Outcome of patients hospitalized for COVID‐19 and exposure to angiotensin‐converting enzyme inhibitors and angiotensin‐receptor blockers in France: results of the ACE‐CoV study

Data are lacking on the impact of ACEI/ARB exposure on unfavorable outcome in the population of patients hospitalized for COVID‐19 with hypertension/cardiovascular disease, particularly in Europe. The ACE‐CoV study was designed to assess this question. The study was conducted in the Covid‐Clinic‐Toul cohort, which contains data about all patients hospitalized at Toulouse University hospital, France with a SARS‐CoV‐2 infection since March, 2020. We selected the patients with a history of cardiovascular disease (heart failure or coronary disease) and/or arterial hypertension. We conducted a subgroup analysis in patients with arterial hypertension. ACEI/ARB exposures at admission were assessed. The outcome was composite: admission to intensive care unit, need of mechanical ventilation or death during the 14 days after admission to hospital. We used logistic regression models with propensity scores (PS) weighted by overlap weighting (OW) and inverse probability of treatment weighting (IPTW). Between March 2020 and April 20, 2020, the Covid‐Clinic‐Toul included 263 patients. Among them, 111 were included in the ACE‐CoV study population. In OW‐PS‐adjusted analyses, the association of exposure to ACEIs or ARBs with outcome occurrence was OR: 1.56 (95% CI: 0.73–3.33). It was 0.99 (95% CI: 0.68–1.45) for ACEIs and 1.64 (95% CI: 0.77–3.50) for ARBs. Analyses with weighting by the IPTW‐PS method gave similar results. Results were similar when considering the subgroup of patients with arterial hypertension. The ACE‐CoV study found no association between exposure to ACEIs or ARBs and unfavorable outcome in hospitalized patients for COVID‐19 with a history of cardiovascular disease/arterial hypertension.     

Clinical significance of the serum IgM and IgG to SARS‐CoV‐2 in coronavirus disease‐2019

ObjectiveTo explore the clinical value of serum IgM and IgG to SARS‐CoV‐2 in COVID‐19.Methods105 COVID‐19 patients were enrolled as the disease group. 197 non‐COVID‐19 patients served as the control group. Magnetic chemiluminescent immunoassay (MCLIA) was used to detect the IgM and IgG.ResultsThe peak of positive rates of SARS‐CoV‐2 IgM was about 1 week earlier than that of IgG. It reached to peak within 15–21 days and then began a slowly decline. The positive rates of IgG were increased with the disease course and reached the peak between 22 and 39 days. The differences in sensitivity of the three detection modes (IgM, IgG, and IgM + IgG) were statistically significant. The largest group of test cases (illness onset 15–21 days) showed that the positive rate of IgG was higher than IgM. Also, the sensitivity of IgM combined with IgG was higher than IgM or IgG. IgM and IgG were monitored dynamically for 16 patients with COVID‐19, the results showed that serological transformation of IgM was carried out simultaneously with IgG in seven patients, which was earlier than IgG in four patients and later than IgG in five patients.ConclusionThe detection of SARS‐CoV‐2 IgM and IgG is very important to determine the course of COVID‐19. Nucleic acid detection combined with serum antibody of SARS‐CoV‐2 may be the best laboratory indicator for the diagnosis of SARS‐CoV‐2 infection and the phrase and predication for prognosis of COVID‐19.     

Informing emergency care for COVID‐19 patients: The COVID‐19 Emergency Department Quality Improvement Project protocol

Objectives: There is an urgency to support Australian ED clinicians with real‐time tools as the COVID‐19 pandemic evolves. The COVID‐19 Emergency Department (COVED) Quality Improvement Project has commenced and will provide flexible and responsive clinical tools to determine the predictors of key ED‐relevant clinical outcomes. Methods: The COVED Project includes all adult patients presenting to a participating ED and meeting contemporary testing criteria for COVID‐19. The dataset has been embedded in the electronic medical record and the COVED Registry has been developed. Results: Outcomes measured include being COVID‐19 positive and requiring intensive respiratory support. Regression methodology will be used to generate clinical prediction tools. Conclusion: This project will support EDs during this pandemic.     

Coagulopathy in COVID‐19

The COVID‐19 pandemic has become an urgent issue in every country. Based on recent reports, the most severely ill patients present with coagulopathy, and disseminated intravascular coagulation (DIC)‐like massive intravascular clot formation is frequently seen in this cohort. Therefore, coagulation tests may be considered useful to discriminate severe cases of COVID‐19. The clinical presentation of COVID‐19‐associated coagulopathy is organ dysfunction primarily, whereas hemorrhagic events are less frequent. Changes in hemostatic biomarkers represented by increase in D‐dimer and fibrin/fibrinogen degradation products indicate the essence of coagulopathy is massive fibrin formation. In comparison with bacterial‐sepsis‐associated coagulopathy/DIC, prolongation of prothrombin time, and activated partial thromboplastin time, and decrease in antithrombin activity is less frequent and thrombocytopenia is relatively uncommon in COVID‐19. The mechanisms of the coagulopathy are not fully elucidated, however. It is speculated that the dysregulated immune responses orchestrated by inflammatory cytokines, lymphocyte cell death, hypoxia, and endothelial damage are involved. Bleeding tendency is uncommon, but the incidence of thrombosis in COVID‐19 and the adequacy of current recommendations regarding standard venous thromboembolic dosing are uncertain.     

The protective rather than prothrombotic fibrinogen in COVID‐19 and other inflammatory states

Hypercoagulability has been recognized as a common complication of COVID‐19. Exact mechanisms for this extreme coagulation activation have not yet been elucidated. However, one of the consistent laboratory finding is the increase in fibrinogen, in some cases, marked elevation. High circulating levels of fibrinogen have been linked to thrombosis for years and for this reason, hyperfibrinogenemia is considered one of the mechanisms for COVID‐19 coagulopathy. In this forum article, instead of the prothrombotic role, a protective function for fibrinogen is discussed. Fibrinogen, like the other well‐known acute phase reactants, is increased in COVID‐19 possibly to protect the host.     

Cardiac injury is associated with inflammation in geriatric COVID‐19 patients

BackgroundGeriatric patients with coronavirus disease (COVID‐19) are at high risk of developing cardiac injury. Identifying the factors that affect high‐sensitivity cardiac troponin I may indicate the cause of cardiac injury in elderly patients, and this could hopefully assist in protecting heart function in this patient population.MethodsOne hundred and eighty inpatients who were admitted for COVID‐19 were screened. Patients older than 60 years were included in this study, and the clinical characteristics and laboratory results of the cohort were analyzed. The correlation between cardiac injury and clinical/laboratory variables was statistically analyzed, and further logistic regression was performed to determine how these variables influence cardiac injury in geriatric patients.ResultsAge (p < 0.001) significantly correlated with cardiac injury, whereas sex (p = 0.372) and coexisting diseases did not. Rising procalcitonin (p = 0.001), interleukin‐2 receptor (p < 0.001), interleukin 6 (p = 0.001), interleukin 10 (p < 0.001), tumor necrosis factor α (p = 0.001), high‐sensitivity C‐reactive protein (p = 0.001), D‐dimer (p < 0.001), white blood cells (p < 0.001), neutrophils (p = 0.001), declining lymphocytes (p < 0.001), and natural killer cells (p = 0.005) were associated with cardiac injury and showed predictive ability in the multivariate logistic regression.ConclusionOur results suggest that age and inflammatory factors influence cardiac injury in elderly patients. Interfering with inflammation in this patient population may potentially confer cardiac protection.     

COVID‐19: A collision of complement,coagulation and inflammatory pathways

COVID‐19 is frequently accompanied by a hypercoagulable inflammatory state with microangiopathic pulmonary changes that can precede the diffuse alveolar damage characteristic of typical acute respiratory distress syndrome (ARDS) seen in other severe pathogenic infections. Parallels with systemic inflammatory disorders such as atypical hemolytic uremic syndrome (aHUS) have implicated the complement pathway in the pathogenesis of COVID‐19, and particularly the anaphylatoxins C3a and C5a released from cleavage of C3 and C5, respectively. C5a is a potent cell signalling protein that activates a cytokine storm—a hyper‐inflammatory phenomenon—within hours of infection and the innate immune response. However, excess C5a can result in a pro‐inflammatory environment orchestrated through a plethora of mechanisms that propagate lung injury, lymphocyte exhaustion, and an immune paresis. Furthermore, disruption of the homeostatic interactions between complement and extrinsic and intrinsic coagulation pathways contributes to a net pro‐coagulant state in the microvasculature of critical organs. Fatal COVID‐19 has been associated with a systemic inflammatory response accompanied by a pro‐coagulant state and organ damage, particularly microvascular thrombi in the lungs and kidneys. Pathologic studies report strong evidence of complement activation. C5 blockade reduces inflammatory cytokines and their manifestations in animal studies, and has shown benefits in patients with aHUS, prompting investigation of this approach in the treatment of COVID‐19. This review describes the role of the complement pathway and particularly C5a and its aberrations in highly pathogenic virus infections, and therefore its potential as a therapeutic target in COVID‐19.