Serological Assessment of COVID-19 Patients in Brazil: Levels, Avidity, and Subclasses of IgG Against RBD

Abstract

SARS-CoV-2 is considered a global emergency, resulting in an exacerbated crisis in the health public in the world. Although there are advances in vaccine development, it is still not available for many countries. On the other hand, an immunological response that mediates protective immunity or indicates that predict disease outcome in SARS-CoV-2 infection remains undefined. This work aimed to assess the antibody levels, avidity, and subclasses of IgG to RBD protein, in symptomatic patients with severe and mild forms of COVID-19 in Brazil using an adapted in-house RBD-IgG ELISA. The RDB IgG-ELISA showed 100% of specificity and 94.3% of sensibility on detecting antibodies in the sera of hospitalized patients. Patients who presented severe COVID-19 had higher anti-RBD IgG levels compared to patients with mild disease. Additionally, most patients analyzed displayed low antibody avidity, with 64.4% of the samples of patients who recovered from the disease and 84.6% of those who died in this avidity range. Our data also reveals an increase of IgG1 and IgG3 levels since the 8th day after symptoms onset, while IgG4 levels maintained less detectable during the study period. Surprisingly, patients who died during 8-14 and 15-21 days also showed higher anti-RBD IgG4 levels in comparison with the recovered (P < 0.05), suggesting that some life-threatening patients can elicit IgG4 to RBD antibody response in the first weeks of symptoms onset. Our findings constitute the effort to clarify IgG antibodies' kinetics, avidity, and subclasses against SARS-CoV-2 RDB in symptomatic patients with COVID-19 in Brazil, highlighting the importance of IgG antibody avidity in association with IgG4 detection as tool laboratory in the follow-up of hospitalized patients with more significant potential for life-threatening.

Vaccination versus infection with SARS‐CoV‐2: Establishment of a high avidity IgG response versus incomplete avidity maturation

“…Even within 1 year after the onset of clinical symptoms, the vast majority of COVID‐19 outpatients in our study did not develop high avidity IgG toward SARS‐CoV‐2 NP, and 68% of the patients showed no high avidity IgG toward SARS‐CoV‐2 RBD. These findings of incomplete avidity maturation after natural infection with SARS‐CoV‐2 are in line with the findings by several other groups 9,10,17–20 . Also, the study by Luo et al 24 is indirectly confirming this view, as Luo et al used 3 M urea.…”

“…An initial analysis revealed that avidity maturation after SARS‐CoV‐2 infection remained at an untypical low level in most cases 12 . This is in line with the reports by other groups 9,10,17–20 …”

“…However, as the important findings by Kaneko et al 21 have been established in lymph nodes derived from patients who had died from COVID‐19, it is uncertain whether this mechanism also applies to patients with milder disease. Furthermore, the relative increase in avidity in patients, who required hospitalization compared with outpatients, as shown in Figure S11 , and also reported by other groups, 7 , 20 , 30 cannot be explained by the findings presented by Kaneko et al 21 It rather could be explained by a higher viral load and longer time of interaction with SARS‐CoV‐2 in patients with more severe disease and a lower viral load in patients with milder disease.…”

“…These findings of incomplete avidity maturation after natural infection with SARS‐CoV‐2 are in line with the findings by several other groups. 9 , 10 , 17 , 18 , 19 , 20 Also, the study by Luo et al 24 is indirectly confirming this view, as Luo et al used 3 M urea. This resulted in an overestimation of avidity in comparison with the use of the discriminatory concentration of 7 M urea.…”

Humoral response to spike S1 and S2 and nucleocapsid proteins on microarray after SARS‐CoV‐2 infection

“…A different study that enrolled IIER patients confirmed the result. 19 In COVID-19, obesity increases the chance of the patient being hospitalized in intensive care units, it is usually associated with other aggravating factors, like hypertension and diabetes; and has been related to immunological impairments, like increased inflammation and decrease of Treg activity, which may contribute to inadequate immune response. 20 This information highlights the need to observe comorbidities in the risk assessment of COVID-19 patients.…”