A prothrombotic state is reported with severe COVID-19 infection, which can manifest in venous and arterial thrombotic events. Coagulopathy is reflective of more severe disease and anticoagulant thromboprophylaxis is recommended in hospitalized patients. However, the prevalence of thrombosis on the intensive care unit (ICU) remains unclear, including whether this is sufficiently addressed by conventional anticoagulant thromboprophylaxis. We aimed to identify the rate of thrombotic complications in ICU-treated patients with COVID-19, to inform recommendations for diagnosis and management. A systematic review was conducted to assess the incidence of thrombotic complications in ICU-treated patients with COVID-19. Observational studies and registries reporting thrombotic complications in ICU-treated patients were included. Information extracted included patient demographics, use of thromboprophylaxis or anticoagulation, method of identifying thrombotic complications, and reported patient outcomes. In 28 studies including 2928 patients, thrombotic complications occurred in 34% of ICU-managed patients, with deep venous thrombosis reported in 16.1% and pulmonary embolism in 12.6% of patients, despite anticoagulant thromboprophylaxis, and were associated with high mortality. Studies adopting systematic screening for venous thrombosis with Duplex ultrasound reported a significantly higher incidence of venous thrombosis compared to those relying on clinical suspicion (56.3% vs. 11.0%, p < 0.001). Despite thromboprophylaxis, there is a very high incidence of thrombotic complications in patients with COVID-19 on the ICU. Systematic screening identifies many thrombotic complications that would be missed by relying on clinical suspicion and should be employed, with consideration given to increased dose anticoagulant thromboprophylaxis, whilst awaiting results of prospective trials of anticoagulation in this cohort.

There is an increasing need to understand the leukocytes and soluble mediators that drive acute inflammation and bring about its resolution in humans. We therefore carried out an extensive characterisation of the cantharidin skin blister model in healthy male volunteers. A novel fluorescence staining protocol was designed and implemented, which facilitated the identification of cell populations by flow cytometry. We observed that at the onset phase, 24 h after blister formation, the predominant cells were CD16hi/CD66b+ PMNs followed by HLA-DR+/CD14+ monocytes/macrophages, CD11c+ and CD141+ dendritic cells as well as Siglec-8+ eosinophils. CD3+ T cells, CD19+ B cells and CD56+ NK cells were also present, but in comparatively fewer numbers. During resolution, 72 h following blister induction, numbers of PMNs declined whilst the numbers of monocyte/macrophages remain unchanged, though they upregulated expression of CD16 and CD163. In contrast, the overall numbers of dendritic cells and Siglec-8+ eosinophils increased. Post hoc analysis of these data revealed that of the inflammatory cytokines measured, TNF-α but not IL-1β or IL-8 correlated with increased PMN numbers at the onset. Volunteers with the greatest PMN infiltration at onset displayed the fastest clearance rates for these cells at resolution. Collectively, these data provide insight into the cells that occupy acute resolving blister in humans, the soluble mediators that may control their influx as well as the phenotype of mononuclear phagocytes that predominate the resolution phase. Further use of this model will improve our understanding of the evolution and resolution of inflammation in humans, how defects in these over-lapping pathways may contribute to the variability in disease longevity/chronicity, and lends itself to the screen of putative anti-inflammatory or pro-resolution therapies.

A high incidence of thrombosis in hospitalised patients with COVID-19 was identified early during the pandemic. Accurately quantifying thrombotic risk may assist prognosis and guide appropriate thromboprophylaxis. Observational studies have estimated the rate of thrombosis in both hospitalised and non-hospitalised patients with COVID-19, and how this corresponds to the severity of illness. In this review, we provide an overview of the incidence and prevalence of arterial and venous thrombotic events in patients with COVID-19 and highlight the limitations in the studies to date. Asymptomatic individuals with COVID-19 and those with mild symptoms are at very low risk of thrombotic complications. However, rates of thrombosis are substantially increased in hospitalised patients, and are strikingly high in those patients who are critically-ill requiring treatment on the intensive care unit and especially those requiring extracorporeal membrane oxygenation. Clinicians managing such patients need to be aware of these risks and take appropriate steps with respect to thromboprophylaxis and heightened clinical vigilance. Large prospective observational studies will more accurately quantify thrombotic rate, and randomized controlled trials are currently investigating optimal thromboprophylactic strategies.

High rates of both venous and arterial thromboembolic events were observed early during the global COVID-19 pandemic, with severity of illness and need for intensive care unit admission correlating with increased thrombotic risk.Study Summary: This paper is a review of several observational studies that document the relatively high rates of thrombosis seen in hospitalized patients with COVID-19. Overall, the aggregate data demonstrate that the rates of arterial and venous thrombotic complications in patients with COVID-19 were low in nonhospitalized individuals with asymptomatic or mild disease. Also, thrombotic risk increased with severity of COVID-19 illness (up to 31%), with patients needing intensive care being at greatest risk. Caveats were the retrospective nature of the reports, variable reporting of types of thrombosis, the variable use or availability of screening or imaging studies in symptomatic patients, and resource utilization such as extracorporeal membrane oxygenation. Venous thrombotic events were much more commonly seen than arterial thromboses, and the risk of thrombosis did not disappear at hospital discharge.Commentary: This was a frightening year. The guidance from medical colleagues around the world as they experienced surges in SARS-CoV2 infections at differing time points helped others be better prepared. Most facilities had to triage patients, redeploy physicians, limit use of technicians, support persons, and scanner in attempts to spread resources and prevent exposure. The ongoing multisystem inflammatory state of COVID-19 beyond the acute illness has made the development of thromboprophylaxis guidelines, best practices for treatment, and therapy strategies paramount.

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