Low Viral Load Patients Research Articles

SARS-CoV-2 Viral Load Is Correlated With the Disease Severity and Mortality in Patients With Cancer.

The correlation between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral load and risk of disease severity in cancer patients is poorly understood. Given the fact that cancer patients are at increased risk of severe coronavirus disease 2019 (COVID-19), analysis of viral load and disease outcome in COVID-19-infected cancer patients is needed. Here, we measured the SARS-CoV-2 viral load using qPCR cycle threshold (Ct) values collected from 120 noncancer and 64 cancer patients’ nasopharyngeal swab samples who are admitted to hospitals. Our results showed that the in-hospital mortality for high viral load cancer patients was 41.38%, 23.81% for medium viral load and 14.29% for low viral load patients (p < −0.01). On the other hand, the mortality rate for noncancer patients was lower: 22.22% among patients with high viral load, 5.13% among patients with medium viral load, and 1.85% among patients with low viral load (p < 0.05). In addition, patients with lung and hematologic cancer showed higher possibilities of severe events in proportion to high viral load. Higher attributable mortality and severity were directly proportional to high viral load particularly in patients who are receiving anticancer treatment. Importantly, we found that the incubation period and serial interval time is shorter in cancer patients compared with noncancer cases. Our report suggests that high SARS-CoV-2 viral loads may play a significant role in the overall mortality and severity of COVID-19-positive cancer patients, and this warrants further study to explore the disease pathogenesis and their use as prognostic tools.

Human cytomegalovirus (HCMV)-specific T cell but not neutralizing or IgG binding antibody responses to glycoprotein complexes gB, gHgLgO, and pUL128L correlate with protection against high HCMV viral load reactivation in solid-organ transplant recipients.

Immune correlates of protection against human cytomegalovirus (HCMV) infection are still debated. This study aimed to investigate which arm of the immune response plays a major role in protection against HCMV infection in kidney transplant recipients (n = 40) and heart transplant recipients (n = 12). Overall, patients were divided into 2 groups: one including 37 patients with low viral load (LVL), and the other including 15 patients with high viral load (HVL). All LVL patients resolved the infection spontaneously, whereas HVL patients were all treated with one or more courses of antivirals. In HVL patients, viral DNAemia, which was more than 100 times higher than LVL, appeared and peaked at significantly earlier times, but disappeared much later than in LVL patients. During a 1-year follow-up, all LVL patients had levels of HCMV-specific CD4+ (and CD8+ ) T cells significantly higher than HVL patients. On the contrary, titers of neutralizing antibodies and enzyme-linked immunosorbent assay-IgG antibodies to gB, gHgLgO, and pentamer gHgLpUL128L were overlapping in the 2 patient groups. In conclusion, while a valid HCMV-specific T-cell response was detected in more than 90% of LVL patients, >90% of HVL patients lacked an adequate T-cell response. Antibody responses did not appear to be associated directly or indirectly with protection.

Mir-155 expression is downregulated in kidney transplant patients with human cytomegalovirus infection

MicroRNAs are small, noncoding RNAs that control expression of target genes through inhibiting protein translation or inducing degradation of mRNA transcripts of target genes. According to the latest update, 2578 unique mature miRNAs are currently annotated in the human genome and participate in the regulation of multiple events, such as cellular proliferation or apoptosis.Herpesvirus family comprehends many viruses able to control and modulate host-cell processes permitting the survival by a latency phase after primary infection. Recently has been attested that Human Cytomegalovirus, which belongs to Herpesvirus family, can alter human miRNAs expression in vitro, and, in particular, downregulate mir-155 expression.In this study 20 kidney transplant patients positive to Human Cytomegalovirus infection and 11 negative were enrolled. The patients' positive to Human Cytomegalovirus infections have been subdivided into two groups: one group including patients with a low viral load and one including patients with a high viral load. The mir-155 expression profile has been evaluated by a stem-loop Real Time PCR in all these conditions to observe differences among the groups and compare the results obtained with the literature.The comparison between kidney transplant patients negative to Human Cytomegalovirus infection and patients with a high viral load showed a not significant difference in terms of mir-155 expression.However, considering low viral load group or the group including both high and low viral load patients, mir-155 expression levels decreased significantly. Considering this data together, it is possible confirm data published before and assert that Human Cytomegalovirus is responsible of mir-155 downregulation.

Induction of OAS gene family in HIV monocyte infected patients with high and low viral load

BackgroundThe innate immunity plays a predominant role in the early control of HIV infection, before the induction of adaptive immune responses. The cytokine secretion operated by the CD4+ T helper cells is able to induce a response in the innate immunity cells and significantly affect HIV-1 persistence and replication. One of the pathways activated by monocytes to restrain viral infection is the 2′ -5′ -oligoadenylate synthetase (OAS)/RNase L pathway. OAS is activated by dsRNA and IFNs to produce 2′ -5′ oligoadenylates, which are activators of RNase L. This enzyme degrades viral and cellular RNAs, thus restricting viral infection. Materials and methodsWe analyzed a microarray dataset obtained from the NCBI Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/) databank (accession number GSE18464) in order to verify the modulation of the OAS gene family in CD14 + monocytes isolated from 55 subjects, 22 with HIV-1 HVL (high viral load), and 22 with HIV-1 LVL (low viral load), as well as in 11 HIV-1 seronegative controls. We have validated the data on the expression levels of the OAS genes by performing real-time PCR on monocyte from a cohort of HIV infected patients (n = 20), with clinical characteristics similar to those of the patients recruited in the study present in the microarray. ResultsMicroarray analysis showed that OAS gene family are significantly upregulated in monocyte of HIV-1 patients with HVL, as compared to LVL patients and to healthy donors. Furthermore, we showed a significant correlation between the OAS gene family and the log2 viral load and CD4 count. These results were confirmed by the in vitro validation. ConclusionsData from this study suggest an involvement for the OAS gene family in the control of HIV-1 infection.

Predictors of Histologic Severity in Chronic Hepatitis B-infected Patients

The role of liver biopsy in chronic Hepatitis B treatment guidelines remains incompletely defined. Our aim was to correlate histologic disease severity with demographic, biochemical and virologic parameters as currently used in Hepatitis B treatment guidelines. We conducted an Institutional Review Board (IRB) approved retrospective cross-sectional study of chronic Hepatitis B patients between January 2001 and July 2009. Patients with at least two Alanine Aminotransferase (ALT) values (6 months apart), with detectable Hepatitis B DNA quantitative levels at the time of initial evaluation, unchanged HBeAg status over a minimum of 6 months but no prior history of antiviral therapy, alcohol abuse, co-infection, hepatocellular carcinoma, iron overload or liver decompensation were reviewed. Advanced histological disease was defined as a METAVIR score of greater than or equal to stage and/or grade 3 (≥S/G 3). Multivariable binary logistic regression was used to determine the independent predictors of advanced histology. One hundred and twenty-eight patients met inclusion criteria. On multivariate logistic regression analysis, viral load was not an independent predictor. However, age ≥40, abnormal ALT and HBeAg(+) were independent predictors of ≥S/G3. Controlling for ALT and HBeAg status, patients ≥40 years old had 14.5 times the adjusted odds of ≥S/G3 (95% CI, 4.24–49.54) while 31% of HBeAg(-) /Low Viral load patients had ≥S/G3. Current HBV-treatment guidelines do not fully predict advanced histological disease. In the group where all the current guidelines recommend observation without treatment, one third had advanced histology on liver biopsy.

The Impact of EBV Load on T-Cell Immunity in Pediatric Thoracic Transplant Recipients

Immunologic monitoring of pediatric transplant (Tx) recipients, who are at increased risk of Epstein-Barr virus (EBV)-driven posttransplant lymphoproliferative disease, is an important goal in clinical transplantation. Here, we investigated the impact of EBV load on T-cell immunity from pediatric Tx recipients, using clinically applicable tests for improved assessment of T-cell immune competence. Thirty-five asymptomatic pediatric thoracic Tx patients were categorized into three groups according to their EBV load levels as follows: undetectable viral load (UVL), chronic low viral load (LVL) and chronic high viral load (HVL). Global and EBV-specific T-cell immunity were assessed by ATP release using Cylex Immuknow and T Cell Memory assays. UVL patients exhibited normal ATP release to Concanavalin A (ConA) and phytohemagglutinin (PHA; 190+/-86 ng/mL, 328+/-163 ng/mL) and detectable EBV-specific (37+/-34 ng/mL) ATP responses. LVL patients displayed significantly stronger responses to ConA (373+/-174 ng/mL), PHA (498+/-196 ng/mL) and EBV (152+/-179 ng/mL), when compared with UVL or to HVL patients (ConA 185+/-114 ng/mL, PHA 318+/-173 ng/mL, and EBV 33+/-42 ng/mL). Moreover, HVL patients displayed significant inverse correlation between CD4+ T-cell ATP levels and EBV loads. Evaluation of global and EBV-specific T-cell immunity provides a rapid assessment of patients' immune competence. It is still unclear whether selective oversuppressed ATP release by CD4+ T cells reflects HVL patients at risk of posttransplant lymphoproliferative disease. Further longitudinal studies will determine the importance of Immuknow test in identifying asymptomatic HVL patients vulnerable to EBV complications.