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Background. COVID-19 is a severe acute respiratory disease caused by SARS-CoV-2, a virus belonging to the Coronaviridae family. This disease has spread rapidly around the world and soon became an international public health emergency leading to an unpredicted pressure on the hospital emergency units. Early routine blood biomarkers could be key predicting factors of COVID-19 morbidity and mortality as suggested for C-reactive protein (CRP), IL-6, prothrombin and D-dimer. This study aims to identify other early routine blood biomarkers for COVID-19 severity prediction disclosed directly into the emergency section. Methods. Our research was conducted on 156 COVID-19 patients hospitalized at the Sapienza University Hospital “Policlinico Umberto I” of Rome, Italy, between March 2020 and April 2020 during the paroxysm’s initial phase of the pandemic. In this retrospective study, patients were divided into three groups according to their outcome: (1) emergency group (patients who entered the emergency room and were discharged shortly after because they did not show severe symptoms); (2) intensive care unit (ICU) group (patients who attended the ICU after admission to the emergency unit); (3) the deceased group (patients with a fatal outcome who attended the emergency and, afterward, the ICU units). Routine laboratory tests from medical records were collected when patients were admitted to the emergency unit. We focused on Aspartate transaminase (AST), Alanine transaminase (ALT), Lactate dehydrogenase (LDH), Creatine kinase (CK), Myoglobin (MGB), Ferritin, CRP, and D-dimer. Results. As expected, ANOVA data show an age morbidity increase in both ICU and deceased groups compared with the emergency group. A main effect of morbidity was revealed by ANOVA for all the analyzed parameters with an elevation between the emergency group and the deceased group. Furthermore, a significant increase in LDH, Ferritin, CRP, and D-dimer was also observed between the ICU group and the emergency group and between the deceased group and ICU group. Receiver operating characteristic (ROC) analyses confirmed and extended these findings. Conclusions. This study suggests that the contemporaneous presence of high levels of LDH, Ferritin, and as expected, CRP, and D-dimer could be considered as potential predictors of COVID-19 severity and death.

The ongoing COVID-19 pandemic has forced the clinical and scientific community to try drug repurposing of existing antiviral agents as a quick option against SARS-CoV-2. Under this scenario, the interferon-β 1a (IFN-β 1a) whose antiviral potential is already known, and is a drug currently used in the clinical management of multiple sclerosis, may represent as a potential candidate. In this report, we demonstrate that IFN-β 1a was highly effective in inhibiting in vitro SARS-CoV-2 replication at clinically achievable concentration when administered after virus infection.

Background: Gastrointestinal disorders are frequent in COVID-19 and SARS-CoV-2 has been hypothesized to impact on host microbial flora and gut inflammation, infecting intestinal epithelial cells. Since there are currently no coded therapies or guidelines for treatment of COVID-19, this study aimed to evaluate the possible role of a specific oral bacteriotherapy as complementary therapeutic strategy to avoid the progression of COVID-19. Methods: We provide a report of 70 patients positive for COVID-19, hospitalized between March 9th and April 4th, 2020. All the patients had fever, required non-invasive oxygen therapy and presented a CT lung involvement on imaging more than 50%. Forty-two patients received hydroxychloroquine, antibiotics, and tocilizumab, alone or in combination. A second group of 28 subjects received the same therapy added with oral bacteriotherapy, using a multistrain formulation. Results: The two cohorts of patients were comparable for age, sex, laboratory values, concomitant pathologies, and the modality of oxygen support. Within 72 h, nearly all patients treated with bacteriotherapy showed remission of diarrhea and other symptoms as compared to less than half of the not supplemented group. The estimated risk of developing respiratory failure was eight-fold lower in patients receiving oral bacteriotherapy. Both the prevalence of patients transferred to ICU and mortality were higher among the patients not treated with oral bacteriotherapy. Conclusions: A specific bacterial formulation showed a significant ameliorating impact on the clinical conditions of patients positive for SARS-CoV-2 infection. These results also stress the importance of the gut-lung axis in controlling the COVID-19 disease.

Monitoring the human virome has been recently suggested as a promising and novel area of research for identifying new biomarkers which would help physicians in the management of transplant patients. Imbalance of the immune system in transplant recipients has a significant impact on replication of Torquetenovirus (TTV), the most representative and abundant virus of human virome. TTV kinetic was studied by real-time PCR in 280 liver or kidney transplant recipients who underwent different drug regimens to maintain immunosuppression. During one-year post-transplant follow-up, TTV viremia fluctuated irrespective of transplanted organ type but consistent with the immunosuppression regimen. TTV kinetic in patients who manifested cytomegalovirus (CMV) reactivation within the first four months post-transplant differed from that observed in patients who did not experience CMV complications. Importantly, plasma TTV load measured between day 0 and 10 post-transplant was significantly higher in CMV DNA positive than in CMV DNA negative patients. TTV viremia above 3.45 log DNA copies/ml within the first 10 days post-transplant correlates with higher propensity to CMV reactivation following transplantation. This study provides further evidence for using early post-transplant TTV viremia to predict CMV reactivation in liver or kidney transplant recipients.

Despite the widespread use of molecular biology techniques, standardized methods for the measurement of HIV-1 proviral DNA are currently lacking and several discordant results are still present in different studies. To assess the clinical meaning of the proviral DNA load, a study group comprising seven different laboratories was set up to standardize a HIV-1 proviral DNA quantification method able to assess the DNA proviral load of the most relevant circulating HIV-1 subtypes. Reference samples (24 cellular samples infected with HIV-1 clade B, and 40 samples of peripheral blood mononuclear cells containing different concentrations of plasmids expressing different HIV-1 clades) were distributed and tested blindly. All laboratories employed hTERT gene as housekeeping gene and primers within the gag gene to quantify different HIV-1 clades. Inter-laboratory results did not differ statistically but showed only minor variations concerning HIV-1 DNA amounts and different HIV clades, with a good agreement among the laboratories participating in the study. Since test standardization represents a key step for future application in clinical practice, further studies of the patients' samples are in progress to establish the real meaning and utility of the proviral DNA load for clinical management of HIV-1 infected patients.

There is currently an urgent need to identify effective antiviral agents that will prevent and treat severe acute respiratory syndrome coronavirus (SARS-CoV) infection. In this study, we have investigated and compared the antiviral effect of different interferons (IFNs) on SARS-CoV replication in the epithelial kidney monkey Vero cell line. The results showed that SARS-CoV grown in Vero cells is moderately sensitive to IFN-β and only weakly sensitive to IFN-α and IFN-γ, in comparison to other IFN-sensitive viruses, such as those for encephalomyocarditis, vesicular stomatitis and Newcastle disease. Simultaneous incubation of Vero cells with IFN-β and IFN-γ indicated that they may act synergistically against SARS-CoV replication. The IFN-induced MxA protein was detected in the IFN-treated Vero cells. The data, however, suggest that the antiviral activity of IFN against SARS-CoV virus is independent of MxA expression.

OBJECTIVE: HIV-1-associated dysbiosis is most commonly characterized by overall decreased diversity, with abundance of the genus Prevotella, recently related to inflammatory responses. DESIGN: A pilot study including 10 antiretroviral therapy-treated HIV-1-infected men and 50 uninfected controls was performed to identify the main gut dysbiosis determinants (e.g. Prevotella enrichment), that may affect mucosal antiviral defenses and T cell immunity in HIV-1-infected individuals. METHODS: 16rRNA gene sequencing was applied to the HIV-1-infected individuals' fecal microbiota and compared with controls. Measurements of CD4 and CD8 T cell activation [CD38, human leukocyte antigen (HLA)-DR, CD38 HLA-DR] and frequencies of Th17, obtained from lamina propria lymphocytes isolated from five different intestinal sites, were performed by flow cytometry. IFNβ, IFNAR1 and MxA gene expression level was evaluated by real-time PCR in lamina propria lymphocytes. Nonparametric t tests were used for statistical analysis. RESULTS: HIV-1-infected men had a significant fecal microbial communities' imbalance, including different levels of genera Faecalibacterium, Prevotella, Alistipes and Bacteroides, compared with controls. Notably, Prevotella abundance positively correlated with frequencies of CD4 T cells expressing CD38 or HLA-DR and coexpressing CD38 and HLA-DR (P

Interferons (IFNs) are critically important in the control of influenza A virus infections. To better understand the pathogenic characteristics of the pandemic 2009 H1N1 influenza virus (pH1N1) from an innate immunity viewpoint, we investigated whether in vitro pH1N1 is sensitive to the antiviral activity of IFN beta, leukocyte IFN alpha, and several IFN alpha subtypes in a human lung adenocarcinoma epithelial cell line under single-growth cycle conditions. The results showed that 50% inhibitory concentration values against pH1N1 for various type I IFN preparations were higher than those against the IFN-sensitive encephalomyocarditis virus. Leukocyte IFN alpha and IFN alpha 5, 7, 8, 10, 14, 17, and 21 subtypes also appeared to be less active against pH1N1 than the Puerto Rico/8/34 H1N1 human influenza strain A. Taken together, the results provide new insights into the contributions of the various IFN alpha subtypes toward the regulation of innate immunity against pH1N1.

Interferon (IFN)-alpha, -beta and -gamma have been shown to be only marginally effective against severe acute respiratory syndrome coronavirus (SARS-CoV) replication in Vero cell lines. We investigated the combination of type I IFNs (IFN-alpha or -beta) and IFN-gamma for antiviral activity and found that such combinations synergistically inhibited SARS-CoV replication in Vero cells, using yield reduction assay and the isobologram and combination index methods of Chou and Talalay for evaluation. The highly synergistic anti-SARS-CoV action of type I IFNs and IFN-gamma parallels the marked increase in 2'-5'-oligoadenylate synthetase and p56 mRNAs following exposure in Vero cells to either IFN-alpha or -beta and IFN-gamma compared with the transcriptional levels obtained after stimulation with either IFN alone. These results demonstrate that SARS-CoV, although only moderately sensitive to the antiviral action of the individual types of IFN, is highly sensitive to a combination of type I and II IFNs, which suggests that such combinations may have potential in the treatment of SARS-CoV infections.