May 1, 2020

Umifenovir does not appear to improve outcomes in patients with COVID-19, pulmonary embolisms may occur after the cytokine storm

By Denise Baez

NEW YORK -- May 1, 2020 -- In this DG Alert, we cover effectiveness and safety of umifenovir for coronavirus disease 2019 (COVID-19), and pulmonary embolisms after the cytokine storm in patients with COVID-19.

According to a study published in Clinical Microbiology and Infection, treatment with umifenovir is not associated with improved outcomes in patients with COVID-19.

Ningfan Lian, MD, The First Affiliated Hospital of Fujian, Fujian, China, and colleagues retrospectively analysed data from patients admitted to a non-intensive care unit ward in Jinyintan Hospital, Wuhan, China, from February 2, 2020, to March 20, 2020.

Patients were divided according to whether they received treatment with umifenovir (n = 45) or not (n = 36). The primary outcome was the negative rate of pharyngeal swab’s test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within 1 week after admission, as well as the duration for virus turning negative (2 consecutive tests).

Of the patients in umifenovir group, 33 (73.3%) tested negative within 7 days after admission compared with 28 (77.8%) patients in control group (P = 0.19). The median time from onset symptoms to SARS-CoV-2 turning negative was 18 days in the umifenovir group and 16 days in the control group (P = 0.42). Patients in the umifenovir group had a longer hospital stay than patients in control group (13 days vs 11 days; P = 0.04).

The authors noted that a randomised control clinical trial is needed to further assess the efficacy of umifenovir.

Another study, published in Emerging Infectious Diseases, suggests that pulmonary embolisms (PEs) can occur after the cytokine storm in patients with COVID-19, despite deep vein thrombosis prophylaxis.

Daniel O. Griffin, MD, Columbia University Medical Center, New York, New York, and colleagues reported on 3 patients with COVID-19 admitted to Northwell Plainview Hospital, Plainview, New York. All patients received azithromycin and hydroxychloroquine, but their respiratory status declined during their hospital stay.

During what was assumed to be the cytokine storm phase, on the basis of laboratory parameters and an increasing requirement for oxygen, the patients received intravenous steroids and intravenous tocilizumab 400 mg. Patients showed improvement and did not require intubation, but later developed persistent hypoxemia with increases in levels of d-dimer. Computed tomography angiograms confirmed bilateral PEs, and the patients required supplemental oxygen.

“After initial improvements, patients might continue to have high or increasing oxygen requirements because of development of thromboembolic disease,” the authors wrote. “Previous studies showed that low levels of platelets, increased levels of d-dimer, and increasing levels of prothrombin in COVID-19 were associated with poor outcome, which might be explained by thromboembolic complications in patients with severe disease. Platelet counts remained within reference ranges for 2 of our patients and only decreased for 1 patient. Two patients had increases in d-dimer levels, and the third patient was admitted with a highly increased d-dimer level.”

“Although certain underlying conditions might have influenced the coagulation process in these patients, the hypothesis that hypercoagulability is driven by endothelial dysfunction is plausible. These case studies support the earlier observation that anticoagulation is associated with a decrease in mortality rates for patients with COVID-19. Monitoring disseminated intravascular coagulation and measurement of platelet counts, d-dimer, and fibrinogen levels, and trending International Society of Thrombosis and Haemostasis scores might be beneficial for early diagnosis of PE in patients with COVID-19.”

SOURCE: Clinical Microbiology and Infection, Emerging Infectious Diseases