How effective is the BNT162b2 mRNA vaccine against SARS-CoV-2 transmission and infection? A national programme analysis in Monaco, July 2021 to September 2022.

BACKGROUND: We quantified SARS-CoV-2 dynamics in different community settings and the direct and indirect effect of the BNT162b2 mRNA vaccine in Monaco for different variants of concern (VOC). METHODS: Between July 2021 and September 2022, we prospectively investigated 20,443 contacts from 6320 index cases using data from the Monaco COVID-19 Public Health Programme. We calculated secondary attack rates (SARs) in households (n = 13,877), schools (n = 2508) and occupational (n = 6499) settings. We used binomial regression with a complementary log-log link function to measure adjusted hazard ratios (aHR) and vaccine effectiveness (aVE) for index cases to infect contacts and contacts to be infected in households. RESULTS: In households, the SAR was 55% (95% CI 54-57) and 50% (48-51) among unvaccinated and vaccinated contacts, respectively. The SAR was 32% (28-36) and 12% (10-13) in workplaces, and 7% (6-9) and 6% (3-10) in schools, among unvaccinated and vaccinated contacts respectively. In household, the aHR was lower in contacts than in index cases (aHR 0.68 [0.55-0.83] and 0.93 [0.74-1.1] for delta; aHR 0.73 [0.66-0.81] and 0.89 [0.80-0.99] for omicron BA.1&2, respectively). Vaccination had no significant effect on either direct or indirect aVE for omicron BA.4&5. The direct aVE in contacts was 32% (17, 45) and 27% (19, 34), and for index cases the indirect aVE was 7% (- 17, 26) and 11% (1, 20) for delta and omicron BA.1&2, respectively. The greatest aVE was in contacts with a previous SARS-CoV-2 infection and a single vaccine dose during the omicron BA.1&2 period (45% [27, 59]), while the lowest were found in contacts with either three vaccine doses (aVE - 24% [- 63, 6]) or one single dose and a previous SARS-CoV-2 infection (aVE - 36% [- 198, 38]) during the omicron BA.4&5 period. CONCLUSIONS: Protection conferred by the BNT162b2 mRNA vaccine against transmission and infection was low for delta and omicron BA.1&2, regardless of the number of vaccine doses and previous SARS-CoV-2 infection. There was no significant vaccine effect for omicron BA.4&5. Health authorities carrying out vaccination campaigns should bear in mind that the current generation of COVID-19 vaccines may not represent an effective tool in protecting individuals from either transmitting or acquiring SARS-CoV-2 infection.

Effectiveness of Vitamin D and Alpha-Lipoic Acid in COVID-19 Infection: A Literature Review.

Over three years since the World Health Organization (WHO) declared COVID-19 a pandemic, it is still a global burden. Vaccines against COVID-19, caused by SARS-CoV-2, are available and effective for preventing disease. However, their protective effects are not 100%. Currently, the U.S. Food and Drug Administration (FDA) has only approved a limited number of inpatient treatments for COVID-19, such as remdesivir, baricitinib, and tocilizumab. These medications have indications and contraindications applicable to a select patient population. Finding additional effective therapies that are widely available with limited risk could be vital in optimizing treatment strategies for this viral illness. Some vitamins and supplements have been identified as potential options for managing COVID-19. Vitamin D (VD) deficiency has been associated with respiratory tract infections. Moreover, alpha-lipoic acid (ALA) is a powerful antioxidant and helps reduce inflammatory responses in many pathologic conditions. This review aims to analyze the current evidence regarding the effectiveness of VD and alpha-lipoic acid in COVID-19 infection in both outpatient and hospitalized patients. Relevant randomized controlled trials (RCTs) were identified via the PubMed database from January 1, 2021, to December 31, 2023. Inclusion criteria were as follows: the study design was a randomized controlled trial (RCT), the usage of a constant dose during the intervention period without any additional boluses, and a research ethics committee approved it. Exclusion criteria included a lack of an outcome or apparent intervention, additional boluses, or a single-dose regimen in all the interventional groups. There were 11 studies with a total sample size of 35,717 patients that met the criteria for this review. A total of 10 RCTs examined the efficacy of VD, and one RCT that reviewed the efficacy of ALA was identified. All of the articles investigated the use of VD or ALA during the treatment of COVID-19. The endpoints of each study varied, including length of stay in hospital, viral load, SARS-CoV-2 infection rate, mechanical ventilation, inflammatory markers, clinical symptoms, Sequential Organ Failure Assessment (SOFA) score, and mortality. In 8/10 VD supplementation trials, significant differences were identified between the interventional and placebo groups in the aforementioned parameters. In 2/10 VD supplementation trials, no significant differences were identified. The ALA supplementation RCT found no differences between the interventional and placebo groups in the SOFA score and 30-day all-cause mortality rate. The current literature suggests that VD can potentially reduce the SARS-CoV-2 infection rate, oxygen requirements, inflammatory markers, clinical symptoms, and mortality. Regarding ALA, although there was a suggestion of benefit, it was not statistically significant. Common limitations among the different studies included relatively small sample sizes, different geographical patient locations among studies, and differences in dosages. Trials investigating the effects of higher doses of VD supplementation on SARS-CoV-2 infection should be conducted. More research is needed to define best practices and optimal dosing protocols for the use of VD in COVID-19.

Recombinant ACE2 - Opportunities and Challenges in COVID-19 Treatment.

It was in 2019 that the world experienced the devastation caused by SARS-COV-2, contributing to a large number of deaths. This contagious virus not only challenged the health care system but has also hit the economy very badly. There has been a lot of research on effective vaccine development, and there has been some success in the same, but no effective antiviral drugs are available in the market. No doubt vaccination can prevent the disease, but it doesn't have the potential to cure an infected person, for which there is a dire need to develop some effective drug. Angiotensin convertase enzyme 2 (ACE2) played a substantial role in SARS-COV2 pathogenesis and thus has gained much attention during the pandemic. Moreover, it has opened up new avenues for the cure of COVID-19.

Epidemiological and clinical insights into the enterovirus D68 upsurge in Europe 2021/22 and the emergence of novel B3-derived lineages, ENPEN multicentre study.

Enterovirus D68 (EV-D68) infections are associated with severe respiratory disease and acute flaccid myelitis (AFM). The European Non-Polio Enterovirus Network (ENPEN) aimed to investigate the epidemiological and genetic characteristics of EV-D68 and its clinical impact during the fall-winter season of 2021/22. From 19 European countries, 58 institutes reported 10,481 (6.8%) EV-positive samples of which 1,004 (9.6%) were identified as EV-D68 (852 respiratory samples). Clinical data was reported for 969 cases. 78.9% of infections were reported in children (0-5 years); 37.9% of cases were hospitalised. Acute respiratory distress was commonly noted (93.1%) followed by fever (49.4%). Neurological problems were observed in 6.4% of cases with six reported with AFM. Phylodynamic/Nextstrain and phylogenetic analyses based on 694 sequences showed the emergence of two novel B3-derived lineages, with no regional clustering. In conclusion, we describe a large-scale EV-D68 European upsurge with severe clinical impact and the emergence of B3-derived lineages.

Advances in In Vitro Blood-Air Barrier Models and the Use of Nanoparticles in COVID-19 Research.

Respiratory infections caused by coronaviruses (CoVs) have become a major public health concern in the past two decades as revealed by the emergence of SARS-CoV in 2002, MERS-CoV in 2012, and SARS-CoV-2 in 2019. The most severe clinical phenotypes commonly arise from exacerbation of immune response following the infection of alveolar epithelial cells localized at the pulmonary blood-air barrier. Preclinical rodent models do not adequately represent the essential genetic properties of the barrier, thus necessitating the use of humanized transgenic models. However, existing monolayer cell culture models have so far been unable to mimic the complex lung microenvironment. In this respect, air-liquid interface models, tissue engineered models, and organ-on-a-chip systems, which aim to better imitate the infection site microenvironment and microphysiology, are being developed to replace the commonly used monolayer cell culture models, and their use is becoming more widespread every day. On the contrary, studies on the development of nanoparticles (NPs) that mimic respiratory viruses, and those NPs used in therapy are progressing rapidly. The first part of this review describes in vitro models that mimic the blood-air barrier, the tissue interface that plays a central role in COVID-19 progression. In the second part of the review, NPs mimicking the virus and/or designed to carry therapeutic agents are explained and exemplified.

Exploring the Impact of Bereavement During the COVID-19 Pandemic on Children and Young People: A Scoping Review.

Experiencing bereavement as a child or young person (CYP) can have long-lasting effects. The societal and environmental burdens of the SARS-CoV-2 pandemic exacerbated the experience of loss and grief for many CYP, who were unable to access their usual the support networks. However, it is still unclear what is currently known and not known about the experiences of CYP bereaved during the SARS-CoV-2 pandemic. This review used the framework of Arksey and O'Malley and included five stages: (1) identifying the research question; (2) identifying relevant studies; (3) study selection; (4) charting the data; (5) collating, summarizing, and reporting the results. The methodological quality of the included studies was also assessed using the Critical Appraisal Skills Programme tool. The PRISMA framework was used for reporting the results. The electronic databases Medline, PsychINFO, CINAHL, and PubMed were searched for relevant articles. A total of three papers meeting the inclusion criteria were included in this review and two main themes identified: (1) support (which included sub-themes; social isolation and the impact on support; support from family and friends; wider support networks); (2) Emotional impact of bereavement during a pandemic. Access to support networks is crucial for CYP to understand and process their emotions relating to their bereavement experience. The pandemic meant that many usual support networks such as family and friends were inaccessible to CYP, who struggled to deal with their experience of grief during this time. Schools are a valuable support mechanism and can help CYP understand their emotions through open discussions about their bereavement. The limited empirical evidence currently available in this area of research demonstrates an important need to further understanding of the long-term impacts of dealing with pandemic-related loss in childhood.

Complications following COVID-19 infection or vaccination in Libyan International Medical University students and their Families

Coronavirus disease 2019 (COVID-19) caused by a novel strain of coronavirus belonging to the genus Beta coronavirus named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) emerged as a major pandemic worldwide. This contagious virus had spread in many different forms, and patients have demonstrated a wide range of symptoms, ranging from moderate to severe illness. This study aims to highlight the important associations between SARS-CoV-2 infection, vaccination, and possible complications at the Libyan International Medical University, Benghazi. This crosssectional survey was conducted among students and their families at Libyan International Medical University in Benghazi, Libya. Among the 100 participants, 72% were between the ages of 18 and 39. Up to (59%) of participants were men. As for the infection with COVID-19, 77% of participants were infected. Most of the participants had no chronic diseases (69%); however, the most common chronic disease was diabetes mellitus (13%). 82% of participants were vaccinated; the most common types of vaccines administered were Sinopharm and Sputnik V (24%). Following vaccination, 71% of participants had no COVID-19 infection, while 29% did get the infection. Regarding this study, after COVID-19 infection, 66% of participants had no complications; however, 17% had pulmonary complications, which was the most common complication among the participants. As for the complications following the vaccination, 81% of participants had none, while there were pulmonary and neurological complications in 7­6%. The results of the study showed that the most frequent complications noticed among the participants following the COVID-19 infection and vaccination were pulmonary and neurological complications.

Differences in the inflammatory response among hospitalized patients with distinct variants of SARS-CoV-2.

The SARS-CoV-2 variants demonstrate diverse transmission patterns, modifications in infectivity, and immune response. Changes in disease manifestation may be attributed to vaccination and the virus's reduced capacity to induce inflammation. Objectives: To investigate the relationship between the inflammatory response and the characteristics of COVID-19 across successive waves. Methods: A retrospective cross-sectional study was conducted to evaluate sociodemographic, clinical, and laboratory data of Alpha (G1), Delta (G2), and Omicron (G3) variants. Results: A total of 300 patients from a hospital in Madrid, Spain, were included. The groups exhibited similar sociodemographic and baseline characteristics. The Alpha variant predominantly affected younger patients, while the Omicron variant affected patients with a higher prevalence of comorbidities. The Alpha group had the lowest vaccination rate compared to the highest rate in the Omicron group. The Alpha group received a higher proportion of tocilizumab compared to the other groups. Despite these differences, the severity scores were similar among the three variants. Regarding laboratory parameters, differences were observed in haemoglobin, D-dimer, alkaline phosphatase, and potassium levels. The Omicron variant showed higher D-dimer levels (p=0.04). In the multivariate analysis, differences in leukocyte count, haemoglobin, alkaline phosphatase, and potassium levels were consistently observed among patients from different waves. Omicron exhibited a higher absolute leukocyte count than the Alpha variant (p=0.003). Conclusion: No significant differences were found in inflammation biomarkers among the three variants. Furthermore, there were no significant disparities in mortality or disease severity. The level of inflammatory response in patients may be determined by the severity of COVID-19, rather than the specific viral variant.

Human microbiota dysbiosis after SARS-CoV-2 infection have the potential to predict disease prognosis.

BACKGROUND: The studies on SARS-CoV-2 and human microbiota have yielded inconsistent results regarding microbiota α-diversity and key microbiota. To address these issues and explore the predictive ability of human microbiota for the prognosis of SARS-CoV-2 infection, we conducted a reanalysis of existing studies. METHODS: We reviewed the existing studies on SARS-CoV-2 and human microbiota in the Pubmed and Bioproject databases (from inception through October 29, 2021) and extracted the available raw 16S rRNA sequencing data of human microbiota. Firstly, we used meta-analysis and bioinformatics methods to reanalyze the raw data and evaluate the impact of SARS-CoV-2 on human microbial α-diversity. Secondly, machine learning (ML) was employed to assess the ability of microbiota to predict the prognosis of SARS-CoV-2 infection. Finally, we aimed to identify the key microbiota associated with SARS-CoV-2 infection. RESULTS: A total of 20 studies related to SARS-CoV-2 and human microbiota were included, involving gut (n = 9), respiratory (n = 11), oral (n = 3), and skin (n = 1) microbiota. Meta-analysis showed that in gut studies, when limiting factors were studies ruled out the effect of antibiotics, cross-sectional and case-control studies, Chinese studies, American studies, and Illumina MiSeq sequencing studies, SARS-CoV-2 infection was associated with down-regulation of microbiota α-diversity (P < 0.05). In respiratory studies, SARS-CoV-2 infection was associated with down-regulation of α-diversity when the limiting factor was V4 sequencing region (P < 0.05). Additionally, the α-diversity of skin microbiota was down-regulated at multiple time points following SARS-CoV-2 infection (P < 0.05). However, no significant difference in oral microbiota α-diversity was observed after SARS-CoV-2 infection. ML models based on baseline respiratory (oropharynx) microbiota profiles exhibited the ability to predict outcomes (survival and death, Random Forest, AUC = 0.847, Sensitivity = 0.833, Specificity = 0.750) after SARS-CoV-2 infection. The shared differential Prevotella and Streptococcus in the gut, respiratory tract, and oral cavity was associated with the severity and recovery of SARS-CoV-2 infection. CONCLUSIONS: SARS-CoV-2 infection was related to the down-regulation of α-diversity in the human gut and respiratory microbiota. The respiratory microbiota had the potential to predict the prognosis of individuals infected with SARS-CoV-2. Prevotella and Streptococcus might be key microbiota in SARS-CoV-2 infection.

Nonadverse COVID-19 evolution predictors: the CoNAE scale. / Predictores de evolución no adversa en pacientes con COVID-19: escala CoNAE (COVID-19 non-adverse evolution).

OBJECTIVES: Tools to identify patients with mild to moderate COVID-19 are as yet unavailable. Our aims were to identify factors associated with nonadverse outcomes and develop a scale to predict nonadverse evolution in patients with COVID-19 (the CoNAE scale) in hospital emergency departments. MATERIAL AND METHODS: Retrospective cohort study of patients who came to one of our area's national health service hospitals for treatment of SARS-CoV-2 infection from July 1, 2020, to July 31, 2021. From case records we collected sociodemographic information, underlying comorbidity and ongoing treatments, other relevant medical history details, and vital constants on arrival for triage. Multilevel multivariable logistic regression models were used to identify predictors. RESULTS: The model showed that patients who had nonadverse outcomes were younger, female, and vaccinated against COVID-19 (2 doses at the time of the study). They arrived with normal vital signs (heart rate, diastolic and systolic pressures, temperature, and oxygen saturation) and had none of the following concomitant diseases or factors: heart failure other heart disease, hypertension, diabetes, liver disease, dementia, history of malignant tumors, and they were not being treated with oral or other systemic corticosteroids or immunosuppressant therapy. The area under the receiver operating characteristic curve for the model was 0.840 (95% CI, 0.834-0.847). CONCLUSION: We developed the CoNAE scale to predict nonadverse outcomes. This scale may be useful in triage for evaluating patients with COVID-19. It may also help predict safe discharge or plan the level of care that patients require not only in a hospital emergency department but also in urgent primary care settings or out-of-hospital emergency care.

OBJETIVO: Faltan herramientas para identificar a los pacientes con COVID-19 moderado o leve. El objetivo de este estudio fue identificar variables asociadas a la evolución no adversa y diseñar un modelo predictivo de evolución favorable en pacientes atendidos en servicios de urgencias hospitalarios (SUH) por infección por SARS-CoV-2. METODO: Estudio de cohorte retrospectivo de pacientes con infección por SARS-CoV-2 que acudieron a alguno de los SUH de hospitales públicos de una área por una infección por COVID-19 entre el 1 de julio de 2020 y el 31 de julio de 2021. Los datos recogidos para este estudio incluyeron información sociodemográfica, comorbilidades basales y tratamientos, otros datos de antecedentes y registro de los signos vitales a la llegada (triaje) al SUH. Se utilizaron modelos de regresión logística multivariable multinivel para desarrollar los modelos predictivos. RESULTADOS: Las personas que tuvieron resultados no adversos eran más jóvenes, mujeres, habían recibido dos dosis de la vacuna COVID-19 en el momento del estudio, tenían signos vitales (frecuencia cardiaca-presión diastólica/sistólica, temperatura y saturación de oxígeno) dentro de un rango normal al llegar al triaje del SUH, y no tenían ninguna de las siguientes comorbilidades: insuficiencia cardiaca, enfermedad coronaria, hipertensión arterial, diabetes, enfermedad hepática, demencia, antecedentes de tumores malignos o prescripción de corticosteroides orales sistémicos o inmunosupresores como medicación basal. El modelo tenía un área bajo la curva (ABC) de 0,8404 (IC 95%: 0,8342-0,8466). CONCLUSIONES: Se ha desarrollado una escala de predicción de resultados no adversos que pueden ser útil como herramienta de triaje, así como para determinar el alta segura y para adaptar el nivel de atención que el paciente requiere, no sólo en el SUH, sino también a nivel de atención de emergencia primaria o extrahospitalaria.

Prevalence and risk of new-onset diabetes mellitus after COVID-19: a systematic review and meta-analysis.

Aims: After the acute phase of SARS-CoV-2 infection, the onset of glycemic impairment and diabetes have been reported. Nevertheless, the exact burden of glycemic impairment and diabetes after COVID-19 has not been clearly described. Materials and methods: Electronic search was run in Pubmed (MEDLINE), Web of Science, Scopus, and ClinicalTrial.org for reports published from database inception to September 2022. We included observational studies reporting quantitative data on diabetes prevalence or its onset in subjects with a history of SARS-CoV-2 infection from at least 60 days. Risk of bias was assessed by the JBI's critical appraisal checklist. Random effect model was used to calculate pooled data. The review protocol was registered on PROSPERO (CRD42022310722). Results: Among 1,630 records screened, 20 studies were included in the analysis. The mean or median age of participants ranged from ~ 35 to 64 years, with a percentage of males ranging from 28% to 80%. Only two studies were considered at low risk of bias. The estimate of diabetes prevalence, calculated on a total of 320,948 participants pooled with 38,731 cases, was 16% (95%CI: 11-22%). The estimate of proportion of incident cases of diabetes was 1.6% (95%CI: 0.8-2.7%). Subgroup analysis showed that previous hospitalization increased the prevalence of diabetes and the proportion of incident cases. Conclusion: Diabetes is common in individuals who have experienced SARS-CoV-2 infection, especially if they required hospitalization. This data may be helpful to screen for diabetes and manage its complications in individuals who experienced COVID-19. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022310722, identifier CRD42022310722.

La pandemia de COVID-19 y el cumplimiento de las guías alimentarias en una comunidad universitaria de Chile / COVID-19 pandemic and adherence to food- based dietary guidelines in a Chilean university community

Introducción. La pandemia de SARS-CoV-2/COVID-19 y las restricciones sanitarias afectaron la disponibilidad, acceso y consumo de alimentos, impactando la alimentación y el estado nutricional. Objetivo. Determinar el efecto de la pandemia SARS-CoV-2/COVID-19 sobre el cumplimiento de las Guías Alimentarias Basadas en Alimentos de Chile, en una comunidad universitaria, antes y durante la pandemia. Materiales y métodos. Estudio de cohorte retrospectiva con 427 participantes. Se aplicó una encuesta online con preguntas basadas en los mensajes de las GABA. La encuesta se validó por juicio de expertos y análisis psicométrico, evaluando la concordancia con el estadístico de Kappa (K=89,95) y la confiabilidad con el coeficiente Alfa de Cronbach (=0,97). Se fijó como período antes de la pandemia al tiempo anterior a marzo del año 2020, y durante la pandemia, entre marzo del 2020 y octubre del 2021. Para medir los cambios antes y durante la pandemia se aplicó el test de simetría considerando un p <0,05 con un intervalo de confianza del 95%, mediante el software estadístico STATA versión 16. Resultados. Se observaron cambios estadísticamente significativos antes y durante la pandemia en los mensajes relacionados con el estado nutricional (p=0,000), consumo semanal de: productos de pastelería (p=0,0040), cecinas y embutidos (p=0,0034), frituras (p=0,0070), legumbres (p=0,0000), aguas (p=0,0000) y lectura e información nutricional de los productos (p=0,0000). Conclusiones. La pandemia de SARS-CoV-2/COVID-19 generó cambios en la alimentación y estado nutricional respecto a los mensajes de las guías. Se precisan políticas alimentarias y estrategias educativas en alimentación y en nutrición para emergencias sanitarias(AU)

Introduction. The SARS-CoV-2/COVID-19 pandemic, as well as health restrictions, impacted food availability, access and consumption, affecting dietary habits and nutritional status. Objective. To determine the effect of the SARS-CoV-2/ COVID-19 pandemic on the adherence to Chilean Food-Based Dietary Guidelines, within a university community, both before and during the pandemic. Materials and methods. A retrospective cohort study involving 427 participants was conducted. An online survey was administered, with questions based on the FBDGs' messages. The survey was validated through expert judgment and psychometric analysis, and agreement was assessed using the Kappa statistic (K = 89.95) while reliability was determined using the Cronbach's Alpha coefficient ( = 0.97). The period before the pandemic was defined as the time prior to March 2020, and the pandemic period was set between March 2020 and October 2021. Changes before and during the pandemic were measured using the symmetry test, considering a p value of <0.05 and a 95% confidence level, using the STATA 16 statistical software. Results. Statistically significant changes were observed before and during the pandemic in messages related to nutritional status (p = 0.000), weekly consumption of bakery products (p = 0.0040), cold meats (p = 0.0034), fried foods (p = 0.0070), legumes (p = 0.0000), water (p = 0.0000), and messages related to reading and nutrition information of products (p = 0.0000). Conclusions. The pandemic led to dietary changes in relation to FBDGs messages. Food policies and food and nutrition education strategies are required to address health emergency contexts(AU)

Enhancing global preparedness during an ongoing pandemic from partial and noisy data.

As the coronavirus disease 2019 spread globally, emerging variants such as B.1.1.529 quickly became dominant worldwide. Sustained community transmission favors the proliferation of mutated sub-lineages with pandemic potential, due to cross-national mobility flows, which are responsible for consecutive cases surge worldwide. We show that, in the early stages of an emerging variant, integrating data from national genomic surveillance and global human mobility with large-scale epidemic modeling allows to quantify its pandemic potential, providing quantifiable indicators for pro-active policy interventions. We validate our framework on worldwide spreading variants and gain insights about the pandemic potential of BA.5, BA.2.75, and other sub- and lineages. We combine the different sources of information in a simple estimate of the pandemic delay and show that only in combination, the pandemic potentials of the lineages are correctly assessed relative to each other. Compared to a country-level epidemic intelligence, our scalable integrated approach, that is pandemic intelligence, permits to enhance global preparedness to contrast the pandemic of respiratory pathogens such as SARS-CoV-2.

Dynamics of SARS-CoV-2 seroassay sensitivity: a systematic review and modelling study.

BackgroundSerological surveys have been the gold standard to estimate numbers of SARS-CoV-2 infections, the dynamics of the epidemic, and disease severity. Serological assays have decaying sensitivity with time that can bias their results, but there is a lack of guidelines to account for this phenomenon for SARS-CoV-2.AimOur goal was to assess the sensitivity decay of seroassays for detecting SARS-CoV-2 infections, the dependence of this decay on assay characteristics, and to provide a simple method to correct for this phenomenon.MethodsWe performed a systematic review and meta-analysis of SARS-CoV-2 serology studies. We included studies testing previously diagnosed, unvaccinated individuals, and excluded studies of cohorts highly unrepresentative of the general population (e.g. hospitalised patients).ResultsOf the 488 screened studies, 76 studies reporting on 50 different seroassays were included in the analysis. Sensitivity decay depended strongly on the antigen and the analytic technique used by the assay, with average sensitivities ranging between 26% and 98% at 6 months after infection, depending on assay characteristics. We found that a third of the included assays departed considerably from manufacturer specifications after 6 months.ConclusionsSeroassay sensitivity decay depends on assay characteristics, and for some types of assays, it can make manufacturer specifications highly unreliable. We provide a tool to correct for this phenomenon and to assess the risk of decay for a given assay. Our analysis can guide the design and interpretation of serosurveys for SARS-CoV-2 and other pathogens and quantify systematic biases in the existing serology literature.

Macrophage phagocytosis of SARS-CoV-2-infected cells mediates potent plasmacytoid dendritic cell activation.

Early and strong interferon type I (IFN-I) responses are usually associated with mild COVID-19 disease, whereas persistent or unregulated proinflammatory cytokine responses are associated with severe disease outcomes. Previous work suggested that monocyte-derived macrophages (MDMs) are resistant and unresponsive to SARS-CoV-2 infection. Here, we demonstrate that upon phagocytosis of SARS-CoV-2-infected cells, MDMs are activated and secrete IL-6 and TNF. Importantly, activated MDMs in turn mediate strong activation of plasmacytoid dendritic cells (pDCs), leading to the secretion of high levels of IFN-α and TNF. Furthermore, pDC activation promoted IL-6 production by MDMs. This kind of pDC activation was dependent on direct integrin-mediated cell‒cell contacts and involved stimulation of the TLR7 and STING signaling pathways. Overall, the present study describes a novel and potent pathway of pDC activation that is linked to the macrophage-mediated clearance of infected cells. These findings suggest that a high infection rate by SARS-CoV-2 may lead to exaggerated cytokine responses, which may contribute to tissue damage and severe disease.

Long COVID: Is there a kidney link?

Metabolic causes such as altered bioenergetics and amino acid metabolism may play a major role in Long COVID. Renal-metabolic regulation is an integral part of these pathways but has not been systematically or routinely investigated in Long COVID. Here we discuss the biochemistry of renal tubular injury as it may contribute to Long COVID symptoms. We propose three potential mechanisms that could be involved in Long COVID namely creatine phosphate metabolism, un-reclaimed glomerular filtrate and COVID specific proximal tubule cells (PTC) injury-a tryptophan paradigm. This approach is intended to allow for improved diagnostics and therapy for the long-haul sufferers.

Parental Decision Making Regarding COVID-19 Vaccines for Children under Age 5: Does Decision Self-Efficacy Play a Role?

BACKGROUND: COVID-19 vaccines are now available under Emergency Use Authorization for children ages 6 months to 5 years. We examined parents' intentions to vaccinate their children under the age of 5 years and assessed whether their confidence in making an informed decision about vaccination (decision self-efficacy) was associated with these intentions. METHOD: We conducted a cross-sectional online survey of U.S. parents between 23 March and 5 April 2022. We examined associations between parental intention to vaccinate their young children (

Impact of Omicron BA.1 infection on BA.4/5 immunity in transplant recipients.

Mutations in the spike protein of SARS-CoV-2 have allowed Omicron subvariants to escape neutralizing antibodies. The degree to which this occurs in transplant recipients is poorly understood. We measured BA.4/5 cross-neutralizing responses in 75 mostly vaccinated transplant recipients who recovered from BA.1 infection. Sera were collected at 1 and 6 months post-BA.1 infection, and a lentivirus pseudovirus neutralization assay was performed using spike constructs corresponding to BA.1 and BA.4/5. Uninfected immunized transplant recipients and health care worker controls were used for comparison. Following BA.1 infection, the proportion of transplant recipients with neutralizing antibody responses was 88.0% (66/75) against BA.1 and 69.3% (52/75) against BA.4/5 (P = .005). The neutralization level against BA.4/5 was approximately 17-fold lower than that against BA.1 (IQR 10.6- to 45.1-fold lower, P < .0001). BA.4/5 responses declined over time and by ≥0.5 log10 (approximately 3-fold) in almost half of the patients by 6 months. BA.4/5-neutralizing antibody titers in transplant recipients with breakthrough BA.1 infection were similar to those in immunized health care workers but significantly lower than those in uninfected triple-vaccinated transplant recipients. These results provide evidence that transplant recipients are at ongoing risk for BA.4/5 infection despite vaccination and prior Omicron strain infection, and additional mitigation strategies may be required to prevent severe disease in this cohort.

Drug-drug interactions of ritonavir-boosted SARS-CoV-2 protease inhibitors in solid organ transplant recipients: experience from the initial use of lopinavir-ritonavir.

OBJECTIVES: To review the drug-drug interactions between tacrolimus and lopinavir/ritonavir in 23 patients who received solid organ transplant during the first wave of COVID-19 and to determine the efficacy as well as safety of prednisone monotherapy. METHODS: Observational study performed between March and June 2020 in solid organ transplant recipients admitted with an established diagnosis of SARS-CoV-2 infection who received lopinavir/ritonavir (≥2 doses). Once lopinavir/ritonavir therapy was initiated, calcineurin inhibitor treatment was temporarily switched to prednisone monotherapy (15-20 mg/d) to avoid drug-drug interactions and toxicity. After lopinavir/ritonavir treatment completion, immunosuppressive treatment was restarted with reduced doses of prednisone-tacrolimus (target minimum blood concentration -C0- approximately 5 ng/mL). Patients were observed for 3 months to confirm the absence of rejection. RESULTS: The median time from discontinuation of tacrolimus to initiation of lopinavir/ritonavir was 14 hours (interquartile range [IQR], 12-15) and from discontinuation of lopinavir/ritonavir to resumption of tacrolimus 58 hours (IQR, 47-81). The duration of lopinavir/ritonavir treatment was 7 days (IQR, 5-7). Nine of the 21 (42.8%) patients on tacrolimus treatment had C0 above the cutoff point after lopinavir/ritonavir initiation, despite having been substituted with prednisone before lopinavir/ritonavir initiation. Three patients had very high concentrations (>40 ng/mL) and developed toxicity. No episodes of acute rejection were diagnosed. DISCUSSION: We did not observe toxicity in patients for whom tacrolimus was discontinued 24 hours before starting lopinavir/ritonavir and reintroduced at half dose 48 to 72 hours after lopinavir/ritonavir discontinuation. Prednisone monotherapy during lopinavir/ritonavir therapy was safe with no episodes of acute rejection. Experience with lopinavir/ritonavir may be applicable to the use of nirmatrelvir/ritonavir, but larger multicentre studies are needed to confirm these findings.

COVID-19 infection and ginseng: Predictive influenza virus strains and non-predictive COVID-19 vaccine strains.

Vaccines help protect people from infections. However, Coronavirus 2019 (COVID-19) vaccinees often still become infected with COVID-19 variants (breakthrough infections) and may go on to suffer from long COVID symptoms due to short-lasting immunity and less-effective protection provided by available vaccines. Moreover, the current COVID-19 vaccines do not prevent viral transmission and ward off only about 15% of breakthrough infections. To prepare more effective vaccines, it is essential to predict the viral strains that will be circulating based on available epidemiological data. The World Health Organization recommends in advance which influenza strains are expected to be prevalent during influenza season to guide the production of influenza vaccines by pharmaceutical companies. However, future emerging COVID-19 strain(s) have not been possible to predict since no sound epidemiological information has been established. Thus, for more effective protection, immune stimulators alone or in combination with vaccines would be preferable to protect people from COVID-19 infection. One of those remedies would be ginseng, which has been used for potentiating immunity in the past.