Relationship between the Viral Load in Patients with Different COVID-19 Severities and SARS-CoV-2 Variants.

SARS-CoV-2 has spread throughout the world since 2019, changing in its genome and leading to the appearance of new variants. This gave it different evolutionary advantages, such as greater infectivity and/or a greater ability to avoid the immune response, which could lead to an increased severity of COVID-19 cases. There is no consistent information about the viral load that occurs in infection with the different SARS-CoV-2 variants, hence, in this study we quantify the viral load of more than 16,800 samples taken from the Mexican population with confirmed diagnosis of COVID-19 and we analyze the relation between different demographic and disease variables. We detected that the viral load caused by different variants differs only in the first two days after the onset of symptoms, being higher when infections are caused by the delta variant and lower when caused by omicron. Furthermore, the viral load appears to be higher in outpatients compared to hospitalized patients or in cases of death. On the other hand, no differences were found in the viral load produced in vaccinated and unvaccinated patients, nor did it differ between genders.

Impact of vaccination on infection or death from COVID-19 in individuals with laboratory-confirmed cases: Case-control study.

OBJECTIVES: The objective of this study is to estimate the effectiveness of COVID-19 vaccines in people treated within the social security system whose vaccination status was reported to the epidemiological surveillance system. STUDY DESIGN: Case-control study. METHODS: This was a case-control study conducted. The records of individuals with suspected cases of COVID-19 registered in the epidemiological surveillance system between February 1 and June 30, 2021, were studied. RT-qPCR was performed to determine SARS-CoV-2 infection; those with a positive result were considered cases, and those with a negative result were considered controls. The ratio between cases and controls was 1:1.3. The crude and adjusted vaccine effectiveness was considered the prevention of symptomatic infection and death and calculated as the difference between the dose and the risk, with a survival analysis among vaccinated people. RESULTS: A total of 94,416 individuals were included, of whom 40,192 were considered cases and 54,224 controls; 3,781 (4.00%) had been vaccinated against COVID-19. Vaccination also proved to be a protective factor against COVID-19, especially in the population who received a second dose (OR = 0.31; 95% CI 0.28-0.35). With the application of the vaccine, there was a protective effect against mortality (OR = 0.76; 95% CI 0.66-0.87). Disease prevention was higher for the BNT162-2 mRNA vaccine (82%) followed by the ChAdOx1 vaccine (33%). In the survival analysis, vaccination provided a protective effect. CONCLUSIONS: There was a positive impact of vaccines for the prevention of symptomatic COVID-19, with a second dose generating greater efficacy and a reduction in deaths.

Diversity, composition, and networking of saliva microbiota distinguish the severity of COVID-19 episodes as revealed by an analysis of 16S rRNA variable V1-V3 region sequences.

Studies on the role of the oral microbiome in SARS-CoV-2 infection and severity of the disease are limited. We aimed to characterize the bacterial communities present in the saliva of patients with varied COVID-19 severity to learn if there are differences in the characteristics of the microbiome among the clinical groups. We included 31 asymptomatic subjects with no previous COVID-19 infection or vaccination; 176 patients with mild respiratory symptoms, positive or negative for SARS-CoV-2 infection; 57 patients that required hospitalization because of severe COVID-19 with oxygen saturation below 92%, and 18 fatal cases of COVID-19. Saliva samples collected before any treatment were tested for SARS-CoV-2 by PCR. Oral microbiota in saliva was studied by amplification and sequencing of the V1-V3 variable regions of 16S gene using an Illumina MiSeq platform. We found significant changes in diversity, composition, and networking in saliva microbiota of patients with COVID-19, as well as patterns associated with severity of disease. The presence or abundance of several commensal species and opportunistic pathogens were associated with each clinical stage. Patterns of networking were also found associated with severity of disease: a highly regulated bacterial community (normonetting) was found in healthy people whereas poorly regulated populations (disnetting) were characteristic of severe cases. Characterization of microbiota in saliva may offer important clues in the pathogenesis of COVID-19 and may also identify potential markers for prognosis in the severity of the disease. IMPORTANCE SARS-CoV-2 infection is the most severe pandemic of humankind in the last hundred years. The outcome of the infection ranges from asymptomatic or mild to severe and even fatal cases, but reasons for this remain unknown. Microbes normally colonizing the respiratory tract form communities that may mitigate the transmission, symptoms, and severity of viral infections, but very little is known on the role of these microbial communities in the severity of COVID-19. We aimed to characterize the bacterial communities in saliva of patients with different severity of COVID-19 disease, from mild to fatal cases. Our results revealed clear differences in the composition and in the nature of interactions (networking) of the bacterial species present in the different clinical groups and show community-patterns associated with disease severity. Characterization of the microbial communities in saliva may offer important clues to learn ways COVID-19 patients may suffer from different disease severities.

Longevity and Neutralizing Capacity of IgG Antibodies against SARS-CoV-2 Generated by the Application of BNT162b2, AZD1222, Convidecia, Sputnik V, and CoronaVac Vaccines: a Cohort Study in the Mexican Population.

The WHO has approved the use of several vaccines during the COVID-19 pandemic; experience over the last 2 years has indicated that dose demand can only be covered using more than one design. Therefore, having scientific evidence of the performance of the different vaccines applied in a country is highly relevant. In Mexico, 5 vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were used, allowing a cohort study to analyze the generation of anti-S1/S2 IgG antibodies and anti-RBD antibodies with neutralizing activity at 0, 21, 90, and 180 days after vaccination. Five groups of participants were formed on the basis of the type of vaccine received and were divided on the basis of whether they previously had or did not have COVID-19. After completing the vaccination schedule, the seroprevalence was 95.5, 97.5, 81.0, 95.2, and 90.0% (BNT162b2, AZD1222, Convidecia, Sputnik V, and CoronaVac, respectively). Among the participants without COVID-19 prior to vaccination, the largest amount of antibodies in the 90-day period was observed in the BNT162b2 group, and the amount of antibodies in the Sputnik V group decreased the least over time. Even though the percentages of seroconversion obtained in this study were lower than those currently reported in other parts of the world, the tested vaccines are able, in most cases, to induce a good production of IgG antibodies anti-S1/S2 and neutralizing capacity. The fact that there are people who have not produced antibodies during the study leaves open some questions that must be investigated to avoid the appearance of serious cases of COVID-19. IMPORTANCE Since the start of the vaccination programs against COVID-19 in 2020, it was evident that due to global shortages, the demand for the dose required in Mexico could only be covered by acquiring different vaccines. Therefore, determining the effectiveness of these and the longevity of acquired immunity is extremely important in a scenario where SARS-CoV-2 circulation becomes endemic and booster doses are required periodically. Our data reveal significant differences both in the generation of antibodies as well as in their longevity for the vaccines applied in the country but suggest that, in general, the Mexican population can reach a high capacity to neutralize the virus, therefore, regarding less the variant for which they were designed.

[Etiology of bacterial pneumonias in patients with COVID-19]. / Etiología de neumonías bacterianas en pacientes con COVID-19.

Background: Aggregate bacterial pneumonia plays a fundamental role in mortality of patients hospitalized with COVID-19. Objective: To estimate the association of aggregated bacterial pneumonia with mortality in patients at Hospital Especialidades "La Raza". Material and methods: Analytical cross-sectional study, 252 COVID-19 patients, chest x-ray and culture of bronchial secretion or expectoration. Data taken from the SIOC electronic file and the IZASAlab platform. Results: 252 participants, positive culture, 89 patients, 35.3%, isolation of K. pneumoniae (22.5%), A. baumannii (20.2%), P. aeruginosa (13.5%) and S. aureus (11.2%), antimicrobial resistance 37.1%. 43.7% died, lung damage greater than 50% RMa 2.25 (95% CI 1.01-5.11) p=0.04 against minor lung damage; microorganism in culture RMa 9.04 (95% CI 3.06-26.74) p=0.000; antimicrobial resistance RMa 7.57 (95% CI 1.34-42.79) p=0.02; S. aureus RMa 1.24 (95% CI 0.36-4.23) p=0.73; A. baumannii RMa 3.74 (95% CI 1.41-9.91) p=0.008; K. pneumoniae RMa 4.12 (95% CI 1.55-10.97) p=0.005; and P. aeruginosa RMa 6.89 (95% CI 1.62-17.61) p=0.01. Uncontrolled Diabetes RMa 1.61 (IC95% 1.1-2.9) p=0.018. Conclusions: The development of added bacterial pneumonia increases the probability of death 2 times more, it amounts to 6 times more if there is antimicrobial resistance, it is observed to a greater extent for A. baumannii, K. pneumoniae and P. aeruginosa.

Introducción: la neumonía bacteriana agregada en pacientes COVID-19 tiene un papel determinante en la mortalidad hospitalaria. Objetivo: estimar la asociación de neumonía bacteriana agregada con la mortalidad de pacientes COVID-19 en el Hospital Especialidades de "La Raza". Material y métodos: estudio transversal analítico con 252 pacientes con COVID-19; se obtuvieron los datos del expediente electrónico y plataforma IZASAlab, se tomó Rx de tórax y cultivo de secreción bronquial o expectoración. Resultados: de 252 participantes resultó cultivo positivo en 89 pacientes (35.3%), aislamiento de K. pneumoniae (22.5%), A. baumannii (20.2%), P. aeruginosa (13.5%) y S. aureus (11.2%); hubo resistencia antimicrobiana en 37.1% y fallecieron 43.7%. El daño pulmonar mayor al 50% en la Rx de tórax tuvo RMa 2.25 (IC95%: 1.01-5.11) p = 0.04 para mortalidad; cultivo positivo RMa 9.04 (IC95%: 3.06-26.74) p = 0.000; resistencia antimicrobiana RMa 7.57 (IC95%: 1.34-42.79) p = 0.02; S. aureus RMa 1.24 (IC95%: 0.36-4.23) p = 0.73; A. baumannii RMa 3.74 (IC95%: 1.41-9.91) p = 0.008; K. pneumoniae RMa 4.12 (IC95%: 1.55-10.97) p = 0.005, y P. aeruginosa RMa 6.89 (IC95%: 1.62-17.61) p = 0.01. Diabetes Mellitus descontrolada RMa 1.61 (IC95%: 1.1-2.9) p = 0.018. Conclusiones: el desarrollo neumonía bacteriana agregada en pacientes COVID-19 incrementa dos veces más la probabilidad de muerte y seis veces más si existe resistencia antimicrobiana de A. baumannii, K. pneumoniae o P. aeruginosa.

The Alpha Variant (B.1.1.7) of SARS-CoV-2 Failed to Become Dominant in Mexico.

During the coronavirus disease 2019 (COVID-19) pandemic, the emergence and rapid increase of the B.1.1.7 (Alpha) lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in the United Kingdom in September 2020, was well documented in different areas of the world and became a global public health concern because of its increased transmissibility. The B.1.1.7 lineage was first detected in Mexico during December 2020, showing a slow progressive increase in its circulation frequency, which reached its maximum in May 2021 but never became predominant. In this work, we analyzed the patterns of diversity and distribution of this lineage in Mexico using phylogenetic and haplotype network analyses. Despite the reported increase in transmissibility of the B.1.1.7 lineage, in most Mexican states, it did not displace cocirculating lineages, such as B.1.1.519, which dominated the country from February to May 2021. Our results show that the states with the highest prevalence of B.1.1.7 were those at the Mexico-U.S. border. An apparent pattern of dispersion of this lineage from the northern states of Mexico toward the center or the southeast was observed in the largest transmission chains, indicating possible independent introduction events from the United States. However, other entry points cannot be excluded, as shown by multiple introduction events. Local transmission led to a few successful haplotypes with a localized distribution and specific mutations indicating sustained community transmission. IMPORTANCE The emergence and rapid increase of the B.1.1.7 (Alpha) lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) throughout the world were due to its increased transmissibility. However, it did not displace cocirculating lineages in most of Mexico, particularly B.1.1.519, which dominated the country from February to May 2021. In this work, we analyzed the distribution of B.1.1.7 in Mexico using phylogenetic and haplotype network analyses. Our results show that the states with the highest prevalence of B.1.1.7 (around 30%) were those at the Mexico-U.S. border, which also exhibited the highest lineage diversity, indicating possible introduction events from the United States. Also, several haplotypes were identified with a localized distribution and specific mutations, indicating that sustained community transmission occurred in the country.

[Coinfections by SARS-CoV-2 and other respiratory viruses and their clinical outcome]. / Coinfecciones por SARS-CoV-2 y otros virus respiratorios y su desenlace clínico.

Background: SARS-CoV-2 is a coronavirus described for the first time in China, in December 2019. This virus can cause a disease with a very variable spectrum that ranges from asymptomatic cases to deaths. The most severe cases are normally associated with comorbidities and with the age of the patient. However, there are patients who are not part of these risk groups and develop severe cases. Objetive: To determine the association between coinfections by SARS-CoV-2 and other respiratory viruses and their clincal outcome. Material and methods: RT-qPCR was performed to determine the presence of 16 respiratory viruses in 103 confirmed COVID-19 cases. Demographic and comorbid data were collected, and statistical analyzes were performed to determine associations with severity. Results: Of the 103 analyzed cases, 14 (13.6%) presented a coinfection, of these, 92% did not require hospitalization, even in those cases in which the patient presented advanced age and some comorbidities. Conclusions: These results suggest that coinfection of SARS-CoV-2 and other respiratory viruses is not related to a more severe form of COVID-19 and, in some cases, depending on the virus involved, it could even lead to a better prognosis. These findings lay the foundations for the development of new studies that could determine the biological mechanism of this phenomenon.

Introducción: el SARS-CoV-2 es un coronavirus que fue descrito por primera vez en diciembre de 2019 en Wuhan, China. Este virus causa una enfermedad que varía en un espectro de severidad que va desde casos asintomáticos hasta defunciones. Los casos más severos se asocian normalmente con algunas comorbilidades y con la edad del paciente. Sin embargo, existen pacientes que no son parte de estos grupos de riesgo y aun así desarrollan casos graves. Objetivo: determinar la asociación entre las coinfecciones por SARS-CoV-2 y otros virus respiratorios y su desenlace clínico. Material y métodos: se realizó RT-qPCR para determinar la presencia de 16 virus respiratorios en 103 casos confirmados de COVID-19. Se recolectaron datos demográficos y de comorbilidades, y se realizaron análisis estadísticos para determinar asociaciones con gravedad. Resultados: el 13.6% de los casos (14/103) presentaron alguna coinfección, de estos, el 92% nunca requirió ingreso hospitalario, aun en aquellos casos en los que el paciente presentara comorbilidades y edad avanzada. Conclusiones: estos resultados sugieren que la coinfección no está relacionada con un COVID-19 más grave y que, dependiendo del virus involucrado, incluso podría conducir a un mejor pronóstico. Estos hallazgos sientan las bases para nuevos estudios dirigidos a determinar el mecanismo biológico por el cual ocurre este fenómeno y a proponer las estrategias correspondientes para limitar la progresión a casos severos de COVID-19.

Coinfecciones por SARS-CoV-2 y otros virus respiratorios y su desenlace clínico / Coinfections by SARS-CoV-2 and other respiratory viruses and their clinical outcome

Introducción: el SARS-CoV-2 es un coronavirus que fue descrito por primera vez en diciembre de 2019 en Wuhan, China. Este virus causa una enfermedad que varía en un espectro de severidad que va desde casos asintomáticos hasta defunciones. Los casos más severos se asocian normalmente con algunas comorbilidades y con la edad del paciente. Sin embargo, existen pacientes que no son parte de estos grupos de riesgo y aun así desarrollan casos graves. Objetivo: determinar la asociación entre las coinfecciones por SARS-CoV-2 y otros virus respiratorios y su desenlace clínico. Material y métodos: se realizó RT-qPCR para determinar la presencia de 16 virus respiratorios en 103 casos confirmados de COVID-19. Se recolectaron datos demográficos y de comorbilidades, y se realizaron análisis estadísticos para determinar asociaciones con gravedad. Resultados: el 13.6% de los casos (14/103) presentaron alguna coinfección, de estos, el 92% nunca requirió ingreso hospitalario, aun en aquellos casos en los que el paciente presentara comorbilidades y edad avanzada. Conclusiones: estos resultados sugieren que la coinfección no está relacionada con un COVID-19 más grave y que, dependiendo del virus involucrado, incluso podría conducir a un mejor pronóstico. Estos hallazgos sientan las bases para nuevos estudios dirigidos a determinar el mecanismo biológico por el cual ocurre este fenómeno y a proponer las estrategias correspondientes para limitar la progresión a casos severos de COVID-19.

Background: SARS-CoV-2 is a coronavirus described for the first time in China, in December 2019. This virus can cause a disease with a very variable spectrum that ranges from asymptomatic cases to deaths. The most severe cases are normally associated with comorbidities and with the age of the patient. However, there are patients who are not part of these risk groups and develop severe cases. Objetive: To determine the association between coinfections by SARS-CoV-2 and other respiratory viruses and their clincal outcome. Material and methods: RT-qPCR was performed to determine the presence of 16 respiratory viruses in 103 confirmed COVID-19 cases. Demographic and comorbid data were collected, and statistical analyzes were performed to determine associations with severity. Results: Of the 103 analyzed cases, 14 (13.6%) presented a coinfection, of these, 92% did not require hospitalization, even in those cases in which the patient presented advanced age and some comorbidities. Conclusions: These results suggest that coinfection of SARS-CoV-2 and other respiratory viruses is not related to a more severe form of COVID-19 and, in some cases, depending on the virus involved, it could even lead to a better prognosis. These findings lay the foundations for the development of new studies that could determine the biological mechanism of this phenomenon.

SARS-CoV-2 IgG Antibodies Seroprevalence and Sera Neutralizing Activity in MEXICO: A National Cross-Sectional Study during 2020.

Until recently, the incidence of COVID-19 was primarily estimated using molecular diagnostic methods. However, the number of cases is vastly underreported using these methods. Seroprevalence studies estimate cumulative infection incidences and allow monitoring of transmission dynamics, and the presence of neutralizing antibodies in the population. In February 2020, the Mexican Social Security Institute began conducting anonymous unrelated sampling of residual sera from specimens across the country, excluding patients with fever within the previous two weeks and/or patients with an acute respiratory infection. Sampling was carried out weekly and began 17 days before Mexico's first officially confirmed case. The 24,273 sera obtained were analyzed by chemiluminescent-linked immunosorbent assay (CLIA) IgG S1/S2 and, later, positive cases using this technique were also analyzed to determine the rate of neutralization using the enzyme-linked immunosorbent assay (ELISA). We identified 40 CLIA IgG positive cases before the first official report of SARS-CoV-2 infection in Mexico. The national seroprevalence was 3.5% in February and 33.5% in December. Neutralizing activity among IgG positives patients during overall study period was 86.1%. The extent of the SARS-CoV-2 infection in Mexico is 21 times higher than that reported by molecular techniques. Although the general population is still far from achieving herd immunity, epidemiological indicators should be re-estimated based on serological studies of this type.