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Introduction Disseminated infection due to non-tuberculous mycobacteria has been a major factor of mortality and comorbidity in HIV patients. Until 2018, U.S. American guidelines have recommended antimycobacterial prophylaxis in patients with low CD4 cell counts, a practice that has not been adopted in Europe. This study aimed at examining the impact of disseminated NTM disease on clinical outcome in German HIV patients with a severe immunodeficiency. Materials and methods In this retrospective case control study, HIV patients with disseminated NTM disease were identified by retrospective chart review and matched by their CD4 cell counts to HIV patients without NTM infection in a 1:1 alocation. Primary endpoints were mortality and time to first rehospitalisation. In addition, other opportunistic diseases, as well as antimycobacterial and antiretroviral treatments were examined. Results Between 2006 and 2016, we identified 37 HIV patients with disseminated NTM disease. Most of them were suffering from infections due to M. avium complex (n = 31, 77.5%). Time to event analysis showed a non-significant trend to higher mortality in patients with disseminated NTM disease (p = 0.24). Rehospitalisation took place significantly earlier in patients with disseminated NTM infections (median 40.5 days vs. 109 days, p<0.0001). Conclusion In this retrospective case control study, we could demonstrate that mortality is not significantly higher in HIV patients with disseminated NTM disease in the ART era, but that they require specialised medical attention in the first months following discharge.
Background: To evaluate clinical outcomes after either immediate or deferred initiation of antiretroviral therapy in HIV-1-infected patients, presenting late with pneumocystis pneumonia (PCP) or toxoplasma encephalitis (TE).
Methods: Phase IV, multicenter, prospective, randomized open-label clinical trial. Patients were randomized into an immediate therapy arm (starting antiretroviral therapy (ART) within 7 days after initiation of OI treatment) versus a deferred arm (starting ART after completing the OI-therapy). All patients were followed for 24 weeks. The rates of clinical progression (death, new or relapsing opportunistic infections (OI) and other grade 4 clinical endpoints) were compared, using a combined primary endpoint. Secondary endpoints were hospitalization rates after completion of OI treatment, incidence of immune reconstitution inflammatory syndrome (IRIS), virologic and immunological outcome, adherence to proteinase-inhibitor based antiretroviral therapy (ART) protocol and quality of life.
Results: 61 patients (11 patients suffering TE, 50 with PCP) were enrolled. No differences between the two therapy groups in all examined primary and secondary endpoints could be identified: immunological and virologic outcome was similar in both groups, there was no significant difference in the incidence of IRIS (11 and 10 cases), furthermore 9 events (combined endpoint of death, new/relapsing OI and grade 4 events) occurred in each group.
Conclusions: In summary, this study supports the notion that immediate initiation of ART with a ritonavir-boosted proteinase-inhibitor and two nucleoside reverse transcriptase inhibitors is safe and has no negative effects on incidence of disease progression or IRIS, nor on immunological and virologic outcomes or on quality of life.
Convection-permitting models (CPMs) have proven their usefulness in representing precipitation on a sub-daily scale. However, investigations on sub-hourly scales are still lacking, even though these are the scales for which showers exhibit the most variability. A Lagrangian approach is implemented here to evaluate the representation of showers in a CPM, using the limited-area climate model COSMO-CLM. This approach consists of tracking 5‑min precipitation fields to retrieve different features of showers (e.g., temporal pattern, horizontal speed, lifetime). In total, 312 cases are simulated at a resolution of 0.01 ° over Central Germany, and among these cases, 78 are evaluated against a radar dataset. The model is able to represent most observed features for different types of convective cells. In addition, the CPM reproduced well the observed relationship between the precipitation characteristics and temperature indicating that the COSMO-CLM model is sophisticated enough to represent the climatological features of showers.
Objectives: We explore the importance of SARS-CoV-2 sentinel surveillance testing in primary care during a regional COVID-19 outbreak in Austria.
Design: Prospective cohort study.
Setting: A single sentinel practice serving 22 829 people in the ski-resort of Schladming-Dachstein.
Participants: All 73 patients presenting with mild-to-moderate flu-like symptoms between 24 February and 03 April, 2020.
Intervention: Nasopharyngeal sampling to detect SARS-CoV-2 using real-time reverse transcriptase-quantitative PCR (RT-qPCR).
Outcome measures: We compared RT-qPCR at presentation with confirmed antibody status. We split the outbreak in two parts, by halving the period from the first to the last case, to characterise three cohorts of patients with confirmed infection: early acute (RT-qPCR reactive) in the first half; and late acute (reactive) and late convalescent (non-reactive) in the second half. For each cohort, we report the number of cases detected, the accuracy of RT-qPCR, the duration and variety of symptoms, and the number of viral clades present.
Results: Twenty-two patients were diagnosed with COVID-19 (eight early acute, seven late acute and seven late convalescent), 44 patients tested SARS-CoV-2 negative and 7 were excluded. The sensitivity of RT-qPCR was 100% among all acute cases, dropping to 68.1% when including convalescent. Test specificity was 100%. Mean duration of symptoms for each group were 2 days (range 1–4) among early acute, 4.4 days (1–7) among late acute and 8 days (2–12) among late convalescent. Confirmed infection was associated with loss of taste. Acute infection was associated with loss of taste, nausea/vomiting, breathlessness, sore throat and myalgia; but not anosmia, fever or cough. Transmission clusters of three viral clades (G, GR and L) were identified.
Conclusions: RT-qPCR testing in primary care can rapidly and accurately detect SARS-CoV-2 among people with flu-like illness in a heterogeneous viral outbreak. Targeted testing in primary care can support national sentinel surveillance of COVID-19.
This study presents an evaluation of a pulse height condensation particle counter (PH-CPC) and an expansion condensation particle counter (E-CPC) in terms of measuring ambient and laboratory-generated molecular and ion clusters. Ambient molecular cluster concentrations were measured with both instruments as they were deployed in conjunction with an ion spectrometer and other aerosol instruments in Hyytiälä, Finland at the SMEAR II station between 1 March and 30 June 2007. The observed cluster concentrations varied and ranged from some thousands to 100 000 cm -3. Both instruments showed similar (within a factor of ~5) concentrations. An average size of the detected clusters was approximately 1.8 nm. As the atmospheric measurement of sub 2-nm particles and molecular clusters is a challenging task, we conclude that most likely we were unable to detect the smallest clusters. Nevertheless, the reported concentrations are the best estimates to date for minimum cluster concentrations in a boreal forest environment.
Sulphuric acid, ammonia, amines, and oxidised organics play a crucial role in nanoparticle formation in the atmosphere. In this study, we investigate the composition of nucleated nanoparticles formed from these compounds in the CLOUD chamber experiments at CERN. The investigation is carried out via analysis of the particle hygroscopicity, ethanol affinity, oxidation state, and ion composition. Hygroscopicity was studied by a hygroscopic tandem differential mobility analyser and a cloud condensation nuclei counter, ethanol affinity by an organic differential mobility analyser and particle oxidation level by a high-resolution time-of-flight aerosol mass spectrometer. The ion composition was studied by an atmospheric pressure interface time-of-flight mass spectrometer. The volume fraction of the organics in the particles during their growth from sizes of a few nanometers to tens of nanometers was derived from measured hygroscopicity assuming the Zdanovski-Stokes-Robinson relationship, and compared to values gained from the spectrometers. The ZSR-relationship was also applied to obtain the measured ethanol affinities during the particle growth, which were used to derive the volume fractions of sulphuric acid and the other inorganics (e.g. ammonium salts). In the presence of sulphuric acid and ammonia, particles with a mobility diameter of 150 nm were chemically neutralised to ammonium sulphate. In the presence of oxidation products of pinanediol, the organic volume fraction of freshly nucleated particles increased from 0.4 to ∼0.9, with an increase in diameter from 2 to 63 nm. Conversely, the sulphuric acid volume fraction decreased from 0.6 to 0.1 when the particle diameter increased from 2 to 50 nm. The results provide information on the composition of nucleated aerosol particles during their growth in the presence of various combinations of sulphuric acid, ammonia, dimethylamine and organic oxidation products.
Sulphuric acid, ammonia, amines, and oxidised organics play a crucial role in nanoparticle formation in the atmosphere. In this study, we investigate the composition of nucleated nanoparticles formed from these compounds in the CLOUD (Cosmics Leaving Outdoor Droplets) chamber experiments at CERN (Centre européen pour la recherche nucléaire). The investigation was carried out via analysis of the particle hygroscopicity, ethanol affinity, oxidation state, and ion composition. Hygroscopicity was studied by a hygroscopic tandem differential mobility analyser and a cloud condensation nuclei counter, ethanol affinity by an organic differential mobility analyser and particle oxidation level by a high-resolution time-of-flight aerosol mass spectrometer. The ion composition was studied by an atmospheric pressure interface time-of-flight mass spectrometer. The volume fraction of the organics in the particles during their growth from sizes of a few nanometers to tens of nanometers was derived from measured hygroscopicity assuming the Zdanovskii–Stokes–Robinson relationship, and compared to values gained from the spectrometers. The ZSR-relationship was also applied to obtain the measured ethanol affinities during the particle growth, which were used to derive the volume fractions of sulphuric acid and the other inorganics (e.g. ammonium salts). In the presence of sulphuric acid and ammonia, particles with a mobility diameter of 150 nm were chemically neutralised to ammonium sulphate. In the presence of oxidation products of pinanediol, the organic volume fraction of freshly nucleated particles increased from 0.4 to ~0.9, with an increase in diameter from 2 to 63 nm. Conversely, the sulphuric acid volume fraction decreased from 0.6 to 0.1 when the particle diameter increased from 2 to 50 nm. The results provide information on the composition of nucleated aerosol particles during their growth in the presence of various combinations of sulphuric acid, ammonia, dimethylamine and organic oxidation products.
The ambient and laboratory molecular and ion clusters were investigated. Here we present data on the ambient concentrations of both charged and uncharged molecular clusters as well as the performance of a pulse height condensation particle counter (PH-CPC) and an expansion condensation particle counter (E-CPC). The ambient molecular cluster concentrations were measured using both instruments, and they were deployed in conjunction with ion spectrometers and other aerosol instruments in Hyytiälä, Finland at the SMEAR II station during 1 March to 30 June 2007. The observed cluster concentrations varied and were from ca. 1000 to 100 000 cm−3. Both instruments showed similar concentrations. The average size of detected clusters was approximately 1.8 nm. As the atmospheric measurements at sub 2-nm particles and molecular clusters are a challenging task, and we were most likely unable to detect the smallest clusters, the reported concentrations are our best estimates for minimum cluster concentrations in boreal forest environment.
Amines are potentially important for atmospheric new particle formation, but their concentrations are usually low with typical mixing ratios in the pptv range or even smaller. Therefore, the demand for highly sensitive gas-phase amine measurements has emerged in the last several years. Nitrate chemical ionization mass spectrometry (CIMS) is routinely used for the measurement of gas-phase sulfuric acid in the sub-pptv range. Furthermore, extremely low volatile organic compounds (ELVOCs) can be detected with a nitrate CIMS. In this study we demonstrate that a nitrate CIMS can also be used for the sensitive measurement of dimethylamine (DMA, (CH3)2NH) using the NO3−•(HNO3)1 − 2• (DMA) cluster ion signal. Calibration measurements were made at the CLOUD chamber during two different measurement campaigns. Good linearity between 0 and ∼ 120 pptv of DMA as well as a sub-pptv detection limit of 0.7 pptv for a 10 min integration time are demonstrated at 278 K and 38 % RH.
Background: Antibody detection of SARS-CoV-2 requires an understanding of its variation, course, and duration.
Methods: Antibody response to SARS-CoV-2 was evaluated over 5–430 days on 828 samples across COVID-19 severity levels, for total antibody (TAb), IgG, IgA, IgM, neutralizing antibody (NAb), antibody avidity, and for receptor-binding-domain (RBD), spike (S), or nucleoprotein (N). Specificity was determined on 676 pre-pandemic samples.
Results: Sensitivity at 30–60 days post symptom onset (pso) for TAb-S/RBD, TAb-N, IgG-S, IgG-N, IgA-S, IgM-RBD, and NAb was 96.6%, 99.5%, 89.7%, 94.3%, 80.9%, 76.9% and 92.8%, respectively. Follow-up 430 days pso revealed: TAb-S/RBD increased slightly (100.0%); TAb-N decreased slightly (97.1%); IgG-S and IgA-S decreased moderately (81.4%, 65.7%); NAb remained positive (94.3%), slightly decreasing in activity after 300 days; there was correlation with IgG-S (Rs = 0.88) and IgA-S (Rs = 0.71); IgG-N decreased significantly from day 120 (15.7%); IgM-RBD dropped after 30–60 days (22.9%). High antibody avidity developed against S/RBD steadily with time in 94.3% of patients after 430 days. This correlated with persistent antibody detection depending on antibody-binding efficiency of the test design. Severe COVID-19 correlated with earlier and higher antibody response, mild COVID-19 was heterogeneous with a wide range of antibody reactivities. Specificity of the tests was ≥99%, except for IgA (96%).
Conclusion: Sensitivity of anti-SARS-CoV-2 assays was determined by test design, target antigen, antibody avidity, and COVID-19 severity. Sustained antibody detection was mainly determined by avidity progression for RBD and S. Testing by TAb and for S/RBD provided the highest sensitivity and longest detection duration of 14 months so far.