BACKGROUND: Coronavirus disease 2019 (COVID-19)-induced mortality occurs predominantly in older patients. Several immunomodulating therapies seem less beneficial in these patients. The biological substrate behind these observations is unknown. The aim of this study was to obtain insight into the association between ageing, the host response and mortality in patients with COVID-19. METHODS: We determined 43 biomarkers reflective of alterations in four pathophysiological domains: endothelial cell and coagulation activation, inflammation and organ damage, and cytokine and chemokine release. We used mediation analysis to associate ageing-driven alterations in the host response with 30-day mortality. Biomarkers associated with both ageing and mortality were validated in an intensive care unit and external cohort. RESULTS: 464 general ward patients with COVID-19 were stratified according to age decades. Increasing age was an independent risk factor for 30-day mortality. Ageing was associated with alterations in each of the host response domains, characterised by greater activation of the endothelium and coagulation system and stronger elevation of inflammation and organ damage markers, which was independent of an increase in age-related comorbidities. Soluble tumour necrosis factor receptor 1, soluble triggering receptor expressed on myeloid cells 1 and soluble thrombomodulin showed the strongest correlation with ageing and explained part of the ageing-driven increase in 30-day mortality (proportion mediated: 13.0%, 12.9% and 12.6%, respectively). CONCLUSIONS: Ageing is associated with a strong and broad modification of the host response to COVID-19, and specific immune changes likely contribute to increased mortality in older patients. These results may provide insight into potential age-specific immunomodulatory targets in COVID-19.
COVID-19 , Humans , Aged , Biomarkers , Inflammation , Cytokines , Aging
We describe four secondary fungal infections caused by Mucorales species in COVID-19 patients. Three COVID-19 associated mucormycosis (CAM) occurred in ICU, one outside ICU. All were men aged >â¯50 years, three died. Clinical presentations included pulmonary, rhino-orbital cerebral and disseminated infection. Infections occurred in patients with and without diabetes mellitus. CAM is an emerging disease and our observations underscore the need to be aware of invasive mucormycosis, including in COVID-19 patients without (poorly controlled) diabetes mellitus and outside ICU.
COVID-19 , Mucorales , Mucormycosis , Female , Humans , Male , Mucormycosis/diagnosis , Netherlands/epidemiology , SARS-CoV-2
On 20 November 2019, Lassa fever was diagnosed in a physician repatriated from Sierra Leone to the Netherlands. A second physician with suspected Lassa fever, repatriated a few days later from the same healthcare facility, was confirmed infected with Lassa virus on 21 November. Comprehensive contact monitoring involving high- and low-risk contacts proved to be feasible and follow-up of the contacts did not reveal any case of secondary transmission in the Netherlands.
Contact Tracing , Health Personnel , Lassa Fever/diagnosis , Lassa virus/isolation & purification , Antiviral Agents/therapeutic use , Cross Infection , Female , Humans , Infectious Disease Transmission, Patient-to-Professional , Lassa Fever/drug therapy , Lassa virus/genetics , Male , Netherlands , Reverse Transcriptase Polymerase Chain Reaction , Sierra Leone , Travel , Whole Genome Sequencing
Anti-Bacterial Agents/pharmacology , Clindamycin/pharmacology , Clostridioides difficile/classification , Clostridioides difficile/drug effects , Drug Resistance, Multiple, Bacterial , Clostridioides difficile/genetics , Clostridium Infections/epidemiology , Clostridium Infections/microbiology , Disease Outbreaks , Europe/epidemiology , Humans , Polymerase Chain Reaction
