The Underrated Salivary Virome of Men Who Have Sex With Men Infected With HIV

Salivary virome is important for oral ecosystem, but there are few reports on people living with HIV. We performed metagenomic sequencing to compare composition and functional genes of salivary virobiota between one HIV-negative and four HIV-positive groups in which participants were all men who have sex with men (MSM) with different immunosuppression statuses (five samples per group) to find the evidence that salivary virobiota plays a role in the pathogenesis of oral disease. Acute-stage subjects achieved a positive result of HIV RNA, but HIV antibody negative or indeterminate, whereas individuals with mild, moderate, and severe immunosuppression exhibited CD4+ T-lymphocyte counts of at least 500, 200–499, and less than 200 cells/μL or opportunistic infection, respectively. The results showed the composition of salivary virus genera in subjects with mild immunosuppression was the most similar to that in healthy people, followed by that in the acute stage; under severe immunosuppression, virus genera were suppressed and more similar to that under moderate immunosuppression. Furthermore, abnormally high abundance of Lymphocryptovirus was particularly obvious in MSM with HIV infection. Analysis of KEGG Pathway revealed that Caulobacter cell cycle, which affects cell duplication, became shorter in HIV-positive subjects. It is worth noting that in acute-stage participants, protein digestion and absorption related to the anti-HIV-1 activity of secretory leukocyte protease inhibitor was increased. Moreover, in the severely immunosuppressed subjects, glutathione metabolism, which is associated with the activation of lymphocytes, was enhanced. Nevertheless, the ecological dysbiosis in HIV-positive salivary virobiota possibly depended on the changes in blood viral load, and salivary dysfunction of MSM infected with HIV may be related to CD4 counts. Ribonucleoside diphosphate reductase subunit M1 in purine metabolism was negatively correlated, though weakly, to CD4 counts, which may be related to the promotion of HIV-1 DNA synthesis in peripheral blood lymphocytes. 7-Cyano-7-deazaguanine synthase in folate biosynthesis was weakly positively correlated with HIV viral load, suggesting that this compound was produced excessively to correct oral dysfunction for maintaining normal cell development. Despite the limited number of samples, the present study provided insight into the potential role of salivary virome in the oral function of HIV infected MSM.

Cryptococcal antigen carriage among HIV infected children aged 6 months to 15 years at Laquintinie Hospital in Douala

Background Up to 15% of deaths of people living with HIV is attributable to meningeal cryptococcosis, with nearly 75% occuring in sub-Saharan Africa. Although rare in children, it is a major cause of morbidity and mortality in people living with HIV. A strong association between cryptococcal antigenemia and the development of meningeal cryptococcosis has been shown in adults. Thus, in 2018, the World Health Organization published an updated version of its guidelines for the diagnosis, prevention and management of cryptococcal infection in adults, adolescents and the HIV-infected child. Goal To determine the prevalence of cryptococcal antigenemia and to identify its determinants in children infected with HIV. Methods An analytical cross-sectional study was carried out at the approved treatment center of Laquintinie hospital in Douala over a period of 4 months. Children were recruited consecutively after informed parental consent. Cryptococcal antigenemia and CD4 assay were performed using a Cryptops® immunochromatographic rapid diagnostic test and flow cytometry, respectively. The data collected included the socio-demographic, clinical and paraclinical variables of the children, as well as their antecedents. Data analysis was performed using Epiinfo software version 3.1 and SPSS 21.0. The significance threshold was set at 5%. Results A total of 147 children were enrolled. The mean age was 9.8 ± 4.09 years. The majority were on antiretroviral therapy (142, 96.60%). Only 13 (8.80%) were in severe immunosuppression. No child showed signs of meningeal cryptococcosis. The prevalence of cryptococcal antigenemia was 6.12%. Severe immunosuppression [OR: 10.03 (1.52–65.91), p = 0.016] and contact with pigeons [OR: 9.76 (1.14–83.65), p = 0.037] were independent factors significantly associated with the carriage of the cryptococcal antigen. Conclusion We recommend screening for cryptococcal antigenemia and routine treatment with fluconazole of all HIV positive children with cryptococcal antigen whether symptomatic or not.

Outcomes of COVID-19 in a cohort of pediatric patients with rheumatic diseases

Background There are few reports of COVID-19 in pediatric patients with rheumatic diseases. This study describes the clinical presentation and outcomes of COVID-19 in this population. Methods We analyzed a single-center case series of pediatric patients with rheumatic diseases and laboratory-confirmed COVID-19. Demographic, baseline and COVID-19 associated clinical features were compared between ambulatory and hospitalized patients using univariate analysis. Results Fifty-five cases were identified: 45 (81.8%) in the ambulatory group and 10 (18.2%) hospitalized. African American race (OR 7.78; 95% CI [1.46–55.38]; p = 0.006) and cardiovascular disease (OR 19.40; 95% CI 2.45–254.14; p = 0.001) predominated in hospitalized patients. Active rheumatic disease (OR 11.83; 95% CI 1.43–558.37; p = 0.01), medium/high-dose corticosteroid use (OR 14.12; 95% CI [2.31–106.04]; p = 0.001), mycophenolate use (OR 8.84; 95% CI [1.64–63.88]; p = 0.004), rituximab use (OR 19.40; 95% CI [2.45–254.14]; p = 0.001) and severe immunosuppression (OR 34.80; 95% CI [3.94–1704.26]; p = < 0.001) were associated with increased odds of hospitalization. Fever (OR 7.78; 95% CI [1.46–55.38]; p = 0.006), dyspnea (OR 26.28; 95% CI [2.17–1459.25]; p = 0.003), chest pain (OR 13.20; 95% CI [1.53–175.79]; p = 0.007), and rash (OR 26.28; 95% CI [2.17–1459.25]; p = 0.003) were more commonly observed in hospitalized patients. Rheumatic disease flares were almost exclusive to hospitalized patients (OR 55.95; 95% CI [5.16–3023.74]; p < 0.001).. One patient did not survive. Conclusions Medium/high-dose corticosteroid, mycophenolate and rituximab use, and severe immunosuppression were risk factors for hospitalization. Fever, dyspnea, chest pain, and rash were high-risk symptoms for hospitalization. Rheumatic disease activity and flare could contribute to the need for hospitalization.

Outcomes of COVID-19 in a cohort of pediatric patients with rheumatic diseases

Background There are few reports of COVID-19 in pediatric patients with rheumatic diseases. This study describes the clinical presentation and outcomes of COVID-19 in this population. Methods We analyzed a single-center case series of pediatric patients with rheumatic diseases and laboratory-confirmed COVID-19. Demographic, baseline and COVID-19 associated clinical features were compared between ambulatory and hospitalized patients using univariate analysis. Results Forty cases were identified: 32 (80%) in the ambulatory group and 8 (20%) hospitalized. Older age (median age 18 years vs 16 years; p = 0.01) and African American race (OR 8.42; 95% CI [1.20-101.69]; p = 0.01) predominated in hospitalized patients. Systemic lupus erythematosus (OR 6.77; 95% CI [1.01–56.71]; p = 0.02), medium/high-dose corticosteroid use (OR 10.62; 95% CI [1.46–99.57]; p = 0.008), mycophenolate use (OR 11.91; 95% CI [1.64-149.35]; p = 0.005), and severe immunosuppression (OR 16.83; 95% CI [1.74-861.43]; p = 0.004) were associated with increased odds of hospitalization. Patients with fever (OR 11.91; 95% CI [1.64-149.35]; p = 0.004), dyspnea (OR 16.51; CI [1.10-998.37]; p = 0.02), and myalgias (OR 13.40; 95% CI [1.43-194.56)]; p = 0.009) were more commonly encountered in the hospitalized group. Rheumatic disease flares were almost exclusive to hospitalized patients (OR 42.13; 95% CI [3.40-2463.87]; p < 0.001).. All patients recovered. Conclusions Medium/high-dose corticosteroid use, mycophenolate use, and severe immunosuppression were risk factors for hospitalization. Fever, dyspnea and myalgias were high-risk symptoms. The type of rheumatic disease, as well as disease flare could be contributing factors to the need for hospitalization.

Treatment efficacy and tuberculosis relapses in HIV infected patients with severe immunosuppression who started antiretroviral therapy

The objective: to analyze treatment efficacy and causes of tuberculosis relapses in HIV-infected patients with severe immunosuppression who have started antiretroviral therapy (ART). Subjects and methods. 139 case histories were studied, those case history belonged to the patients with TB/HIV co-infection and CD4 count below 100 cells/μl, a median of 33.2 cells/μl – 4.2%, who started ART in the in-patient unit. The efficacy of inpatient treatment was assessed; 89 patients were followed up after discharge from hospital. The follow-up period lasted from January 2011 to May 2019. Results. ART did not increase the efficacy of the in-patient stage of TB/HIV treatment due to the development of immune reconstitution inflammatory syndrome, which occurred in 34.5% of patients and accounted for 70.0% of hospital lethality cases. After discharge from hospital, 69.7% of patients successfully completed anti-tuberculosis chemotherapy, 25.8% died before completing treatment, the main cause of death was tuberculosis (56.5%), including multiple drug resistance in 30.8% of cases. At the outpatient stage, 29.1% of patients interrupted ART, their death rate was higher (p = 0.007), and tuberculosis and HIV-associated diseases became the cause of death more often (p = 0.042) versus the compliant patients. Tuberculosis relapses developed in 17.7% after 16.7 ± 1.7 months after completion of treatment; 63.6% had multiple drug resistance, patients with tuberculosis relapses interrupted ART more often (p = 0.002), had a lower CD4 count (p = 0.030) versus patients without relapses. As of May 2019, 46.1% of patients survived and had no signs of active tuberculosis; 42.7% died, tuberculosis dominated among the causes of death – 50.0% (in 52.6% – multiple drug resistance) as well as HIV-associated diseases (21.1%).

Non-severe immunosuppression might be associated with a lower risk of moderate-severe acute respiratory distress syndrome in COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that has spread rapidly worldwide. The role of immunosuppression among COVID-19 patients has not been elucidated and management may be challenging. OBJECTIVE: To assess differences in severe outcomes of hospitalized patients with COVID-19 according to immune system state. DESIGN: Retrospective single-center observational study with confirmed COVID-19 patients admitted to Hospital Universitario Ramón y Cajal from March 18, 2020 to April 04, 2020. The final date of follow-up was April 09, 2020.PARTICIPANTS: Confirmed COVID-19 patients. MAIN MEASURES: The primary endpoint was development of moderate-severe acute respiratory distress syndrome (ARDS). Time to moderate-severe ARDS, the need for mechanical or non-invasive ventilation (MV/NIV), death, and a composite of death or MV/NIV were secondary endpoints. KEY RESULTS: Of 138 patients included, 27 (19.6%) were immunosuppressed (IS), with 95 (68.8%) male patients and a median (Q1, Q3) age of 68 (54–78) years. Among the baseline characteristics, no relevant or significant differences were observed between IS and non-immunosuppressed (non-IS) patients, detecting a non-severe immunosupression among IS. A significantly lower proportion of IS patients (22.2% [95%CI, 9.8–43.0%]) compared to non-IS patients (49.5% [95%CI, 40.2–58.9%]) developed moderate-severe ARDS, in both unadjusted (OR 0.29 [95%CI, 0.11–0.76], p=0.014) and adjusted (aOR 0.16 [95%CI, 0.05–0.55], p=0.004) analyses. After stratifying by pathologies, only IS autoimmune diseases remained significant (aOR 0.12 [95%CI, 0.03–0.57], p=0.007). Non-significant trends toward a longer time to moderate or severe ARDS, a lower need for MV/NIV, and a lower risk of death or MV/NIV were detected in IS. CONCLUSIONS: In our cohort of COVID-19 patients, non-severe immunosuppression was associated with a lower risk of moderate-severe ARDS, especially among AD. This suggests a potential protective effect from a hypothesized host hyper-inflammatory response and warrants reconsideration of management of IS patients.

Cardiac arrest and resuscitation activates the hypothalamic-pituitary-adrenal axis and results in severe immunosuppression

In patients who are successfully resuscitated after initial cardiac arrest (CA), mortality and morbidity rates are high, due to ischemia/reperfusion injury to the whole body including the nervous and immune systems. How the interactions between these two critical systems contribute to post-CA outcome remains largely unknown. Using a mouse model of CA and cardiopulmonary resuscitation (CA/CPR), we demonstrate that CA/CPR induced neuroinflammation in the brain, in particular, a marked increase in pro-inflammatory cytokines, which subsequently activated the hypothalamic-pituitary-adrenal (HPA) axis. Importantly, this activation was associated with a severe immunosuppression phenotype after CA. The phenotype was characterized by a striking reduction in size of lymphoid organs accompanied by a massive loss of immune cells and reduced immune function of splenic lymphocytes. The mechanistic link between post-CA immunosuppression and the HPA axis was substantiated, as we discovered that glucocorticoid treatment, which mimics effects of the activated HPA axis, exacerbated post-CA immunosuppression, while RU486 treatment, which suppresses its effects, significantly mitigated lymphopenia and lymphoid organ atrophy and improved CA outcome. Taken together, targeting the HPA axis could be a viable immunomodulatory therapeutic to preserve immune homeostasis after CA/CPR and thus improve prognosis of post-resuscitation CA patients.