Disseminated Cryptococcosis Is a Common Finding among Human Immunodeficiency Virus-Infected Patients with Suspected Sepsis and Is Associated with Higher Mortality Rates.

Cryptococcosis is the leading cause of death among people with HIV in Sub-Saharan Africa. The lack of optimum diagnoses and medications significantly impair the management of the disease. We investigated the burden of cryptococcosis and related mortality among people with HIV and suspected sepsis in Ethiopia. We conducted a prospective study at (1) Adama Hospital Medical College and (2) Asella Referral and Teaching Hospital from September 2019 to November 2020. We enrolled adult, HIV-infected patients presenting with suspected sepsis and assessed their 28-day survival rates. We performed blood cultures and cryptococcal antigen (CrAg) testing. In total, 82 participants were enrolled with a median age of 35 years, and 61% were female. Overall, eleven (13%) had positive CrAg tests, of which five grew Cryptococcus in blood cultures. Despite high-dose fluconazole (1200 mg/d) monotherapy being given to those with positive CrAg tests, the 28-day mortality was 64% (7/11), with mortality being significantly higher than among the CrAg-negative patients (9% (6/71); p < 0.001). Cryptococcosis was the leading cause of mortality among HIV-infected sepsis patients in this Ethiopian cohort. The CrAg screening of HIV-infected patients attending an emergency department can minimize the number of missed cryptococcosis cases irrespective of the CD4 T cell count and viral load. These findings warrant the need for a bundle approach for the diagnosis of HIV-infected persons presenting with sepsis in low- and middle-income countries.

SARS-CoV-2 infection in chronic kidney disease patients with pre-existing dialysis: description across different pandemic intervals and effect on disease course (mortality).

PURPOSE: Patients suffering from chronic kidney disease (CKD) are in general at high risk for severe coronavirus disease (COVID-19) but dialysis-dependency (CKD5D) is poorly understood. We aimed to describe CKD5D patients in the different intervals of the pandemic and to evaluate pre-existing dialysis dependency as a potential risk factor for mortality. METHODS: In this multicentre cohort study, data from German study sites of the Lean European Open Survey on SARS-CoV-2-infected patients (LEOSS) were used. We multiply imputed missing data, performed subsequent analyses in each of the imputed data sets and pooled the results. Cases (CKD5D) and controls (CKD not requiring dialysis) were matched 1:1 by propensity-scoring. Effects on fatal outcome were calculated by multivariable logistic regression. RESULTS: The cohort consisted of 207 patients suffering from CKD5D and 964 potential controls. Multivariable regression of the whole cohort identified age (> 85 years adjusted odds ratio (aOR) 7.34, 95% CI 2.45-21.99), chronic heart failure (aOR 1.67, 95% CI 1.25-2.23), coronary artery disease (aOR 1.41, 95% CI 1.05-1.89) and active oncological disease (aOR 1.73, 95% CI 1.07-2.80) as risk factors for fatal outcome. Dialysis-dependency was not associated with a fatal outcome-neither in this analysis (aOR 1.08, 95% CI 0.75-1.54) nor in the conditional multivariable regression after matching (aOR 1.34, 95% CI 0.70-2.59). CONCLUSIONS: In the present multicentre German cohort, dialysis dependency is not linked to fatal outcome in SARS-CoV-2-infected CKD patients. However, the mortality rate of 26% demonstrates that CKD patients are an extreme vulnerable population, irrespective of pre-existing dialysis-dependency.

COVID-19 Severity and Thrombo-Inflammatory Response Linked to Ethnicity.

Although there is strong evidence that SARS-CoV-2 infection is associated with adverse outcomes in certain ethnic groups, the association of disease severity and risk factors such as comorbidities and biomarkers with racial disparities remains undefined. This retrospective study between March 2020 and February 2021 explores COVID-19 risk factors as predictors for patients' disease progression through country comparison. Disease severity predictors in Germany and Japan were cardiovascular-associated comorbidities, dementia, and age. We adjusted age, sex, body mass index, and history of cardiovascular disease comorbidity in the country cohorts using a propensity score matching (PSM) technique to reduce the influence of differences in sample size and the surprisingly young, lean Japanese cohort. Analysis of the 170 PSM pairs confirmed that 65.29% of German and 85.29% of Japanese patients were in the uncomplicated phase. More German than Japanese patients were admitted in the complicated and critical phase. Ethnic differences were identified in patients without cardiovascular comorbidities. Japanese patients in the uncomplicated phase presented a suppressed inflammatory response and coagulopathy with hypocoagulation. In contrast, German patients exhibited a hyperactive inflammatory response and coagulopathy with hypercoagulation. These differences were less pronounced in patients in the complicated phase or with cardiovascular diseases. Coagulation/fibrinolysis-associated biomarkers rather than inflammatory-related biomarkers predicted disease severity in patients with cardiovascular comorbidities: platelet counts were associated with severe illness in German patients. In contrast, high D-dimer and fibrinogen levels predicted disease severity in Japanese patients. Our comparative study indicates that ethnicity influences COVID-19-associated biomarker expression linked to the inflammatory and coagulation (thrombo-inflammatory) response. Future studies will be necessary to determine whether these differences contributed to the less severe disease progression observed in Japanese COVID-19 patients compared with those in Germany.

Obesity and Impaired Metabolic Health Increase Risk of COVID-19-Related Mortality in Young and Middle-Aged Adults to the Level Observed in Older People: The LEOSS Registry.

Advanced age, followed by male sex, by far poses the greatest risk for severe COVID-19. An unresolved question is the extent to which modifiable comorbidities increase the risk of COVID-19-related mortality among younger patients, in whom COVID-19-related hospitalization strongly increased in 2021. A total of 3,163 patients with SARS-COV-2 diagnosis in the Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS) cohort were studied. LEOSS is a European non-interventional multi-center cohort study established in March 2020 to investigate the epidemiology and clinical course of SARS-CoV-2 infection. Data from hospitalized patients and those who received ambulatory care, with a positive SARS-CoV-2 test, were included in the study. An additive effect of obesity, diabetes and hypertension on the risk of mortality was observed, which was particularly strong in young and middle-aged patients. Compared to young and middle-aged (18-55 years) patients without obesity, diabetes and hypertension (non-obese and metabolically healthy; n = 593), young and middle-aged adult patients with all three risk parameters (obese and metabolically unhealthy; n = 31) had a similar adjusted increased risk of mortality [OR 7.42 (95% CI 1.55-27.3)] as older (56-75 years) non-obese and metabolically healthy patients [n = 339; OR 8.21 (95% CI 4.10-18.3)]. Furthermore, increased CRP levels explained part of the elevated risk of COVID-19-related mortality with age, specifically in the absence of obesity and impaired metabolic health. In conclusion, the modifiable risk factors obesity, diabetes and hypertension increase the risk of COVID-19-related mortality in young and middle-aged patients to the level of risk observed in advanced age.

All-cause mortality and disease progression in SARS-CoV-2-infected patients with or without antibiotic therapy: an analysis of the LEOSS cohort.

PURPOSE: Reported antibiotic use in coronavirus disease 2019 (COVID-19) is far higher than the actual rate of reported bacterial co- and superinfection. A better understanding of antibiotic therapy in COVID-19 is necessary. METHODS: 6457 SARS-CoV-2-infected cases, documented from March 18, 2020, until February 16, 2021, in the LEOSS cohort were analyzed. As primary endpoint, the correlation between any antibiotic treatment and all-cause mortality/progression to the next more advanced phase of disease was calculated for adult patients in the complicated phase of disease and procalcitonin (PCT) ≤ 0.5 ng/ml. The analysis took the confounders gender, age, and comorbidities into account. RESULTS: Three thousand, six hundred twenty-seven cases matched all inclusion criteria for analyses. For the primary endpoint, antibiotic treatment was not correlated with lower all-cause mortality or progression to the next more advanced (critical) phase (n = 996) (both p > 0.05). For the secondary endpoints, patients in the uncomplicated phase (n = 1195), regardless of PCT level, had no lower all-cause mortality and did not progress less to the next more advanced (complicated) phase when treated with antibiotics (p > 0.05). Patients in the complicated phase with PCT > 0.5 ng/ml and antibiotic treatment (n = 286) had a significantly increased all-cause mortality (p = 0.029) but no significantly different probability of progression to the critical phase (p > 0.05). CONCLUSION: In this cohort, antibiotics in SARS-CoV-2-infected patients were not associated with positive effects on all-cause mortality or disease progression. Additional studies are needed. Advice of local antibiotic stewardship- (ABS-) teams and local educational campaigns should be sought to improve rational antibiotic use in COVID-19 patients.

Emergence of the E484K mutation in SARS-COV-2-infected immunocompromised patients treated with bamlanivimab in Germany.

BACKGROUND: Monoclonal antibodies (mAb) have been introduced as a promising new therapeutic approach against SARS-CoV-2. At present, there is little experience regarding their clinical effects in patient populations underrepresented in clinical trials, e.g. immunocompromised patients. Additionally, it is not well known to what extent SARS-CoV-2 treatment with monoclonal antibodies could trigger the selection of immune escape viral variants. METHODS: After identifying immunocompromised patients with viral rebound under treatment with bamlanivimab, we characterized the SARS-CoV-2-isolates by whole genome sequencing. Viral load measurements and sequence analysis were performed consecutively before and after bamlanivimab administration. FINDINGS: After initial decrease of viral load, viral clearance was not achieved in five of six immunocompromised patients treated with bamlanivimab. Instead, viral replication increased again over the course of the following one to two weeks. In these five patients, the E484K substitution - known to confer immune escape - was detected at the time of viral rebound but not before bamlanivimab treatment. INTERPRETATION: Treatment of SARS-CoV-2 with bamlanivimab in immunocompromised patients results in the rapid development of immune escape variants in a significant proportion of cases. Given that the E484K mutation can hamper natural immunity, the effectiveness of vaccination as well as antibody-based therapies, these findings may have important implications not only for individual treatment decisions but may also pose a risk to general prevention and treatment strategies. FUNDING: All authors are employed and all expenses covered by governmental, federal state, or other publicly funded institutions.

Poor outcome of HIV-infected patients with plasmablastic lymphoma: results from the German AIDS-related lymphoma cohort study.

Out of 302 AIDS-related lymphoma (ARL) patients enrolled in the German ARL cohort study, 18 patients had plasmablastic lymphoma (PBL). Twelve out of 18 patients (67%) have died with a median survival of 4 months (range 0-11 months). In univariate analysis, an intermediate or high international prognostic index score was associated with a significantly lower overall survival and progression-free survival. The predominant cause of death was progressive lymphoma (67%). Our data indicate that the outcome of AIDS-related PBL is still very poor.

How individual can personalized antiretroviral treatment be? Deep salvage in an HIV-1-infected patient.

We present an HIV-1-infected male (who is now 52 years old) with a multi-drug-resistant virus and discuss the considerations finally leading to an antiretroviral regimen resulting in long-term viral suppression and excellent immunological response in a deep salvage situation. Even in a desperate situation with high-level multi-class resistance, highly individual, personalized antiretroviral regimes can be tailor-made to achieve unexpected improvements in the health status of a patient.