Research Progress in Antibody Responses Against SARS-CoV-2 Variants of Concern / 中国医学科学院学报

So far,the coronavirus disease 2019(COVID-19)has been persisting for nearly three years,infecting about 700 million people and causing more than 6 million deaths,which has seriously affected the human society.According to Global Initiative on Sharing All Influenza Data,there are more than 12 million SARS-CoV-2 variants,of which the five major variants of concern are Alpha,Beta,Gamma,Delta and Omicron.Their infectivity,pathogencity,and neutralization resistance have changed greatly compared with the original strain,which has brought great pressure to the prevention and control of the pandemic.Antibody level testing is critical for confirming infection,epidemiological investigation,vaccine development,and neutralizing drug preparation.Focusing on the humoral immunity against SARS-CoV-2,this paper introduces the mutation sites,neutralization resistance,and vaccination efficacy of the five variants of concern,and briefly summarizes the evolutionary characteristics,future mutation directions,and host immunity.

Rapid detection and genotyping of SARS-CoV-2 Omicron BA.4/5 variants using a RT-PCR and CRISPR-Cas12a-based assay / 南方医科大学学报

OBJECTIVE@#To establish a rapid detection and genotyping method for SARS-CoV-2 Omicron BA.4/5 variants using CRISPPR-Cas12a gene editing technology.@*METHODS@#We combined reverse transcription-polymerase chain reaction (RT-PCR) and CRISPR gene editing technology and designed a specific CRISPPR RNA (crRNA) with suboptimal protospacer adjacent motifs (PAM) for rapid detection and genotyping of SARS- CoV-2 Omicron BA.4/5 variants. The performance of this RT- PCR/ CRISPPR-Cas12a assay was evaluated using 43 clinical samples of patients infected by wild-type SARS-CoV-2 and the Alpha, Beta, Delta, Omicron BA. 1 and BA. 4/5 variants and 20 SARS- CoV- 2-negative clinical samples infected with 11 respiratory pathogens. With Sanger sequencing method as the gold standard, the specificity, sensitivity, concordance (Kappa) and area under the ROC curve (AUC) of RT-PCR/CRISPPR-Cas12a assay were calculated.@*RESULTS@#This assay was capable of rapid and specific detection of SARS- CoV-2 Omicron BA.4/5 variant within 30 min with the lowest detection limit of 10 copies/μL, and no cross-reaction was observed in SARS-CoV-2-negative clinical samples infected with 11 common respiratory pathogens. The two Omicron BA.4/5 specific crRNAs (crRNA-1 and crRNA-2) allowed the assay to accurately distinguish Omicron BA.4/5 from BA.1 sublineage and other major SARS-CoV-2 variants of concern. For detection of SARS-CoV-2 Omicron BA.4/5 variants, the sensitivity of the established assay using crRNA-1 and crRNA-2 was 97.83% and 100% with specificity of 100% and AUC of 0.998 and 1.000, respectively, and their concordance rate with Sanger sequencing method was 92.83% and 96.41%, respectively.@*CONCLUSION@#By combining RT-PCR and CRISPPR-Cas12a gene editing technology, we successfully developed a new method for rapid detection and identification of SARS-CoV-2 Omicron BA.4/5 variants with a high sensitivity, specificity and reproducibility, which allows rapid detection and genotyping of SARS- CoV-2 variants and monitoring of the emerging variants and their dissemination.

Research and application of the SARS-CoV-2 vaccine based on adenovirus vector technology platform / 中华预防医学杂志

During the global efforts to prevent and control the COVID-19 pandemic, extensive research and development of SARS-CoV-2 vaccines using various technical approaches have taken place. Among these, vaccines based on adenovirus vector have gained substantial knowledge and experience in effectively combating potential emerging infectious diseases, while also providing novel ideas and methodologies for vaccine research and development (R&D). This comprehensive review focuses on the adenovirus vector technology platform in vaccine R&D, emphasizing the importance of mucosal immunity induced by adenoviral vector-based vaccine for COVID-19 prevention. Furthermore, it analyzes the key technical challenges and obstacles encountered in the development of vaccines based on the adenovirus vector technology platform, with the aim of providing valuable insights and references for researchers and professionals in related fields.

Establishment and preliminary application of quantitative real-time PCR assay for the detection of SARS-CoV-2 subgenomic nucleocapsid RNA / 中华预防医学杂志

Objective: To establish a rapid and specific quantitative real-time PCR (qPCR) method for the detection of SARS-CoV-2 subgenomic nucleocapsid RNA (SgN) in patients with COVID-19 or environmental samples. Methods: The qPCR assay was established by designing specific primers and TaqMan probe based on the SARS-CoV-2 genomic sequence in Global Initiative of Sharing All Influenza Data (GISAID) database. The reaction conditions were optimized by using different annealing temperature, different primers and probe concentrations and the standard curve was established. Further, the specificity, sensitivity and repeatability were also assessed. The established SgN and genomic RNA (gRNA) qPCR assays were both applied to detect 21 environmental samples and 351 clinical samples containing 48 recovered patients. In the specimens with both positive gRNA and positive SgN, 25 specimens were inoculated on cells. Results: The primers and probes of SgN had good specificity for SARS-CoV-2. The minimum detection limit of the preliminarily established qPCR detection method for SgN was 1.5×102 copies/ml, with a coefficient of variation less than 1%. The positive rate of gRNA in 372 samples was 97.04% (361/372). The positive rates of SgN in positive environmental samples and positive clinical samples were 36.84% (7/19) and 49.42% (169/342), respectively. The positive rate and copy number of SgN in Wild strain were lower than those of SARS-CoV-2 Delta strain. Among the 25 SgN positive samples, 12 samples within 5 days of sampling time were all isolated with virus; 13 samples sampled for more than 12 days had no cytopathic effect. Conclusion: A qPCR method for the detection of SARS-CoV-2 SgN has been successfully established. The sensitivity, specificity and repeatability of this method are good.

Genomic surveillance and sequencing of SARS-CoV-2 across South America / Vigilancia genómica y secuenciación del SARS-CoV-2 en América del Sur / Vigilância genômica e sequenciamento do SARS-CoV-2 na América do Sul

ABSTRACT After 2 years of the COVID-19 pandemic, the protocols used to control infection lack attention and analysis. We present data about deposits of complete genomic sequences of SARS-CoV-2 in the Global Initiative on Sharing All Influenza Data (GISAID) database made between January 2021 and May 31, 2022. We build the distribution profile of SARS-CoV-2 variants across South America, highlighting the contribution and influence of each variant over time. Monitoring the genomic sequences in GISAID illustrates negligence in the follow up of infected patients in South America and also the discrepancies between the number of complete genomes deposited throughout the pandemic by developed and developing countries. While Europe and North America account for more than 9 million of the genomes deposited in GISAID, Africa and South America deposited less than 400 000 genome sequences. Genomic surveillance is important for detecting early warning signs of new circulating viruses, assisting in the discovery of new variants and controlling pandemics.

RESUMEN Tras dos años de pandemia del COVID-19, los protocolos empleados para controlar la infección carecen de atención y análisis. En este artículo se presentan datos sobre depósitos de secuencias genómicas completas del SARS-CoV-2 en la base de datos de secuenciación GISAID, la Iniciativa mundial para intercambiar todos los datos sobre la gripe aviar, realizadas entre enero del 2021 y el 31 de mayo del 2022. Se creó el perfil de distribución de las variantes del SARS-CoV-2 en América del Sur, en el que se destacaron la contribución y la influencia de cada variante a lo largo del tiempo. El monitoreo de las secuencias genómicas en GISAID ilustra la negligencia en el seguimiento de los pacientes infectados en América del Sur, así como las discrepancias entre el número de genomas completos depositados a lo largo de la pandemia por parte de los países desarrollados y los países en desarrollo. Mientras que Europa y América del Norte han depositado más de 9 millones de genomas en GISAID, África y América del Sur han aportado menos de 400 000 secuencias genómicas. La vigilancia genómica es importante para detectar los primeros signos de alerta de virus nuevos en circulación, ayudar en el descubrimiento de nuevas variantes y controlar las pandemias.

RESUMO Após 2 anos da pandemia de covid-19, os protocolos usados para controlar a infecção necessitam maior atenção e análise. Apresentamos dados sobre as sequências genômicas completas do SARS-CoV-2 depositadas no banco de dados do a iniciativa internacional para o intercâmbio de dados sobre os vírus da influenza (GISAID) entre janeiro de 2021 e 31 de maio de 2022. Construímos o perfil de distribuição das variantes do SARS-CoV-2 na América do Sul, destacando a contribuição e a influência de cada variante ao longo do tempo. O monitoramento das sequências genômicas do GISAID ilustra a negligência no acompanhamento de pacientes infectados na América do Sul e as discrepâncias entre os países desenvolvidos e em desenvolvimento com relação ao número de genomas completos depositados ao longo da pandemia. Enquanto a Europa e a América do Norte respondem por mais de 9 milhões dos genomas depositados no GISAID, a África e a América do Sul depositaram menos de 400 000 sequências genômicas. A vigilância genômica é importante para detectar sinais de alerta precoces de novos vírus circulantes, auxiliar na descoberta de novas variantes e controlar pandemias.

Correlación entre el umbral de ciclo de la RPC en tiempo real y la clasificación clínica de la COVID-19 / Correlation between real-time PCR cycle threshold and clinical classification of COVID-19

INTRODUCCIÓN: El umbral de ciclo (en inglés cycle threshold-Ct) de la reacción de polimerasa en cadena en tiempo real con transcripción reversa (RT-qPCR) indica la concentración relativa de una secuencia de ARN; este valor se ha relacionado con la expresión de cuadros clínicos en infecciones virales. OBJETIVO: Determinar la correlación entre el valor Ct y la clasificación clínica de la COVID-19. MÉTODO: Se realizó un estudio transeccional correlacional; los valores Ct se obtuvieron mediante RT-qPCR dirigida al gen N del SARS-CoV-2 agrupándolos mediante un estimador robusto central y relacionándose con la clasificación clínica de la COVID-19. RESULTADOS: De los 718 casos incluidos en el estudio; 77,7% (558) fueron leves; 21,3% (153) moderados y 1% (7) graves. El valor Ct se agrupó en niveles: Ct bajo 18,83 - 30,10 y Ct alto > 30,10. Existió correlación significativa inversa débil (p = 0,002; rho de Spearman = -0,117) entre el valor Ct y la clasificación clínica. Las características: sexo, edad menor a 65 años, fiebre, escalofrío, diarrea, anosmia y sobrepeso-obesidad estuvieron asociadas al valor de Ct. CONCLUSIÓN: A menor valor Ct se espera una clasificación de mayor gravedad de la COVID-19; no obstante, debido a que la correlación es débil, su utilidad como predictor de gravedad es limitada.

BACKGROUND: The cycle threshold (Ct) of real-time reverse transcription PCR (RT-qPCR) indicates the relative concentration of an RNA sequence, this value has been related to clinical profile in viral infections. AIM: To determine the correlation between the Ct value and the clinical classification of COVID-19. METHOD: A correlational cross-sectional study was carried out, the Ct values were obtained by RT-qPCR directed to the N gene of SARS-CoV-2, grouping them by means of a central robust estimator and related to the clinical classification of COVID-19. RESULTS: Of the 718 cases included in the study; 77.7% (558) were mild; 21.3% (153) moderate and 1% (7) severe. The Ct value was grouped into levels: low Ct 18.83-30.10 and high Ct> 30.10. There was a weak inverse significant correlation (p = 0.002; Spearman's rho = -0.117) between the Ct value and the clinical classification. The characteristics: sex, age under 65 years, fever, chills, diarrhea, anosmia, and overweightobesity were associated with the Ct value. CONCLUSION: The lower the Ct value, a classification of greater severity of COVID-19 is expected, however, because the correlation is weak, its usefulness as a severity predictor is limited.

SARS -CoV -2 Omicron BA.5 infection recurrence after Paxlovid treatment: The first case report in Hunan Province / 中南大学学报(医学版)

We report a case of coronavirus disease 2019 (COVID-19) patient who was cured by oral administration of nirmatrelvir/ritonavir (Paxlovid). The patient was treated with Paxlovid after being first infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.5 variant. On the 11th day after SARS-CoV-2 nucleic acid test turned negative, SARS-CoV-2 nucleic acid test was positive again, and the threshold of nucleic acid cycle number was equivalent to that of the first infection. The results of two whole gene sequencing showed that it was the same virus strain infection, suggesting that the case was re-positive. Without specific treatment, SARS-CoV-2 nucleic acid detection in nasopharyngeal swab turned negative. It is not uncommon for Paxlovid to recover after treating COVID-19, and most of the patients can recover without specific treatment. However, it is necessary to further study the mechanism that may lead to the recovery of SARS-CoV-2.

PathogenTrack and Yeskit: tools for identifying intracellular pathogens from single-cell RNA-sequencing datasets as illustrated by application to COVID-19 / 医学前沿

Pathogenic microbes can induce cellular dysfunction, immune response, and cause infectious disease and other diseases including cancers. However, the cellular distributions of pathogens and their impact on host cells remain rarely explored due to the limited methods. Taking advantage of single-cell RNA-sequencing (scRNA-seq) analysis, we can assess the transcriptomic features at the single-cell level. Still, the tools used to interpret pathogens (such as viruses, bacteria, and fungi) at the single-cell level remain to be explored. Here, we introduced PathogenTrack, a python-based computational pipeline that uses unmapped scRNA-seq data to identify intracellular pathogens at the single-cell level. In addition, we established an R package named Yeskit to import, integrate, analyze, and interpret pathogen abundance and transcriptomic features in host cells. Robustness of these tools has been tested on various real and simulated scRNA-seq datasets. PathogenTrack is competitive to the state-of-the-art tools such as Viral-Track, and the first tools for identifying bacteria at the single-cell level. Using the raw data of bronchoalveolar lavage fluid samples (BALF) from COVID-19 patients in the SRA database, we found the SARS-CoV-2 virus exists in multiple cell types including epithelial cells and macrophages. SARS-CoV-2-positive neutrophils showed increased expression of genes related to type I interferon pathway and antigen presenting module. Additionally, we observed the Haemophilus parahaemolyticus in some macrophage and epithelial cells, indicating a co-infection of the bacterium in some severe cases of COVID-19. The PathogenTrack pipeline and the Yeskit package are publicly available at GitHub.

Assessment of SARS-CoV-2 RNA shedding in semen of 36 males with symptomatic, asymptomatic, and convalescent infection during the first and second wave of COVID-19 pandemic in Italy / 亚洲男科学杂志(英文版)

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) receptor, angiotensin-converting enzyme 2 (ACE2), has been identified in the human testis, but the risk of transmission of SARS-CoV-2 through sexual intercourse still needs to be defined. The goal of our study was to determine if SARS-CoV-2 is detectable in the semen of patients suffering or recovering from coronavirus disease-19 (COVID-19), still testing positive at nasopharyngeal swabs but showing mild or no symptoms at the time of sampling. Detection of SARS-CoV-2 RNA in semen was performed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and nested PCR targeting open reading frame (ORF) 1ab. Medical history of the enrolled patients was taken, including COVID-19-correlated symptoms, both at the time of diagnosis and at the time of interview. Results of real-time RT-PCR and nested PCR in semen showed no evidence of SARS-CoV-2 RNA in the 36 patients suffering or recovering from COVID-19 but still positive in a nasopharyngeal swab, from over 116 patients enrolled in the study. SARS-CoV-2 detection and persistence in semen would have an impact on both clinical practice and public health strategies, but our results would suggest that SARS-CoV-2 is not present in the semen of men recovering from COVID-19.

Isothermal amplification technology based on microfluidic chip / 生物工程学报

Polymerase chain reaction (PCR) is the gold standard for nucleic acid amplification in molecular diagnostics. The PCR includes multiple reaction stages (denaturation, annealing, and extension), and a complicated thermalcycler is required to repetitively provide different temperatures for different stages for 30-40 cycles within at least 1-2 hours. Due to the complicated devices and the long amplification time, it is difficult to adopt conventional PCR in point-of-care testing (POCT). Comparing to conventional PCR, isothermal amplification is able to provide a much faster and more convenient nucleic acid detection because of highly efficient amplification at a constant reaction temperature provided by a simple heating device. When isothermal amplification is combined with microfluidics, a more competent platform for POCT can be established. For example, various diagnosis devices based on isothermal amplification have been used to rapidly and conveniently detect SARS-CoV-2 viruses. This review summarized the recent development and applications of the microfluidics-based isothermal amplification. First, different typical isothermal amplification methods and related detection methods have been introduced. Subsequently, different types of microfluidic systems with isothermal amplification were discussed based on their characteristics, for example, functionality, system structure, flow control, and operation principles. Furthermore, detection of pathogens (e.g. SARS-CoV-2 viruses) based on isothermal amplification was introduced. Finally, the combination of isothermal amplification with other new technologies, e.g. CRISPR, has been introduced as well.

Genomic Epidemiology of Imported Cases of COVID-19 in Guangdong Province, China, October 2020 - May 2021 / 生物医学与环境科学（英文）

Objective@#The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been engendering enormous hazards to the world. We obtained the complete genome sequences of SARS-CoV-2 from imported cases admitted to the Guangzhou Eighth People's Hospital, which was appointed by the Guangdong provincial government to treat coronavirus disease 2019 (COVID-19). The SARS-CoV-2 diversity was analyzed, and the mutation characteristics, time, and regional trend of variant emergence were evaluated.@*Methods@#In total, 177 throat swab samples were obtained from COVID-19 patients (from October 2020 to May 2021). High-throughput sequencing technology was used to detect the viral sequences of patients infected with SARS-CoV-2. Phylogenetic and molecular evolutionary analyses were used to evaluate the mutation characteristics and the time and regional trends of variants.@*Results@#We observed that the imported cases mainly occurred after January 2021, peaking in May 2021, with the highest proportion observed from cases originating from the United States. The main lineages were found in Europe, Africa, and North America, and B.1.1.7 and B.1.351 were the two major sublineages. Sublineage B.1.618 was the Asian lineage (Indian) found in this study, and B.1.1.228 was not included in the lineage list of the Pangolin web. A reasonably high homology was observed among all samples. The total frequency of mutations showed that the open reading frame 1a (ORF1a) protein had the highest mutation density at the nucleotide level, and the D614G mutation in the spike protein was the commonest at the amino acid level. Most importantly, we identified some amino acid mutations in positions S, ORF7b, and ORF9b, and they have neither been reported on the Global Initiative of Sharing All Influenza Data nor published in PubMed among all missense mutations.@*Conclusion@#These results suggested the diversity of lineages and sublineages and the high homology at the amino acid level among imported cases infected with SARS-CoV-2 in Guangdong Province, China.

SARS-CoV-2 with transcription regulatory sequence motif mutation poses a greater threat / 南方医科大学学报

OBJECTIVE@#To analyze the mutations in transcription regulatory sequences (TRSs) of coronaviruss (CoV) to provide the basis for exploring the patterns of SARS-CoV-2 transmission and outbreak.@*METHODS@#A combined evolutionary and molecular functional analysis of all sets of publicly available genomic data of viruses was performed.@*RESULTS@#A leader transcription regulatory sequence (TRS-L) usually comprises the first 60-70 nts of the 5' UTR in a CoV genome, and the body transcription regulatory sequences (TRS-Bs) are located immediately upstream of the genes other than ORF1a and 1b. In each CoV genome, the TRS-L and TRS-Bs share a specific consensus sequence, namely the TRS motif. Any changes of nucleotide residues in the TRS motifs are defined as TRS motif mutations. Mutations in the TRS-L or multiple TRS-Bs result in superattenuated variants. The spread of super-attenuated variants may cause an increase in asymptomatic or mild infections, prolonged incubation periods and a decreased detection rate of the viruses, thus posing new challenges to SARS-CoV-2 prevention and control. The super-attenuated variants also increase their possibility of long-term coexistence with humans. The Delta variant is significantly different from all the previous variants and may lead to a large-scale transmission. The Delta variant (B.1.617.2) with TRS motif mutation has already appeared and shown signs of spreading in Singapore, which, and even the Southeast Asia, may become the new epicenter of the next wave of SARS-CoV-2 outbreak.@*CONCLUSION@#TRS motif mutation will occur in all variants of SARS-CoV-2 and may result in super-attenuated variants. Only super-attenuated variants with TRS motif mutations will eventually lose the abilities of cross-species transmission and causing outbreaks.

Vitamina d: su implicancia en la infección por SARS-CoV-2 y su rol en el desarrollo y prevención de la enfermedad / Vitamin d: the implications in SARS-CoV-2 infection and its role in the development and prevention of the disease

Introducción: La pandemia del SARS-CoV-2 ha sido un desafío para la medicina en estos últimos años por su alta tasa de contagios y muertes asociadas. Progresivamente los investigadores han ido dilucidando vías de transmisión y manifestaciones clínicas más frecuentes, que han facilitado la detección el virus. Con el objetivo de optimizar la prevención y tratamiento en pacientes infectados, investigadores de todo el mundo han evaluado la importancia de la respuesta inmune frente al virus, destacando la acción de algunos inmunomoduladores, como por ejemplo, la vitamina D. Desarrollo: Tras invadir el organismo, el SARS-CoV-2 se une a receptores de las células epiteliales del tracto respiratorio, específicamente en el neumocito tipo II, disminuyendo la producción de surfactante y provocando una producción desregulada de citocinas proinflamatorias, principal responsable de los casos más severos. Se ha demostrado que la Vitamina D puede modular la respuesta inmune tras unirse a su receptor VDR, disminuyendo la liberación de citocinas proinflamatorias. Algunos estudios han determinado que el uso de suplementos de vitamina D en dosis altas pudieran producir efectos protectores frente a infecciones respiratorias agudas. Conclusión: Finalmente, pese a los estudios realizados que relacionan el déficit de vitamina D con casos más severos de COVID-19, aún se requiere más evidencia para recomendar suplementación.

Introduction: The SARS-CoV-2 pandemic has been a challenge for medicine in recent years, due to its high contagion rate and associated deaths. Researchers have progressively elucidated transmission methods and most frequent clinical manifestations, that helps the virus detection. With the objective of optimizing prevention and treatment of infected patients, researchers all over the world have evaluated the importance of the immune system response against the virus, highlighting some immunomodulators, such as vitamin D. Body: After SARS-CoV-2 invades the organism, it binds to the receptor located on the respiratory tract epithelial cells, specifically type 2 pneumocyte, decreasing surfactant production and increasing the production of pro inflammatory cytokines, being the main reason for severe cases. Vitamin D has been shown to modulate the immune response after binding to its receptor, decreasing the release of proinflammatory cytokines. Some studies have shown that vitamin D supplementation in high doses may produce protective effects against acute respiratory infections. Conclusion: Finally, even the studies that correlate vitamin D deficiency and COVID-19 severe cases, we still need more evidence to recommend Vitamin D supplementation.

Variante Ómicron SARS-CoV-2: una nueva variante de preocupación / Ómicron SARS-CoV-2 variant: anew variant of concern

Ha surgido una nueva variante de preocupación de SARS-CoV-2, cuyos efectos en la evolución de la pandemia parecen inciertos. Sin embargo, ha comenzado a surgir evidencia con respecto al comportamiento viral en cuanto a su transmisibilidad, unión a receptor de la célula hospedadora y escape del sistema inmune. Presentamos una revisión actualizada de los datos existentes en la literatura respecto a los aspectos microbiológicos y epidemiológicos que pueden ayudarnos a comprender las futuras investigaciones en esta variante.(AU)

A new variant of concern for SARS-CoV-2 has emerged, the effects of which on the evolution of the pandemic appear uncertain. However, evidence has begun to emerge regarding viral behavior in terms of its transmissibility, receptor binding on the host cell, and escape from the immune system. We present an updated review of the existing data in the literature regarding the microbiological and epidemiological aspects that can help us understand future research on this variant.(AU)

Variantes genéticas del SARS-CoV-2 y sus implicaciones clínicas / Genetic variants of SARS-CoV-2 and its clinical implications

El SARS-CoV-2, agente causal de la actual pandemia de la COVID-19, va sufriendo mutaciones como consecuencia de su ciclo evolutivo, lo que ha originado diferentes variantes genéticas, que han sido agrupadas en dos categorías: preocupante (alfa o británica, beta o sudafricana, gamma o brasileña y delta o india) y de interés (lamdba, mu, épsilon, eta, iota, kappa, zeta, theta); estas conllevan implicaciones clínicas en la transmisibilidad, virulencia y resistencia del SARS-CoV-2 a la inmunidad natural y adquirida, lo que representa un serio desafío para los servicios de salud en todo el mundo. En este artículo se describen dichas variantes genéticas, con énfasis en su probable impacto clínico, y además se plantea la posibilidad de que aparezcan otras, como fenómeno natural en la evolución de los virus.

The SARS-CoV-2, causal agent of the COVID-19 current pandemic, is suffering mutations as a consequence of its evolutive cycle, what has originated different genetic variants that have been grouped in two categories: worrying (alpha or British, beta or South African, gamma or Brazilian and delta or Indian) and of interest (lamdba, mu, epsilon, eta, iota, kappa, zed, theta); these categories bear clinical implications in the transmissibility, virulence and resistance from SARS-CoV-2 to the natural and acquired immunity, what represents a serious challenge in health services worldwide. These genetic variants are described in this work, with emphasis in its probable clinical impact, and the possibility that other variants could appear is also explained, as natural phenomenon in the evolution of viruses.

Venous sinus thrombosis during COVID-19 infection in pregnancy: a case report

ABSTRACT BACKGROUND: Although it is known that the new coronavirus disease (COVID-19), which was first seen in Wuhan, China, in December 2019 and has affected the whole world, mainly targets the respiratory tract, cases of this disease with a wide clinical spectrum are emerging as information is shared. CASE REPORT: We present the case of a pregnant woman who was diagnosed with venous sinus thrombosis after she developed headache and hemiparesis. Polymerase chain reaction (PCR) positivity lasted for two weeks after COVID-19 had been diagnosed. CONCLUSIONS: In patients with suspected COVID-19, especially in the presence of causes of hypercoagu- lability and presence of atypical features, venous sinus thrombosis needs to be kept in mind in making the differential diagnosis.

Evaluación de la efectividad de las vacunas contra la COVID-19: orientación provisional / Evaluation of COVID-19 vaccine effectiveness

En este documento se presenta orientación provisional sobre las mejores prácticas para evaluar la efectividad de las vacunas contra la COVID-19 usando el diseño de estudio observacional. Se examinan las consideraciones esenciales del diseño, el análisis y la interpretación de las evaluaciones de la efectividad de las vacunas contra la COVID-19, dado que se pueden obtener resultados sesgados aun en entornos en los que la exhaustividad y la calidad de los datos son altas. Esta orientación se dirige principalmente a las evaluaciones realizadas en los países de ingresos bajos o medianos, pero la mayoría de los conceptos también son aplicables en entornos de ingresos altos.

Since its emergence in December 2019, SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), has taken a tremendous toll globally; by 28 February 2021, there have been over 110 million cases and 2.5 million deaths worldwide from COVID-19 (1). Although most COVID-19 deaths occur among older adults and persons with chronic comorbid medical conditions, deaths have occurred in persons of all ages. Moreover, the pandemic has caused widespread morbidity and necessitated control measures that have devastated economies worldwide. In response to the pandemic, the global efforts to develop multiple vaccines to protect against COVID-19 disease have been unrivalled in the history of public health. By the end of 2020, three COVID-19 vaccines have received Emergency Use Approval/Listing (EUA/EUL) by maturity level 4 regulatory authorities, based on reaching predefined criteria for safety and efficacy, and at least several dozen more are in clinical trials.

Molecular biology of coronaviruses: an overview of virus-host interactions and pathogenesis / Biología molecular de los coronavirus: una visión panorámica de las interacciones virus-hospedero y de la patogénesis

Abstract Coronaviruses (CoV) are enveloped, plus-strand RNA viruses that have the largest known RNA genomes and infect birds and mammals, causing various diseases. Human coronaviruses (HCoVs) were first identified in the mid-1960s and have been known to cause enteric or respiratory infections. In the last two decades, three HCoVs have emerged, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which initiated the ongoing pandemic. SARS-CoV-2 causes a respiratory illness that presents as a mild upper respiratory disease but may result in acute respiratory distress syndrome, multi-organ failure and can be fatal, especially when underlying comorbidities are present. Children account for a low percentage of coronavirus disease 2019 (COVID-19) cases, with seemingly less severe disease. Most pediatric patients present mild or moderate symptoms or are asymptomatic. However, some cases may be severe. Therefore, SARS-CoV-2 infection and COVID-19 in pediatric patients must be studied in detail. This review describes general features of the molecular biology of CoVs and virus-host interactions that may be implicated in the pathogenesis of SARS-CoV-2.

Resumen Los coronavirus son virus envueltos de ARN de polaridad positiva, con los genomas más grandes que se conocen. Infectan aves y mamíferos, y causan una amplia variedad de enfermedades. Los coronavirus humanos se identificaron a mediados de la década de 1960 y se sabe que causan infecciones entéricas y respiratorias. En las últimas dos décadas han emergido tres coronavirus humanos pandémicos, incluido el coronavirus 2 del síndrome agudo respiratorio grave (SARS-CoV-2) que ha causado la pandemia actual. El SARS-CoV-2 produce enfermedad respiratoria que se presenta con padecimientos moderados de las vías respiratorias altas, pero puede resultar en síndrome respiratorio agudo, falla multiorgánica y muerte, en especial en casos con morbilidad subyacente. Los casos de COVID-19 en niños representan un porcentaje bajo y con síntomas menos graves de la enfermedad. La mayoría de los pacientes pediátricos son asintomáticos o presentan enfermedad leve o moderada; sin embargo, también en niños la enfermedad puede ser grave, por lo que la infección con SARS-CoV-2 y la COVID-19 en pacientes pediátricos deben estudiarse con detalle. En esta revisión se describen las características generales de la biología molecular de los coronavirus y de las interacciones virus-hospedero que se conocen para los coronavirus humanos identificados previamente, y que podrían estar implicados en la patogénesis del SARS-CoV-2.