Thyroid dysfunction in COVID-19 patients.

PURPOSE: "Non thyroidal illness syndrome" (NTIS) or "euthyroid sick syndrome" (ESS) is a possible biochemical finding in euthyroid patients with severe diseases. It is characterized by a reduction of serum T3 (fT3), sometimes followed by reduction of serum T4 (fT4). The relationship between thyroid hormones levels and mortality is well known and different studies showed a direct association between NTIS and mortality. The sudden spread of the 2019 novel coronavirus (SARS-CoV 2) infection (COVID-19) and its high mortality become a world healthcare problem. Our aim in this paper was to investigate if patients affected by COVID-19 presented NTIS and the relationship between thyroid function and severity of this infection. METHODS: We evaluated the thyroid function in two different groups of consecutive patients affected by COVID-19 with respect to a control group of euthyroid patients. Group A included patients hospitalized for COVID-19 pneumonia while patients requiring intensive care unit (ICU) for acute respiratory syndrome formed the group B. Group C identified the control group of euthyroid patients. RESULTS: Patients from group A and group B showed a statistically significant reduction in fT3 and TSH compared to group C. In group B, compared to group A, a further statistically significant reduction of fT3 and TSH was found. CONCLUSIONS: COVID-19 in-patients can present NTIS. FT3 and TSH serum levels are lower in patients with more severe symptoms.

Evolution of HIV-1 transmitted drug resistance in Italy in the 2007-2014 period: A weighted analysis.

BACKGROUND: Recent studies suggest that transmitted drug resistance (TDR) may be decreasing in latest years, likely because of the reduced frequency of acquired resistance. However, specific risk factors, geographical areas and special HIV-infected populations may be disproportionally affected by TDR. OBJECTIVES: Correlates of TDR and time trends were evaluated from 2007 to 2014. STUDY DESIGN: We evaluated the genotypic results of 2155 naïve patients enrolled in the I.Co.N.A cohort at 23 clinical Centers in Italy between 2007 and 2014. A weighted analysis was performed to account for the patients enrolled in the cohort in each clinical Centre at each biennium (total number of patients: 3737). RESULTS: Overall prevalence of TDR was 10.7%. Independent predictors of TDR were sexual risk factor (OR 2.315, p = 0.020) and non-Italian geographical origin (OR 1.57, p = 0.038). The weighted prevalence of TDR was 10.5% with a stable proportion over calendar years. Generally, TDR prevalence was numerically higher, although not significantly, in clinical Centers of metropolitan areas with more than 3 millions of residents as compared to others (11.3% vs. 9.2%). The difference in TDR prevalence between these Centers decreased in more recent years. CONCLUSIONS: A stable frequency of TDR was observed during the most recent years in Italy, with opposite and converging trends in large metropolitan areas as compared to the rest of the country, suggesting a more homogeneous spread of TDR across the country in latest years. Concerns remain for sexual route of infection and non-Italian origin, reinforcing the need for specific prevention strategies prioritizing specific populations.

Virological response and resistance profile in HIV-1-infected patients starting darunavir-containing regimens.

OBJECTIVES: We evaluated the virological response in patients starting a regimen based on darunavir/ritonavir (DRV/r), which is currently the most widely used ritonavir-boosted protease inhibitor. METHODS: Data from 206 drug-naïve and 327 PI-experienced patients starting DRV/r 600/100 mg twice daily (DRV600) or 800/100 mg once daily (DRV800) were examined. The probabilities of virological success (VS) and virological rebound (VR) were evaluated in survival analyses. Baseline DRV/r resistance and its evolution at failure were also examined. RESULTS: DRV600 was preferentially administered in patients with complex requirements (older age, higher viraemia, lower CD4 cell count and DRV/PI resistance) compared with DRV800. By 12 months, the probability of achieving VS was 93.2% and 84.3% in drug-naïve and PI-experienced patients, respectively. The higher the baseline viraemia, the longer was the time required to achieve VS, both in drug-naïve patients [>500 000 HIV-1 RNA copies/mL: median [interquartile range (IQR)] 6.1 (5.1-10.3) months; 100 000-500 000 copies/mL: median (IQR) 4.9 (3.8-6.1) months; <100 000 copies/mL: median (IQR) 3.9 (3.5-4.8) months; P < 0.001] and in PI-experienced patients [≥100 000 copies/mL: median (IQR) 7.2 (5.7-11.6) months; <100 000 copies/mL: median (IQR) 2.8 (2.4-3.3) months; P < 0.001]. In PI-experienced patients, the probability of VR was higher for higher viraemia levels (22.3% for ≥100 000 copies/ml vs. 9.7% for <100 000 copies/mL; P = 0.007). Baseline resistance did not affect the virological response. At failure, a high percentage of patients maintained virus susceptible to all PIs (drug-naïve: 95%; PI-experienced: 80%). Despite being used more often in patients with more complex requirements, DRV600 performed as well as DRV800. CONCLUSIONS: In clinical practice, use of DRV/r (with its flexible dosage) results in high rates of virological response. These data support the use of PI/r in patients whose characteristics require potent drugs with a high genetic barrier.

Pulmonary tuberculosis followed by sarcoidosis in an HIV-infected patient: A case report and a simplified diagnostic flowchart for diagnosis and treatment of sarcoidosis.

The diagnosis of sarcoidosis in a patient living with HIV infection is an uncommon event and a challenge for clinicians. Clinical manifestations are variable and fluctuating depending to adherence to ARV therapy and to the level of CD4 count. We analyze here one chronic case in which sarcoidosis appeared clinically two years after pulmonary tuberculosis. The course of the disease was influenced and prolonged by frequent interruptions of antiretroviral therapy. Moreover the diagnosis and the decision to treat have been delayed by the need of exclusion of other pathologies, principally tuberculosis reactivation/reinfection, other mycobacterial diseases, hematologic malignancies. We propose a simplified flowchart for diagnosis and follow up of sarcoidosis, which may also be applied to patients with HIV infection. Diagnosis of latent tuberculosis infection (LTBI) may be difficult in these patients, because the immunological paradox of sarcoidosis. For this reason, following exclusion of active tuberculosis, we advise to submit all sarcoidosis patients to IPT (isoniazid preventive therapy), when immunosuppressive therapy is started.

Post-caesarean section surgical site infections at a Tanzanian tertiary hospital: a prospective observational study.

Few data are available on the determinants and characteristics of post-caesarean section (CS) surgical site infections (SSIs) in resource-limited settings. We conducted a prospective observational cohort study to evaluate the rates, determinants, and microbiological characteristics of post-CS SSI at the Dodoma Regional Referral Hospital (DRRH) Gynaecology and Obstetrics Department in Tanzania. Spanning a three-month period, all pregnant women who underwent CS were enrolled and followed up for 30 days. SSI following CS occurred in 224 (48%) women. Only 10 (2.1%) women received pre-incision antibiotic prophylaxis. Urgent intervention is needed to prevent and control infections and contain the rising rate of post-CS SSI at the DRRH.

Longitudinal characterization of dysfunctional T cell-activation during human acute Ebola infection.

Data on immune responses during human Ebola virus disease (EVD) are scanty, due to limitations imposed by biosafety requirements and logistics. A sustained activation of T-cells was recently described but functional studies during the acute phase of human EVD are still missing. Aim of this work was to evaluate the kinetics and functionality of T-cell subsets, as well as the expression of activation, autophagy, apoptosis and exhaustion markers during the acute phase of EVD until recovery. Two EVD patients admitted to the Italian National Institute for Infectious Diseases, Lazzaro Spallanzani, were sampled sequentially from soon after symptom onset until recovery and analyzed by flow cytometry and ELISpot assay. An early and sustained decrease of CD4 T-cells was seen in both patients, with an inversion of the CD4/CD8 ratio that was reverted during the recovery period. In parallel with the CD4 T-cell depletion, a massive T-cell activation occurred and was associated with autophagic/apoptotic phenotype, enhanced expression of the exhaustion marker PD-1 and impaired IFN-gamma production. The immunological impairment was accompanied by EBV reactivation. The association of an early and sustained dysfunctional T-cell activation in parallel to an overall CD4 T-cell decline may represent a previously unknown critical point of Ebola virus (EBOV)-induced immune subversion. The recent observation of late occurrence of EBOV-associated neurological disease highlights the importance to monitor the immuno-competence recovery at discharge as a tool to evaluate the risk of late sequelae associated with resumption of EBOV replication. Further studies are required to define the molecular mechanisms of EVD-driven activation/exhaustion and depletion of T-cells.

HIV-1 integrase genotyping is reliable and reproducible for routine clinical detection of integrase resistance mutations even in patients with low-level viraemia.

OBJECTIVES: Integrase drug resistance monitoring deserves attention because of the increasing number of patients being treated with integrase strand-transfer inhibitors. Therefore, we evaluated the integrase genotyping success rate at low-level viraemia (LLV, 51-1000 copies/mL) and resistance in raltegravir-failing patients. METHODS: An integrase genotypic resistance test (GRT) was performed on 1734 HIV-1 samples collected during 2006-13. Genotyping success rate was determined according to the following viraemia levels: 51-500, 501-1000, 1001-10 000, 10 001-100 000 and >100 000 copies/mL. The reproducibility of integrase GRT was evaluated in 41 plasma samples processed in duplicate in two reference centres. The relationship between LLV and resistance prevalence was evaluated in a subset of 120 raltegravir-failing patients. RESULTS: Overall, the integrase genotyping success rate was 95.7%. For viraemia levels 51-500 and 501-1000 copies/mL, the rate of success was 82.1% and 94.0%, respectively. GRT was reproducible, producing sequences with a high similarity and an equal resistance profile regardless of the sequencing centre or viraemia level. Resistance was detected both at LLV and at viraemia >1000 copies/mL (51-500 copies/mL = 18.2%; 501-1000 = 37.5%; 1001-10 000 = 53.7%; 10 001-100 000 = 30.0%; and >100 000 = 30.8%). At viraemia ≤500 copies/mL, Q148H/K/R and N155H had the same prevalence (9.1%), while the Y143C/H/R was completely absent. At early genotyping (within 3 months of raltegravir treatment), Q148H/K/R and N155H mutations were detected regardless of the viraemia level, while Y143C/H/R was observed only in samples with viraemia >1000 copies/mL. CONCLUSIONS: Our findings prove the reliability of HIV-1 integrase genotyping and reinforce the concept that this assay may be useful in the management of failures even at LLV.

An imported case of acute pulmonary coccidioidomycosis in an Italian traveller.

Coccidioidomycosis is a fungal infection caused by the Coccidioides species, which is endemic in the deserts of the southwestern region of the United States, northern Mexico, and in some areas of Central and South America. We describe a case of pulmonary coccidioidomycosis in a 49-year-old Italian man who came to our hospital with fever and joint and muscle pain 10 days after his return to Italy from Venezuela. Computer Tomography revealed multiple bilateral pulmonary nodules with mediastinal lymphadenopathy. Pulmonary coccidioidomycosis was diagnosed by a serological test, and fluconazole was immediately started. The patient improved within 2 weeks, with complete clinical recovery after 6 months of therapy. This case appears to be part of a large serologically unconfirmed outbreak. In order to provide early diagnosis and treatment, healthcare providers should be aware of coccidioidomycosis, even in travellers returning home from short trips to endemic areas.

Topical negative pressure to treat surgical site infections, with a focus on post-sternotomy infections: a systematic review and meta-analysis.

PURPOSE: Topical negative pressure (TNP) has become a common treatment of infected wounds. A systematic review and meta-analysis was performed to investigate TNP efficacy compared to conventional therapy in the treatment of deep surgical site infections (SSIs), particularly post-sternotomy infections. METHODS: MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials were searched for randomized clinical trials (RCTs) and observational studies comparing TNP to conventional treatment in deep SSIs published up to February 2012. Study quality was evaluated through the GRADE system and bias risk through the Newcastle-Ottawa scale (NOS). Primary outcome was infection cure/wound resolution rate. Secondary outcomes were adverse events, length of stay, mortality, and costs. The results are presented with 95 % confidence intervals (95 % CIs) and report estimates as odds ratios (ORs). Heterogeneity was determined through the I (2) test, with >50 % being considered significant. RESULTS: Among 83 studies retrieved, 12 cohort studies including 873 patients were considered. All the studies were of low quality, 11/12 had a medium risk of bias, and none were RCTs. Wound resolution was obtained more frequently in TNP-treated patients as compared with continuous and closed drainage (OR 6.45, 95 % CI 3.46-12.00). TNP use was associated with significant reduction of length of stay compared with standard of care (mean difference: 8.21, 95 % CI -12.19, -4.23). High heterogeneity was detected between studies, explained by the TNP comparator type. CONCLUSIONS: The systematic review and meta-analysis suggest that TNP might be more effective than standard therapy in the cure of deep SSIs. However, multicenter RCTs are needed to confirm the potential value of this treatment.

Drug-resistance development differs between HIV-1-infected patients failing first-line antiretroviral therapy containing nonnucleoside reverse transcriptase inhibitors with and without thymidine analogues.

OBJECTIVES: We evaluated the emergence of drug resistance in patients failing first-line regimens containing one nonnucleoside reverse transcriptase inhibitor (NNRTI) administered with zidovudine (ZDV) + lamivudine (the ZDV group) or non-thymidine analogues (non-TAs) (tenofovir or abacavir, + lamivudine or emtricitabine; the non-TA group). METHODS: Three hundred HIV-1-infected patients failing a first-line NNRTI-containing regimen (nevirapine, n = 148; efavirenz, n = 152) were included in the analysis. Virological failure was defined as viraemia ≥ 400 HIV-1 RNA copies/mL for the first time at least 6 months after starting the NNRTI-based regimen. For each patient, a genotypic resistance test at failure was available. The presence of drug-resistance mutations in HIV-1 reverse transcriptase was evaluated by comparing patients treated with NNRTI + zidovudine + lamivudine vs. those treated with NNRTI + non-TA. RESULTS: A total of 208 patients were failing with NNRTI + zidovudine + lamivudine and 92 with NNRTI + non-TA. No significant differences were observed between the non-TA group and the ZDV group regarding the time of virological failure [median (interquartile range): 12 (8-25) vs. 13 (9-32) months, respectively; P = 0.119] and viraemia [median (interquartile range): 4.0 (3.2-4.9) vs. 4.0 (3.3-4.7) log10 copies/mL, respectively; P = 0.894]. Resistance to reverse transcriptase inhibitors (RTIs) occurred at a significant lower frequency in the non-TA group than in the ZDV group (54.3 vs. 75.5%, respectively; P = 0.001). This difference was mainly attributable to a significantly lower prevalence of NNRTI resistance (54.3 vs. 74.0%, respectively; P = 0.002) and of the nucleoside reverse transcriptase inhibitor (NRTI) mutation M184V (23.9 vs. 63.5%, respectively; P < 0.001) in the non-TA group compared with the ZDV group. As expected, the mutation K65R was found only in the non-TA group (18.5%; P < 0.001). CONCLUSIONS: At first-line regimen failure, a lower prevalence of RTI resistance was found in patients treated with NNRTI + non-TA compared with those treated with NNRTI + zidovudine + lamivudine. These results confirm that the choice of backbone may influence the prevalence of drug resistance at virological failure.

Haemolytic anaemia after oral artemether-lumefantrine treatment in a patient affected by severe imported falciparum malaria.

Artemisinin and its derivatives are essential components of artemisinin-based combination therapies for treating severe falciparum malaria. In this paper, we describe the occurrence of haemolysis after oral artemether-lumefantrine treatment. To the best of our knowledge, this is the second reported case of a patient affected by severe falciparum malaria with haemolytic anaemia that is likely associated with oral artemether-lumefantrine treatment.

Analysis of co-receptor usage of circulating viral and proviral HIV genome quasispecies by ultra-deep pyrosequencing in patients who are candidates for CCR5 antagonist treatment.

UDPS combined with genotypic algorithms for prediction of HIV-1 co-receptor usage may provide quantitative data about the tropism of each variant present in the viral quasispecies. The aim of the present study was to assess co-receptor usage by ultra-deep pyrosequencing (UDPS), in comparison with the reference phenotypic test (Trofile), in patients who are candidates for CCR5 antagonist treatment, in both circulating and proviral HIV-1. Seventeen patients who were tested by Trofile were enrolled. UDPS of the V3 loop region was carried out on both plasma RNA and proviral DNA. Genotypic prediction of co-receptor usage was established by position-specific score matrices (PSSM) and confirmed, in discordant cases, with geno2pheno. Genetic heterogeneity of the RNA and DNA quasispecies was assessed as well. A total of 196,729 V3 sequences were considered (mean coverage per site, 6346). Concordance between phenotypic test and UDPS with PSSM was 0.82. Geno2pheno results were in line with those obtained with PSSM. Proviral quasispecies were more heterogeneous than those found in circulating HIV. In most patients eligible for CCR5 antagonist treatment, X4 variants were detected in proviral DNA, ranging from 1.0% to 52.7%. UDPS combined with genotypic algorithms for co-receptor usage prediction highlighted the presence of minority variants, with a discordant tropism with respect to the predominant population, in both circulating viral and proviral HIV. In most patients treated with Maraviroc the virological response was independent of the presence of X4 in proviral DNA. The clinical impact of minority X4 variants present in patients who are candidates for anti-CCR5 antagonists remains a crucial point to be addressed.

The prevalence of antibodies to human herpesvirus 8 and hepatitis B virus in patients in two hospitals in Tanzania.

The aim of this study was to determine the seroprevalence of human herpesvirus 8 (HHV-8) and the immunization status for hepatitis B virus (HBV) infection in febrile patients in two districts of the United Republic of Tanzania. Between February and March 2007, blood samples were collected in Pemba Island and Tosamaganga from 336 outpatients and sent to the Virology Laboratory in Rome (Italy) for testing. HHV-8 DNA and HBV-DNA were amplified by two in-house molecular methods, anti-HHV-8 antibody titers were determined by an immunofluorescence assay (IFA), and anti-HCV, HBsAg, anti-HBs, and anti-HBc were evaluated by microplate enzyme immunoassay (MEIA). The seroprevalence of HHV-8 was 30.7% (96/313). In Pemba Island, the prevalence was lower than in Tosamaganga (14.4% vs. 46.3%). A higher prevalence of low titers of HHV-8 IgG (<1:80, 81%) was found among those under 5 years of age. HHV-8 DNA was detected in six seropositive patients (6.7%). The prevalence of HBsAg, anti-HBs, and anti-HBc was 4.3%, 37.6%, and 29.3%, respectively. Out of 277 patients, 70 had had a previous infection (25.3%). One case of occult hepatitis was found. The cover of hepatitis B vaccination was higher among children born after 2002 (66.7%) than in patients born before 2002. HHV-8 infection is endemic in Tanzania and the seroprevalence rate was higher in the mainland than on Pemba Island. The 3.9% percentage of HBsAg in children younger than 4 years of age suggests that increased efforts are required in order to achieve universal and compulsory immunization of children against HBV.

Switching of inferred tropism caused by HIV during interruption of antiretroviral therapy.

After interruption of highly active antiretroviral therapy, 15 out of 53 patients with the X4 HIV strain had a significantly larger decrease in CD4(+) T cell count (P = 0.001) and shorter length of treatment interruption (P = 0.02) than patients with the R5 strain. At treatment resumption, HIV inferred tropism switched from the X4 strain to the R5 variant in 9 patients (60%). These patients had a prolonged length of treatment interruption compared to that of those who still carried the X4 strain.

Comparison of real-time PCR methods for measurement of HIV-1 proviral DNA.

The use of HIV-1 DNA quantitation in cellular reservoirs to predict disease progression and treatment outcome in infected patients is hampered by the lack of standardization among the available methods. In the present study, real-time PCR methods used commonly for HIV-1 proviral DNA evaluation were compared, showing strong differences in the results, probably as a consequence of genome variability in the target regions. Standardization of HIV-1 proviral DNA quantitation assays is needed for use in clinical management of patients with HIV-1.