Risk factors for acute kidney injury in patients hospitalized with COVID-19 / Fatores de risco para lesão renal aguda em pacientes hospitalizados com COVID-19

Abstract Introduction: Acute kidney injury (AKI) occurs frequently in COVID-19 patients and is associated with greater morbidity and mortality. Knowing the risks of AKI allows for identification, prevention, and timely treatment. This study aimed to identify the risk factors associated with AKI in hospitalized patients. Methods: A descriptive, retrospective, cross-sectional, and analytical component study of adult patients hospitalized with COVID-19 from March 1 to December 31, 2020 was carried out. AKI was defined by the creatinine criteria of the KDIGO-AKI guidelines. Information, regarding risk factors, was obtained from electronic medical records. Results: Out of the 934 patients, 42.93% developed AKI, 60.59% KDIGO-1, and 9.9% required renal replacement therapy. Patients with AKI had longer hospital stay, higher mortality, and required more intensive care unit (ICU) admission, mechanical ventilation, and vasopressor support. Multivariate analysis showed that age (OR 1.03; 95% CI 1.02-1.04), male sex (OR 2.13; 95% CI 1.49-3.04), diabetes mellitus (DM) (OR 1.55; 95% CI 1.04-2.32), chronic kidney disease (CKD) (OR 2.07; 95% CI 1.06-4.04), C-reactive protein (CRP) (OR 1.02; 95% CI 1.00-1.03), ICU admission (OR 1.81; 95% CI 1.04-3.16), and vasopressor support (OR 7.46; 95% CI 3.34-16.64) were risk factors for AKI, and that bicarbonate (OR 0.89; 95% CI 0.84-0.94) and partial pressure arterial oxygen/inspired oxygen fraction index (OR 0.99; 95% CI 0.98-0.99) could be protective factors. Conclusions: A high frequency of AKI was documented in COVID-19 patients, with several predictors: age, male sex, DM, CKD, CRP, ICU admission, and vasopressor support. AKI occurred more frequently in patients with higher disease severity and was associated with higher mortality and worse outcomes.

RESUMO Introdução: Lesão renal aguda (LRA) ocorre frequentemente em pacientes com COVID-19 e associa-se a maior morbidade e mortalidade. Conhecer riscos da LRA permite a identificação, prevenção e tratamento oportuno. Este estudo teve como objetivo identificar fatores de risco associados à LRA em pacientes hospitalizados. Métodos: Realizou-se estudo descritivo, retrospectivo, transversal e de componente analítico de pacientes adultos hospitalizados com COVID-19 de 1º de março a 31 de dezembro, 2020. Definiu-se a LRA pelos critérios de creatinina das diretrizes KDIGO-LRA. Informações sobre fatores de risco foram obtidas de prontuários eletrônicos. Resultados: Dos 934 pacientes, 42,93% desenvolveram LRA, 60,59% KDIGO-1 e 9,9% necessitaram de terapia renal substitutiva. Pacientes com LRA apresentaram maior tempo de internação, maior mortalidade e necessitaram de mais internações em UTIs, ventilação mecânica e suporte vasopressor. A análise multivariada mostrou que idade (OR 1,03; IC 95% 1,02-1,04), sexo masculino (OR 2,13; IC 95% 1,49-3,04), diabetes mellitus (DM) (OR 1,55; IC 95% 1,04-2,32), doença renal crônica (DRC) (OR 2,07; IC 95% 1,06-4,04), proteína C reativa (PCR) (OR 1,02; IC 95% 1,00-1,03), admissão em UTI (OR 1,81; IC 95% 1,04-3,16) e suporte vasopressor (OR 7,46; IC 95% 3,34-16,64) foram fatores de risco para LRA, e que bicarbonato (OR 0,89; IC 95% 0,84-0,94) e índice de pressão parcial de oxigênio arterial/fração inspirada de oxigênio (OR 0,99; IC 95% 0,98-0,99) poderiam ser fatores de proteção. Conclusões: Documentou-se alta frequência de LRA em pacientes com COVID-19, com diversos preditores: idade, sexo masculino, DM, DRC, PCR, admissão em UTI e suporte vasopressor. LRA ocorreu mais frequentemente em pacientes com maior gravidade da doença e associou-se a maior mortalidade e piores desfechos.

Cobertura de vacunación contra COVID-19 e influenza en personal de salud y administrativo en Paraguay

Introducción: A nivel mundial, la cobertura de vacunación contra el COVID-19, así como contra la influenza es baja tanto en la población general como en los profesionales de la salud a pesar de que la vacuna es gratuita y obligatoria en el personal sanitario. Objetivo: Describir la cobertura de vacunación contra el COVID -19, y la influenza en personal de salud y administrativo de un hospital de referencia del Ministerio de Salud Pública y Bienestar Social en el periodo 2021-2022. Metodología: Estudio observacional descriptivo de corte trasverso. Se hizo la revisión de los registros del personal sanitario y administrativo del centro vacunatorio del Hospital Nacional de Itauguá de la campaña vacunal contra el COVID-19 y de anti-influenza en el periodo 2021- 2022. Resultados: De los 3.586 funcionarios, 999 (27,9 %) eran médicos, 1494 (41,7 %) personal de enfermería, 366 (10,2 %) otra categoría de personal sanitario, y 727 (20,3 %) personal administrativo. En forma global, el 86,5 % de los funcionarios recibió por lo menos las dos dosis que constituyen el esquema primario y el 73 % la dosis de refuerzo. El 2,1 % del personal no recibió ninguna dosis de vacuna anti covid-19, la cifra fue mayor en el personal administrativo (4,8 %). La cobertura de vacunación contra la influenza fue de 20 % en el 2021 y 25 % en el 2022. Discusión: Si bien cobertura de vacunación anti-COVID-19 fue comparable a otros países, la vacunación contra la influenza fue muy baja. Es urgente implementar estrategias dirigidas a aumentar la percepción de riesgo y aceptabilidad de las vacunas obligatorias para el personal sanitario.

Introduction: Worldwide, vaccination coverage against COVID-19, as well as against influenza, is low both in the general population and in health professionals, despite the fact that the vaccine is free and mandatory for health personnel. Objective: To describe the COVID -19 and influenza vaccination coverage in health and administrative personnel of a reference hospital of the Ministry of Public Health and Social Welfare in the period 2021-2022. Methods: Cross-sectional descriptive observational study. Charts of the health and administrative personnel of the vaccination center of the Itauguá National Hospital of the COVID-19 and influenza vaccination campaign in the period 2021-2022 were reviewed. Results: Of the 3,586 personnel, 999 (27.9%) were medical personnel, 1,494 (41.7%) nursing personnel, 366 (10.2%) other category of health personnel, and 727 (20.3%) administrative personnel. Overall, 86.5% of the employees received at least the two doses that constitute the primary schedule and 73% the booster dose; 2.1% of the staff did not receive any dose of the anti COVID-19 vaccine, which was higher in the administrative staff (4.8%). Influenza vaccination coverage was 20% in 2021 and 25% in 2022. Discussion: Even though the vaccination coverage of anti-COVID-19 was comparable to other countries, vaccination anti-influenza was very low. It is urgent to implement strategies aimed at increasing the perception of risk and acceptability of mandatory vaccines for health personnel.

Manifestaciones orales del COVID-19 en Paraguay: resultados de una encuesta en línea

Introducción: Estudios previos han reportado que pacientes infectados con el virus del COVID-19, podrían manifestar sintomatologías a nivel de la cavidad oral. Objetivo: Evaluar la frecuencia de manifestaciones orales asociadas a COVID-19 en un segmento de la población paraguaya y determinar cuáles son las más prevalentes. Metodología: Estudio descriptivo de corte transversal. Fue realizada una encuesta electrónica de enero a marzo del 2022. Los datos fueron presentados como frecuencias y porcentajes y analizados mediante la prueba de chi-cuadrado. El análisis estadístico se realizó con el software R versión 4.0.3. Resultados: La muestra estuvo compuesta por 478 personas. El 79,50 % correspondió al sexo femenino y el 45,19 % tenía entre 25 y 34 años. El 65,48 % informó haber experimentado al menos 1 síntoma o signo oral durante el curso de COVID-19. La pérdida de la sensación de sabores amargos, seguida de la alteración del sabor de los alimentos y la pérdida de la percepción dulce, fueron los síntomas más comunes. Se encontró una proporción significativamente mayor de manifestaciones orales en el rango de 18-24 años (χ²; p= 0,003). Entre las personas que desarrollaron COVID-19 de forma moderada a severa hubo mayor número de manifestaciones de síntomas orales (χ²; p= 0,044). Discusión: Se identificó una alta frecuencia de manifestaciones orales en pacientes con casos de moderados a severos de COVID-19, destacándose los trastornos del gusto como los más predominantes. Los individuos más jóvenes fueron los más afectados.

Introduction: Previous studies have reported that patients infected with the COVID-19 virus could manifest symptoms in the oral cavity. Objective: To evaluate the frequency of oral manifestations associated with COVID-19 in a segment of the Paraguayan population and determine the most prevalent ones. Methods: Descriptive cross-sectional study. An electronic survey was conducted from January to March 2022. The data were presented as frequencies and percentages and analyzed using the chi-square test. Statistical analysis was performed with R software version 4.0.3. Results: The sample consisted of 478 individuals. 79.50% were female, and 45.19% were between 25 and 34 years old. 65.48% reported having experienced at least 1 oral symptom or sign during the course of COVID-19. The loss of the sensation of bitter tastes, followed by the alteration of the taste of foods and the loss of sweetness perception, were the most common symptoms. A significantly higher proportion of oral manifestations was found in the 18-24 age range (χ²; p= 0.003). Among people who developed COVID-19 in a moderate to severe form, a greater number of oral symptom manifestations were observed (χ²; p= 0.044). Discussion: A high frequency of oral manifestations was identified in patients with moderate to severe cases of COVID-19, with taste disorders standing out as the most predominant. Younger individuals were the most affected.

Proporção de casos nosocomiais de COVID-19 no Brasil: análise de seus fatores associados em 1.631.47 registros de 2020 a 2022 / Proporción de casos nosocomiales de COVID-19 en Brasil: análisis de sus factores asociados en 1.631.47 registros de 2020 a 2022 / Proportionof nosocomial cases of COVID-19 in Brazil: analysisof1.631.47 case records from 2020 to 2022

Introdução: Infecções nosocomiais, adquiridas após a internação hospitalar, são o evento adverso mais comum que ameaça a saúde dos pacientes hospitalizados, sendo a pneumonia, incluindo a causada pelo SARS-Cov-2, responsável por mais de 80% das infecções nosocomiais. A pandemia declarada pela OMS em março de 2020 reflete o rápido aumento de casos, impulsionado pela disseminação do vírus através de gotículas e aerossóis. A transmissão nosocomial do SARS-Cov-2 foi observada desde o início do surto em Wuhan, representando um desafio adicional na qualidade de vida dos pacientes. Estudos internacionais em hospitais reportam incidências de infecção nosocomial por COVID-19 entre 11% e 44%.Objetivo: Identificar a proporção de infecção nosocomial por SARS-COV-2 no Brasil entre março de 2020 até dezembro de 2022.Metodologia:Trata-se de um estudo analítico, retrospectivo, de corte transversal, sobre a proporção de infecção nosocomial por Sars-Cov-2 no Brasil, através de dados secundários oriundos do Sistema de Informação da Vigilância Epidemiológica da Gripe. No presente estudo a variável dependente analisada foi a proporção de infecção nosocomial por Sars-cov-2. Como variáveis independentes exploratórias foram utilizadas: faixa etária, sexo, comorbidades e macrorregião de residência. Resultados: O estudo identificou uma proporção de casos nosocomiais de 2,58%, sendo maior no terceiro ano da pandemia 2022 (5,5%) na região Norte (7,57%), entre os indivíduos de 18-59 anos de idade (6,93%)Conclusões: Este estudo sobre casos nosocomiais de COVID-19 no Brasil revela uma proporção de 2,58% entre 2020 e 2022, com associações identificadas em relação à região, idade e comorbidades. Diferenças em relação a estudos internacionais sugerem questões metodológicas específicas. Essa pesquisa é de importância crítica, visto ser de abrangência nacional com grande amplitude, e estabelece uma base sólida para futuros estudos epidemiológicos (AU).

Introduction: Nosocomial infections, acquired after hospital admission, are the most common adverse events threatening patient health, with pneumonia, including that caused by SARS-CoV-2, responsible for over 80% of nosocomial infections. The pandemic declared by the WHO in March 2020 reflects the rapid rise in cases driven by the virus's spread through droplets and aerosols. Nosocomial transmission of SARS-CoV-2 has been observed since the outbreak's onset in Wuhan, posing an additional challenge to patient quality of life. International hospital studies report nosocomial COVID-19 infection rates between 11% and 44%. Objective: Identifying the proportion of nosocomial SARS-CoV-2 infection in Brazil between March 2020 and December 2022.Methodology:This is an analytical, retrospective, cross-sectional study on the proportion of nosocomial SARS-CoV-2 infection in Brazil, using secondary data from the Influenza Epidemiological Surveillance Information System. In this study, the analyzed dependent variable was the proportionof nosocomial SARS-CoV-2 infection. The exploratory independent variables included: age group, gender, comorbidities, and macro-region of residence.Results:The study identified a proportion of nosocomial cases of 2.58%, with a higher proportion in the third year of the pandemic, 2022 (5.5%) in the North region (7.57%), among individuals aged 18-59 years (6.93%). Conclusions: This study on nosocomial cases of COVID-19 in Brazil reveals a proportion of 2.58% between 2020 and 2022, with associations identified regarding region, age, and comorbidities. Differences compared to international studies suggest specific methodological issues. This research is of critical importance, given its national scope and broad coverage, and establishes a solid foundation for future epidemiological studies (AU).

Introducción: Las infecciones nosocomiales, adquiridas tras la hospitalización, son el evento adverso más común que amenaza la salud de los pacientes hospitalizados, siendo la neumonía, incluida la causada por el SARS-Cov-2, la responsable de más del 80% de las infecciones. La pandemia declarada por la OMS en marzo de 2020 refleja el rápido aumento de casos, impulsado por la propagación del virus a través de gotitas y aerosoles. La transmisión nosocomial del SRAS-Cov-2 se ha observado desde el inicio del brote en Wuhan, lo que supone un reto adicional para la calidad de vida de los pacientes. Estudios internacionales realizados en hospitales informan de incidencias de infecciones nosocomiales por COVID-19 de entre el 11% y el 44%. Objetivo: Identificar la proporción de infección nosocomial por SARS-CoV-2 en Brasil entre marzo de 2020 y diciembre de 2022. Metodología: Se trata de un estudio analítico, retrospectivo y transversal sobre la proporción de infección nosocomial por SARS-CoV -2 en Brasil, utilizando datos secundarios del Sistema de Información de Vigilancia Epidemiológica de Influenza. La variable dependiente analizada fue la proporción de infección nosocomial por SARS-CoV-2. Como variables independientes exploratorias se utilizaron: grupo de edad, sexo, comorbilidades y macrorregión de residencia. Resultados:El estudio identificó una proporción de casos nosocomiales del 2,58%, siendo mayor en el tercer año de la pandemia de 2022 (5,5%) en la región Norte (7,57%), entre individuos de 18 a 59 años (6,93%). Conclusiones:Este estudio de casos de COVID-19 hospitalizados en Brasil revela una proporción de 2,58% entre 2020 y 2022, con asociaciones identificadas en relación a la región, edad y comorbilidades. Las disparidades en relación a estudios internacionales sugieren la presencia de cuestiones metodológicas específicas. Esta investigación es de extrema importancia para orientar estrategias preventivas y mejorar el control de las infecciones hospitalarias (AU).

Costo y porcentaje de gasto en salud por COVID-19 en primer nivel de atención / Cost and percentage of health spending by COVID-19 at the first level of care

Antecedentes. Ante la pandemia de COVID-19 el sistema de salud reasignó recursos económicos para la atención. Objetivo. Determinar el costo de la atención y el porcentaje del gasto en salud por COVID-19 en una unidad de medicina familiar de primer nivel de atención. Metodología. Estudio de costo y porcentaje de gasto en COVID-19 en una unidad de primer nivel de atención. Se identificaron los servicios generales y finales, para construir el costo fijo se utilizó la técnica de tiempos y movimientos, se identificaron el total de partidas presupuestales ejercidas en la unidad médica para cada uno de los servicios, para desagregar el gasto de los servicios generales a los finales se construyeron ponderadores. El costo variable se realizó con la técnica consenso de expertos y microcosteo. El costo promedio se relacionó con la productividad por servicio y con el total de pacientes atendidos por COVID-19, el resultado se relacionó con el presupuesto ejercido de la unidad. Resultados. El costo anual de la atención de COVID-19 en módulo respiratorio fue 158.597,25 dólares americanos, en medicina familiar fue 192.549,36 dólares americanos, el costo total ejercido en el año 2021 para atención de SARS COV 2 en una unidad de primera atención fue 351.146,61 dólares americanos. Esta cantidad representa el 9,6 % del gasto en salud. Conclusión. El costo en atención de COVID-19 y el porcentaje del gasto en salud en primer nivel de atención es elevado (AU)

Background. In the COVID-19 pandemic, the health system reallocated financial resources for care. Objetive. To determine the cost of care and the percentage of health spending due to COVID-19 in a first level care family medicine unit. Metodology. Study of the cost and percentage of spending on COVID-19 in a first-level care unit. The general and final services were identified, to construct the fixed cost, the technique of times and movements was used, the total budget items exercised in the medical unit for each of the services were identified, to disaggregate the expense of general services to the endings were constructed weights. Variable costing was performed using the expert consensus technique and microcosting. The average cost was related to productivity per service and to the total number of patients treated for COVID-19, the result was related to the budget used by the unit. Results. The annual cost of COVID-19 care in the respiratory module was 158.597,25 US dollars, in family medicine it was 192.549,36 US dollars, the total cost incurred in 2021 for SARS COV 2 care in a unit of first attention was 351.146,61 US dollars. This amount represents 9,6% of health spending. Conclusion. The cost of COVID-19 care and the percentage of health spending at the first level of care is high (AU)

Lineamientos técnicos para la vacunación contra el SARS-CoV-2 / Technical guidelines for vaccination against SARS-CoV-2

El objetivo general de los presentes lineamientos es establecer las disposiciones técnicas para la realización de las acciones para continuar la vacunación de la población contra el SARS-CoV-2. La priorización vacunal es una estrategia para proteger poblaciones de riesgo, evitando caer en el error de no vacunar a otros grupos cuyo riesgo puede ser bajo, pero que pueden generar enfermedad severa, complicaciones, hospitalizaciones y muerte asociada a COVID-19. En razón de lo anterior se actualizan los esquemas de vacunación frente a COVID-19, a partir de priorización de grupos poblacionales

The general objective of these guidelines is to establish technical provisions for the implementation of actions to continue the vaccination of the population against SARS-CoV-2. Vaccine prioritization is a strategy to protect at-risk populations, avoiding the error of not vaccinating other groups whose risk may be low, but which can lead to severe disease, complications, hospitalizations and death associated with VOCID-19. In view of the foregoing, vaccination schemes against VOCID-19 are updated, based on the prioritization of population groups

Telemedicine for diagnosis or treatment during Covid-19: systematic review

OBJECTIVE: To describe the use of telemedicine by health professionals for diagnosis or treatment of patients during the Covid-19 pandemic. METHOD: This is a systematic literature review of observational studies. Five databases were used. The assessment of the studies methodological quality occurred individually among the revisors and the Joanna Briggs Institute (JBI) tool was used. RESULTS: The reviewers selected 22 articles from 6,180 works. The services provided through telemedicine were consultation/screening, consultation/follow-up or monitoring, test reports, medication prescriptions and case discussions. The technological resources used were platforms using video and telephone (audio and video). The use of telemedicine made it possible to reduce their exposure to Covid-19, reduce social panic and anxiety, quickly medical specialties access and the possibility of access to diagnosis and treatment of patients with chronic and acute diseases. CONCLUSION: Telemedicine can be an important tool in healthcare, keeping patients and healthcare professionals safe during the Covid-19 pandemic.

Mecanismo y diseño de vacunas para el sars-cov-2, revisión narrativa / Mechanism and design of vaccines against sars-cov-2, narrative review / Mecanismo e desenho de vacinas para sars-cov-2, revisão narrativa

La infección por el virus SARS-CoV-2, conocida como COVID-19, ha causado alta morbilidad y mortalidad en el mundo. Después de haber descifrado el código genético del virus y haber desarrollado un gran trabajo investigativo en la creación de vacunas, con diversas estrategias de acción, se ha logrado disminuir la morbi mortalidad. Fue necesario acelerar el proceso de producción de vacunas, lo cual estuvo facilitado por el avanzado conocimiento científico en el campo de la genética y la virología, para brindar a la especie humana una protección eficaz y segura contra la agresiva y progresiva infección. Las vacunas se clasifican de acuerdo con su mecanismo de acción, existen vacunas basadas en vectores virales que no se replican, vacunas recombinantes, otras basadas en virus atenuados y virus inactivos, y (la gran novedad de la ciencia actual) las vacunas basadas en ARN mensajero y ADN. Estas últimas han demostrado una gran eficacia y seguridad en la prevención de la infección por el SARS-CoV-2, también han impactado de manera fuerte, por lo que han reducido la infección y la mortalidad en la población. En consecuencia, cada día que pasa desde que se inició el periodo de vacunación mundial, se evidencia una reducción en la curva de contagio y mortalidad por COVID-19.

The infection produced by the SARS-CoV-2 virus, known as COVID-19, has caused high morbidity and mortality across the world. After having deciphered the virus's genoma and carried out investigative endeavors that led to the creation of a variety of vaccines with different mechanisms of action, it has been possible to decrease the morbidity and mortality associated with the virus. It was necessary to accelerate the vaccine production process, which was facilitated by advanced scientific knowledge within the disciplines of genetics and virology, in order to provide the human species with a safe and effective form of protection against the aggressive and progressive infection. Vaccines are classified differently depending on their action mechanisms: there are some based on non-replicating viral vectors, recombinant vaccines, ones that are based on attenuated or inactivated viruses, and (the greatest novelty of current scientific developments) vaccines based on DNA and messenger RNA. The latter has demonstrated significant efficacy and safety in the prevention of the SARS-CoV-2 infection as observed in preliminary studies, and they have meaningfully impacted the population by reducing the rates of infection and mortality. As a result, decreased levels of spread of and mortality from COVID-19 have been evidenced across the globe following the beginning of the vaccine distribution period.

A infecção pelo vírus SARS-CoV-2, conhecido como COVID-19, tem causado elevada morbidade e mortalidade no mundo. Depois de ter decifrado o código genético do virus e de ter realizado um grande trabalho de investigação na criação de vacinas, com diversas estratégias de ação, a morbilidade e a mortalidade foram reduzidas. Foi necessário acelerar o processo de produção de vacinas, facilitado por conhecimentos científicos avançados no domínio da genética e da virologia, para proporcionar à espécie humana uma proteção eficaz e segura contra a infecção agressiva e progressiva. As vacinas são classificadas de acordo com seu mecanismo de ação, existem vacinas baseadas em vetores virais que não se replicam, vacinas recombinantes, outras baseadas em virus atenuados e vírus inativos, e (a grande novidade da ciência atual) vacinas baseadas em RNA mensageiro e ADN. Estas últimas demonstraram grande eficácia e segurança na prevenção da infecção por SARS-CoV-2, mas também tiveram um forte impacto, razão pela qual reduziram a infecção e a mortalidade na população. Consequentemente, a cada dia que passa desde o início do período global de vacinação, fica evidente uma redução na curva de contágio e mortalidade por COVID-19.

Pathogenesis of liver injury caused by antiviral drugs for coronavirus disease 2019 / 临床肝胆病杂志

Drug-induced liver injury is caused by the drug itself and/or its metabolites during drug use or occurs due to hypersensitivity or reduced tolerance to the drug in a particular body type. In the last three years of the diagnosis and treatment of coronavirus disease 2019 （COVID-19）， antiviral drugs have played a very important role， but there are many reports on liver injury caused by anti-COVID-19 drugs in China and globally， with unknown pathogenesis of liver injury caused by such drugs. This article reviews the research advances in the types of antiviral drugs for COVID-19 and their mechanism in inducing liver injury， in order to promote the rational use of antiviral drugs.

Synthesis and evaluation for anti-HCoV-OC43 activity of novel aloperine derivatives with different core structures / 药学学报

In this study, we designed and synthesized 12 novel aloperine derivatives with different core structures. Among them, compound 3 with a ten-membered ring core was obtained through a special ring expansion reaction after γ-H Huffman elimination of quaternary ammonium salt, and the structure was verified by X-single crystal diffraction. Furthermore, their antiviral activity against human β-coronavirus HCoV-OC43 was evaluated by CCK-8 assay. Quaternary ammonium salt 2a and 3 had a good inhibitory effect against HCoV-OC43, and 2a had the highest anti-HCoV-OC43 activity with an EC50 values of 3.77 μmol·L-1 and a SI value of over 53.1. Schrӧdinger molecular docking results showed that both 2a and 3 might display their anti-HCoV-OC43 activity by directly acting on host TMPRSS2 and SR-B1. The results expanded the structural types of endocyclic aloperine and the function against coronavirus, and provided useful scientific data for the development of pharmaceutical applications of these compounds.

Synthesis and anti-SARS-CoV-2 activity and mechanism research of lycorine derivatives / 药学学报

We designed and synthesized eighteen lycorine derivatives with five different structural types, and evaluated their antiviral activities on a HCoV-OC43-infected H460 cell model. Structure-activity relationships suggested that the introduction of appropriate substituents on the 6N atom of lycorine was beneficial to activity. Compound 6a gave a good activity with the half effective concentration (EC50) and selectivity index (SI) values of 2.36 μmol·L-1 and 16.52, respectively. Surface plasmon resonance (SPR) result indicated that 6a might target the non-structural protein 12 (NSP12) subunit in RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 with the dissociation constant (KD) value of 1.36 μmol·L-1. Molecular docking indicated that 6a might act on nidovirus RdRp-associated nucleotidyltransferase (NiRAN) catalytic center of NSP12, distinct from the mechanism of nucleoside-like drugs such as remdesivir. This study provides scientific data for the development of lycorine derivatives into a new class of anti-SARS-CoV-2 small molecule inhibitors.

Recent advances in drug screening methods of SARS-CoV-2 spike protein / 药学学报

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a serious impact on global public health and the economy. SARS-CoV-2 infiltrates host cells via its surface spike protein, which binds to angiotensin-converting enzyme 2 on the host cell membrane. As a result, small molecules targeting spike protein have emerged as a hotspot in anti-SARS-CoV-2 drug research. Activity screening is an important step in seeking small molecule drugs. Therefore, this article aims to review the biological activity evaluation methods of small molecule inhibitors targeting SARS-CoV-2 spike protein, with the goal of laying the foundation for the discovery of new anti-SARS-CoV-2 drugs.

Anti-SARS-CoV-2 activity of small molecule inhibitors of cathepsin L / 药学学报

The coronavirus disease 2019 (COVID-19) is an acute infectious disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to serious worldwide economic burden. Due to the continuous emergence of variants, vaccines and monoclonal antibodies are only partial effective against infections caused by distinct strains of SARS-CoV-2. Therefore, it is still of great importance to call for the development of broad-spectrum and effective small molecule drugs to combat both current and future outbreaks triggered by SARS-CoV-2. Cathepsin L (CatL) cleaves the spike glycoprotein (S) of SARS-CoV-2, playing an indispensable role in enhancing virus entry into host cells. Therefore CatL is one of the ideal targets for the development of pan-coronavirus inhibitor-based drugs. In this study, a CatL enzyme inhibitor screening model was established based on fluorescein labeled substrate. Two CatL inhibitors IMB 6290 and IMB 8014 with low cytotoxicity were obtained through high-throughput screening, the half inhibition concentrations (IC50) of which were 11.53 ± 0.68 and 1.56 ± 1.10 μmol·L-1, respectively. SDS-PAGE and cell-cell fusion experiments confirmed that the compounds inhibited the hydrolysis of S protein by CatL in a concentration-dependent manner. Surface plasmon resonance (SPR) detection showed that both compounds exhibited moderate binding affinity with CatL. Molecular docking revealed the binding mode between the compound and the CatL active pocket. The pseudovirus experiment further confirmed the inhibitory effects of IMB 8014 on the S protein mediated entry process. In vitro pharmacokinetic evaluation indicated that the compounds had relatively good drug-likeness properties. Our research suggested that these two compounds have the potential to be further developed as antiviral drugs for COVID-19 treatment.

SARS-CoV-2 antibody level one month after COVID-19 infection in healthcare workers in Pudong New Area of Shanghai / 上海预防医学

ObjectiveTo investigate the levels of serum antibodies against novel coronavirus （SARS-CoV-2） in healthcare workers after one month of natural infection， to explore the influencing factors and their correlations with the levels of antibodies， and to provide reference for strengthening the protection of healthcare workers and preventive intervention in Pudong New Area in Shanghai. MethodsVenous blood samples were collected from 1 102 medical staff in Pudong hospitals one month after infection. The serum levels of new coronavirus specific antibodies IgM， IgG and neutralizing antibodies were detected by chemiluminescent immunoassay. The information of gender， age， position， infection severity， vaccination， basic diseases and use of immunosuppressants were obtained by questionnaire to explore the influencing factors and their correlation with the antibody level. ResultsOne month after natural infection， 99.00% （1 091/1 102） of the subjects were found to be positive for IgG antibody against the new coronavirus， 17.79% （196/1 102） of the subjects were IgM antibody positive， and 99.00% （1 091/1 102） of the samples were positive for the neutralizing antibody. The level of antibody might be influenced by the severity of infection， the time of the last dose of vaccination， and the long-term use of immunosuppressants. The more severe the disease， the stronger the neutralizing antibody response. The antibody level in the people who received the final dose of vaccine within 6 months was higher than that of the people who received the vaccine 6 months ago， and the difference was statistically significant. The antibody levels were low in the subjects who received long-term immunosuppressants. ConclusionThe specific IgM， IgG and neutralizing antibody were found， one month after infection， in the medical workers in Pudong New Area， Shanghai， and the antibody titers were high， which had a good protective effect. The antibody level of the people who were vaccinated within 6 months was higher， it is recommended that people who receive the last vacination more than 6 months should be re-vaccinated with the booster vaccine， to improve the autoimmunity against the novel coronavirus.

Analysis of cases of reinfection of past SARS-CoV-2 patients in Pudong New Area of Shanghai / 上海预防医学

ObjectiveTo identify the rate， population characteristics， and vaccination history of repeat infections among previously infected people in the current epidemic based on the rate of repeat infection and population characteristics of different mutant strains at different times in Pudong New Area of Shanghai， and to provide reference for the prevention and control strategies of novel coronavirus repeat infections. MethodsA total of 9 250 investigated subjects were randomly selected from the new cases of asymptomatic infection and confirmed cases reported by Pudong New Area from March to May 2022. The investigation mainly focused on demographic characteristics， nucleic acid or antigen test results， and symptoms after infection. The repeat infection rates among different populations were compared， and logistic regression was used to analyze the impact of gender， age， and vaccination status on repeat infections. ResultsThe survey sample of 9 250 people had a response rate of 81.85%. There were 4 043 males （53.40%） and 3 528 females （46.60%）， with a median age of 34 years old （P25， P75： 7， 61）. The overall vaccine uptake rate was 59.44% （4 500/7 571）. In December of 2022， there were 563 cases of repeat infection， with an infection rate of 7.44%. The lowest rate of repeat infection was seen in the 3‒ year-old group （2.86%） and the highest rate in the 30‒ year-old group （12.42%）， with significant differences between different age groups. The repeated infection rate for those who had completed their vaccinations was significantly lower （6.57%） compared to those who had not （7.11%）. The age groups of 3‒ years， 70‒79 years， as well as individuals who completed full vaccination and received booster shots were protective factors against repeat infections. ConclusionThe overall rate of reinfection among the infected in Shanghai during the spring of 2022 was low in the outbreak of the Omicron variant， and the rate of reinfection in the 3‒ year-old group was significantly lower than in other age groups. Completing the full course of vaccination significantly reduces the risk of reinfection. Although the reinfection rate is high in individuals who received booster shots， it remains a mitigating factor compared to those who do not receive the vaccine. It is recommended to continue monitoring reinfections in key populations and further strengthen immunization efforts.

Safety of G-CSF in patients with COVID-19 / 中国临床药理学与治疗学

COVID-19, a disease caused by SARSCoV-2 infection, has caused a global pandemic in a short time. The key immunopathological features of COVID-19 include lymphopenia, neutropenia, cytokine storm and related Immune damage to parenchymal organs such as lung. Granulocyte colony stimulating factor (G-CSF) can cause excessive inflammatory reaction, which may aggravate the condition of some patients. Therefore, it is controversial whether COVID-19 should be treated with G-CSF, and clinicians need to evaluate the effectiveness and safety of G-CSF according to the specific conditions of each patient.

Establishment and validation of a universal test method in vitro for SARS-CoV-2 mRNA vaccine potency / 中国生物制品学杂志

@#Objective To establish and verify a universal and stable potency test method in vitro for SARS-CoV-2 mRNA vaccine,so as to use it for the quality control of SARS-CoV-2 mRNA vaccine.Methods ELISA kits that could bind well to S protein of SARS-CoV-2 variants,as well as transfected cells,cell plating concentrations and doses for transfection were screened,and then a potency test method for SARS-CoV-2 mRNA vaccine in vitro was established and verified.Results An ELISA kit was found with good binding ability to S protein of each variant,and HEK293T cells were determined as the transfection cells,with the plating concentration of 2.5 × 10~5 cells/mL and the transfection dose of 4 μg/well in the 6-well plate.An universal and stable potency test method for SARS-CoV-2 mRNA vaccine in vitro was established.The verification results showed that the method met the quality control needs.Conclusion The established potency test method in vitro for SARS-CoV-2 mRNA vaccine has good relative accuracy,linearity,intermediate precision and range,and can be applied to the quality control of SARS-CoV-2 mRNA vaccines.

Effects of signal peptide on secretory expression of SARS-CoV-2 S1,RBD and RBD dimer proteins in Expisf9 insect cells / 中国生物制品学杂志

@#Objective To compare the effects of different signal peptides on the secretion and expression of SARS-CoV-2S1,receptor binding domain(RBD) and RBD dimer proteins in Expisf9 insect cells.Methods The gene sequences of three proteins,SARS-CoV-2 S1(M1-E661),RBD(R319-P545) and RBD dimer(R319-K537 tandem),were selected and divided into 25 groups according to the different N-terminal signal peptide sequences(Endo,honeybee melittin(HBM),GP64,GP67,chitinase(Chi) and HIV-ENV) and C-terminal label sequences.25 recombinant baculoviruses were constructed by Bac-to-Bac system,and 25 groups of tertiary strain banks were prepared.B2 and C4 viruses were inoculated to logarithmic prestage cells(2.8 × 10~6 cells/mL) and logarithmic metaphase cells(1.2 × 10~7 cells/mL),respectively.The viruses of each group were cultured to 100 mL(500 mL shaker) for protein expression,and samples were taken for SDSPAGE electrophoresis,Western-blot and ELISA detection.Two groups with higher expression levels of S1,RBD and RBD dimer proteins were selected for repeated verification.Results When B2 and C4 were inoculated to high cell density,the secretion expression level showed no increase,while there were significant difference between 4 and 5 d after inoculation.The expression level of A7(Endo-S1-tag) was significantly lower than that of A9(HIV-ENV-S1-tag),the expression level of A4(Gp67-S1-tag) was the highest,and the secreted expression level of A1(Endo-Endo-Sl-tag) was significantly lower than that of A7(Endo-S1-tag).The secretion and expression of B6(HIV-ENV-RBD-tag) was signifi-cantly higher than that of B4(Gp67-RBD-tag) and other signal peptide groups,and C4(Gp67-RBD-dimer-tag) expression was significantly higher than that of C3(Gp64-RBD-dimer-tag).Two groups with high expression of each protein were selected separately for repeated verification(A4,A9;B4,B6;C3,C4) and the results showed that A4,B6 and C4 had the highest secretion expression levels.Conclusion The signal peptide for the highest secretion expression of S1 and RBD dimer proteins is the same,which is GP67 signal peptide,while the most suitable signal peptide for RBD protein is HIV-ENV,indicating that the N-terminal sequence can affect protein secretion,signal peptide sequence is universal to a certain extent,but is also related to the target protein sequence to be expressed.

Immunogenicity evaluation of prototype and variant inactivated SARS-CoV-2 vaccines in rats / 中国生物制品学杂志

@#Objective To evaluate the immunogenicity of prototype strain,Beta strain,Gamma strain and Delta strain of SARS-CoV-2 inactivated vaccines in rats.Methods Five female Wistar rats were immunized with SARS-CoV-2 inactivated vaccines of prototype,Beta,Gamma and Delta strains through thigh muscle twice at an interval of 14 d,with an immunization dose of 3 μg virus protein/(0.5 mL per rat).Serum samples were collected and isolated by vein 14,28 and 42 d after the first immunization.The serum IgG antibody levels were detected by indirect ELISA,the titers of serum neutralizing antibody were measured by microneutralization,and the antigenic ratios of the serum neutralizing antibody titers were calculated to evaluate the antigenicity difference between different strains.Results at 14 d after the first immunization,IgG antibodies against four strains of virus were detected in all immunized serum samples.The levels of IgG antibodies increased by more than 10 times at 28 d compared with those at 14 d,and decreased slightly at 42 d.At 14 d after the first immunization,all the neutralizing antibodies against the four strains were positive in the serum of rats immunized with prototype strain or Delta strain vaccine;In the serum samples of rats immunized with Beta and Gamma strains,all the neutralizing antibodies against Beta and Gamma strains were positive,while some neutralizing antibodies against prototype or Delta strains were positive.At 28 d after the first immunization,the neutralizing antibodies in the immune serum of the four strains were positive,and the titers of neutralizing antibodies were significantly higher than those at 14 d;The neutralizing antibody titers were slightly lower at 42 d after the first immunization than 28 d.There was small difference in the antigenicity between Beta and Gamma,prototype and Gamma,but significant difference in the antigenicity between prototype and Beta strains.Conclusion The prototype strain,Beta strain,Gamma strain and Delta strain of SARS-CoV-2 inactivated vaccines can stimulate rats to produce neutralizing antibodies with high titer,while the immunogenicity has difference.

Efficacy of ursodeoxycholic acid in the prevention and treatment of COVID-19 in patients with chronic hepatitis B / 临床肝胆病杂志

ObjectiveTo investigate the potential effect of ursodeoxycholic acid （UDCA） in the prevention and treatment of COVID-19 in patients with chronic hepatitis B. MethodsClinical data were collected from 324 patients with chronic hepatitis B who were treated in Beijing Ditan Hospital， Capital Medical University， from January to December 2022， and according to whether UDCA was administered， they were divided into UDCA group and control group. The propensity score matching （PSM） method was used to balance the confounding factors such as age， sex， and chronic complications， and the two groups were compared in terms of SARS-CoV-2 infection rate， symptoms， and recovery time after COVID-19. The two groups were also compared in terms of related laboratory markers （white blood cell count ［WBC］， hemoglobin ［Hb］， platelet count ［PLT］， alanine aminotransferase ［ALT］， aspartate aminotransferase ［AST］， albumin ［Alb］， alkaline phosphatase ［ALP］， total bilirubin ［TBil］， triglyceride ［TG］， and total cholesterol ［TC］）， vaccination， and the incidence rate of liver disease symptoms after COVID-19. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of data with skewed distribution between the two groups； the chi-square test and the continuously corrected chi-square test were used for comparison of categorical data between two groups. The binary Logistic regression model was used for univariate and multivariate analyses to investigate the influencing factors for COVID-19 after matching. ResultsThere were 87 patients in the UDCA group and 237 patients in the control group， and after PSM， there were 78 patients in the UDCA group and 137 patients in the control group， with good balance between the two groups. There was a significant difference in SARS-CoV-2 infection rate between the UDCA group and the control group ［82.1% （64/78） vs 95.6% （131/137）， χ2=10.847， P=0.001］. After COVID-19， compared with the control group， the UDCA group had a significantly lower proportion of the patients with chill （10.9% vs 38.9%， χ2=16.124， P<0.001） and cough （56.3% vs 74.8%， χ2=6.889， P=0.009）. There was a significant difference between the UDCA group and the control group in the proportion of the patients with a recovery time of ≤7 days after COVID-19 （79.7% vs 61.1%， χ2=6.760， P=0.009）. Both univariate and multivariate logistic regression analyses showed that UDCA was an independent influencing factor for COVID-19 （odds ratio=0.21 and 0.17， both P<0.05）. ConclusionUDCA is an protective factor against COVID-19 in patients with chronic hepatitis B and can alleviate related symptoms to some extent and shorten the recovery time， and therefore， it has an important value in the prevention and treatment of COVID-19.