Dietary Vitamin D Mitigates Coronavirus-Induced Lung Inflammation and Damage in Mice.

The COVID-19 pandemic caused by the SARS-CoV-2 (ß-CoV) betacoronavirus has posed a significant threat to global health. Despite the availability of vaccines, the virus continues to spread, and there is a need for alternative strategies to alleviate its impact. Vitamin D, a secosteroid hormone best known for its role in bone health, exhibits immunomodulatory effects in certain viral infections. Here, we have shown that bioactive vitamin D (calcitriol) limits in vitro replication of SARS-CoV-2 and murine coronaviruses MHV-3 and MHV-A59. Comparative studies involving wild-type mice intranasally infected with MHV-3, a model for studying ß-CoV respiratory infections, confirmed the protective effect of vitamin D in vivo. Accordingly, mice fed a standard diet rapidly succumbed to MHV-3 infection, whereas those on a vitamin D-rich diet (10,000 IU of Vitamin D3/kg) displayed increased resistance to acute respiratory damage and systemic complications. Consistent with these findings, the vitamin D-supplemented group exhibited lower viral titers in their lungs and reduced levels of TNF, IL-6, IL-1ß, and IFN-γ, alongside an enhanced type I interferon response. Altogether, our findings suggest vitamin D supplementation ameliorates ß-CoV-triggered respiratory illness and systemic complications in mice, likely via modulation of the host's immune response to the virus.

Clinical management of COVID-19: living guideline - 15 September 2022

The WHO COVID-19 Clinical management: living guidance contains the Organization's most up-to-date recommendations for the clinical management of people with COVID-19. Providing guidance that is comprehensive and holistic for the optimal care of COVID-19 patients throughout their entire illness is important. The latest version of this living guideline is available in pdf format (via the 'Download' button) and via an online platform, and is updated regularly as new evidence emerges. No further updates to the previous existing recommendations were made in this latest version. This updated (fifth) version contains 16 new recommendations for the rehabilitation of adults with post COVID-19 condition (see Chapter 24), which includes: strong recommendation that exertional desaturation and cardiac impairment following COVID-19 should be ruled out and managed before consideration of physical exercise training

Inhibition of Human Respiratory Influenza A Virus and Human Betacoronavirus-1 by the Blend of Double-Standardized Extracts of Aronia melanocarpa (Michx.) Elliot and Sambucus nigra L.

Viral and bacterial diseases are among the greatest concerns of humankind since ancient times. Despite tremendous pharmacological progress, there is still a need to search for new drugs that could treat or support the healing processes. A rich source of bioactive compounds with antiviral potency include plants such as black chokeberry and elderberry. The aim of this study was to assess the in vitro antiviral ability of an originally designed double-standardized blend of extracts from Aronia melanocarpa (Michx.) Elliot and Sambucus nigra L. (EAM-ESN) or separated extracts of A. melanocarpa (EAM) or S. nigra (ESN) against four human respiratory tract viruses: influenza A virus (A/H1N1), betacoronavirus-1 (HCoV-OC43) belonging to the same ß-coronaviruses as the current pandemic SARS-CoV-2, human herpesvirus type 1 (HHV-1), and human adenovirus type 5 (HAdV-5). Antiviral assays (AVAs) were used to evaluate the antiviral activity of the plant extracts in a cell-present environment with extracts tested before, simultaneously, or after viral infection. The virus replication was assessed using the CPE scale or luminescent assay. The EAM-ESN blend strongly inhibited A/H1N1 replication as well as HCoV-OC43, while having a limited effect against HHV-1 and HAdV-5. This activity likely depends mostly on the presence of the extract of S. nigra. However, the EAM-ESN blend possesses more effective inhibitory activity toward virus replication than its constituent extracts. A post-infection mechanism of action of the EAM-ESN make this blend the most relevant for potential drugs and supportive treatments; thus, the EAM-ESN blend might be considered as a natural remedy in mild, seasonal respiratory viral infections.

Azadirachta indica A. Juss bark extract and its Nimbin isomers restrict ß-coronaviral infection and replication.

Emerging mutations in the SARS-CoV-2 genome pose a challenge for vaccine development and antiviral therapy. The antiviral efficacy of Azadirachta indica bark extract (NBE) was assessed against SARS-CoV-2 and m-CoV-RSA59 infection. Effects of in vivo intranasal or oral NBE administration on viral load, inflammatory response, and histopathological changes were assessed in m-CoV-RSA59-infection. NBE administered inhibits SARS-CoV-2 and m-CoV-RSA59 infection and replication in vitro, reducing Envelope and Nucleocapsid gene expression. NBE ameliorates neuroinflammation and hepatitis in vivo by restricting viral replication and spread. Isolated fractions of NBE enriched in Nimbin isomers shows potent inhibition of m-CoV-RSA59 infection in vitro. In silico studies revealed that NBE could target Spike and RdRp of m-CoV and SARS-CoV-2 with high affinity. NBE has a triterpenoids origin that may allow them to competitively target panoply of viral proteins to inhibit mouse and different strains of human coronavirus infections, suggesting its potential as an antiviral against pan-ß-Coronaviruses.

Características clínicas y evolución de los síntomas en pacientes con covid-19 / Clinical characteristics and evolution of symptoms in patients with COVID-19

RESUMEN Introducción: muchos casos de covid-19 son asintomáticos al ingresar. El desarrollo de síntomas pudiera tener relación con la terapéutica empleada. Objetivo: caracterizar clínicamente los pacientes infectados con SARS-CoV-2 y la evolución de los síntomas en relación con el ingreso, en el Hospital Militar Docente Dr. Mario Muñoz Monroy, de Matanzas. Materiales y métodos: estudio retrospectivo de las historias clínicas de pacientes ingresados confirmados con SARS-CoV-2 hasta el 26 de junio de 2020. Se estudiaron 145 pacientes, divididos en dos grupos: sintomáticos y asintomáticos al ingresar. Se recabaron datos demográficos, antecedentes patológicos personales, síntomas y evolución, parámetros humorales, tratamiento, estadía hospitalaria y complicaciones. Se utilizaron las pruebas de Chi cuadrado y de U de Mann-Whitney, según el tipo de variable. Resultados: la mayoría de los pacientes ingresó sintomático. Solo hasta 19 años predominaron los asintomáticos. Los hipertensos, diabéticos y con insuficiencia renal tuvieron mayor proporción de sintomáticos al momento del ingreso. Un pequeño grupo (n= 38) nunca desarrollo síntomas. En los sintomáticos predominaron tos, malestar general, fiebre, dolor faríngeo, congestión nasal, anosmia y falta de aire. Posterior al ingreso prevalecieron diarreas, dispepsia y vómitos. Los sintomáticos tuvieron mayores valores de enzimas hepáticas, más infección respiratoria baja y distress respiratorio, así como estadía hospitalaria extensa, ingreso en cuidados intensivos y fallecidos. Conclusiones: más de la mitad de los pacientes ingresaron con predominio de síntomas generales y respiratorios. Después del ingreso predominó la sintomatología digestiva, posiblemente relacionada con la terapéutica empleada. Los pacientes sintomáticos al ingresar, tuvieron peores parámetros humorales, más complicaciones y estadía hospitalaria más prolongada (AU).

ABSTRACT Introduction: many cases of covid-19 are asymptomatic when admitted to the hospital. The development of symptoms may be related to the therapies used. Objective: to characterize clinically the patients infected with SARS-CoV-2 and the evolution of symptoms in relation to admission, in the Military Hospital Dr. Mario Muñoz Monroy, of Matanzas. Materials and methods: retrospective study of clinical records of SARS-CoV-2-confirmed patients admitted up to June 26, 2020. 145 patients were studied, divided into two groups: symptomatic and asymptomatic ones at admission. Demographic data, personal pathological history, symptoms and evolution, humoral parameters, treatment, hospital stay and complications were collected. The Chi square and Mann-Whire U tests were used, depending on the type of variable. Results: most patients were symptomatic at admission. Asymptomatic ones predominated only up to 19 years. Hypertensive, diabetic and renal impaired patients had a higher proportion of symptoms at admission. A small group (n = 38) never developed symptoms. Cough, general discomfort, fever, pharyngeal pain, nasal congestion, anosmia and shortness of breath were the predominated symptoms. Diarrhea, dyspepsia and vomiting prevailed after admission. The symptomatic patients showed higher liver enzyme values, more low respiratory infection and respiratory distress, and also had more extended hospital stay, admission to intensive care and deceases. Conclusions: more than half of the patients were admitted with predominance of general and respiratory symptoms. After admission, digestive symptoms predominated, possibly related to the therapies used. Symptomatic patients on admission had worse humoral parameters, more complications and longer hospital stay (AU).

Gastrointestinal manifestations and nutritional therapy during COVID-19 pandemic: a practical guide for pediatricians / Sintomas gastrintestinais e abordagem nutricional durante a pandemia de COVID-19: guia prático para pediatras

ABSTRACT Coronavirus disease 2019 (COVID-19) is a disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has spread globally in pandemic proportions. Accumulative evidence suggests SARS-CoV-2 can be transmitted through the digestive system, the so-called fecal-oral route of transmission, and may induce several gastrointestinal manifestations. MEDLINE® and Embase databases were extensively searched for major clinical manifestations of gastrointestinal involvement in children and adolescents with COVID-19 reported in medical literature, and for nutritional therapy-related data. Findings and recommendations were pragmatically described to facilitate overall pediatric approach. A total of 196 studies addressing gastrointestinal or nutritional aspects associated with the global COVID-19 pandemic were found. Of these, only 17 focused specifically on pediatric patients with regard to aforementioned gastrointestinal or nutritional aspects. Most articles were descriptive and six addressed guidelines, established protocols, or expert opinions. Children and adolescents with gastrointestinal symptoms, such as nausea, vomiting and diarrhea, should be seriously suspected of COVID-19. Gastrointestinal signs and symptoms may occur in 3% to 79% of children, adolescents and adults with COVID-19, and are more common in severe cases. These include diarrhea (2% to 50%), anorexia (40% to 50%), vomiting (4% to 67%), nausea (1% to 30%), abdominal pain (2% to 6%) and gastrointestinal bleeding (4% to 14%). Patients with inflammatory bowel disease or chronic liver disease are not at greater risk of infection by SARS-CoV-2 relative to the general population. Nutritional support plays an important role in treatment of pediatric patients, particularly those with severe or critical forms of the disease. The digestive system may be a potential route of COVID-19 transmission. Further research is needed to determine whether the fecal-oral route may be involved in viral spread. Nutritional therapy is vital to prevent malnutrition and sarcopenia in severe cases.

RESUMO A doença pelo coronavírus 2019 (COVID-19) é causada pelo coronavírus da síndrome respiratória aguda grave 2 (SARS-CoV-2) e foi amplamente disseminada em todo o mundo em proporções pandêmicas. Evidências crescentes sugerem que o sistema digestivo pode ser uma via potencial para a infecção pelo SARS-CoV-2, para a disseminação do vírus por via fecal-oral, e estar relacionado com vários sintomas gastrintestinais. Realizamos uma extensa revisão da literatura médica utilizando os bancos de dados MEDLINE® e Embase, com o objetivo de identificar as principais manifestações clínicas do envolvimento gastrintestinal e analisar a terapia nutricional em crianças e adolescentes com COVID-19. Os achados e as recomendações foram descritos de maneira pragmática, para facilitar a abordagem do pediatra em geral. Foram analisados 196 estudos relacionados ao envolvimento do trato gastrintestinal ou aspectos nutricionais associados à pandemia de COVID-19 em todo o mundo. Destes estudos, apenas 17 incluíram a população pediátrica exclusivamente com aspectos gastrintestinais ou nutricionais específicos. Os artigos, em sua maioria, foram descritivos, sendo seis relacionados a diretrizes, protocolos instituídos ou opiniões de especialistas. Crianças e adolescentes com sintomas gastrintestinais, como náusea, vômito e diarreia, devem ser avaliados como pacientes suspeitos de COVID-19. Os sinais e sintomas gastrintestinais podem ocorrer em 3% a 79% das crianças, adolescentes e adultos com COVID-19, estando mais frequentemente presentes em casos graves. Incluem diarreia (2% a 50%), anorexia (40% a 50%), vômitos (4% a 67%), náusea (1% a 30%), dor abdominal (2% a 6%) e sangramento gastrintestinal (4% a 14%). Pacientes com doença inflamatória intestinal ou doenças hepáticas crônicas não apresentam maior risco de infecção por SARS-CoV-2 do que a população em geral. O suporte nutricional é parte muito importante do tratamento de pacientes pediátricos, principalmente nas formas graves ou críticas da doença. O trato gastrintestinal pode ser uma via potencial para a infecção por COVID-19. Mais pesquisas são necessárias para determinar a possibilidade da transmissão fecal-oral, importante para a disseminação viral. A terapia nutricional é essencial para prevenir desnutrição e sarcopenia nos casos graves.

Middle East respiratory syndrome: obstacles and prospects for vaccine development.

The recent emergence of Middle East respiratory syndrome (MERS) highlights the need to engineer new methods for expediting vaccine development against emerging diseases. However, several obstacles prevent pursuit of a licensable MERS vaccine. First, the lack of a suitable animal model for MERS complicates the in vivo testing of candidate vaccines. Second, due to the low number of MERS cases, pharmaceutical companies have little incentive to pursue MERS vaccine production as the costs of clinical trials are high. In addition, the timeline from bench research to approved vaccine use is 10 years or longer. Using novel methods and cost-saving strategies, genetically engineered vaccines can be produced quickly and cost-effectively. Along with progress in MERS animal model development, these obstacles can be circumvented or at least mitigated.