ABSTRACT
For the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, clinical manifestations are broad and highly heterogeneous for both sexes. We aimed to determine how biological sex and age impact immune gene expression, particularly influencing the humoral neutralizing antibody (NAb) response and the cytokine production in coronavirus disease 2019 (COVID-19) subjects. The immune gene expression, according to biological sex and age, was assessed using the genome wide expression profile of blood proteins from healthy individuals using the Genotype Tissue Expression (GTEx) database. Moreover, anti-SARS-CoV-2 neutralizing antibody titers and cytokine levels were determined in blood samples from 141 COVID-19 individuals from Medellín, Colombia. Among subjects with COVID-19, males had statistically significantly higher median NAb titers and serum concentrations of interleukin-6 and CC chemokine ligand 3 than females. Overall, our findings point out a more robust innate immune response in women that could help recognize and restrain the virus faster than in men.
ABSTRACT
Background: The COVID-19 pandemic remains a global health problem. As in other viral infections, the humoral immune response against SARS-CoV-2 is thought to be crucial for controlling the infection. However, the dynamic of B cells in the clinical spectrum of this disease is still controversial. This study aimed to characterize B cell subsets and neutralizing responses in COVID-19 patients according to disease severity through a one-month follow-up. Methods: A cohort of 71 individuals with SARS-CoV-2 infection confirmed by RT-PCR were recruited and classified into four groups: i) asymptomatic; ii) symptomatic outpatients; iii) hospitalized in ward, and iv) intensive care unit patients (ICU). Samples were taken at days 0 (inclusion to the study), 7 and 30. B cell subsets and neutralizing antibodies were assessed using multiparametric flow cytometry and plaque reduction neutralization, respectively. Results: Older age, male gender and body mass index over 25 were common factors among hospitalized and ICU patients, compared to those with milder clinical presentations. In addition, those requiring hospitalization had more comorbidities. A significant increase in the frequencies of CD19+ cells at day 0 was observed in hospitalized and ICU patients compared to asymptomatic and symptomatic groups. Likewise, the frequency of plasmablasts was significantly increased at the first sample in the ICU group compared to the asymptomatic group, but then waned over time. The frequency of naïve B cells decreased at days 7 and 30 compared to day 0 in hospitalized and ICU patients. The neutralizing antibody titers were higher as the severity of COVID-19 increased; in asymptomatic individuals, it was strongly correlated with the percentage of IgM+ switched memory B cells, and a moderate correlation was found with plasmablasts. Conclusion: The humoral immune response is variable among SARS-CoV-2 infected people depending on the severity and time of clinical evolution. In severe COVID-19 patients, a higher plasmablast frequency and neutralizing antibody response were observed, suggesting that, despite having a robust humoral immunity, this response could be late, having a low impact on disease outcome.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Male , Immunity, Humoral , Pandemics , Antibodies, NeutralizingABSTRACT
Introducción: Los brotes de enfermedades causados por los virus Zika (VZIK) y Chikungunya (VCHIK) representan un problema de salud pública para muchos países tropicales y subtropicales. Objetivo: Discutir las implicaciones del hallazgo del VZIK y del VCHIK en el semen, y su relación con la transmisión sexual y la fertilidad masculina. Métodos: Se realizó una revisión narrativa de la literatura usando artículos indexados en PubMed (Medline), Embase y Scopus. Información, análisis y síntesis: Si bien los mosquitos del género Aedes son el vector principal y transmiten ambos virus, la transmisión sexual es una vía de infección significativa del VZIK y una posible ruta alterna para el VCHIK. La diseminación de estas arbovirosis vía linfática y sanguínea contribuye a la infección de diversos tejidos, incluyendo el tracto reproductivo masculino, donde el VZIK puede persistir. La infección de los testículos y quizás también de las glándulas accesorias del sistema reproductor masculino, se asocia con síntomas genitourinarios o alteraciones espermáticas, relacionadas con la detección del virus por largos periodos. Aunque no hay evidencia contundente sobre la presencia del VCHIK en el tracto genital masculino, se ha hallado en orina y semen. Además, se ha sugerido una posible persistencia en macrófagos que pueden infiltrar diferentes tejidos periféricos y cumplir una función de reservorio. Conclusiones: Hay presencia y persistencia de los virus Zika y Chikungunya en el tracto reproductor masculino. La infección en el semen se asocia con la transmisión sexual del virus, y con la alteración en la producción y calidad de los espermatozoides, con consecuencias clínicas graves en la salud sexual y reproductiva de los hombres infectados(AU)
Introduction: Disease outbreaks caused by Zika (ZIKV) and Chikungunya (CHIKV) viruses represent a public health problem for many tropical and subtropical countries. Objective: To discuss the implications of finding ZIKV and CHIKV in semen, and their relationship to sexual transmission and male fertility. Methods: A narrative review of the literature was carried out using articles indexed in PubMed (Medline), Embase and Scopus. Information, Analysis and Synthesis: Although Aedes mosquitoes are the primary vector and transmit both viruses, sexual transmission is a significant route of infection for ZIKV and a possible alternate route for CHIKV. Spread of these arboviruses via lymphatic and blood routes contributes to infection of various tissues, including the male reproductive tract, where ZIKV may persist. Infection of the testes and probably of the accessory glands of the male reproductive system is associated with genitourinary symptoms or sperm alterations, related to the detection of the virus for long periods. Although there is no conclusive evidence of the presence of CHIKV in the male genital tract, it has been found in urine and semen. In addition, a possible persistence in macrophages that can infiltrate different peripheral tissues and function as reservoir has been suggested. Conclusions: Zika and Chikungunya viruses can be present and persist in the male reproductive tract. Infection in semen is associated with sexual transmission of the virus and with alterations in the production and quality of spermatozoa, with serious clinical consequences in the sexual and reproductive health of infected men(AU)
Subject(s)
Humans , MaleABSTRACT
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide as a severe pandemic. Although its seroprevalence is highly variable among territories, it has been reported at around 10%, but higher in health workers. Evidence regarding cross-neutralizing response between SARS-CoV and SARS-CoV-2 is still controversial. However, other previous coronaviruses may interfere with SARS-CoV-2 infection, since they are phylogenetically related and share the same target receptor. Further, the seroconversion of IgM and IgG occurs at around 12 days post onset of symptoms and most patients have neutralizing titers on days 14-20, with great titer variability. Neutralizing antibodies correlate positively with age, male sex, and severity of the disease. Moreover, the use of convalescent plasma has shown controversial results in terms of safety and efficacy, and due to the variable immune response among individuals, measuring antibody titers before transfusion is mostly required. Similarly, cellular immunity seems to be crucial in the resolution of the infection, as SARS-CoV-2-specific CD4+ and CD8+ T cells circulate to some extent in recovered patients. Of note, the duration of the antibody response has not been well established yet.
