Biomarkers may predict which medications are effective for patients hospitalized for COVID-19
Two studies looked at biomarkers that could be used to identify high-risk hospital patients who would likely benefit from medications for COVID-19, while another recent analysis provided reassuring data on the aftereffects of acute kidney injury during COVID-19 hospitalization.
Two recent studies offered data to target therapies for hospitalized patients with COVID-19, while another analyzed such patients' risks of lasting kidney damage.
The first study, published by Annals of Internal Medicine on Feb. 27, was a post hoc analysis of the ACTT-2 trial, which included 999 hospitalized COVID-19 patients from eight countries (85% in the U.S.) and focused on the effects of baricitinib by baseline risk profile. Patients were considered high risk based on low absolute lymphocyte count (ALC), high absolute neutrophil count (ANC), and low platelet count. All study patients received remdesivir plus either baricitinib or placebo. In the highest risk quartile of patients, baricitinib was associated with lower risk of 28-day mortality (hazard ratio [HR], 0.38 [95% CI, 0.16 to 0.86]; P=0.020) or progression to ventilation or death (HR, 0.57 [95% CI, 0.35 to 0.93]; P=0.024) and an improved recovery rate (HR, 1.53 [95% CI, 1.16 to 2.02]; P=0.002). At five days, patients who got baricitinib had significantly larger increases in ALC and decreases in ANC than those on placebo.
"Although respiratory status is used in major treatment guidelines to guide management, the findings presented here suggest that a biomarker-based approach utilizing simple parameters found in a bedside complete blood count provides complementary information on who might benefit from baricitinib treatment," said the study authors, who noted that their previous research showed the benefit of remdesivir in this same high-risk group. "Therefore, we hypothesize that parameters reflected in the profile, including levels of lymphocytes and neutrophils in the blood at baseline, capture a patient phenotype of responsiveness to treatment. This phenotype may comprise persons who are unable to effectively reduce viral burden or limit deleterious inflammation and who derive particular benefit from an antiviral or an immunomodulator," they wrote.
The second study, published by Clinical Infectious Diseases on Feb. 20, included 2,625 patients from around the world who were hospitalized for COVID-19 and were randomized to an antiviral therapy or placebo. This analysis looked at their 90-day mortality by markers including viral RNA on an upper respiratory swab, plasma antibodies, SARS-CoV-2 nucleocapsid antigen (viral Ag), and interleukin-6 (IL-6) levels. It found higher mortality with elevated viral Ag (adjusted HR, 2.07 [95% CI, 1.29 to 3.34] for ≥4500 ng/L vs. <200 ng/L), viral RNA (adjusted HRs, 2.42 [95% CI, 1.09 to 5.34] for <35,000 copies/mL and 2.84 [95% CI, 1.29 to 6.28] for ≥35,000 copies/mL, both compared to undetectable), and IL-6 (adjusted HR, 2.54 [95% CI, 1.74 to 3.70] for >5.8 ng/L). Need for respiratory support or noninvasive ventilation and renal impairment was also associated with mortality.
"Our findings support continued assessment of therapies that reduce plasma viral replication or target pathways of tissue injury to attempt to limit organ damage and related clinical outcomes," the study authors said. They noted, however, that the current absence of real-time assays for viral antigen, RNA, or IL-6 makes it hard to apply the findings in practice. An accompanying editorial highlighted that plasma viral antigen levels, need for respiratory support, and elevated IL-6 levels appeared to have an additive effect on risk, "which is a novel finding, with potential therapeutic consequences." The findings "strengthen the rationale for considering antiviral treatment in certain patients classified as severe coronavirus disease," the editorial added.
Finally, a study published by JAMA Internal Medicine on Feb. 26 compared the risk of lasting kidney damage in patients who developed acute kidney injury (AKI) while hospitalized with COVID-19 versus those who got AKI from the flu or another illness. Patients at one U.S. center were followed for a maximum of two years after discharge. The 987 patients with AKI from COVID-19 were slightly younger, with a higher baseline estimated glomerular filtration rate (eGFR), worse baseline comorbidity scores, higher markers of illness severity, and longer hospital stays than the 276 patients with influenza-associated AKI and 8,361 with AKI from other illnesses. The patients with COVID-19 and AKI had lower risk of the study's primary outcome, a composite of mortality and worsened kidney function, defined as an eGFR decline of at least 25% after discharge or kidney failure requiring dialysis (adjusted HR, 0.67 [95% CI, 0.59 to 0.75]), as well as significant reductions in each of the outcomes separately (adjusted HRs, 0.31 [95% CI, 0.24 to 0.39] and 0.78 [95% CI, 0.69 to 0.88], respectively). "Contrary to existing concerns, survivors of COVID-AKI appear to be a resilient population with overall better long-term survival and kidney outcomes compared with AKI associated with influenza or other illnesses," the study authors wrote.
