A Regional Observational Study on COVID-19-Associated Pulmonary Aspergillosis (CAPA) within Intensive Care Unit: Trying to Break the Mold.

The reported incidence of COVID-19-associated pulmonary aspergillosis (CAPA) ranges between 2.4% and 35% in intensive care unit (ICU) patients, and awareness in the medical community is rising. We performed a regional retrospective observational study including patients diagnosed with CAPA defined according to the Modified AspICU Dutch/Belgian Mycosis Study Group and CAPA-EECMM, from five different ICUs, admitted between March, 2020 and September, 2021. Forty-five patients were included. The median age was 64 (IQR 60-72), mostly (73%) males. At ICU admission, the median Charlson comorbidity index was 3 (2-5), and the simplified acute physiology score (SAPS)-II score was 42 (31-56). The main underlying diseases were hypertension (46%), diabetes (36%) and pulmonary diseases (15%). CAPA was diagnosed within a median of 17 days (IQR 10-21.75) after symptoms onset and 9 days (IQR 3-11) after ICU admission. The overall 28-day mortality rate was 58%, and at univariate analysis, it was significantly associated with older age (p = 0.009) and SAPS-II score at admission (p = 0.032). The use of immunomodulatory agents, p = 0.061; broad-spectrum antibiotics, p = 0.091; positive culture for Aspergillus on BAL, p = 0.065; and hypertension, p = 0.083, were near reaching statistical significance. None of them were confirmed in multivariate analysis. In critically ill COVID-19 patients, CAPA acquired clinical relevance in terms of incidence and reported mortality. However, the risk between underdiagnosis-in the absence of specific invasive investigations, and with a consequent possible increase in mortality-and over-diagnosis (case identification with galactomannan on broncho-alveolar fluid alone) might be considered. Realistic incidence rates, based on local, real-life epidemiological data, might be helpful in guiding clinicians.

Disseminated Cryptococcosis Complicating Severe SARS-CoV-2 Infection

Opportunistic invasive fungal infections (IFI) have been described in severe SARS-CoV-2 infection. COVID-19-related cytokine storm, immune dysregulation and lymphopenia may increase IFI susceptibility in comorbid patients. We described the case of a 64-year-old man with respiratory failure due to SARS-CoV-2 infection complicated with disseminated cryptococosis. We analyzed the role played by the SARS-CoV-2-associated lymphopenia and the cumulative risk factors that lead to secondary infection by Cryptococcus neoformans, and its part in the dysregulation of the immunity response.

Monoclonal antibodies for the treatment of COVID-19 patients: An umbrella to overcome the storm?

The world is facing up the most considerable vaccination effort in history to end the Coronavirus disease 2019 (COVID-19) pandemic. Several monoclonal antibodies (mAbs) direct against the Receptor binding domain of the S protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) received an Emergency Use Authorization for outpatient management of mild to moderate manifestation from COVID-19. MAbs could prevent the transmission SARS-CoV-2 infection and protect individuals from progression to severe disease. Under the pressure of different treatment strategies, SARS-CoV-2 has been demonstrated to select for different sets of mutations named "variants" that could impair the effectiveness of mAbs by modifying target epitopes. We provide an overview of both completed and unpublished, or ongoing clinical trials of mAbs used and review state of art in order to describe clinical options, possible indications, and the place in therapy for these agents in the treatment of COVID-19 with a particular focus on anti-spike agents. Then, we reassume the current evidence on mutations of the SARS-CoV-2 that might confer resistance to neutralization by multiple mAbs.

Early low-molecular-weight heparin administration is associated with shorter time to SARS-CoV-2 swab negativity.

BACKGROUND: Antiviral and immune-modulating properties of low-molecular-weight heparin (LMWH) against Coronaviridae have been reported by in vitro studies, but no in vivo evidence is yet available. We sought to know whether the timing of prophylactic doses of LMWH during the course of COVID-19 may affect the time to SARS-CoV-2 nasal-oropharyngeal swab negativization. METHODS: Retrospective monocentric cross-sectional study on patients requiring sub-intensive ward admission due to first SARS-CoV-2 infection and undergoing early (EH; within 7 days from COVID-19 signs and symptoms onset) versus delayed prophylactic LMWH (DH; after 7 days). SARS-CoV-2 RNA was measured by reverse transcription real-time PCR according to scheduled time points: first swab after 2 weeks from COVID-19 onset, then at 1-week intervals until negativity. RESULTS: Time to SARS-CoV-2 swab negativity was shorter in EH (38 patients) compared with DH (55 patients): 22 versus 37 days (P=0.004). The number of confirmative negative swabs in EH was significantly higher compared with DH at week 2 (21.1% versus 3.6%; P=0.017) and 4 (60.0% versus 19.6%; P<0.001). At univariate, EH differed from DH for several disease severity and clinical management parameters. Nevertheless, after accounting for the differences, Cox regression showed early LMWH administration (hazard ratio [HR] 2.91 [1.51, 5.63]; P=0.002) and higher lymphocytes nadir (HR 1.04 [1.01, 1.08]; P=0.020) as predictors of shorter time to swab negativity. CONCLUSIONS: This potential antiviral and/or immune-modulating activity of LMWH needs further in vivo confirmations by randomized controlled trials.