COVID-19 research focuses on steroids, clots, hydroxychloroquine, zinc

Steroids' effects varied by C-reactive protein level, clots occurred despite prophylaxis, and hydroxychloroquine and zinc were ineffective for COVID-19, according to newly published studies.

More data on the efficacy of glucocorticoids for some hospitalized patients with COVID-19 was provided by a brief report published by the Journal of Hospital Medicine on July 22. The observational study looked at 1,806 hospitalized COVID-19 patients, 140 of whom were treated with glucocorticoids within 48 hours of admission. Overall, glucocorticoids were not associated with any difference in mortality or mechanical ventilation, but in the subgroup of patients with initial C-reactive protein (CRP) levels of 20 mg/dL or above, these outcomes were significantly reduced (odds ratio [OR], 0.23; 95% CI, 0.08 to 0.70). However, in patients with CRP levels less than 10 mg/dL, steroids were associated with significantly increased risk of mortality or mechanical ventilation (OR, 2.64; 95% CI, 1.39 to 5.03). The study authors noted that their findings are in accordance with the recent RECOVERY trial and add to it by offering a method for identifying which patients are likely to get benefit or harm from steroids. The results should be confirmed in prospective, randomized trials, they said.

Two recent studies analyzed the rate of thrombosis among hospitalized patients. One, published as a research letter in JAMA on July 20, included 3,334 patients from one hospital, 829 of them treated in the ICU. Most received low-dose anticoagulation for thromboprophylaxis. Rates of thrombotic events were 11.5% in ward patients and 29.4% in ICU patients. The authors noted that D-dimer level at presentation was independently associated with thrombotic events.

The second, published as a research letter by CHEST on July 22, included 210 patients, 102 of them treated in the ICU. Overall, 90.5% of patients received anticoagulation at admission. No ward patients had symptomatic venous thromboembolisms (VTE), but 9.3% of ICU patients did. “Our findings suggest that standard dose VTE prophylaxis is effective for ward patients, but may be insufficient to prevent VTE in COVID-19 ICU patients,” the authors said.

Hydroxychloroquine failed to show benefit in a new study, published by the New England Journal of Medicine on July 23. The Brazilian trial, which was funded in part by EMS Pharma, randomized hospitalized patients with mild to moderate COVID-19 (a maximum of 4 L/min supplemental oxygen) to standard care, standard care plus hydroxychloroquine, or standard care plus hydroxychloroquine and azithromycin. Among the 504 patients included in the modified intention-to-treat analysis, clinical status at 15 days did not differ with hydroxychloroquine alone (OR, 1.21; 95% CI, 0.69 to 2.11; P=1.00) or hydroxychloroquine plus azithromycin (OR, 0.99; 95% CI, 0.57 to 1.73; P=1.00) compared to standard care. The authors did note several limitations to their trial, including that it could not definitively rule out either a substantial benefit or harm from the drugs, that it was not blinded, that some patients in the standard care group had received the drugs for up to 24 hours before enrollment, and that although the median time from symptom onset to randomization was seven days, some patients were randomized as late as 14 days.

Zinc also failed to show a beneficial effect on hospitalized patients in a study published by CHEST on July 22. The retrospective study looked at all 242 patients admitted to one U.S. medical center with COVID-19, 81.0% of whom received zinc sulfate. The study found no significant difference in days to inpatient mortality between patients who did and didn't receive zinc, including in subgroups stratified by severity of illness. The authors cautioned that the study was limited by its small size and risk of confounding, so an effect could not be ruled out, and randomized trials are needed to establish the efficacy of zinc in COVID-19.