As of 28 February 2020, Italy had 888 cases of SARS-CoV-2 infections, with most cases in Northern Italy in the Lombardia and Veneto regions. Travel-related cases were the main source of COVID-19 cases during the early stages of the current epidemic in Italy. The month of February, however, has been dominated by two large clusters of outbreaks in Northern Italy, south of Milan, with mainly local transmission the source of infections. Contact tracing has failed to identify patient zero in one of the outbreaks. As of 28 February 2020, twenty-one cases of COVID-19 have died. Comparison between case fatality rates in China and Italy are identical at 2.3. Additionally, deaths are similar in both countries with fatalities in mostly the elderly with known comorbidities. It will be important to develop point-of-care devices to aid clinicians in stratifying elderly patients as early as possible to determine the potential level of care they will require to improve their chances of survival from COVID-19 disease.

Background: COVID-19 can course with respiratory and extrapulmonary disease. SARS-CoV-2 RNA is detected in respiratory samples but also in blood, stool and urine. Severe COVID-19 is characterized by a dysregulated host response to this virus. We studied whether viral RNAemia or viral RNA load in plasma is associated with severe COVID-19 and also to this dysregulated response.Methods: A total of 250 patients with COVID-19 were recruited (50 outpatients, 100 hospitalized ward patients and 100 critically ill). Viral RNA detection and quantification in plasma was performed using droplet digital PCR, targeting the N1 and N2 regions of the SARS-CoV-2 nucleoprotein gene. The association between SARS-CoV-2 RNAemia and viral RNA load in plasma with severity was evaluated by multivariate logistic regression. Correlations between viral RNA load and biomarkers evidencing dysregulation of host response were evaluated by calculating the Spearman correlation coefficients.Results: The frequency of viral RNAemia was higher in the critically ill patients (78%) compared to ward patients (27%) and outpatients (2%) (p < 0.001). Critical patients had higher viral RNA loads in plasma than non-critically ill patients, with non-survivors showing the highest values. When outpatients and ward patients were compared, viral RNAemia did not show significant associations in the multivariate analysis. In contrast, when ward patients were compared with ICU patients, both viral RNAemia and viral RNA load in plasma were associated with critical illness (OR [CI 95%],p): RNAemia (3.92 [1.183–12.968], 0.025), viral RNA load (N1) (1.962 [1.244–3.096], 0.004); viral RNA load (N2) (2.229 [1.382–3.595], 0.001). Viral RNA load in plasma correlated with higher levels of chemokines (CXCL10, CCL2), biomarkers indicative of a systemic inflammatory response (IL-6, CRP, ferritin), activation of NK cells (IL-15), endothelial dysfunction (VCAM-1, angiopoietin-2, ICAM-1), coagulation activation (D-Dimer and INR), tissue damage (LDH, GPT), neutrophil response (neutrophils counts, myeloperoxidase, GM-CSF) and immunodepression (PD-L1, IL-10, lymphopenia and monocytopenia).Conclusions: SARS-CoV-2 RNAemia and viral RNA load in plasma are associated with critical illness in COVID-19. Viral RNA load in plasma correlates with key signatures of dysregulated host responses, suggesting a major role of uncontrolled viral replication in the pathogenesis of this disease.

The gut microbiota has been proposed as a promising determinant for human health. Centenarians as a model for extreme aging may help us understand the correlation of gut microbiota with healthy aging and longevity. Here we confirmed that centenarians had microbiota elements usually associated with benefits to health. Our finding of a high capacity of glycolysis and related SCFA production represented a healthy microbiome and environment that is regarded as beneficial for host gut epithelium. The low abundance of genes encoding components of pathways involved in carbohydrate degradation was also found in the gut microbiota of Sardinian centenarians and is often associated with poor gut health. Overall, our study here represents an expansion of previous research investigating the age-related changes in gut microbiota. Furthermore, our study provides a new prospective for potential targets for gut microbiota intervention directed at limiting gut inflammation and pathology and enhancing a healthy gut barrier.

On 31 December 2019 the Wuhan Health Commission reported a cluster of atypical pneumonia cases that was linked to a wet market in the city of Wuhan, China. The first patients began experiencing symptoms of illness in mid-December 2019. Clinical isolates were found to contain a novel coronavirus with similarity to bat coronaviruses. As of 28 January 2020, there are in excess of 4,500 laboratory-confirmed cases, with > 100 known deaths. As with the SARS-CoV, infections in children appear to be rare. Travel-related cases have been confirmed in multiple countries and regions outside mainland China including Germany, France, Thailand, Japan, South Korea, Vietnam, Canada, and the United States, as well as Hong Kong and Taiwan. Domestically in China, the virus has also been noted in several cities and provinces with cases in all but one provinence. While zoonotic transmission appears to be the original source of infections, the most alarming development is that human-to-human transmission is now prevelant. Of particular concern is that many healthcare workers have been infected in the current epidemic. There are several critical clinical questions that need to be resolved, including how efficient is human-to-human transmission? What is the animal reservoir? Is there an intermediate animal reservoir? Do the vaccines generated to the SARS-CoV or MERS-CoV or their proteins offer protection against 2019-nCoV? We offer a research perspective on the next steps for the generation of vaccines. We also present data on the use of in silico docking in gaining insight into 2019-nCoV Spike-receptor binding to aid in therapeutic development. Diagnostic PCR protocols can be found at https://www.who.int/health-topics/coronavirus/laboratory-diagnostics-for-novel-coronavirus.

Pandemic H1N1 influenza A (H1N1pdm) is currently a dominant circulating influenza strain worldwide. Severe cases of H1N1pdm infection are characterized by prolonged activation of the immune response, yet the specific role of inflammatory mediators in disease is poorly understood. The inflammatory cytokine IL-6 has been implicated in both seasonal and severe pandemic H1N1 influenza A (H1N1pdm) infection. Here, we investigated the role of IL-6 in severe H1N1pdm infection. We found IL-6 to be an important feature of the host response in both humans and mice infected with H1N1pdm. Elevated levels of IL-6 were associated with severe disease in patients hospitalized with H1N1pdm infection. Notably, serum IL-6 levels associated strongly with the requirement of critical care admission and were predictive of fatal outcome. In C57BL/6J, BALB/cJ, and B6129SF2/J mice, infection with A/Mexico/4108/2009 (H1N1pdm) consistently triggered severe disease and increased IL-6 levels in both lung and serum. Furthermore, in our lethal C57BL/6J mouse model of H1N1pdm infection, global gene expression analysis indicated a pronounced IL-6 associated inflammatory response. Subsequently, we examined disease and outcome in IL-6 deficient mice infected with H1N1pdm. No significant differences in survival, weight loss, viral load, or pathology were observed between IL-6 deficient and wild-type mice following infection. Taken together, our findings suggest IL-6 may be a potential disease severity biomarker, but may not be a suitable therapeutic target in cases of severe H1N1pdm infection due to our mouse data.

Human endogenous retroviruses (HERVs) are derived from exogenous retrovirus infections in the evolution of primates and account for about 8% of the human genome. They were considered as silent passengers within our genomes for a long time, however, reactivation of HERVs has been associated with tumors and autoimmune diseases, especially the HERV-K (HML-2) family, the most recent integration groups with the least number of mutations and the most biologically active to encode functional retroviral proteins and produce retrovirus-like particles. Increasing studies are committed to determining the potential role of HERV-K (HML-2) in pathogenicity. Although there is still no evidence for HERV-K (HML-2) as a direct cause of diseases, aberrant expression profiles of the HERV-K (HML-2) transcripts and their regulatory function to their proximal host-genes were identified in different diseases. In this review, we summarized the advances between HERV-K (HML-2) and diseases to provide basis for further studies on the causal relationship between HERV-K (HML-2) and diseases. We recommended more attention to polymorphic integrated HERV-K (HML-2) loci which could be genetic causative factors and be associated with inter-individual differences in tumorigenesis and autoimmune diseases.