelo trauma mecânico provocado pela passagem das hemácias em diferentes modelos de bombas de infusão de soluções, em concentrados de hemácias com até dez dias de armazenamento, preparados com Sag-Manitol. Foram utilizados três modelos de bombas (Nutrimat, Infusomat Compact e Volumed), com quatro aparelhos de cada modelo, testados em três velocidades de infusão (120 mL/h, 240 mL/h e 360 mL/h). Os parâmetros utilizados para evidenciar o grau de hemólise foram o percentual de hemólise e os níveis de hemoglobina e potássio livres no plasma. As amostras foram coletadas antes da passagem do concentrado de hemácias pelas bombas, na metade do tempo de infusão e no final da infusão, nas diferentes velocidades. Não ocorreu variação significativa entre os valores dos parâmetros analisados nas amostras controle e naquelas coletadas nas diferentes velocidades, marcas de bombas, mecanismos de infusão entre as bombas da mesma marca e entre os diferentes tempos de infusão. A principal variação encontrada foi relacionada com o potássio livre, devido à variação inerente aos próprios concentrados, o que foi evidenciado ao se compararem os valores obtidos nas amostras controle e nas amostras colhidas nos tempos médio e final em cada bomba. De acordo com os resultados obtidos, não houve alteração estatisticamente significativa do percentual de hemólise após a passagem pelas bombas de infusão nos modelos analisados.

The lyses of red blood cells, both for immune or non-immune reasons, can cause an elevation in plasmatic hemoglobin, inducing harmful effects mainly in the kidneys and cardiovascular system. This work aims at identifying the possible hemolytic effect, related to mechanical trauma due to the use of different models of infusion pumps, on red blood cells transfused after up to ten days of storage. Three models of pumps were studied (Nutrimat, Infusomat Compact and Volumed), (four devices of each model) with three infusion speeds being tested (120 mL/h, 240 mL/h and 360 mL/h). The parameters used to report the degree of hemolysis were the percentile of hemolysis, hemoglobin levels and free potassium in the plasma. Samples were collected before infusion of red blood cells using the pumps, half way through infusion (1/2 T) and at the end of infusion (T), for the three different speeds. Significant variations were not seen in the analyzed parameters between the control samples and those collected at different speeds, using different models of pumps and infusion mechanisms and among pumps of the same brand and at different infusion times. The greatest variation found involved free potassium, probably due to the different levels found in red blood cell concentrates seen when control samples were compared to values obtained half way through and at the end of infusion for each pump. In agreement with the obtained results changes in the percentile of hemolysis were not found after infusion of the cells using the different infusion pumps.

Avaliação das subclasses IgG1 e IgG3 na doença hemolítica perinatal / Assessment of IgG1 and IgG3 subclasses in perinatal hemolytic disease

A doença hemolítica perinatal (DHPN) ainda é um problema clínico. Nenhum teste isolado prediz, com segurança, a gravidade do quadro hemolítico. O objetivo do presente estudo foi determinar as subclasses de anticorpos IgG1 e IgG3 por citometria de fluxo no soro de 42 gestantes isoimunizadas e correlacionar os dados obtidos com a gravidade da DHPN. A distribuição dos fetos ou neonatos segundo a gravidade do quadro hemolítico evidenciou 13 casos com doença leve, 16 casos com doença moderada e 13 com doença grave. As subclasses foram detectadas em 33/42 (79 por cento) amostras. A subclasse IgG1, isoladamente, foi evidenciada em 14/33 (42,4 por cento) casos. Na relação entre gravidade da doença e subclasses de IgG, observou-se que IgG1 isolada foi encontrada em todos os grupos, e os valores da mediana de intensidade de fluorescência (MIF) foram significativamente mais altos nas formas mais graves da DHPN (p<0,01). Contrariamente, os valores da MIF para IgG3 se apresentaram mais homogêneos em todas as categorias (p=0,11). A presença de IgG3 parece, portanto, estar mais associada à hemólise leve. A associação das subclasses IgG1 e IgG3 está relacionada à situação clínica mais grave, o que se deve, possivelmente, à presença de IgG1 associada. Apesar dos altos valores para IgG1 e a associação de IgG1 com IgG3 indicarem maior gravidade da DHPN, sugere-se que outras variáveis sejam analisadas conjuntamente, uma vez que os relatos existentes na literatura, até o momento, não dão suporte para seu uso como instrumento exclusivo de avaliação de gravidade e prognóstico da doença.

The hemolytic disease of the newborn (HDN) continuesto be a clinical problem in spite of prophylaxis. Todate, none of the available tests, developed to predictthe severity of HDN, has provided complete reliability.The objective of the present study was to determinethe IgG1 and IgG3 subclasses in 42 isoimmunizedpregnant women, and to correlate them with clinicalseverity of hemolytic disease. The IgG subclasses weredetermined employing flow cytometry. According tothe clinical severity of HDN, fetuses and newbornbabies were classified as 13 mild, 16 moderate and 13severe cases. The IgG subclasses were detected in 33 ofthe 42 pregnant women. Of these, IgG1 waspredominant in 72.7% of the cases; either isolated(42.4%) or in association with IgG3 (30.3%). IgG1 waspresent in all the three clinical severity categories,however, its values were significantly higher in caseswith greater clinical severity of HDN (p<0.01). On theother hand, the distribution of IgG3 values within eachgroup was not statistically significant (p=0.11). IgG3seems to be more associated with the mild hemolyticform of the disease, whereas the association of IgG1and IgG3 suggested a clinically more severe form ofHDN. It is possible, however, that the severity in thesecases is related to the presence of IgG1. These resultssuggest that IgG1 and IgG3 isotypes should be includedin multi-parametric protocols for the evaluation ofclinical severity of HDN, as International literaturedoes not give support to the use of IgG subclassdetermination alone as a reliable indicator to predictseverity or prognosis of the disease.