8 research outputs found
Polymorphisms in the MBL2 gene are associated with the plasma levels of MBL and the cytokines IL-6 and TNF-α in severe COVID-19
IntroductionMannose-binding lectin (MBL) promotes opsonization, favoring phagocytosis and activation of the complement system in response to different microorganisms, and may influence the synthesis of inflammatory cytokines. This study investigated the association of MBL2 gene polymorphisms with the plasma levels of MBL and inflammatory cytokines in COVID-19.MethodsBlood samples from 385 individuals (208 with acute COVID-19 and 117 post-COVID-19) were subjected to real-time PCR genotyping. Plasma measurements of MBL and cytokines were performed by enzyme-linked immunosorbent assay and flow cytometry, respectively.ResultsThe frequencies of the polymorphic MBL2 genotype (OO) and allele (O) were higher in patients with severe COVID-19 (p< 0.05). The polymorphic genotypes (AO and OO) were associated with lower MBL levels (p< 0.05). IL-6 and TNF-α were higher in patients with low MBL and severe COVID-19 (p< 0.05). No association of polymorphisms, MBL levels, or cytokine levels with long COVID was observed.DiscussionThe results suggest that, besides MBL2 polymorphisms promoting a reduction in MBL levels and therefore in its function, they may also contribute to the development of a more intense inflammatory process responsible for the severity of COVID-19
Antibody Response to the SARS-CoV-2 Spike and Nucleocapsid Proteins in Patients with Different COVID-19 Clinical Profiles
The first case of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in Brazil was diagnosed on February 26, 2020. Due to the important epidemiological impact of COVID-19, the present study aimed to analyze the specificity of IgG antibody responses to the S1, S2 and N proteins of SARS-CoV-2 in different COVID-19 clinical profiles. This study enrolled 136 individuals who were diagnosed with or without COVID-19 based on clinical findings and laboratory results and classified as asymptomatic or as having mild, moderate or severe disease. Data collection was performed through a semistructured questionnaire to obtain demographic information and main clinical manifestations. IgG antibody responses to the S1 and S2 subunits of the spike (S) protein and the nucleocapsid (N) protein were evaluated using an enzyme-linked immunosorbent assay (ELISA) according to the manufacturer’s instructions. The results showed that among the participants, 87.5% (119/136) exhibited IgG responses to the S1 subunit and 88.25% (120/136) to N. Conversely, only 14.44% of the subjects (21/136) displayed S2 subunit responses. When analyzing the IgG antibody response while considering the different proteins of the virus, patients with severe disease had significantly higher antibody responses to N and S1 than asymptomatic individuals (p ≤ 0.0001), whereas most of the participants had low antibody titers against the S2 subunit. In addition, individuals with long COVID-19 showed a greater IgG response profile than those with symptomatology of a short duration. Based on the results of this study, it is concluded that levels of IgG antibodies may be related to the clinical evolution of COVID-19, with high levels of IgG antibodies against S1 and N in severe cases and in individuals with long COVID-19
Thrombophilia and immune-related genetic markers in long COVID
Secretary of Science, Technology and Higher, Professional and Technological Education of the State of Pará (SECTET #09/2021), Amazon Foundation for Research Support (FAPESPA)—#006/2020 and #060/2020, The Coordination for the Improvement of Higher Education Personnel (CAPES), National Council for Scientific and Technological Development (CNPQ)—#401235/2020-3.Federal University of Pará. Institute of Biological Sciences. Laboratory of Genetics of Complex Diseases. Belém, PA, Brazil / Federal University of Pará. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Genetics of Complex Diseases. Belém, PA, Brazil / Federal University of Pará. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Genetics of Complex Diseases. Belém, PA, Brazil / Federal University of Pará. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Genetics of Complex Diseases. Belém, PA, Brazil / Federal University of Pará. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Genetics of Complex Diseases. Belém, PA, Brazil / Federal University of Pará. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Genetics of Complex Diseases. Belém, PA, Brazil / Federal University of Pará. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Genetics of Complex Diseases. Belém, PA, Brazil / Federal University of Pará. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Genetics of Complex Diseases. Belém, PA, Brazil / Federal University of Pará. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Genetics of Complex Diseases. Belém, PA, Brazil / Federal University of Pará. Graduate Program in Clinical Analysis. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Genetics of Complex Diseases. Belém, PA, Brazil / Federal University of Pará. Graduate Program in Clinical Analysis. Belém, PA, Brazil.Federal University of Pará. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil.Federal University of Pará. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Federal University of Pará. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil / Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Laboratório de Pesquisa Básica da Malária. Ananindeua, PA, Brasil.Federal University of Pará. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil / State University of Pará. Center for Biological and Health Sciences. Belém, PA, Brazil.State University of Pará. Center for Biological and Health Sciences. Belém, PA, Brazil.Federal University of Pará. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Genetics of Complex Diseases. Belém, PA, Brazil / Federal University of Pará. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil / Federal University of Pará. Graduate Program in Clinical Analysis. Belém, PA, Brazil.Aiming to evaluate the role of ten functional polymorphisms in long COVID, involved in major inflammatory, immune response and thrombophilia pathways, a cross-sectional sample composed of 199 long COVID (LC) patients and a cohort composed of 79 COVID-19 patients whose follow-up by over six months did not reveal any evidence of long COVID (NLC) were investigated to detect genetic susceptibility to long COVID. Ten functional polymorphisms located in thrombophilia-related and immune response genes were genotyped by real time PCR. In terms of clinical outcomes, LC patients presented higher prevalence of heart disease as preexistent comorbidity. In general, the proportions of symptoms in acute phase of the disease were higher among LC patients. The genotype AA of the interferon gamma (IFNG) gene was observed in higher frequency among LC patients (60%; p = 0.033). Moreover, the genotype CC of the methylenetetrahydrofolate reductase (MTHFR) gene was also more frequent among LC patients (49%; p = 0.045). Additionally, the frequencies of LC symptoms were higher among carriers of IFNG genotypes AA than among non-AA genotypes (Z = 5.08; p < 0.0001). Two polymorphisms were associated with LC in both inflammatory and thrombophilia pathways, thus reinforcing their role in LC. The higher frequencies of acute phase symptoms among LC and higher frequency of underlying comorbidities might suggest that acute disease severity and the triggering of preexisting condition may play a role in LC development
Antibody response to the SARS-CoV-2 spike and nucleocapsid proteins in patients with different COVID-19 clinical profiles
National Council for Scientific and Technological Development (CNPQ #401235/2020-3; #302935/2021-5), Fundação Amazônia de Amparo a Estudos e Pesquisa do Pará (FAPESPA #005/2020 and #006/2020) and Secretaria de Ciência, Tecnologia e Educação Superior, Profissional e Tecnológica (SECTET #09/2021)Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Virologia. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Virologia. Belém, PA, Brazil / Universidade Federal do Pará. Programa de Pós-Graduação em Biologia de Agentes Infecciosos e Parasitários. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Virologia. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Genética de Doenças Complexas. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Genética de Doenças Complexas. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Genética de Doenças Complexas. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Genética de Doenças Complexas. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Genética de Doenças Complexas. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Genética de Doenças Complexas. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Genética de Doenças Complexas. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Genética de Doenças Complexas. Belém, PA, Brazil.Hospital Adventista de Belém. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Virologia. Belém, PA, Brazil / Universidade Federal do Pará. Programa de Pós-Graduação em Biologia de Agentes Infecciosos e Parasitários. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Virologia. Belém, PA, Brazil / Universidade Federal do Pará. Programa de Pós-Graduação em Biologia de Agentes Infecciosos e Parasitários. Belém, PA, Brazil.Universidade Federal do Pará. Programa de Pós-Graduação em Biologia de Agentes Infecciosos e Parasitários. Belém, PA, Brazil / Universidade do Estado do Pará. Centro de Ciências Biológicas e da Saúde. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Universidade Federal do Pará. Programa de Pós-Graduação em Biologia de Agentes Infecciosos e Parasitários. Belém, PA, Brazil / Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Universidade do Estado do Pará. Centro de Ciências Biológicas e da Saúde. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Genética de Doenças Complexas. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Virologia. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Virologia. Belém, PA, Brazil / Universidade Federal do Pará. Programa de Pós-Graduação em Biologia de Agentes Infecciosos e Parasitários. Belém, PA, Brazil.The first case of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in Brazil was diagnosed on February 26, 2020. Due to the important epidemiological impact of COVID-19, the present study aimed to analyze the specificity of IgG antibody responses to the S1, S2 and N proteins of SARS-CoV-2 in different COVID-19 clinical profiles. This study enrolled 136 individuals who were diagnosed with or without COVID-19 based on clinical findings and laboratory results and classified as asymptomatic or as having mild, moderate or severe disease. Data collection was performed through a semistructured questionnaire to obtain demographic information and main clinical manifestations. IgG antibody responses to the S1 and S2 subunits of the spike (S) protein and the nucleocapsid (N) protein were evaluated using an enzyme-linked immunosorbent assay (ELISA) according to the manufacturer’s instructions. The results showed that among the participants, 87.5% (119/136) exhibited IgG responses to the S1 subunit and 88.25% (120/136) to N. Conversely, only 14.44% of the subjects (21/136) displayed S2 subunit responses. When analyzing the IgG antibody response while considering the different proteins of the virus, patients with severe disease had significantly higher antibody responses to N and S1 than asymptomatic individuals (p ≤ 0.0001), whereas most of the participants had low antibody titers against the S2 subunit. In addition, individuals with long COVID-19 showed a greater IgG response profile than those with symptomatology of a short duration. Based on the results of this study, it is concluded that levels of IgG antibodies may be related to the clinical evolution of COVID-19, with high levels of IgG antibodies against S1 and N in severe cases and in individuals with long COVID-19
Association of polymorphisms of IL-6 pathway genes (IL6, IL6R and IL6ST) with COVID-19 severity in an amazonian population
Amazon Foundation for Research Support (FAPESPA)—#005/2020; The Coordination for the Improvement of Higher Education Personnel (CAPES), National Council for Scientific and Technological Development (CNPQ)—#401235/2020-3.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Genética de Doenças Complexas. Belém, PA, Brazil / Universidade Federal do Pará. Programa de Pós-Graduação em Biologia de Agentes Infecciosos e Parasitários. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Genética de Doenças Complexas. Belém, PA, Brazil / Universidade Federal do Pará. Programa de Pós-Graduação em Biologia de Agentes Infecciosos e Parasitários. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Genética de Doenças Complexas. Belém, PA, Brazil / Universidade Federal do Pará. Programa de Pós-Graduação em Biologia de Agentes Infecciosos e Parasitários. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Genética de Doenças Complexas. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Genética de Doenças Complexas. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Genética de Doenças Complexas. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Genética de Doenças Complexas. Belém, PA, Brazil / Universidade Federal do Pará. Programa de Pós-Graduação em Biologia de Agentes Infecciosos e Parasitários. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Genética de Doenças Complexas. Belém, PA, Brazil / Universidade Federal do Pará. Programa de Pós-Graduação em Biologia de Agentes Infecciosos e Parasitários. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Genética de Doenças Complexas. Belém, PA, Brazil / Universidade Federal do Pará. Programa de Pós-Graduação em Biologia de Agentes Infecciosos e Parasitários. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Genética de Doenças Complexas. Belém, PA, Brazil / Universidade Federal do Pará. Programa de Pós-Graduação em Biologia de Agentes Infecciosos e Parasitários. Belém, PA, Brazil.Hospital Adventista de Belém. Belém, PA, Brazil.Hospital Adventista de Belém, Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Laboratório de Imunologia. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Laboratório de Imunologia. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Laboratório de Imunologia. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Laboratório de Pesquisas Básicas em Malária. Ananindeua, PA, Brasil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Virologia. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Virologia. Belém, PA, BrazilUniversidade Federal do Pará. Programa de Pós-Graduação em Biologia de Agentes Infecciosos e Parasitários. Belém, PA, Brazil / Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Virologia. Belém, PA, Brazil.Universidade Federal do Pará. Programa de Pós-Graduação em Biologia de Agentes Infecciosos e Parasitários. Belém, PA, Brazil / Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Virologia. Belém, PA, Brazil.Universidade Federal do Pará. Programa de Pós-Graduação em Biologia de Agentes Infecciosos e Parasitários. Belém, PA, Brazil / Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Virologia. Belém, PA, Brazil.Universidade Federal do Pará. Programa de Pós-Graduação em Biologia de Agentes Infecciosos e Parasitários. Belém, PA, Brazil / Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Virologia. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Virologia. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Genética de Doenças Complexas. Belém, PA, Brazil.Interleukin-6 has been recognized as a major role player in COVID-19 severity, being an important regulator of the cytokine storm. Hence, the evaluation of the influence of polymorphisms in key genes of the IL-6 pathway, namely IL6, IL6R, and IL6ST, may provide valuable prognostic/predictive markers for COVID-19. The present cross-sectional study genotyped three SNPs (rs1800795, rs2228145, and rs7730934) at IL6. IL6R and IL6ST genes, respectively, in 227 COVID-19 patients (132 hospitalized and 95 non-hospitalized). Genotype frequencies were compared between these groups. As a control group, published data on gene and genotype frequencies were gathered from published studies before the pandemic started. Our major results point to an association of the IL6 C allele with COVID-19 severity. Moreover, IL-6 plasmatic levels were higher among IL6 CC genotype carriers. Additionally, the frequency of symptoms was higher at IL6 CC and IL6R CC genotypes. In conclusion, the data suggest an important role of IL6 C allele and IL6R CC genotype on COVID-19 severity, in agreement with indirect evidence from the literature about the association of these genotypes with mortality rates, pneumonia, and heightening of protein plasmatic levels pro-inflammatory driven effects
Severe COVID-19 and long COVID are associated with high expression of STING, cGAS and IFN-α
Abstract The cGAS-STING pathway appears to contribute to dysregulated inflammation during coronavirus disease 2019 (COVID-19); however, inflammatory factors related to long COVID are still being investigated. In the present study, we evaluated the association of cGAS and STING gene expression levels and plasma IFN-α, TNF-α and IL-6 levels with COVID-19 severity in acute infection and long COVID, based on analysis of blood samples from 148 individuals, 87 with acute COVID-19 and 61 in the post-COVID-19 period. Quantification of gene expression was performed by real-time PCR, and cytokine levels were quantified by ELISA and flow cytometry. In acute COVID-19, cGAS, STING, IFN-α, TNF-α, and IL-6 levels were higher in patients with severe disease than in those with nonsevere manifestations (p < 0.05). Long COVID was associated with elevated cGAS, STING and IFN-α levels (p < 0.05). Activation of the cGAS-STING pathway may contribute to an intense systemic inflammatory state in severe COVID-19 and, after infection resolution, induce an autoinflammatory disease in some tissues, resulting in long COVID
Polymorphisms in the MBL2 gene are associated with the plasma levels of MBL and the cytokines IL-6 and TNF-α in severe COVID-19
National Council for Scientific and Technological Development (CNPQ #401235/2020-3); Fundação Amazônia de Amparo a Estudos e Pesquisa do Pará (FAPESPA #005/2020 and #006/2020), Secretaria de Estado de Ciência, Tecnologia e Educação Profissional e Tecnológica (#09/ 2021) and Universidade Federal do Pará (PAPQ/2022)Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil / Ministério da Saúde. Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos. Instituto Evandro Chagas. Programa de Pós-Graduação em Virologia. Ananindeua, PA, Brasil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil / Ministério da Saúde. Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos. Instituto Evandro Chagas. Programa de Pós-Graduação em Virologia. Ananindeua, PA, Brasil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Laboratory of Genetics of Complex Diseases. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Laboratory of Genetics of Complex Diseases. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Laboratory of Genetics of Complex Diseases. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Laboratory of Genetics of Complex Diseases. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Genetics of Complex Diseases. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Genetics of Complex Diseases. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Genetics of Complex Diseases. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Laboratory of Genetics of Complex Diseases. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Laboratory of Genetics of Complex Diseases. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Laboratory of Genetics of Complex Diseases. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Laboratório de Pesquisa Básica em Malária, Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Laboratório de Pesquisa Básica em Malária, Ananindeua, PA, Brasil / Federal University of Pará. Institute of Medical Sciences. School of Medicine. Belém, PA, Brazil.Belém Adventist Hospital. Belém, PA, Brazil.Belém Adventist Hospital. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Laboratório de Imunologia. Ananindeua, PA, Brasil / Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Laboratório de Imunologia. Ananindeua, PA, Brasil / Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Laboratório de Imunologia. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos. Instituto Evandro Chagas. Programa de Pós-Graduação em Virologia. Ananindeua, PA, Brasil / Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Laboratório de Imunologia. Ananindeua, PA, Brasil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos. Instituto Evandro Chagas. Programa de Pós-Graduação em Virologia. Ananindeua, PA, Brasil / Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Laboratório de Imunologia. Ananindeua, PA, Brasil.University of the State of Pará. Center of Biological and Health Sciences. Belém, PA, Brazil.University of the State of Pará. Center of Biological and Health Sciences. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Laboratory of Genetics of Complex Diseases. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil.Introduction: Mannose-binding lectin (MBL) promotes opsonization, favoring phagocytosis and activation of the complement system in response to different microorganisms, and may influence the synthesis of inflammatory cytokines. This study investigated the association of MBL2 gene polymorphisms with the plasma levels of MBL and inflammatory cytokines in COVID-19. Methods: Blood samples from 385 individuals (208 with acute COVID-19 and 117 post-COVID-19) were subjected to real-time PCR genotyping. Plasma measurements of MBL and cytokines were performed by enzyme-linked immunosorbent assay and flow cytometry, respectively. Results: The frequencies of the polymorphic MBL2 genotype (OO) and allele (O) were higher in patients with severe COVID-19 (p< 0.05). The polymorphic genotypes (AO and OO) were associated with lower MBL levels (p< 0.05). IL-6 and TNF-α were higher in patients with low MBL and severe COVID-19 (p< 0.05). No association of polymorphisms, MBL levels, or cytokine levels with long COVID was observed. Discussion: The results suggest that, besides MBL2 polymorphisms promoting a reduction in MBL levels and therefore in its function, they may also contribute to the development of a more intense inflammatory process responsible for the severity of COVID-19
Cytokine profiles associated with acute COVID-19 and long COVID-19 syndrome
National Council for Scientific
and Technological Development (CNPQ #401235/2020-3);
Fundação Amazônia de Amparo a Estudos e Pesquisa do Pará
(FAPESPA #005/2020 and #006/2020) and Secretaria de Estado
de Ciência, Tecnologia e Educação Profissional e Tecnológica
(#09/2021).Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Virologia. Belém, PA, Brazil.Universidade do Estado do Pará. Instituto de Ciências Biológicas e da Saúde. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Virologia. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Virologia. Belém, PA, Brazil / Universidade Federal do Pará. Programa de Pós-Graduação em Biologia de Agentes Infecciosos e Parasitários. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Virologia. Belém, PA, Brazil / Universidade Federal do Pará. Programa de Pós-Graduação em Biologia de Agentes Infecciosos e Parasitários. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Virologia. Belém, PA, Brazil / Universidade Federal do Pará. Programa de Pós-Graduação em Biologia de Agentes Infecciosos e Parasitários. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Virologia. Belém, PA, Brazil / Universidade Federal do Pará. Programa de Pós-Graduação em Biologia de Agentes Infecciosos e Parasitários. Belém, PA, Brazil.Universidade Federal do Pará. Programa de Pós-Graduação em Biologia de Agentes Infecciosos e Parasitários. Belém, PA, Brazil / Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Genética de Doenças Complexas. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Genética de Doenças Complexas. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Genética de Doenças Complexas. Belém, PA, Brazil.Universidade Federal do Pará. Programa de Pós-Graduação em Biologia de Agentes Infecciosos e Parasitários. Belém, PA, Brazil / Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Genética de Doenças Complexas. Belém, PA, Brazil.Universidade Federal do Pará. Programa de Pós-Graduação em Biologia de Agentes Infecciosos e Parasitários. Belém, PA, Brazil / Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Genética de Doenças Complexas. Belém, PA, Brazil.Universidade Federal do Pará. Programa de Pós-Graduação em Biologia de Agentes Infecciosos e Parasitários. Belém, PA, Brazil / Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Genética de Doenças Complexas. Belém, PA, Brazil.Universidade Federal do Pará. Programa de Pós-Graduação em Biologia de Agentes Infecciosos e Parasitários. Belém, PA, Brazil / Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Genética de Doenças Complexas. Belém, PA, Brazil.Universidade Federal do Pará. Programa de Pós-Graduação em Biologia de Agentes Infecciosos e Parasitários. Belém, PA, Brazil / Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Genética de Doenças Complexas. Belém, PA, Brazil.Universidade Federal do Pará. Programa de Pós-Graduação em Biologia de Agentes Infecciosos e Parasitários. Belém, PA, Brazil / Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Genética de Doenças Complexas. Belém, PA, Brazil.Universidade Federal do Pará. Programa de Pós-Graduação em Biologia de Agentes Infecciosos e Parasitários. Belém, PA, Brazil / Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Genética de Doenças Complexas. Belém, PA, Brazil.Universidade do Estado do Pará. Instituto de Ciências Biológicas e da Saúde. Belém, PA, Brazil.Universidade do Estado do Pará. Instituto de Ciências Biológicas e da Saúde. Belém, PA, Brazil.Hospital Adventista de Belém. Belém, PA, Brazil.Hospital Adventista de Belém. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Imunologia. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Imunologia. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Pesquisas Básicas em Malária. Ananindeua, PA, Brasil.Universidade do Estado do Pará. Instituto de Ciências Biológicas e da Saúde. Belém, PA, Brazil.Universidade do Estado do Pará. Instituto de Ciências Biológicas e da Saúde. Belém, PA, Brazil.Universidade do Estado do Pará. Instituto de Ciências Biológicas e da Saúde. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Imunologia. Ananindeua, PA, Brasil.Universidade Federal do Pará. Programa de Pós-Graduação em Biologia de Agentes Infecciosos e Parasitários. Belém, PA, Brazil.Universidade do Estado do Pará. Instituto de Ciências Biológicas e da Saúde. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Virologia. Belém, PA, Brazil.The duration and severity of COVID-19 are related to age, comorbidities, and cytokine synthesis. This study evaluated the impact of these factors on patients with clinical presentations of COVID-19 in a Brazilian cohort. A total of 317 patients diagnosed with COVID-19 were included; cases were distributed according to clinical status as severe (n=91), moderate (n=56) and mild (n=170). Of these patients, 92 had acute COVID-19 at sample collection, 90 had already recovered from COVID-19 without sequelae, and 135 had sequelae (long COVID syndrome). In the acute COVID-19 group, patients with the severe form had higher IL-6 levels (p=0.0260). In the post-COVID-19 group, there was no significant difference in cytokine levels between groups with different clinical conditions. In the acute COVID-19 group, younger patients had higher levels of TNF-alpha, and patients without comorbidities had higher levels of TNF-alpha, IL-4 and IL-2 (p<0.05). In contrast, patients over age 60 with comorbidities had higher levels of IL-6. In the post-COVID-19 group, subjects with long COVID-19 had higher levels of IL-17 and IL-2 (p<0.05), and subjects without sequelae had higher levels of IL-10, IL-6 and IL- 4 (p<0.05). Our results suggest that advanced age, comorbidities and elevated serum IL-6 levels are associated with severe COVID-19 and are good markers to differentiate severe from mild cases. Furthermore, high serum levels of IL-17 and IL-2 and low levels of IL-4 and IL-10 appear to constitute a cytokine profile of long COVID-19, and these markers are potential targets for COVID-19 treatment and prevention strategies