A stronger antibody response in increased disease severity of SARS-CoV-2.

BACKGROUND: An assessment of the factors that interfere with serum levels and the persistence of anti-SARs-CoV-2 IgG antibodies is essential in order to estimate the risk of reinfection and to plan vaccination. We analyzed the impact of the severity of coronavirus disease 2019 (COVID-19) and the clinical and biological factors regarding the persistence of SARs-CoV-2 anti-spike protein (IgG-S) antibodies at 12 months. METHODS: This was an observational, longitudinal study with individuals who had recovered from COVID-19 between August 2020 and June 2021. Peripheral blood samples were collected from volunteers who were hospitalized (SERIOUS COVID-19) and those who required no hospitalization (COVID-19 LIGHT). Samples were grouped according to days after symptom onset: up to 90, between 91 and 180, ≥ 180 days after symptom onset. A semiquantitative test for IgG anti-spike protein S1(IgG-S1) was used. RESULTS: We analyzed 238 individuals who had recovered from COVID-19, of whom 87 had been hospitalized and 151 had not. They provided 148 and 220 samples, respectively. Among those hospitalized, males (65.5%), volunteers aged over 60 years (41.1%), comorbidities such as arterial hypertension (67.8%) and diabetes mellitus (37.9%) were most frequent. We observed higher median serum IgG-S1 titers among those who had recovered from COVID-19 and had been hospitalized, at all collection time intervals (p < 0.001). We observed a weak correlation of increasing age with humoral IgG-S1 response (Spearman correlation = 0.298). There was a greater probability of IgG-S1 antibody persistence over time among samples from hospitalized individuals compared to samples from non-hospitalized participants (p = 0.001). CONCLUSION: This study has revealed higher titers and a higher probability of the persistence of IgG-S1 in severe cases after SARs-CoV-2 primary infection in unvaccinated recovered patients. Thus, in this study, the severe clinical presentation of COVID-19 was the main factor influencing serum levels and the persistence of IgG-S1 antibodies in COVID-19.

Levels of soluble TNF receptors (sTNFR1 and sTNFR2) increase with clinical worsening of patients and are related to COVID-19 mortality.

The present study aimed to inspect the serum levels of the soluble receptors, sTNFR1 and sTNFR2, in patients with COVID-19. The large production of inflammatory cytokines is an essential process in the pathogenesis of COVID-19. TNF is a multifaceted proinflammatory cytokine which has soluble and membrane receptors. Thus, knowing the role of these receptors will help better understand this disease's immunopathogenesis. We included 131 patients confirmed for SARS-CoV-2, separated into three groups: ward patients without O2 support, group A (n = 14); ward patients with O2 support, group B (n = 85), and patients in an intensive care unit (ICU), group C (n = 32), making up the receptors dosed by flow cytometry. The results showed that sTNFR1 and sTNFR2 are associated with disease severity, being higher in group C when compared to group A. As for the levels of receptors and their relationship with the degree of lung involvement, we found higher values of sTNFR1 in patients in group 1 (pulmonary involvement < 25%), suggesting that inflammatory processes related to TNF are not necessarily associated with the primary site of infection. When we analysed the patients who passed away compared to those who recovered, both receptors significantly increased the mortality numbers. These findings suggest a relevant influence of soluble receptors in the inflammatory processes involved in the pathogenesis of COVID-19. Wherefore, we suggest using these receptors as biomarkers of severity and mortality of the disease.

Association of NFκB and related-cytokines with the viral load and development of antibodies against HHV-8 in people living with HIV/AIDS.

Human gammaherpesvirus 8 (HHV-8) replication is influenced by a complex interaction between viral and host elements. Here, we evaluated the expression of NFκB and TNF-α in B (CD19 +) and T (CD3 +) lymphocytes, and the serum concentration of IL-1ß and IL-12 cytokines in people living with HIV/AIDS (PLHA), negative for HHV-8-related diseases, and who presented antibodies to latent or lytic antigens from HHV-8. In addition, we also evaluated the correlation of HHV-8 viral load with NFκB, TNF-α, IL-1ß and IL-12 levels. The expression of NFκB (p < 0.0001) or TNF-α (p < 0.0001) in B lymphocytes (CD19 +) and the IL-1ß (p < 0.0266) and IL-12 (p < 0.0001) concentrations were associated with the presence of antibodies to HHV-8 lytic antigens. The CD19 + NFκB + TNF-α + and CD3 + NFκB + TNF-α + cells were also associated with the presence of antibodies to lytic infection (p < 0.0001). Among all PLHA evaluated, only individuals with the highest titers of lytic antibodies, i.e., 1:320, had detectable HHV-8 viral load. In these, HHV-8 viral load was correlated to NFκB (r = 0.6, p = 0.003) and TNF-α (r = 0.5, p = 0.01) (both in CD19 + lymphocytes) and with IL-1ß (r = 0.5, p = 0.01) and IL-12 (r = 0.6, p = 0.006) levels. We believe that viral replication and/or reactivation, in addition to being associated with the development of lytic antibodies against HHV-8, may be associated with inflammatory response via NFκB. Finally, although immune response imbalance has been previously related to HHV-8-associated diseases, our results indicate that important changes in immunity, mainly in the inflammatory response, may be clearly observed in individuals with HHV-8, but who have not yet presented clinical manifestations.