Low performance of Sinovac vaccine and effect of Belatacept therapy in a study with different types of COVID-19 vaccines in transplanted patients

The huge impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on organ transplant recipients makes it necessary to optimise vaccine efficacy in this population. To effectively implement multiple strategies, it is crucial to understand the performance of each type of available vaccine. In our study the antibody titre was measured, and the presence of antibodies against SARS-CoV-2 was evaluated after 90 days of immunisation, furthermore, the differences between hybrid immunity, immunity by vaccination and immunosuppressant type were identified. As a result, of the patients included in this study (n=160), 53% showed antibodies against SARS-CoV-2 at 90 days after the first dose in patients who had completed the vaccination schedule. Antibody titres were higher in patients with hybrid immunity, and the proportion of non-responsive patients was higher among those who received the immunosuppressant Belatacept in their post-transplant regimen (p = 0.01). Only 15% of patients treated with this medicine seroconverted, and patients vaccinated with CoronaVac and treated with Belatacept showed no response. In conclusion, a reduced response to vaccines against SARS-CoV-2 was identified in the transplant population, and this response varied with the type of vaccine administered and the immunosuppressive treatment.

Low Performance of Sinovac Vaccine Particularly With Belatacept Therapy in a Study With Different Types of COVID-19 Vaccines in Transplanted Patients.

The huge impact of SARS-CoV-2 infections on organ transplant recipients makes it necessary to optimize vaccine efficacy in this population. To effectively implement multiple strategies, it is crucial to understand the performance of each type of available vaccine. In our study, the antibody titer was measured, and the presence of antibodies against SARS-CoV-2 was evaluated after 90 days of immunization; furthermore, the differences between hybrid immunity, immunity by vaccination, and immunosuppressant type were identified. As a result, of the patients included in this study (n = 160), 53% showed antibodies against SARS-CoV-2 90 days after the first dose in patients who had completed the vaccination schedule. Antibody titers were higher in patients with hybrid immunity, and the proportion of nonresponsive patients was higher among those who received the immunosuppressant belatacept in their post-transplant regimen (P = .01). Only 15% of patients treated with this medicine seroconverted and patients vaccinated with CoronaVac and treated with belatacept showed no response. In conclusion, a reduced response to vaccines against SARS-CoV-2 was identified in the transplant population, and this response varied with the type of vaccine administered and the immunosuppressive treatment.

Comparison of Anti-SARS-CoV-2 IgG Antibody Responses Generated by the Administration of Ad26.COV2.S, AZD1222, BNT162b2, or CoronaVac: Longitudinal Prospective Cohort Study in the Colombian Population, 2021/2022.

To mitigate the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), vaccines have been rapidly developed and introduced in many countries. In Colombia, the population was vaccinated with four vaccines. Therefore, this research aimed to determine the ability of the vaccines introduced in the National Vaccination Plan to prevent SARS-CoV-2 infection and induce seroconversion and sought to investigate the longevity of antibodies in the blood. We conducted a prospective, nonprobabilistic, consecutive cross-sectional cohort study in a population with access to vaccination with CoronaVac, Ad26.COV2.S, AZD1222, and BNT162b2 from March 2021 to March 2022. The study included 1327 vaccinated people. A plurality of participants were vaccinated with BNT162b2 (36.1%; n = 480), followed by Ad26.COV2.S (26.9%; n = 358), CoronaVac (24%; n = 331), and AZD1222 (11.9%; n = 158). The crude seroprevalence on day zero varied between 18.1% and 57.8%. Participants who received BNT162b2 had a lower risk of SARS-CoV-2 infection than those who received the other vaccines. Participants who were immunized with BNT162b2 and AZD1222 had a higher probability of losing reactivity on day 210 after receiving the vaccine.

Seroprevalence of anti-SARS-CoV-2 antibodies in Colombia, 2020: A population-based study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to cause very high morbidity and mortality throughout Latin American countries. However, few population-based seroprevalence surveys have been conducted to quantify attack rates and characterize drivers of transmission. METHODS: We conducted a population-based cross-sectional study to assess the seroprevalence of antibodies against SARS-CoV-2 in ten cities in Colombia between September and December 2020. The study involved multi-stage cluster sampling at each city. Participants provided a serum sample and answered a demographic and risk factor questionnaire. Prior infection by SARS-CoV-2 was ascertained using the "SARS-CoV-2 Total (COV2T) Advia Centaur - Siemens" chemiluminescence assay. FINDINGS: A total of 17863 participants from 7320 households participated in the study. Seroprevalence varied substantially between cities, ranging from 26% (95%CI 23-29 %) in Medellín to 68% (95%CI 62-74 %) in Guapi. There were no differences in seroprevalence by sex, but seropositivity was higher in certain ethnic groups. There was substantial heterogeneity in seroprevalence within cities, driven to a large extent by a strong association between socioeconomic stratum and seropositivity. INTERPRETATION: Colombia has been one of the Latin American countries most affected by the COVID-19 pandemic. This study documented very high attack rates in several Colombian cities by the end of 2020 and identified key drivers of heterogeneities including ethnicity and socioeconomic stratum. Few studies of seroprevalence of SARS-CoV-2 have been conducted in Latin America, and therefore this study contributes to the fundamental understanding of the pandemic in the region. FUNDING: The study was sponsored by, Ministerio de Ciencia y Tecnología e Innovación -CT361/2020, Ministerio de Salud y Protección Social, Fundación Universitaria del Norte, Imperial College of London, Universidad Nacional de Colombia (Sede Medellín), Universidad de Córdoba, California University, Unidad Nacional de Gestión del Riesgo, Centro de Atención y Diagnóstico de Enfermedades Infecciosas -CDI-, Centro Internacional de Entrenamiento e Investigaciones Médicas -CIDEIM-, Departamento Administrativo Nacional de Estadística - DANE, Fondo Nacional de Turismo -FONTUR-, Secretarías de Salud Departamentales, Distritales y Municipales and Instituto Nacional de Salud.

Novel Highly Divergent SARS-CoV-2 Lineage With the Spike Substitutions L249S and E484K.

COVID-19 pandemics has led to genetic diversification of SARS-CoV-2 and the appearance of variants with potential impact in transmissibility and viral escape from acquired immunity. We report a new and highly divergent lineage containing 21 distinctive mutations (10 non-synonymous, eight synonymous, and three substitutions in non-coding regions). The amino acid changes L249S and E484K located at the CTD and RBD of the Spike protein could be of special interest due to their potential biological role in the virus-host relationship. Further studies are required for monitoring the epidemiologic impact of this new lineage.

Genomic Epidemiology of Severe Acute Respiratory Syndrome Coronavirus 2, Colombia.

Coronavirus disease (COVID-19) in Colombia was first diagnosed in a traveler arriving from Italy on February 26, 2020. However, limited data are available on the origins and number of introductions of COVID-19 into the country. We sequenced the causative agent of COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), from 43 clinical samples we collected, along with another 79 genome sequences available from Colombia. We investigated the emergence and importation routes for SARS-CoV-2 into Colombia by using epidemiologic, historical air travel, and phylogenetic observations. Our study provides evidence of multiple introductions, mostly from Europe, and documents >12 lineages. Phylogenetic findings validate the lineage diversity, support multiple importation events, and demonstrate the evolutionary relationship of epidemiologically linked transmission chains. Our results reconstruct the early evolutionary history of SARS-CoV-2 in Colombia and highlight the advantages of genome sequencing to complement COVID-19 outbreak investigations.

Substitutions in Spike and Nucleocapsid proteins of SARS-CoV-2 circulating in South America.

SARS-CoV-2 is a new member of the genus Betacoronavirus, responsible for the COVID-19 pandemic. The virus crossed the species barrier and established in the human population taking advantage of the spike protein high affinity for the ACE receptor to infect the lower respiratory tract. The Nucleocapsid (N) and Spike (S) are highly immunogenic structural proteins and most commercial COVID-19 diagnostic assays target these proteins. In an unpredictable epidemic, it is essential to know about their genetic variability. The objective of this study was to describe the substitution frequency of the S and N proteins of SARS-CoV-2 in South America. A total of 504 amino acid and nucleotide sequences of the S and N proteins of SARS-CoV-2 from seven South American countries (Argentina, Brazil, Chile, Ecuador, Peru, Uruguay, and Colombia), reported as of June 3, and corresponding to samples collected between March and April 2020, were compared through substitution matrices using the Muscle algorithm. Forty-three sequences from 13 Colombian departments were obtained in this study using the Oxford Nanopore and Illumina MiSeq technologies, following the amplicon-based ARTIC network protocol. The substitutions D614G in S and R203K/G204R in N were the most frequent in South America, observed in 83% and 34% of the sequences respectively. Strikingly, genomes with the conserved position D614 were almost completely replaced by genomes with the G614 substitution between March to April 2020. A similar replacement pattern was observed with R203K/G204R although more marked in Chile, Argentina and Brazil, suggesting similar introduction history and/or control strategies of SARS-CoV-2 in these countries. It is necessary to continue with the genomic surveillance of S and N proteins during the SARS-CoV-2 pandemic as this information can be useful for developing vaccines, therapeutics and diagnostic tests.

Molecular analysis of several in-house rRT-PCR protocols for SARS-CoV-2 detection in the context of genetic variability of the virus in Colombia.

The COVID-19 pandemic caused by SARS-CoV-2 is a public health problem unprecedented in the recent history of humanity. Different in-house real-time RT-PCR (rRT-PCR) methods for SARS-CoV-2 diagnosis and the appearance of genomes with mutations in primer regions have been reported. Hence, whole-genome data from locally-circulating SARS-CoV-2 strains contribute to the knowledge of its global variability and the development and fine tuning of diagnostic protocols. To describe the genetic variability of Colombian SARS-CoV-2 genomes in hybridization regions of oligonucleotides of the main in-house methods for SARS-CoV-2 detection, RNA samples with confirmed SARS-CoV-2 molecular diagnosis were processed through next-generation sequencing. Primers/probes sequences from 13 target regions for SARS-CoV-2 detection suggested by 7 institutions and consolidated by WHO during the early stage of the pandemic were aligned with Muscle tool to assess the genetic variability potentially affecting their performance. Finally, the corresponding codon positions at the 3' end of each primer, the open reading frame inspection was identified for each gene/protein product. Complete SARS-CoV-2 genomes were obtained from 30 COVID-19 cases, representative of the current epidemiology in the country. Mismatches between at least one Colombian sequence and five oligonucleotides targeting the RdRP and N genes were observed. The 3' end of 4 primers aligned to the third codon position, showed high risk of nucleotide substitution and potential mismatches at this critical position. Genetic variability was detected in Colombian SARS-CoV-2 sequences in some of the primer/probe regions for in-house rRT-PCR diagnostic tests available at WHO COVID-19 technical guidelines; its impact on the performance and rates of false-negative results should be experimentally evaluated. The genomic surveillance of SARS-CoV-2 is highly recommended for the early identification of mutations in critical regions and to issue recommendations on specific diagnostic tests to ensure the coverage of locally-circulating genetic variants.