In late December 2019, the incidence of atypical pneumonia cases of unknown cause was reported in the Chinese city of Wuhan. Since then, a successive series of spreads have been generated on a global scale what would be the COVID-19 pandemic, which represents the largest global public health crisis of this generation, and potentially, since the 1918 pandemic influenza outbreak (1).
The need to control the transmissibility and mortality associated with SARS-CoV-2 has made vaccines a critical resource to mitigate the devastating effects of the current pandemic. The emergence of new variants reinforces the need to accelerate vaccination rates in all countries. However, despite the speed of research, development and implementation of different vaccines worldwide remains limited as regards their availability in developing countries (2, 3).
Serological testing for SARS-CoV-2 employs enzyme-linked immunosorbent assay (ELISA), immunofluorescence and lateral flow techniques to detect antibodies directed against the nucleocapsid (N) and/or spike (S) proteins of the viral proteome. The S protein, which plays a key role in receptor recognition and in the cell membrane fusion process, is composed of two subunits, S1 and S2. The S1 subunit contains a receptor binding domain (RBD) which recognizes and binds to the host receptor (angiotensin-converting enzyme 2 [ACE2]). The N protein plays a vital role in transcription and replication and, because of its abundance, it has been suggested to be the ideal antigen for detecting early infections (4). IgG antibodies directed to S have been shown to be more specific, whereas those directed against N may be more abundant at the earliest stage of infection. The sensitivity and specificity of most serological tests have been validated with specimens drawn from patients who endure the acute phase of infection. It has been assumed that determination of antibody responses against either protein would be equally adequate in population-based seroprevalence studies. However, anti-S and anti-RBD antibodies correlate better with virus neutralization (4). This has been determined by virus neutralization testing (VNT) (the gold standard for measuring neutralization). Because this assay is very laborious and requires highly trained personnel working under BSL3 conditions, it is not suitable for high-throughput detections. In contrast, ELISA with recombinant S and/or RBD as substrate show a strong correlation with neutralization assay results. Furthermore, as most vaccines approved to date carry the genetic information of S or its RBD domain, only tests that determine anti-S or anti-RBD antibodies can assess individual and population seroconversions triggered by vaccination. The use of RBD not only streamlines the diagnostic kit production process, but also provides a more specific target for neutralizing antibodies. Therefore, determination of anti-S or anti-RBD antibody titers, rather than anti-N, provides more valuable information.
Tucumán is a province located in northwestern Argentina, and one of the most densely populated in the country. It has been one of the cities most affected by the pandemic, with more than 143,000 infections and 2,400 deaths due to COVID in a population of 1.5 million inhabitants. Currently, while the Government is moving forward with more relaxations and the announcement of a reinforcement of doses against Covid-19, Tucumán continues to add consecutive days without deaths. Although new cases continue to be confirmed in Tucumán, the number of infected people reached 199,694, 194,287 recovered and 3,430 patients died since the beginning of the pandemic.
During the year 2021, after the second wave that had a milder upward profile, incidence peaked between Epidemiological Weeks 20 and 24, and then declined. On the other hand, we are currently in a stage of community transmission of the Omicron strain. An example of this is the continuous epidemiological surveillance carried out by the Ministry of Public Health, through which it was observed that in the town of Famaillá, confirmed patients for Covid with the Delta variant were detected, which were processed in the Public Health Laboratory of Tucumán. In these cases, patients were isolated, followed up and medically treated by the Ministry (asymptomatic or with mild symptomatology patients).
Since the initial genomic characterization of SARSCoV-2, the virus has generated different genetic variants. They are classified into two major groups: Variants of Concern (VOC) and Variants of Interest (VOI). One of the objectives of genomic surveillance is to monitor the geographical and temporal trends of SARS-CoV-2 variants circulating in Argentina. Samples are processed at the National Reference Laboratory (ANLIS - Dr. Carlos C. Malbrán), and it is performed according to epidemiological surveillance criteria (traveler surveillance, unusual events, population sampling). So far (October 2021), out of a total of 484 samples analyzed by genomic sequencing, 81% corresponded to the VOC group.
In this context of new variants and the same already circulating in the community in our province, it became necessary to reinforce the vaccination schedule. Tucumán presents heterogeneity of vaccines applied, but this work took this situation into account and worked with relatively homogeneous groups. In this case, the anti-RBD antibody response was studied in two different population groups, a group of geriatric patients who had received two doses of AstraZeneca and received a third dose of the same vaccine, and on the other hand, a group of health personnel who had received two doses of Sputnik V and received AstraZeneca in the third dose. In both cases, the third dose corresponded to AstraZeneca.
Primary Objective
To evaluate the effect on the ability to generate Anti-Anti RBD antibodies (Anti-SAR-CoV 2-Spike-RBD) to the third dose of the AstraZeneca vaccine in two at-risk populations in the Province of Tucumán.
Secondary Objectives
-To study the presence of hybrid humoral immunity, determining if the history of previous COVID disease can modify or potentiate the titers reached after the application of the third dose of Anti-Anti RBD antibodies.
-To study by follow-up, the permanence of Anti-Anti RBD antibodies by means of repeated measurements determining their titers at day zero or inoculation day, at day 14 and at day 28.