A call to caution when hydroxychloroquine is given to elderly patients with COVID-19.

INTRODUCTION: Use of hydroxychloroquine in patients with coronavirus disease 2019 (COVID-19) was widespread and uncontrolled until recently. Patients vulnerable to severe COVID-19 are at risk of hydroxychloroquine interactions with co-morbidities and co-medications contributing to detrimental, including fatal, adverse treatment effects. METHODS: A retrospective survey was undertaken of health conditions and co-medications of patients with COVID-19 who were pre-screened for enrolment in a randomized, double-blind, placebo-controlled hydroxychloroquine multi-centre trial. RESULTS: The survey involved 305 patients [median age 71 (interquartile range 59-81) years]. The majority of patients (n = 279, 92%) considered for inclusion in the clinical trial were not eligible, mainly due to safety concerns caused by health conditions or co-medications. The most common were QT-prolonging drugs (n = 188, 62%) and haematologic/haemato-oncologic diseases (n = 39, 13%) which prohibited the administration of hydroxychloroquine. In addition, 165 (54%) patients had health conditions and 167 (55%) patients were on co-medications that did not prohibit the use of hydroxychloroquine but had a risk of adverse interactions with hydroxychloroquine. The most common were diabetes (n = 86, 28%), renal insufficiency (n = 69, 23%) and heart failure (n = 58, 19%). CONCLUSION: The majority of hospitalized patients with COVID-19 had health conditions or took co-medications precluding safe treatment with hydroxychloroquine. Therefore, hydroxychloroquine should be administered with extreme caution in elderly patients with COVID-19, and only in clinical trials.

Describing nearly two decades of Chagas disease in Germany and the lessons learned: a retrospective study on screening, detection, diagnosis, and treatment of Trypanosoma cruzi infection from 2000 - 2018.

BACKGROUND: The highly complex and largely neglected Chagas disease (CD) has become a global health problem due to population movements between Latin America and non-endemic countries, as well as non-vectorial transmission routes. Data on CD testing and treatment from routine patient care in Germany of almost two decades was collected and analysed. METHODS: German laboratories offering diagnostics for chronic Trypanosoma cruzi (T. cruzi) infection in routine patient care were identified. All retrievable data on tests performed during the years of 2000-2018 were analysed. Additional clinical information regarding patients diagnosed with CD was collected through questionnaires. RESULTS: Five German laboratories with diagnostics for T. cruzi infection in routine patient care were identified. Centres in Hamburg and Munich offered two independent serological tests to confirm the CD diagnosis, as recommended by WHO during the entire time period 2000-2018. Overall, a total of n = 10,728 independent tests involving n = 5991 individuals were identified with a progressive increase in testing rates over time, only n = 130 (16.0%) of the tested individuals with known nationality came from CD endemic countries. Of all test units conducted at the included institutes, a total of n = 347/10,728 (3.2%) tests on CD were positive, of which n = 200/347 (57.6%) were ELISA, n = 133/347 (38.3%) IFT, n = 10/347 (2.9%) PCR, and n = 4/347 (1.2%) RDT. Of the n = 5991 individuals only n = 81 (1.4%) with chronic infection were identified, n = 52 females and n = 28 males. Additional clinical information could only be collected from n = 47. CONCLUSION: The results of this study give insight into the deployment of screening, detection, diagnosis, and treatment of T. cruzi over the last two decades in Germany and existing deficits therein; the creation of guidelines for Germany could be a step forward to improve the existing gaps.

Intrafamilial transmission of human cytomegalovirus (HCMV): long-term dynamics of epitope-specific antibody response in context of avidity maturation.

BACKGROUND: The role of a special early family formation (PEKiP), which is popular in Germany, as a potential origin of HCMV-transmission to seronegative mothers is not documented. OBJECTIVES: To describe the clinical courses, to identify the virological origin and to evaluate a new tool for diagnosis of a cascade of intrafamilial HCMV primary infections. STUDY DESIGN: This prospectively analyzed long-term course of HCMV primary infection leading to hospitalization of two family members, included the evaluation of different IgG/IgM/IgG avidity-assays with an epitope-specific recombinant immunoblot-assay. Additionally, neutralization (NT) assays using fibroblast-and epithelial-target cells were performed to correlate NT50 values to avidity maturation. HCMV gN/gO/gB-RFLP-genotyping and phylogenetic analyses were performed using urine viral isolates. RESULTS: The clinical courses of the sequentially occurring intrafamilial HCMV primary infections were unusual, leading to hospitalization. Long-term-serology of the mother revealed concordant results for an unimodal IgG-course and a rapid decrease of IgM-indices from week 7 to week 21 p.i. Interestingly, the cut-off definitions for low and high avidity ranged discordantly from 15 to 25 weeks, and from 18 to 42 weeks p.i., respectively. A good correlation was found between the increase of fibroblast-adapted NT50 values and the appearance of high avidity using the epitope-specific immunoblot (>18 weeks p.i.). RFLP-genotyping and sequencing could identify the index patient as member of PEKiP-meetings. CONCLUSIONS: PEKiP-meetings with naked babies may be an important source of horizontal HCMV-transmission to seronegative pregnant mothers in Germany. Using epitope-specific immunoblots, persisting HCMVp150-IgM-reactivities and good concordance between high IgG-avidity and increase of fibroblast adapted neutralization capacity were found.

Infectious pulmonary complications after stem cell transplantation or chemotherapy: diagnostic yield of bronchoalveolar lavage.

Hematologic patients are at high risk for infectious pulmonary complications after stem cell transplantation (SCT) or chemotherapy. The aim of this study was to detect the range of pulmonary pathogens in these patients, analyzing 95 bronchoalveolar lavage (BAL) samples with classic and molecular (polymerase chain reaction [PCR]) detection methods. Human cytomegalovirus (HCMV) was detected in 33, herpes simplex virus in 21, human herpesvirus 6 in 24, and other viruses in 16 samples. Aspergillus species were detected in 19, Candida species in 25, and Gram-positive bacteria in 29 samples. The additional use of PCR detection methods increased the diagnostic yield from 56% to 73%, especially concerning viral and fungal infections in BAL samples. No infectious agent was detected in 26 samples. Interestingly, a high incidence of polymicrobial infections (50/95) was detected, dominated by HCMV co-infections, especially after allogeneic SCT. Within 3 years of follow-up, a poor outcome of co-infections of Aspergillus species with HCMV in 9 of 10 cases could be documented, whereas only 7 of 20 patients died with noninfectious BAL results. Herpesviruses, fungi, and Gram-positive bacteria were detected most frequently, and in 53%, polymicrobial infections were diagnosed.

Isolation and expansion of human cytomegalovirus- specific cytotoxic T lymphocytes using interferon-gamma secretion assay.

OBJECTIVE: The aim of this study was to isolate and expand donor-derived human cytomegalovirus (HCMV)-specific cytotoxic T lymphocytes (CTLs) for adoptive transfer of 10(7) cells per m(2) of body surface area to restore protective immunity after stem cell transplantation. MATERIALS AND METHODS: A new strategy to generate HCMV-specific CTLs using the interferon-gamma (IFN-gamma) secretion assay, followed by expansion to numbers sufficient for clinical application with interleukin-2 and feeder cell stimulation, is described. RESULTS: From 1 to 5 x 10(4) HCMV peptide-specific T lymphocytes (greater than 90% CD3(+)CD8(+)) were isolated from 1 to 2 x 10(8) peripheral blood mononuclear cells comparable to 50 to 100 mL of blood from HLA-A*0201 HCMV seropositive blood donors (n = 14) and expanded ex vivo after a median of 16 days (range 8-28 days; n = 13) to greater than 10(7)/m(2) HCMV peptide-specific CTLs using autologous (n = 2) or allogeneic (n = 11) feeder cell stimulation. In three experiments, expansion to 6 weeks was performed, achieving a median of 1.6 x 10(9) cells (range 6.1 x 10(8)-3.3 x 10(9)). Characterization of these HCMV-specific CTL lines revealed an average purity of 89.2% (range 66.2-99.3%) using HCMV pp65 peptide HLA-A*0201 tetramer staining (n = 14) and 89.4% (range 64.4-99.5%) by peptide-specific IFN-gamma secretion (n = 7). A median of 82.6% (range 76.0-88.0%) showed perforin secretion (n = 3) and 57.5% (range 22.2-80.7%) specific lysis of peptide-pulsed T2 cells (n = 5). A median of 52.2% (range 35.2-7.3%) revealed specific killing of HCMV-infected autologous, but not allogeneic, fibroblasts (n = 6). CONCLUSIONS: IFN-gamma secretion assay allows development of a simple and rapid protocol with short expansion times for generation of greater than 10(7)/m(2) HCMV-specific CTLs for adoptive immunotherapy.