Acute Pulmonary Embolism and COVID-19

Poyiadji N, Cormier P, Patel PY, et al. Radiology. 2020 May 14:201955.  [CrossRef] [PubMed]

Patients with COVID-19 with a body mass index (BMI) >30 kg/m² have increased odds of developing pulmonary embolism (PE), according to an online research letter. The authors assessed the clinical characteristics of COVID-19 patients who developed PE in a retrospective analysis involving 328 COVID-19 patients who underwent pulmonary computed tomography (CT) angiography. Thy found that 22 percent of the patients had PE. Patients with a BMI >30 kg/m² were observed more often in the PE versus the non-PE group (58 versus 44 percent). Compared with the non-PE cohort, fewer patients with PE were on statin therapy prior to admission (27 versus 46 percent). In a multivariate model, patients taking statin therapy prior to admission had significantly reduced odds of developing PE (adjusted odds ratio, 0.4), while those with a BMI >30 kg/m² had an adjusted odds ratio of 2.7. The odds ratio was 4.8 for PE with a 6 µg/mL increase in D-dimer. The area under the receiver operating characteristic curve (AUC) was 0.86 for the multivariable model. A D-dimer of 3.11 µg/mL had sensitivity and specificity of 78 and 81 percent, respectively, for development of PE (AUC, 0.85). The authors advocate for early evaluation with pulmonary CT angiography in COVID-19 patients who are at increased risk for developing pulmonary embolism based on demographic, clinical, and laboratory variables.

Hydroxychloroquine or Chloroquine with or Without a Macrolide for Treatment of Covid-19: A Multinational Registry Analysis

Mehra MR, Desai SS, Ruschitzka F, Patel AN. Lancet. May 22, 2020. [Epub ahead of print]. [CrossRef]

Hydroxychloroquine or chloroquine, often in combination with a second-generation macrolide, are being widely used for treatment of COVID-19, despite no conclusive evidence of their benefit. Although generally safe when used for approved indications such as autoimmune disease or malaria, the safety and benefit of these treatment regimens are poorly evaluated in COVID-19. The authors did a multinational registry analysis of the use of hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19. The registry comprised data from 671 hospitals in six continents. The main outcomes of interest were in-hospital mortality and the occurrence of de-novo ventricular arrhythmias (non-sustained or sustained ventricular tachycardia or ventricular fibrillation). 14 888 patients were in the treatment groups (1868 received chloroquine, 3783 received chloroquine with a macrolide, 3016 received hydroxychloroquine, and 6221 received hydroxychloroquine with a macrolide) and 81 144 patients were in the control group. 10 698 (11·1%) patients died in hospital. After controlling for multiple confounding factors (age, sex, race or ethnicity, body-mass index, underlying cardiovascular disease and its risk factors, diabetes, underlying lung disease, smoking, immunosuppressed condition, and baseline disease severity), when compared with mortality in the control group (9·3%), hydroxychloroquine (18·0%; hazard ratio 1·335, 95% CI 1·223–1·457), hydroxychloroquine with a macrolide (23·8%; 1·447, 1·368–1·531), chloroquine (16·4%; 1·365, 1·218–1·531), and chloroquine with a macrolide (22·2%; 1·368, 1·273–1·469) were each independently associated with an increased risk of in-hospital mortality. Compared with the control group (0·3%), hydroxychloroquine (6·1%; 2·369, 1·935–2·900), hydroxychloroquine with a macrolide (8·1%; 5·106, 4·106–5·983), chloroquine (4·3%; 3·561, 2·760–4·596), and chloroquine with a macrolide (6·5%; 4·011, 3·344–4·812) were independently associated with an increased risk of de-novo ventricular arrhythmia. The authors were unable to confirm a benefit of hydroxychloroquine or chloroquine, when used alone or with a macrolide, on in-hospital outcomes for COVID-19. Each of these drug regimens was associated with decreased in-hospital survival and an increased frequency of ventricular arrhythmias when used for treatment of COVID-19.

Remdesivir In Adults with Severe COVID-19: A Randomised, Double-Blind, Placebo-Controlled, Multicentre Trial

Wang Y, Zhang D, Du G, et al. Lancet. 2020; 395:1569-78. [CrossRef]

No specific antiviral drug has been proven effective for treatment of patients with severe coronavirus disease 2019 (COVID-19). The authors did a randomised, double-blind, placebo-controlled, multicentre trial at ten hospitals in Hubei, China. Eligible patients were adults (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia. Patients were randomly assigned in a 2:1 ratio to intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2–10 in single daily infusions) or the same volume of placebo infusions for 10 days. The primary endpoint was time to clinical improvement up to day 28. Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1·23 [95% CI 0·87–1·75]). Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early. The authors conclude that remdesivir was not associated with statistically significant clinical benefits.

Association of Treatment Dose Anticoagulation with In-Hospital Survival Among Hospitalized Patients with COVID-19

Paranjpe I, Fuster V, Lala A, et al. J Am Coll Cardiol. 2020 May 5. pii: S0735-1097(20)35218-9. [Epub ahead of print] [CrossRef] [PubMed] 

The novel coronavirus 2019 (COVID-19) has been associated with reports of increased thromboembolic events and anecdotal observations of improved outcomes with systemic anticoagulation (AC). The authors assessed the association between administration of in-hospital AC and survival in a large cohort of hospitalized patients with COVID-19. Between March 14 and April 11, 2020, 2,773 patients were hospitalized with laboratory\confirmed COVID-19 within the Mount Sinai Health System in New York City. The authors used a Cox proportional hazards model to evaluate the effect of treatment-dose systemic AC (including oral, subcutaneous, or intravenous forms) on in-hospital mortality. 786 (28%) received systemic AC during their hospital course. In-hospital mortality for patients treated with AC was 22.5% with a median survival of 21 days, compared to 22.8% and median survival of 14 days in patients who did not receive AC. In patients who required mechanical ventilation (N=395), in-hospital mortality was 29.1% with a median survival of 21 days for those treated with AC as compared to 62.7% with a median survival of 9 days in patients who did not receive AC. In a multivariate proportional hazards model, longer duration of AC treatment was associated with a reduced risk of mortality (adjusted HR of 0.86 per day, 95% confidence interval 0.82-0.89, p<0.001). Although limited by its observational nature, unobserved confounding, unknown indication for AC, lack of metrics to further classify illness severity in the mechanically ventilated subgroup, and indication bias, the findings suggest that systemic AC may be associated with improved outcomes among patients hospitalized with COVID-19. It should be noted that similar arguments were made for systemic anticoagulation in ARDS but when subjected to randomized trials, anticoagulation made no mortality difference.

Assessment of N95 Respirator Decontamination and Re-Use for SARS-Cov-2

Fischer RJ, Morris DJ, Doremalen N, et al. medRxiv. April 15, 2020. [CrossRef]

A shortage of N95 masks designed for single has forced many to reuse masks and attempt to sterilize the masks between uses. In a not as yet peer-reviewed preprint, the authors analyzed four different decontamination methods – UV radiation (260 – 285 nm), 70ºC heat, 70% ethanol and vaporized hydrogen peroxide (VHP) – for their ability to reduce contamination with infectious SARS-CoV-2 (COVID-19) and their effect on N95 respirator function. Vaporized hydrogen peroxide, ethanol and heat yielded extremely rapid inactivation but UV inactivated SARS-CoV-2 more slowly. Quantitative fit tests showed that the filtration performance of the N95 respirator was not markedly reduced after a single decontamination for any of the four decontamination methods. Subsequent rounds of decontamination caused sharp drops in filtration performance of the ethanol-treated masks, and to a slightly lesser degree, the heat-treated masks. The VHP- and UV-treated masks retained comparable filtration performance to the control group after two rounds of decontamination, and maintained acceptable performance after three rounds. The authors recommend VHP for decontamination based on their data that the VHP treatment exhibited the best combination of rapid inactivation of SARS-CoV-2 and preservation of N95 respirator integrity.