Search

Background The aim of this randomized, controlled trial is to determine whether antisevere acute respiratory syndrome coronavirus 2 hyperimmune globulin (COVIG) protects against severe coronavirus disease 2019 (COVID-19) in severely immunocompromised, hospitalized, COVID-19 patients. Methods Patients were randomly assigned to receive COVIG or intravenous immunoglobulin (IVIG) without SARS-CoV-2 antibodies. Results Severe COVID-19 was observed in 2 of 10 (20%) patients treated with COVIG compared to 7 of 8 (88%) in the IVIG control group (P = .015, Fisher’s exact test). Conclusions Antisevere acute respiratory syndrome coronavirus 2 hyperimmune globulin may be a valuable treatment in severely immunocompromised, hospitalized, COVID-19 patients and should be considered when no monoclonal antibody therapies are available.

BACKGROUND: Invasive aspergillosis(IA) by a triazole resistant Aspergillus fumigatus is associated with a high mortality. Real-time resistance detection will result in earlier initiation of appropriate therapy. METHODS: In a prospective study in the Netherlands and Belgium, we evaluated the clinical value of the multiplex AsperGenius®PCR in hematology patients from 12 centers. This PCR detects the most frequent cyp51A mutations in A. fumigatus conferring azole-resistance. Patients were included when a CT-scan showed a pulmonary infiltrate and bronchoalveolar lavage(BALf) sampling was performed. The primary endpoint was antifungal treatment failure in patients with azole-resistant IA. Patients with mixed azole-susceptible/resistant infections were excluded. RESULTS: Of 323 patients enrolled, complete mycological and radiological information was available in 276/323(94%) and probable IA diagnosed in 99/276(36%). Sufficient BALf for PCR testing was available in 293/323(91%). Aspergillus DNA was detected in 116/293(40%) and A.fumigatus DNA in 89/293(30%). The resistance PCR was conclusive in 58/89(65%) and resistance detected in 8/58(14%). Two had a mixed azole-susceptible/resistant infection. In the 6 remaining patients, treatment failure was observed in one. Galactomannan positivity was associated with higher mortality(p=0.004). In contrast, mortality of patients with an isolated positive Aspergillus PCR was comparable to those with a negative PCR(p=0.83). CONCLUSIONS: Real-time PCR-based resistance testing may help to limit the clinical impact of triazole resistance. In contrast, the clinical impact of an isolated positive Aspergillus PCR on BALf seems limited. The interpretation of the EORTC/MSGERC PCR criterion for BALf may need further specification (e.g. minimum Ct-value and/or PCR positive on >1 BALf sample).

[This corrects the article DOI: 10.1371/journal.pmed.1003979.].

Fig 3 panel B contains a mislabeled axis. The label ‘Pre—HIV negative’ should be ‘Post—HIV negative.’ Please see the correct Fig 3 below.

Data on convalescent plasma (CP) treatment in COVID-19 outpatients are scarce. We aimed to assess whether CP administered during the first week of symptoms reduced the disease progression or risk of hospitalization of outpatients. Two multicenter, double-blind randomized trials (NCT04621123, NCT04589949) were merged with data pooling starting when Trial registration: Clinicaltrials.gov NCT04621123 and NCT04589949. Registration: NCT04621123 and NCT04589949 on https://www.clinicaltrials.gov

Applied immunology; Predictive markers; Viral infection Immunologia aplicada; Marcadors predictius; Infecció viral Inmunología aplicada; Marcadores predictivos; Infección viral Quantitative or qualitative differences in immunity may drive clinical severity in COVID-19. Although longitudinal studies to record the course of immunological changes are ample, they do not necessarily predict clinical progression at the time of hospital admission. Here we show, by a machine learning approach using serum pro-inflammatory, anti-inflammatory and anti-viral cytokine and anti-SARS-CoV-2 antibody measurements as input data, that COVID-19 patients cluster into three distinct immune phenotype groups. These immune-types, determined by unsupervised hierarchical clustering that is agnostic to severity, predict clinical course. The identified immune-types do not associate with disease duration at hospital admittance, but rather reflect variations in the nature and kinetics of individual patient’s immune response. Thus, our work provides an immune-type based scheme to stratify COVID-19 patients at hospital admittance into high and low risk clinical categories with distinct cytokine and antibody profiles that may guide personalized therapy. This work was supported by Health Holland LSHM20056 grant (PDK), in part from the European Union’s Horizon 2020 research and innovation program under grant agreement No 779295 (PDK), in part supported by the Erasmus foundation (BJAR), grant PI20/00416 from the Instituto de Salud Carlos III (RPB) and the European Regional Development Fund (ERDF) (RPB).

Background: Direct acting antivirals (DAA) cure 95% of patients infected with hepatitis C (HCV). Modeling studies predict that universal HCV treatment will lead to a decrease in the incidence of new infections but real-life data are lacking. The incidence of HCV among Dutch HIV-positive men who have sex with men (MSM) has been high for >10 years. In 2015 DAA became available to all Dutch HCV patients and resulted in a rapid treatment uptake in HIV-positive MSM. We assessed whether this uptake was followed by a decrease in the incidence of HCV infections. Methods: Two prospective acute HCV treatment studies enrolled patients in 17 Dutch HIV centers, having 76% of the total HIV-positive MSM population in care in the Netherlands. Patients were recruited in 2014 and 2016, the year preceding and following unrestricted DAA availability. We compared the HCV incidence in both years. Results: The acute HCV incidence decreased from 93 infections during 8290 person years of follow up in 2014 (11.2/1000 PYFU, 95% CI 9.1-13.7) to 49 during 8961 PYFU in 2016 (5.5/1000, 95% CI 4.1-7.2). The incidence rate ratio of 2016 compared with 2014 was 0.49 (95% C.I. 0.35-0.69). Simultaneously, a significant increase in the percentage positive syphilis (+2.2%) and gonorrhea (+2.8%) tests in HIV-positive MSM was observed at sexual health clinics across the Netherlands and contradicts a decrease in risk behavior as an alternative explanation. Conclusions: Unrestricted DAA availability in the Netherlands was followed by a 51% decrease in acute HCV infections among HIV-positive MSM.

Background: The Netherlands has provided unrestricted access to direct-acting antivirals (DAAs) since November 2015. We analyzed the nationwide hepatitis C virus (HCV) treatment uptake among patients coinfected with human immunodeficiency virus (HIV) and HCV. Methods: Data were obtained from the ATHENA HIV observational cohort in which >98% of HIV-infected patients ever registered since 1998 are included. Patients were included if they ever had 1 positive HCV RNA result, did not have spontaneous clearance, and were known to still be in care. Treatment uptake and outcome were assessed. When patients were treated more than once, data were included from only the most recent treatment episode. Data were updated until February 2017. In addition, each treatment center was queried in April 2017 for a data update on DAA treatment and achieved sustained virological response. Results: Of 23574 HIV-infected patients ever linked to care, 1471 HCV-coinfected patients (69% men who have sex with men, 15% persons who [formerly] injected drugs, and 15% with another HIV transmission route) fulfilled the inclusion criteria. Of these, 87% (1284 of 1471) had ever initiated HCV treatment between 2000 and 2017, 76% (1124 of 1471) had their HCV infection cured; DAA treatment results were pending in 6% (92 of 1471). Among men who have sex with men, 83% (844 of 1022) had their HCV infection cured, and DAA treatment results were pending in 6% (66 of 1022). Overall, 187 patients had never initiated treatment, DAAs had failed in 14, and a pegylated interferon-alfa-based regimen had failed in 54. Conclusions: Fifteen months after unrestricted DAA availability the majority of HIV/HCV-coinfected patients in the Netherlands have their HCV infection cured (76%) or are awaiting DAA treatment results (6%). This rapid treatment scale-up may contribute to future HCV elimination among these patients.

The Netherlands has provided unrestricted access to direct-acting antivirals (DAAs) since November 2015. We analyzed the nationwide HCV treatment uptake among HIV/HCV-coinfected patients. Data were obtained from the ATHENA HIV observational cohort in which >98% of HIV-infected patients ever registered since 1998 are included. Patients were included if they ever had 1 positive HCV RNA, did not spontaneously clear and were known to still be in care. Treatment uptake and outcome were assessed. When patients were treated more than once, only data of the most recent treatment episode were included. Data were updated until February 2017. In addition, each treatment center was queried in April 2017 for a data update on DAA treatment and achieved SVR. Of 23,574 HIV-infected patients ever linked to care, 1471 HCV-coinfected patients (69% men who have sex with men (MSM), 15% people who (formerly) inject drugs and 15% another HIV transmission route) fulfilled the inclusion criteria. Eighty-seven percent (1284/1471) had ever initiated HCV treatment between 2000 and 2017, 76% (1124/1471) were cured and in 6% (92/1471) DAA treatment results were pending. Among MSM 83% (844/1022) were cured and in 6% (66/1022) DAA treatment results were pending. Overall 187 patients had never initiated treatment, 14 patients failed DAAs and 54 patients failed a pegylated-interferon-alpha based regimen. Fifteen months after unrestricted DAA availability the majority of HIV/HCV-coinfected patients in the Netherlands are cured (76%) or awaiting DAA treatment results (6%). This rapid treatment scale-up may contribute to future HCV elimination among these patients

OBJECTIVES:: To investigate the incidence and risk factors of immune reconstitution inflammatory syndrome (IRIS) associated with toxoplasmic encephalitis (TE) in patients starting cART. DESIGN:: A historical multicenter cohort study. METHODS:: We included all HIV-infected patients diagnosed with TE in six Dutch hospitals between 1996 and 2016. Diagnosis of TE-IRIS was made using predefined IRIS criteria. We distinguished paradoxical TE-IRIS (worsening of underlying treated infection) from unmasking TE-IRIS (unmasking of subclinical infection after start of cART). We compared CD4 count, plasma viral load and timing of cART initiation between patients with and without paradoxical TE-IRIS. RESULTS:: 211 TE cases were included. Among 143 cases at risk for paradoxical TE-IRIS, we identified five cases of paradoxical TE-IRIS (3.5%). In six other cases we could not differentiate paradoxical TE-IRIS from recurrence of disease due to inadequate secondary Toxoplasma prophylaxis. There was no difference in time between start of TE treatment and cART initiation for patients who did or did not develop paradoxical TE-IRIS (p = 0.50). Within the group of 2228 patients who started cART while having a CD4 count below 200?×?10/L and receiving adequate primary prophylaxis, we identified eight cases of unmasking TE-IRIS (0.36%). Unmasking TE-IRIS could not be differentiated from a newly occurring TE in six other patients, as they were not receiving adequate primary prophylaxis against Toxoplasma. CONCLUSION:: Unmasking TE-IRIS was rare in this cohort, whereas paradoxical TE-IRIS did occur more often. We found no relationship between the timing of cART initiation and the occurrence of paradoxical TE-IRIS.