ABSTRACT
BACKGROUND: A possible association between COVID-19 infection and thrombosis, either as a direct consequence of the virus or as a complication of inflammation, is emerging in the literature. Data on the incidence of venous thromboembolism (VTE) are extremely limited. METHODS: We describe three cases of thromboembolism refractory to heparin treatment, the incidence of VTE in an inpatient cohort, and a case-control study to identify risk factors associated with VTE. RESULTS: We identified 274 confirmed (208) or probable (66) COVID-19 patients. 21 (7.7%) were diagnosed with VTE. D-dimer was elevated in both cases (confirmed VTE) and controls (no confirmed VTE) but higher levels were seen in confirmed VTE cases (4.1 vs 1.2 µg/mL, p<0.001). CONCLUSION: Incidence of VTE is high in patients hospitalised with COVID-19. Urgent clinical trials are needed to evaluate the role of anticoagulation in COVID-19. Monitoring of D-dimer and anti-factor Xa levels may be beneficial in guiding management.
Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Fibrin Fibrinogen Degradation Products/metabolism , Pneumonia, Viral/complications , Venous Thromboembolism/blood , Venous Thromboembolism/epidemiology , Aged , Aged, 80 and over , Anticoagulants/therapeutic use , Biomarkers/blood , COVID-19 , Case-Control Studies , Coronavirus Infections/blood , Female , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Incidence , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Retrospective Studies , Risk Factors , SARS-CoV-2 , Venous Thromboembolism/drug therapy , Venous Thromboembolism/virologyABSTRACT
COVID-19, caused by infection with SARS-CoV-2, is a disease characterised by cough, fever and fatigue, which progresses to life-threatening lung injury in approximately 5% of patients. The SARS-CoV-2 virus enters the cell via ACE2. ACE2 is a component of the renin-angiotensin system (RAS) which has an important counterregulatory effect on the classical ACE-dependent pathway. Several antihypertensives increase ACE2 expression or activity, leading to concern that this may facilitate SARS-CoV-2 entry and worsen COVID-19 disease. However, ACE2 is protective against lung injury while ANG II (which is catabolised by ACE2) is associated with lung injury both in mice and humans. We propose that medications which inhibit the RAS ACE-dependent pathway may be beneficial in treating COVID-19 and should be explored in animal models and clinical trials. Here we give an overview of the RAS pathway with respect to COVID-19 and argue that strategies which manipulate this pathway might reduce the destructive lung manifestations of COVID-19 and improve patient outcomes.
Subject(s)
Angiotensin II/metabolism , Antihypertensive Agents/therapeutic use , Betacoronavirus/physiology , Coronavirus Infections/metabolism , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/metabolism , Renin-Angiotensin System , Amides/therapeutic use , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme 2 , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Animals , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Fumarates/therapeutic use , Humans , Lung Injury/metabolism , Lung Injury/virology , Mice , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , SARS-CoV-2 , Virus InternalizationABSTRACT
The novel coronavirus SARS-CoV-2, causing the disease COVID-19, first emerged in Wuhan, China in December 2019 and has now spread to 203 countries or territories, infected over 2 million people and caused over 133,000 deaths. There is an urgent need for specific treatments. One potential treatment is chloroquine and its derivatives, including hydroxychloroquine, which have both antiviral and anti-inflammatory effects. These compounds are effective against SARS-CoV-2 in vitro, but in vivo data are lacking. Although some encouraging outcomes have been reported, and these results have been received enthusiastically, we recommend careful and critical evaluation of current evidence only when all methods and data are available for peer review. Chloroquine is safe and cheap. However, further evidence from coordinated multicentre trials is required before it can be confidently said whether it is effective against the current pandemic.
