Ancestral SARS-CoV-2, but not Omicron, replicates less efficiently in primary pediatric nasal epithelial cells.

Children typically experience more mild symptoms of Coronavirus Disease 2019 (COVID-19) when compared to adults. There is a strong body of evidence that children are also less susceptible to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection with the ancestral viral isolate. However, the emergence of SARS-CoV-2 variants of concern (VOCs) has been associated with an increased number of pediatric infections. Whether this is the result of widespread adult vaccination or fundamental changes in the biology of SARS-CoV-2 remain to be determined. Here, we use primary nasal epithelial cells (NECs) from children and adults, differentiated at an air-liquid interface to show that the ancestral SARS-CoV-2 replicates to significantly lower titers in the NECs of children compared to those of adults. This was associated with a heightened antiviral response to SARS-CoV-2 in the NECs of children. Importantly, the Delta variant also replicated to significantly lower titers in the NECs of children. This trend was markedly less pronounced in the case of Omicron. It is also striking to note that, at least in terms of viral RNA, Omicron replicated better in pediatric NECs compared to both Delta and the ancestral virus. Taken together, these data show that the nasal epithelium of children supports lower infection and replication of ancestral SARS-CoV-2, although this may be changing as the virus evolves.

Lactobacillus rhamnosus dampens cytokine and chemokine secretion from primary human nasal epithelial cells infected with rhinovirus.

AIMS: To investigate the effect of Lactobacillus rhamnosus on viral replication and cellular response to human rhinovirus (HRV) infection, including the secretion of antiviral and inflammatory mediators from well-differentiated nasal epithelial cells (WD-NECs). METHODS AND RESULTS: The WD-NECs from healthy adult donors (N = 6) were cultured in vitro, exposed to different strains of L. rhamnosus (D3189, D3160, or LB21), and infected with HRV (RV-A16) after 24 h. Survival and adherence capacity of L. rhamnosus in a NEC environment were confirmed using CFSE-labelled isolates, immunofluorescent staining, and confocal microscopy. Shed virus and viral replication were quantified using TCID50 assays and RT-qPCR, respectively. Cytotoxicity was measured by lactate dehydrogenase (LDH) activity. Pro-inflammatory mediators were measured by multiplex immunoassay, and interferon (IFN)-λ1/3 was measured using a standard ELISA kit. Lactobacillus rhamnosus was able to adhere to and colonize WD-NECs prior to the RV-A16 infection. Lactobacillus rhamnosus did not affect shed RV-A16, viral replication, RV-A16-induced IFN-λ1/3 production, or LDH release. Pre-exposure to L. rhamnosus, particularly D3189, reduced the secretion of RV-A16-induced pro-inflammatory mediators by WD-NECs. CONCLUSIONS: These findings demonstrate that L. rhamnosus differentially modulates RV-A16-induced innate inflammatory immune responses in primary NECs from healthy adults.

Circular RNA sequencing identified circARNTL2 as a pathogenic factor in psoriasis by facilitating proliferation and cell cycle progression of keratinocytes.

Psoriasis is a chronic recurrent skin disease, with excessive proliferation of keratinocytes. Recent studies indicated the pathogenic roles of circular RNA (circRNA) in psoriasis. Here, we screened the circRNA profiles from five psoriatic skin lesions and five normal skin tissues by circRNA sequencing and identified 1118 differentially expressed circRNAs (DECs) between psoriatic and normal groups. Among these DECs, high abundant circARNTL2 has been proven upregulated in psoriatic skin lesions by RT-qPCR assay. Then, the head-to-tail structure of circARNTL2 was validated by Sanger sequencing and RNase R digestion assay. Moreover, we determined cytoplastic location of circARNTL2 by RT-qPCR assay of nuclear/cytoplasmic RNA and FISH analysis. Further experiments demonstrated that silencing circARNTL2 expression could block cell proliferation and cell cycle progression of keratinocytes. Mechanistically, circARNTL2 can bind to and regulate Serpin B4 which also affects the proliferation of keratinocytes. These findings provide evidence for the role of circARNTL2 in psoriasis.

Low-dose IL-2 therapy invigorates CD8+ T cells for viral control in systemic lupus erythematosus.

Autoimmune diseases are often treated by glucocorticoids and immunosuppressive drugs that could increase the risk for infection, which in turn deteriorate disease and cause mortality. Low-dose IL-2 (Ld-IL2) therapy emerges as a new treatment for a wide range of autoimmune diseases. To examine its influence on infection, we retrospectively studied 665 patients with systemic lupus erythematosus (SLE) including about one third receiving Ld-IL2 therapy, where Ld-IL2 therapy was found beneficial in reducing the incidence of infections. In line with this clinical observation, IL-2 treatment accelerated viral clearance in mice infected with influenza A virus or lymphocytic choriomeningitis virus (LCMV). Noticeably, despite enhancing anti-viral immunity in LCMV infection, IL-2 treatment exacerbated CD8+ T cell-mediated immunopathology. In summary, Ld-IL2 therapy reduced the risk of infections in SLE patients and enhanced the control of viral infection, but caution should be taken to avoid potential CD8+ T cell-mediated immunopathology.

The role of children in transmission of SARS-CoV-2 variants of concern within households: an updated systematic review and meta-analysis, as at 30 June 2022.

BackgroundMeta-analyses and single-site studies have established that children are less infectious than adults within a household when positive for ancestral SARS-CoV-2. In addition, children appear less susceptible to infection when exposed to ancestral SARS-CoV-2 within a household. The emergence of SARS-CoV-2 variants of concern (VOC) has been associated with an increased number of paediatric infections worldwide. However, the role of children in the household transmission of VOC, relative to the ancestral virus, remains unclear.AimWe aimed to evaluate children's role in household transmission of SARS-CoV-2 VOC.MethodsWe perform a meta-analysis of the role of children in household transmission of both ancestral SARS-CoV-2 and SARS-CoV-2 VOC.ResultsUnlike with the ancestral virus, children infected with VOC spread SARS-CoV-2 to an equivalent number of household contacts as infected adults and were equally as likely to acquire SARS-CoV-2 VOC from an infected family member. Interestingly, the same was observed when unvaccinated children exposed to VOC were compared with unvaccinated adults exposed to VOC.ConclusionsThese data suggest that the emergence of VOC was associated with a fundamental shift in the epidemiology of SARS-CoV-2. It is unlikely that this is solely the result of age-dependent differences in vaccination during the VOC period and may instead reflect virus evolution over the course of the pandemic.

A Meta-analysis on the Role of Children in Severe Acute Respiratory Syndrome Coronavirus 2 in Household Transmission Clusters.

The role of children in the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains highly controversial. To address this issue, we performed a meta-analysis of the published literature on household SARS-CoV-2 transmission clusters (n = 213 from 12 countries). Only 8 (3.8%) transmission clusters were identified as having a pediatric index case. Asymptomatic index cases were associated with a lower secondary attack in contacts than symptomatic index cases (estimate risk ratio [RR], 0.17; 95% confidence interval [CI], 0.09-0.29). To determine the susceptibility of children to household infections the secondary attack rate in pediatric household contacts was assessed. The secondary attack rate in pediatric household contacts was lower than in adult household contacts (RR, 0.62; 95% CI, 0.42-0.91). These data have important implications for the ongoing management of the COVID-19 pandemic, including potential vaccine prioritization strategies.

The relationship between the expression of Ki-67 and the prognosis of osteosarcoma.

BACKGROUND: A number of studies have linked positive Ki-67 expression with the prognosis of osteosarcoma (OS) patients. However, the results have been conflicting. To address this controversy, we conducted an analysis using a meta-analysis and a TCGA dataset to estimate the value of Ki-67 expression in the prognosis of OS. METHODS: A comprehensive search for relevant papers was conducted using NCBI PubMed, Embase, Springer, ISI Web of Knowledge, the Cochrane Library, and CNKI regardless of the publication year. The associations between Ki-67 expression and the clinical features and main prognostic outcomes of OS were measured. The TCGA dataset was also analyzed. The pooled odds ratio (OR) and its 95% confidential intervals (CIs) were utilized for statistical analysis. RESULTS: Overall, a total of 12 studies with 500 cases were included, and the results indicated that the expression of Ki-67 was significantly associated with Enneking stage (OR = 6.88, 95% CI: 2.92-16.22, p < 0.05), distant metastasis (OR = 3.04, 95% CI: 1.51-6.12, p < 0.05) and overall survival (OR = 8.82, 95% CI: 4.68-16.65, p < 0.05) in OS patients. Additionally, we observed no significant heterogeneity among all retrieved studies. Associations between Ki-67 expression and overall survival and disease-free survival of sarcoma were confirmed using the TCGA and Kaplan-Meier plotter datasets. CONCLUSION: The present study strongly suggests that positive Ki-67 expression was associated with Enneking stage, distant metastasis, and overall survival of OS, and it may be used as a potential biomarker to predict prognosis and guide clinical therapy for OS.

Oral manifestations of patients with systemic sclerosis: a meta-analysis for case-controlled studies.

BACKGROUND: Systemic sclerosis (SSc) is a multisystem rheumatic disease. Orofacial manifestations are commonly in SSc but maybe usually ignored and overshadowed by other systemic complications. Multiple comparative studies have been conducted to investigate the possible links between SSc and oral manifestations. The present study aimed to investigate the oral health status in patients with SSc. METHODS: Pubmed, Embase, Web of Science, and Scopus were searched up to July 2020. Following outcomes were evaluated: Probing depth (PD), Attachment loss (AL), Bleeding on probing (BOP), Number or percentage of Sites with PD ≥ 4 mm, Prevalence of periodontitis, Number of teeth, Decayed Teeth, Missing teeth, Filled teeth, DMFT index, and the interincisal distance. Newcastle-Ottawa Scale (NOS) were applied for quality assessment. The statistical analysis was processed using the software STATA. RESULTS: 11 eligible studies were included. The maximum interincisor distance was significantly restricted in SSc patients (SMD - 1.061; 95 %CI [- 1.546, - 0.576]; Z = 4.29, P = 0.000).The prevalence of Periodontitis (OR 7.007; 95 %CI [3.529, 13.915]; Z = 5.56, P = 0.000), PD (SMD 3.101; 95 %CI [1.374, 4.829]; Z = 3.52, P = 0.000), AL(SMD 2.584; 95 %CI [0.321, 4.846]; Z = 2.24, P = 0.025), sites with PD ≥ 4mm (SMD 2.071 ; 95 %CI [0.267, 3.875]; Z = 2.25, P = 0.024) and the number of decayed teeth (SMD, 0.186; 95 %CI [0.007, 0.365]; Z = 2.04, P = 0.041) were increased significantly in SSc population in comparison with the controls. CONCLUSIONS: SSc patients have limited mouth opening, higher periodontitis prevalence, and worse periodontal status, as well as an increased number of decayed teeth. Routinely oral hygiene instruction and initial periodontal treatment is recommended for SSc patients.

A Comparative Study of Associated Microbiota Between Pig Farm and Pig Slaughterhouse in Guangdong, China.

The goal of this study was to compare the microbiota in different pig-present settings in China. Bioaerosol samples from pig farms and slaughterhouses and nasal samples from pig farmers and slaughterhouse workers were collected in Guangdong, southern China. The bacterial genomic DNA was isolated and subjected to 16S sequencing. The data were analyzed using QIIME2 with the DADA2 pipeline. A total of 14,923,551 clean reads and 2785 operational taxonomic units (OTUs) were obtained, which were mostly grouped into 4 phyla (Proteobacteria, Bacteroidetes, Firmicutes, and Actinobacteria) and 220 families. The microbiota richness of nasal samples in pig-present workers was higher than that of bioaerosols collected in the vicinity of the pig enclosures. There were 31.7% (620/1954) shared OTUs between pig farm bioaerosols and pig farmers which was higher than that between pig slaughterhouses and slaughterhouse workers (23.4%, 364/1553) (p < 0.001). Acinetobacter and Pseudomonas were the most abundant in pig-present bioaerosols, and Staphylococcus, Pseudomonas, and Corynebacterium were dominant bacterial genus in pig farmers. The bacterial patterns are also specific to the location of sample collected. The results suggest that bioaerosol microbiota interact with human nasal microbes in the vicinity of the pig farm enclosures, providing the basis for further analysis of microbial transmission across hosts in pig-present settings.

A prediction model for reactivation of Langerhans cell histiocytosis based on machine-learning algorithms.

Langerhans cell histiocytosis (LCH) is a rare inflammatory myeloid neoplasm characterized by the clonal proliferation of myeloid progenitor cells. The reactivation rate of LCH exceeds 30%. However, an effective prediction model to predict reactivation is lacking. To select potential prognostic factors of LCH and construct an easy-to-use predictive model based on machine-learning algorithms. Clinical records of LCH inpatients in the Second Xiangya Hospital of Central South University, from 2008 to 2022, were retrospectively studied. Seventy-six patients were classified into a reactivated/progressive group or a stable group. Clinical features and laboratory outcomes were compared, and machine-learning algorithms were used for building prognostic prediction models. Clinical classification (single-system LCH, multiple-system LCH, and central nervous system/lung LCH), level of anemia, bone involvement, skin involvement, and elevated monocyte count were the best performing factors and were finally chosen for the construction of the prediction models. Our results show that the above-mentioned five factors can be used together in a prediction model for the prognosis of LCH patients. The major limitations of this study include its retrospective nature and the relatively small sample size.

The dysregulation of circulating innate lymphoid cells is related to autoantibodies in pemphigus vulgaris.

BACKGROUND: Pemphigus vulgaris (PV) is a typical autoimmune disease caused by autoantibodies. Innate lymphoid cells (ILCs) are non-antigen-dependent populations composed of different subsets, also known as "mirror cells" of T cells, which play a crucial role in immune inflammatory diseases. However, the characteristics of ILCs in PV are unclear. METHODS: Patients diagnosed with PV along with healthy controls in Second Xiangya Hospital of Central South University were studied. Flow cytometry was used to detect the proportion of ILC subsets in the peripheral blood. Anti-desmoglein (DSG) 1 and anti-DSG3 antibody levels of PV patients were detected. RESULTS: Thirty-eight PV patients and 37 healthy controls were enrolled. There were no differences in sex or age between the two groups. Compared with controls, ILCs/CD45+ lymphocytes were significantly decreased in patients with PV. The frequency of ILC1s increased in patients with PV and was positively correlated with anti-DSG3 antibodies. However, the frequency of ILC3s decreased in patients with PV and was negatively correlated with anti-DSG1 antibodies. After methylprednisolone treatment, ILC1/ILC levels significantly decreased. CONCLUSIONS: Circulating ILC subsets are associated with PV pathogenesis. Upregulated ILC1s seem to correlate positively with PV severity and can be restored after treatment.

Clinical features and prognostic factors of severe cutaneous adverse drug reactions: A single-center retrospective study of 209 cases in China.

BACKGROUND: Severe cutaneous adverse drug reactions (SCAR) are life-threatening and contain drug reactions with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP). METHODS: We aimed to evaluate clinical features and prognostic factors for SCAR patients. From January 2010 to April 2022, 209 patients with SCAR (DRESS, n = 46, SJS/TEN, n = 128, AGEP, n = 35) were included in this study. Clinical symptoms, laboratory tests, causative drugs, disease courses, treatments, and outcomes were investigated. RESULTS: Antibiotics ranked first (35.9 %) followed by traditional Chinese medicine (15.8 %) and antiepileptic drugs (14.8 %) among causative drugs of SCAR. One patient (2.2 %) with DRESS and seven patients (5.5 %) with SJS/TEN died in the hospital, while there was no AGEP-related mortality. The multivariate logistic regression analysis showed that high Registry of Severe Cutaneous Adverse Reactions score (OR = 2.340, 95 % CI = 1.192-4.591) and hemoglobin < 100 g/L (OR = 0.126, 95 % CI = 0.016-0.983) were independent risk factors of DRESS. Anemia (OR = 0.191, 95 % CI = 0.037-0.984) and body surface area detached involved at day 1 (OR = 2.749, 95 % CI = 1.115-6.778) were independent risk factors of SJS/TEN for severe acute complications and hospital death (P < 0.05). Lymphocytopenia (OR = 0.004, 95 % CI = 0.000-0.553) was a risk factor of AGEP for acute complications (P = 0.028). CONCLUSION: This study reveals the clinical features and independent prognostic factors for SCAR, which may be helpful in the clinical management for SCAR patients.

Ferroptosis Activation Contributes to the Formation of Skin Lesions in Psoriasis Vulgaris.

(1) Background: Ferroptosis is a newly coined form of programmed cell death marked by lethal accumulation of lipid peroxidation and ferrous iron overload. A few studies on the specific mechanism of ferroptosis in the genesis and development of psoriasis are available. (2) Methods: Levels of lipid reactive oxygen species (ROS) and ferrous iron were measured by flow cytometry. Ultrastructure analysis was performed by transmission electron microscopy. Imiquimod-induced psoriasis-like mice were treated with a ferroptosis inducer. The expressions of mRNA of genes were measured by qRT-PCR. HaCaT cells were used to explore the function of Cyb561d2. (3) Results: In this work, we observed that levels of lipid ROS and ferrous iron in the epidermis of psoriasis vulgaris (PV) patients were increased. The existence of ferroptosis activation in the epidermis of individuals with PV was confirmed by transmission electron microscope both in patients with PV and psoriasis-like mice models. Intradermal injection of the ferroptosis inducer RSL3 in psoriasis-like mice significantly promoted and aggravated the development of psoriasis-like dermatitis, and the level of serum transferrin was also increased in PV samples. Moreover, abnormal expression of some genes related to iron metabolism was also proved in the epidermis of PV cases, among which Cyb561d2 was shown to promote ferrous iron overload and lipid peroxidation accumulation in HaCaT cells. (4) Conclusions: In summary, our study suggested that ferroptosis activation owing to iron overload may be a novel mechanism underlying the formation of skin lesions in individuals with PV.

International Pediatric COVID-19 Severity Over the Course of the Pandemic.

Importance: Multiple SARS-CoV-2 variants have emerged over the COVID-19 pandemic. The implications for COVID-19 severity in children worldwide are unclear. Objective: To determine whether the dominant circulating SARS-CoV-2 variants of concern (VOCs) were associated with differences in COVID-19 severity among hospitalized children. Design, Setting, and Participants: Clinical data from hospitalized children and adolescents (younger than 18 years) who were SARS-CoV-2 positive were obtained from 9 countries (Australia, Brazil, Italy, Portugal, South Africa, Switzerland, Thailand, UK, and the US) during 3 different time frames. Time frames 1 (T1), 2 (T2), and 3 (T3) were defined to represent periods of dominance by the ancestral virus, pre-Omicron VOCs, and Omicron, respectively. Age groups for analysis were younger than 6 months, 6 months to younger than 5 years, and 5 to younger than 18 years. Children with an incidental positive test result for SARS-CoV-2 were excluded. Exposures: SARS-CoV-2 hospitalization during the stipulated time frame. Main Outcomes and Measures: The severity of disease was assessed by admission to intensive care unit (ICU), the need for ventilatory support, or oxygen therapy. Results: Among 31 785 hospitalized children and adolescents, the median age was 4 (IQR 1-12) years and 16 639 were male (52.3%). In children younger than 5 years, across successive SARS-CoV-2 waves, there was a reduction in ICU admission (T3 vs T1: risk ratio [RR], 0.56; 95% CI, 0.42-0.75 [younger than 6 months]; RR, 0.61, 95% CI; 0.47-0.79 [6 months to younger than 5 years]), but not ventilatory support or oxygen therapy. In contrast, ICU admission (T3 vs T1: RR, 0.39, 95% CI, 0.32-0.48), ventilatory support (T3 vs T1: RR, 0.37; 95% CI, 0.27-0.51), and oxygen therapy (T3 vs T1: RR, 0.47; 95% CI, 0.32-0.70) decreased across SARS-CoV-2 waves in children 5 years to younger than 18 years old. The results were consistent when data were restricted to unvaccinated children. Conclusions and Relevance: This study provides valuable insights into the impact of SARS-CoV-2 VOCs on the severity of COVID-19 in hospitalized children across different age groups and countries, suggesting that while ICU admissions decreased across the pandemic in all age groups, ventilatory and oxygen support generally did not decrease over time in children aged younger than 5 years. These findings highlight the importance of considering different pediatric age groups when assessing disease severity in COVID-19.

DNA methylation markers in peripheral blood for psoriatic arthritis.

BACKGROUND: The clinical manifestations of psoriatic arthritis (PsA) are highly heterogeneous and no reliable diagnostic biomarkers exist. OBJECTIVE: We explored the role of DNA methylation CpG markers in the diagnosis of PsA. METHODS: DNA methylation array was used to screen for differentially methylated sites (DMSs) in the discovery phase (PsA, n = 25; healthy controls [HCs], n = 19; psoriasis vulgaris [PsV], n = 20). In the validation phase, pyrosequencing was used to identify the DMSs in an expanded cohort (PsA, n = 60; HCs, n = 91; PsV, n = 48; rheumatoid arthritis [RA], n = 60). Logistic regression prediction models were established based on the identified DMSs for the diagnosis of PsA. RESULTS: A total of 17 DMSs differentiating PsA and HCs as well as 11 DMSs differentiating PsA and PsV were screened in the discovery phase. A total of six DMSs (chr14: cg07940072, chr14: 38061320, chr9: cg15734589, chr6: cg12800266, chr3: cg12992827, chr6: cg24500972) differentiating PsA and HCs and two DMSs (chr12: cg16459382, chr2: cg16348668) differentiating PsA and PsV were identified using pyrosequencing. Three logistic regression prediction models were established based on the identified DMSs, which distinguished PsA, RA, PsV, and HCs (P < 0.001). The models performed well in differentiating PsA from HCs, RA, and PsV (AUC: 0.858, 0.851, and 0.976, respectively). CONCLUSIONS: The models based on methylated CpG sites are useful for distinguishing patients with PsA from HCs and those with RA or PsV and are a highly sensitive and specific diagnostic biomarker for PsA.

Decreased microRNA-126 expression in psoriatic CD4+ T cells promotes T-helper 17 cell differentiation and the formation of dermatitis in imiquimod-induced psoriasis-like mice.

Psoriasis is a chronic inflammatory skin disease with multiple genetic backgrounds, whose etiology and pathogenesis are still unclear. Complex T-cell immune imbalance has been demonstrated to play an important role in pathogenesis of psoriasis. This study reported that microRNA-126 (miR-126) expression was decreased in CD4+ T cells of both psoriasis patients and psoriasis-like mouse models and its expression was negatively correlated with the Psoriasis Area and Severity Index (PASI) score of psoriasis patients. Conditional Mir126 knockout in mouse CD4+ T cells can obviously aggravate the psoriasis-like dermatitis and promote T-helper (Th)1 and Th17 cells' infiltration in spleen of imiquimod (IMQ)-induced psoriasis-like mouse model. In addition, the mRNA expression of Il17a and Il17f were significantly increased in mouse naïve CD4+ T cells with Mir126 knockout after stimulating with CD3 and CD28. Compared with naïve CD4+ T cells, the expression of Mir126 was decreased in Th17 cells, and Mir126 knockout notably promoted the differentiation of naïve CD4+ T cells to Th17 cells as well as the mRNA expression of Il17a, Il17f, Rorc, and Il23R. Our results revealed that decreased miR-126 in psoriatic CD4+ T cells might accelerate the formation of skin lesions through promoting the differentiation of Th17 cells, thus suggesting a potential intervention target for psoriasis.

IFI27 transcription is an early predictor for COVID-19 outcomes, a multi-cohort observational study.

Purpose: Robust biomarkers that predict disease outcomes amongst COVID-19 patients are necessary for both patient triage and resource prioritisation. Numerous candidate biomarkers have been proposed for COVID-19. However, at present, there is no consensus on the best diagnostic approach to predict outcomes in infected patients. Moreover, it is not clear whether such tools would apply to other potentially pandemic pathogens and therefore of use as stockpile for future pandemic preparedness. Methods: We conducted a multi-cohort observational study to investigate the biology and the prognostic role of interferon alpha-inducible protein 27 (IFI27) in COVID-19 patients. Results: We show that IFI27 is expressed in the respiratory tract of COVID-19 patients and elevated IFI27 expression in the lower respiratory tract is associated with the presence of a high viral load. We further demonstrate that the systemic host response, as measured by blood IFI27 expression, is associated with COVID-19 infection. For clinical outcome prediction (e.g., respiratory failure), IFI27 expression displays a high sensitivity (0.95) and specificity (0.83), outperforming other known predictors of COVID-19 outcomes. Furthermore, IFI27 is upregulated in the blood of infected patients in response to other respiratory viruses. For example, in the pandemic H1N1/09 influenza virus infection, IFI27-like genes were highly upregulated in the blood samples of severely infected patients. Conclusion: These data suggest that prognostic biomarkers targeting the family of IFI27 genes could potentially supplement conventional diagnostic tools in future virus pandemics, independent of whether such pandemics are caused by a coronavirus, an influenza virus or another as yet-to-be discovered respiratory virus.

Genomic characterization of Wenzhou mammarenavirus detected in wild rodents in Guangzhou City, China.

Wenzhou mammarenavirus (WENV) is a zoonotic pathogen newly discovered in east and southeast Asia. WENV has been found in wild rodent animals around the world while its standing is barely understood in Guangzhou city, where is known as a region of outbreak hotspot for zoonotic emerging infectious diseases. To investigate the prevalence and genomic characteristics of mammarenavirus in Guangzhou City, lung tissue samples from wild rodent species were collected from five districts of Guangzhou City in the year 2015 and 2016. The viral RNA was extracted and then subjected to mammarenavirus-specific PCR. The result revealed approximately 1.0% (3/306) nucleic acid positivity for lung tissue samples obtained from three rodent species: Mus musculus, Rattus flavipectus, and Rattus norvegicus. Viral metagenomic sequencing of three samples was then carried out and two full segment L and three full segment S sequences were obtained. Phylogenetics analysis indicated the sequences of the new mammarenavirus strain have 76.2% - 94.4% similarity to known WENV encoded genes, with the highest similarity to the WENV 9-24 strain. Population structure analysis grouped all known WENV into seven lineages, and this WENV Guangzhou strain was grouped with WENV 9-24 as well. Though the seroprevalence result was not available, our data provides the first nucleic acid evidence of circulating WENV in Guangzhou city, and it suggested WENV had a broader host tropism than previously known.

Diabetes and Overweight/Obesity Are Independent, Nonadditive Risk Factors for In-Hospital Severity of COVID-19: An International, Multicenter Retrospective Meta-analysis.

OBJECTIVE: Obesity is an established risk factor for severe coronavirus disease 2019 (COVID-19), but the contribution of overweight and/or diabetes remains unclear. In a multicenter, international study, we investigated if overweight, obesity, and diabetes were independently associated with COVID-19 severity and whether the BMI-associated risk was increased among those with diabetes. RESEARCH DESIGN AND METHODS: We retrospectively extracted data from health care records and regional databases of hospitalized adult patients with COVID-19 from 18 sites in 11 countries. We used standardized definitions and analyses to generate site-specific estimates, modeling the odds of each outcome (supplemental oxygen/noninvasive ventilatory support, invasive mechanical ventilatory support, and in-hospital mortality) by BMI category (reference, overweight, obese), adjusting for age, sex, and prespecified comorbidities. Subgroup analysis was performed on patients with preexisting diabetes. Site-specific estimates were combined in a meta-analysis. RESULTS: Among 7,244 patients (65.6% overweight/obese), those with overweight were more likely to require oxygen/noninvasive ventilatory support (random effects adjusted odds ratio [aOR], 1.44; 95% CI 1.15-1.80) and invasive mechanical ventilatory support (aOR, 1.22; 95% CI 1.03-1.46). There was no association between overweight and in-hospital mortality (aOR, 0.88; 95% CI 0.74-1.04). Similar effects were observed in patients with obesity or diabetes. In the subgroup analysis, the aOR for any outcome was not additionally increased in those with diabetes and overweight or obesity. CONCLUSIONS: In adults hospitalized with COVID-19, overweight, obesity, and diabetes were associated with increased odds of requiring respiratory support but were not associated with death. In patients with diabetes, the odds of severe COVID-19 were not increased above the BMI-associated risk.

A meta-analysis on the role of pre-existing chronic disease in the cardiac complications of SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with multiple direct and indirect cardiovascular complications. We sought to analyze the association of host co-morbidities (chronic respiratory illnesses, cardiovascular disease [CVD], hypertension or diabetes mellitus [DM]) with the acute cardiovascular complications associated with SARS-CoV-2 infection. Individual analyses of the majority of studies found median age was higher by ~10 years in patients with cardiovascular complications. Pooled analyses showed development of SARS-CoV-2 cardiovascular complications was significantly increased in patients with chronic respiratory illness (odds ratio (OR): 1.67 [1.48, 1.88]), CVD (OR: 3.37 [2.57, 4.43]), hypertension (OR: 2.68 [2.11, 3.41]), DM (OR: 1.60 [1.31, 1.95]) and male sex (OR: 1.31 [1.21, 1.42]), findings that were mostly conserved during sub-analysis of studies stratified into global geographic regions. Age, chronic respiratory illness, CVD, hypertension, DM, and male sex may represent prognostic factors for the development of cardiovascular complications in COVID-19 disease, highlighting the need for a multidisciplinary approach to chronic disease patient management.