Immunoglobulin G Immune Complexes May Contribute to Neutrophil Activation in the Course of Severe Coronavirus Disease 2019.

Severe coronavirus disease 2019 (COVID-19) is associated with an overactive inflammatory response mediated by macrophages. Here, we analyzed the phenotype and function of neutrophils in patients with COVID-19. We found that neutrophils from patients with severe COVID-19 express high levels of CD11b and CD66b, spontaneously produce CXCL8 and CCL2, and show a strong association with platelets. Production of CXCL8 correlated with plasma concentrations of lactate dehydrogenase and D-dimer. Whole blood assays revealed that neutrophils from patients with severe COVID-19 show a clear association with immunoglobulin G (IgG) immune complexes. Moreover, we found that sera from patients with severe disease contain high levels of immune complexes and activate neutrophils through a mechanism partially dependent on FcγRII (CD32). Interestingly, when integrated in immune complexes, anti-severe acute respiratory syndrome coronavirus 2 IgG antibodies from patients with severe COVID-19 displayed a higher proinflammatory profile compared with antibodies from patients with mild disease. Our study suggests that IgG immune complexes might promote the acquisition of an inflammatory signature by neutrophils, worsening the course of COVID-19.

Análisis de los primeros 100 pacientes internados por COVID-19 en el Hospital de Clínicas José de San Martín, Universidad de Buenos Aires / Analysis of the first 100 patients with COVID-19 admitted to internal medicine wards at the Hospital de Clínicas José de San Martin, Buenos Aires University

Resumen Se analiza, en un estudio descriptivo retrospectivo, las características clínicas y epidemiológicas, la evolución de la enfermedad y su asociación con los marcadores del laboratorio de mal pronóstico, en los primeros 100 pacientes internados en clínica médica con COVID-19 en el Hospital de Clínicas José de San Martín de la Universidad de Buenos Aires. El 31% de los pacientes provenían de geriátricos, las manifestaciones clínicas más comunes fueron fiebre, tos y odinofagia. En relación a las comorbilidades, la obesidad fue la más frecuente y la hipertensión arterial la más prevalente en los pacientes con neumonía. La edad y la presencia de neumonía fueron los predictores más importantes de mortalidad. Los pacientes mayores de 70 años presentaron reactantes de fase aguda más elevados mostrando una respuesta inflamatoria exagerada. La mortalidad fue elevada (13%), en comparación con la mayoría de las comunicaciones (5%), probablemente como consecuencia de la edad avanzada de nuestra población y las condiciones clínicas desfavorables que presentaron a su ingreso.

Abstract This retrospective descriptive study analyzes the clinical and epidemiological characteristics, the disease evolution and its association with laboratory markers of poor prognosis of the first 100 patients with COVID-19 admitted to internal medicine wards at the Hospital de Clínicas José de San Martín, University of Buenos Aires. Thirty-one patients were nursing home residents, the most common clinical manifestations were fever, cough and odynophagia. Regarding comorbidities, obesity was the most frequent one and hypertension was the most prevalent in patients with pneumonia. The most important predictors of mortality were age and pneumonia. Patients older than 70 years had higher acute phase reactants showing an exaggerated inflammatory response. Mortality was high (13%), compared to most reports (5%), probably because of the advanced age of our population and the unfavorable clinical conditions they presented at admission.

[Analysis of the first 100 patients with COVID-19 admitted to internal medicine wards at the Hospital de Clínicas José de San Martin, Buenos Aires University]. / Análisis de los primeros 100 pacientes internados por COVID-19 en el Hospital de Clínicas José de San Martín, Universidad de Buenos Aires.

This retrospective descriptive study analyzes the clinical and epidemiological characteristics, the disease evolution and its association with laboratory markers of poor prognosis of the first 100 patients with COVID-19 admitted to internal medicine wards at the Hospital de Clínicas José de San Martín, University of Buenos Aires. Thirty-one patients were nursing home residents, the most common clinical manifestations were fever, cough and odynophagia. Regarding comorbidities, obesity was the most frequent one and hypertension was the most prevalent in patients with pneumonia. The most important predictors of mortality were age and pneumonia. Patients older than 70 years had higher acute phase reactants showing an exaggerated inflammatory response. Mortality was high (13%), compared to most reports (5%), probably because of the advanced age of our population and the unfavorable clinical conditions they presented at admission.

Se analiza, en un estudio descriptivo retrospectivo, las características clínicas y epidemiológicas, la evolución de la enfermedad y su asociación con los marcadores del laboratorio de mal pronóstico, en los primeros 100 pacientes internados en clínica médica con COVID-19 en el Hospital de Clínicas José de San Martín de la Universidad de Buenos Aires. El 31% de los pacientes provenían de geriátricos, las manifestaciones clínicas más comunes fueron fiebre, tos y odinofagia. En relación a las comorbilidades, la obesidad fue la más frecuente y la hipertensión arterial la más prevalente en los pacientes con neumonía. La edad y la presencia de neumonía fueron los predictores más importantes de mortalidad. Los pacientes mayores de 70 años presentaron reactantes de fase aguda más elevados mostrando una respuesta inflamatoria exagerada. La mortalidad fue elevada (13%), en comparación con la mayoría de las comunicaciones (5%), probablemente como consecuencia de la edad avanzada de nuestra población y las condiciones clínicas desfavorables que presentaron a su ingreso.

[Immune reconstitution syndrome in an HIV-infected patient and Pneumocystis jirovecii pneumonia]. / Síndrome de reconstitución inmune en HIV y neumonía por Pneumocystis jirovecii.

Immune reconstitution syndrome is a set of acute inflammatory phenomena that occur as a result of restored immunity generating a paradoxical worsening of a prior infection or an inflammatory process. This syndrome occurs in human immunodeficiency virus infected patients after starting antiretroviral treatment. The most frequent associated infections are those produced by mycobacteria, herpes, cryptococcosis, hepatitis B, cytomegalovirus, Pneumocystis jirovecii and worsening of progressive multifocal leukoencephalopathy secondary to JC virus. We present the case of a patient with human immunodeficiency virus who developed the immune reconstitution syndrome secondary to Pneumocystis jirovecii.

Síndrome de reconstitución inmune en HIV y neumonía por Pneumocystis jirovecii / Immune reconstitution syndrome in an HIV-infected patient and Pneumocystis jirovecii pneumonia

El síndrome de reconstitución inmune es un conjunto de fenómenos inflamatorios agudos, que se producen como consecuencia de la recuperación de la inmunidad, generando un empeoramiento paradójico de una infección o de un proceso inflamatorio previo. En los pacientes infectados con el virus de inmunodeficiencia humana este síndrome se produce luego de iniciado el tratamiento antirretroviral. Las infecciones más frecuentes asociadas a esta entidad son las producidas por micobacterias, herpes, criptococosis, hepatitis B, citomegalovirus, Pneumocystis jirovecii y el empeoramiento de la leucoencenfalopatía multifocal progresiva por el virus JC. Presentamos un paciente con virus de inmunodeficiencia humana que desarrolló el síndrome de reconstitución inmune por Pneumocystis jirovecii.

Immune reconstitution syndrome is a set of acute inflammatory phenomena that occur as a result of restored immunity generating a paradoxical worsening of a prior infection or an inflammatory process. This syndrome occurs in human immunodeficiency virus infected patients after starting antiretroviral treatment. The most frequent associated infections are those produced by mycobacteria, herpes, cryptococcosis, hepatitis B, cytomegalovirus, Pneumocystis jirovecii and worsening of progressive multifocal leukoencephalopathy secondary to JC virus. We present the case of a patient with human immunodeficiency virus who developed the immune reconstitution syndrome secondary to Pneumocystis jirovecii.

Síndrome de reconstitución inmune en HIV y neumonía por Pneumocystis jirovecii / Immune reconstitution syndrome in an HIV-infected patient and Pneumocystis jirovecii pneumonia

El síndrome de reconstitución inmune es un conjunto de fenómenos inflamatorios agudos, que se producen como consecuencia de la recuperación de la inmunidad, generando un empeoramiento paradójico de una infección o de un proceso inflamatorio previo. En los pacientes infectados con el virus de inmunodeficiencia humana este síndrome se produce luego de iniciado el tratamiento antirretroviral. Las infecciones más frecuentes asociadas a esta entidad son las producidas por micobacterias, herpes, criptococosis, hepatitis B, citomegalovirus, Pneumocystis jirovecii y el empeoramiento de la leucoencenfalopatía multifocal progresiva por el virus JC. Presentamos un paciente con virus de inmunodeficiencia humana que desarrolló el síndrome de reconstitución inmune por Pneumocystis jirovecii.(AU)

Immune reconstitution syndrome is a set of acute inflammatory phenomena that occur as a result of restored immunity generating a paradoxical worsening of a prior infection or an inflammatory process. This syndrome occurs in human immunodeficiency virus infected patients after starting antiretroviral treatment. The most frequent associated infections are those produced by mycobacteria, herpes, cryptococcosis, hepatitis B, cytomegalovirus, Pneumocystis jirovecii and worsening of progressive multifocal leukoencephalopathy secondary to JC virus. We present the case of a patient with human immunodeficiency virus who developed the immune reconstitution syndrome secondary to Pneumocystis jirovecii.(AU)

Pandemic influenza A/H1N1 2009 antibodies in the metropolitan area of Buenos Aires in Argentina.

OBJECTIVE: To estimate the infection prevalence in Buenos Aires during the outbreak of pandemic influenza A/H1N1 2009 virus (A(H1N1)pdm09). METHODS: A(H1N1)pdm09-specific antibodies were measured by hemagglutination inhibition assay in human serum samples collected 6 months after the outbreak and before the introduction of the A(H1N1)pdm09 vaccine in Argentina. Baseline levels of cross-reactive antibodies to A(H1N1)pdm09 were determined by testing 162 serum samples collected before 2009. RESULTS: The overall seroprevalence of A(H1N1)pdm09 in 150 children and 427 adults was 28.9% (95% confidence interval (CI) 25-33%), with a 58.0% prevalence in children <19 years of age and an 18.7% prevalence in adults ≥19 years of age (p<0.001). The prevalence was 43.5% in children <5 years old and 60.6% among children aged 5-18 years. The prevalence in adults declined with increasing age: 24.9% in 19-39-year-olds, 9.7% in 40-59-year-olds, and 8.1% in those ≥60 years old. The prevalence of specific A(H1N1)pdm09 antibodies was higher compared with the baseline in children (p=0.014), adolescents (p<0.001), and adults <40 years old (p=0.017). Seroprevalence in health care workers was not different from the rest of the population (13.6% vs. 19.3%, respectively; p=0.421). CONCLUSIONS: The prevalence of specific A(H1N1)pdm09 antibodies was high at 28.9%. The highest prevalence was observed in children, adolescents, and young adults.

Síndrome de reconstitución inmune en HIV y neumonía por Pneumocystis jirovecii. / [Immune reconstitution syndrome in an HIV-infected patient and Pneumocystis jirovecii pneumonia].

Immune reconstitution syndrome is a set of acute inflammatory phenomena that occur as a result of restored immunity generating a paradoxical worsening of a prior infection or an inflammatory process. This syndrome occurs in human immunodeficiency virus infected patients after starting antiretroviral treatment. The most frequent associated infections are those produced by mycobacteria, herpes, cryptococcosis, hepatitis B, cytomegalovirus, Pneumocystis jirovecii and worsening of progressive multifocal leukoencephalopathy secondary to JC virus. We present the case of a patient with human immunodeficiency virus who developed the immune reconstitution syndrome secondary to Pneumocystis jirovecii.

Neumonía aguda grave de la comunidad en menores de 65 años sin comorbilidades conocidas previamente: estudio multicéntrico retrospectivo / Severe community acquired pneumonia in healthy adults: a multicenter retrospective study

Objetivo: analizar las características epidemiológicas, clínicas y de estudios complementarios en pacientes jóvenes y sanos con neumonía aguda grave de la comunidad (NACG). Material y Método: evaluación retrospectiva de historias clínicas de adultos menores de 65 años, sin comorbilidades, internados con NACG entre 1998 y 2008. Resultados: se identificaron 40 pacientes (M/F = 0.48), edad promedio 37.8 ± 14.1años (16-61). El 42.5% requirió ventilación mecánica y el 57.5% inotrópicos. La PaO2/FiO2 inicial fue 203.6 ± 91.4 mmHg (50-366.7) y las anomalías de laboratorio más frecuentesincluyeron anemia, leucocitosis, hipoalbuminemia y urea y creatinina elevadas. El tratamiento antibiótico empírico consistió en ceftriaxona o ß-lactámico/inhibidor de ß-lactamasas (BL) + macrólido en el 70% de los casos. La etiología se reveló en el 50%,los patógenos y su frecuencia fueron: Streptococcus Pneumoniae, 35%; Leptospira, 15%; Hantavirus y Mycoplasma pneumoniae, 10% y Legionella pneumophila, Pneumocystisjirovecii, Histoplasma capsulatum, Klebsiella pneumoniae, Haemophilus influenzae BL (-) y Staphylococcus aureus sensible a meticilina, 5%. El 77.5% de los pacientes presentócomplicaciones, las más frecuentes fueron shock, insuficiencia respiratoria, insuficiencia renal aguda y derrame pleural. Ocho pacientes presentaron comorbilidades desconocidas,incluyendo HIV positivo, diabetes mellitus, asma, insuficiencia cardíaca e hipotiroidismo. La mortalidad fue 12.5%. Hipotensión arterial diastólica, taquicardia, requerimiento dehemodiálisis y tratamiento inadecuado se asociaron independientemente a mortalidad. Conclusiones: el 20% de los menores de 65 años con NACG, presumiblemente sanos, tenían comorbilidades. El patógeno más frecuente fue neumococo y la mortalidad se asoció a la gravedad de la sepsis e inadecuación del tratamiento.

Aims: to analyze epidemiologic, clinical and other abnormalities in healthy young adults with severe community acquired pneumonia (SCAP). Methods: retrospective analysis of clinical records of adults younger than 65 years, with SCAP and without previously known comorbidities, admitted from 1998 to 2008. Results: forty patients were included (M/F = 0.48), age 37.8 ± 14.1 years (range 16 - 61). Mechanical ventilation was used in 42.5% and vasopressors in 57.5% of patients. Initial PaO2/FIO2 ratio was 203.6 ± 91.4 mmHg (50 - 366.7); frequent laboratory abnormalities included: anemia, leukocytosis, hypoalbuminemia and high urea and creatinine levels.The empiric antimicrobial therapy was ceftriaxone or ß-lactam/ß - lactamases (BL) inhibitor plus macrolide in 70% of cases. The etiology was established in 50%; the specific pathogens were: Streptococcus pneumoniae, 35%; Leptospira, 15%; Hantavirus and Mycoplasma pneumoniae, 10%; and Legionella pneumophila, Pneumocystisjirovecii, Histoplasma capsulatum, Klebsiella pneumoniae, Haemophilus influenzae BL (-) and methicillin susceptible Staphylococcus aureus, 5%. Complications were present in 77.5% including shock, respiratory failure, acute renal failure and pleural effusion.Eight patients presented previously unknown comorbidities including HIV infection, diabetes mellitus, asthma, congestive cardiac failure and hypothyroidism. Mortality was 12.5 %. Diastolic arterial hypotension, taquichycardia, requirement of hemodialysis and inadequate therapy were significantly associated to mortality. Conclusions: 20% of young and presumably healthy adults with SCAP had comorbidities. S. pneumoniae was the commonest pathogen; mortality was associated with severity of sepsis and inadequate therapy.

Decreased mitochondrial nitric oxide synthase activity and hydrogen peroxide relate persistent tumoral proliferation to embryonic behavior.

Differential expression and activity of constitutive mitochondrial nitric oxide synthase (mtNOS) in the mitochondrial compartment is followed by significant variations in matrix nitric oxide (NO) steady-state concentration. The mitochondrial utilization of NO involves the production of superoxide anion and H(2)O(2), a species freely diffusible outside the mitochondria that participates in the modulation of cell proliferation and apoptosis and in cell transformation and cancer. On these bases, we analyzed the modulation of mtNOS in the frame of cellular redox state in M3, MM3, and P07 murine tumors and their respective cell lines, as compared with normal proliferating and quiescent tissues. The results showed that: (a) tumoral and proliferating mitochondria only retain 10-50% of the activity of complexes I, II-III, and IV and Mn-SOD of quiescent tissues; (b) normal proliferating tissues, like embryonic liver or pregnant mammary gland, have 10-20% of mtNOS expression and activity and mitochondrial H(2)O(2) yield than quiescent nonproliferating tissues; (c) similarly but irrespective of mtNOS expression, tumoral mitochondria have no >5% of mtNOS activity and H(2)O(2) yield of mature tissues; and (d) in opposition to stable tissues, both tumoral and normal proliferating cells exhibit high cyclin D1 expression and low pro-apoptotic p38mitogen-activated protein kinase activity. Dually, H(2)O(2) stimulated tumor cell proliferation (<10 microM) or markedly inhibited it (>10 microM) with parallel variations of cyclin D1, phospho-extracellular-regulated kinase1/2, and phospho-p38mitogen-activated protein kinase. It is surmised that decreased oxidative phosphorylation, defective tumoral mtNOS, and low mitochondrial NO-dependent H(2)O(2) may be a platform to link persistent tumoral growth to embryonic behavior.