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BackgroundInvasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential.MethodsTo achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved.ResultsThere is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses.ConclusionsThese updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk.

Objectives A reappraisal of the validity of the conclusions of systematic reviews (SRs) related to nirmatrelvir/ritonavir for the treatment of COVID-19. Methods An overview of SRs (umbrella review). The methodological quality of the SRs was assessed using the AMSTAR 2 checklist; quality of the evidence from the trials included in each SR was appraised following the GRADE approach. Results Sixteen SRs with meta-analysis published between 2020 and 2023 were included in this overview. The SRs reported data from 108 overlapping reports, based on 43 individual primary studies [3 randomized clinical trials (RCTs), 40 non-RCTs]. In outpatient settings the use of nirmatrelvir/ritonavir reduced overall mortality, hospital admission and progression of disease compared with controls (from moderate to low certainty of evidence); nirmatrelvir/ritonavir reduced mortality, hospital admission and progression of disease in both immunized and non-immunized patients. No differences in the occurrence of any adverse events between groups were observed in the large majority of SRs; serious adverse events, including adverse events requiring discontinuation of treatment, were reported with lower prevalence in nirmatrelvir recipients compared with controls (from low to moderate certainty of evidence). Conclusions There is low to moderate certainty of evidence from SRs that nirmatrelvir/ritonavir reduces mortality, clinical progression and hospitalization rate in COVID-19 patients compared with controls, without increasing the occurrence of overall and serious adverse events. Based on the overall methodological assessment, on average we can have high confidence in the quality of results generated by the SRs. [ABSTRACT FROM AUTHOR]

This article is a systematic review and meta-analysis of randomized controlled trials (RCTs) that assess the safety of COVID-19 convalescent plasma (CCP). The review found that CCP is generally safe, with rates of adverse reactions and serious adverse events similar between CCP recipients and controls. The analysis also showed that the incidence of treatment-related adverse reactions and venous and arterial thrombotic events was comparable between CCP and control groups. The review provides the largest analysis of CCP safety to date and aims to provide definitive answers on its safety. However, it is important to note that most of the included studies were judged to have a high or unclear risk of bias, and the evidence of safety was of low or moderate certainty. [Extracted from the article]

This COVID‐19 outpatient randomized controlled trials (RCTs) systematic review compares hospitalization outcomes amongst four treatment classes over pandemic period, geography, variants, and vaccine status. Outpatient RCTs with hospitalization endpoint were identified in Pubmed searches through May 2023, excluding RCTs <30 participants (PROSPERO‐CRD42022369181). Risk of bias was extracted from COVID‐19‐NMA, with odds ratio utilized for pooled comparison. Searches identified 281 studies with 61 published RCTs for 33 diverse interventions analyzed. RCTs were largely unvaccinated cohorts with at least one COVID‐19 hospitalization risk factor. Grouping by class, monoclonal antibodies (mAbs) (OR = 0.31 [95% CI = 0.24−0.40]) had highest hospital reduction efficacy, followed by COVID‐19 convalescent plasma (CCP) (OR = 0.69 [95% CI = 0.53−0.90]), small molecule antivirals (OR = 0.78 [95% CI = 0.48−1.33]), and repurposed drugs (OR = 0.82 [95% CI: 0.72−0.93]). Earlier in disease onset interventions performed better than later. This meta‐analysis allows approximate head‐to‐head comparisons of diverse outpatient interventions. Omicron sublineages (XBB and BQ.1.1) are resistant to mAbs Despite trial heterogeneity, this pooled comparison by intervention class indicated oral antivirals are the preferred outpatient treatment where available, but intravenous interventions from convalescent plasma to remdesivir are also effective and necessary in constrained medical resource settings or for acute and chronic COVID‐19 in the immunocompromised. [ABSTRACT FROM AUTHOR]