According to a study of more than 2,500 people led by Stanford Medicine researchers, a one-time test could predict which people hospitalized with COVID-19 are likely to get significantly worse during their stay, even if they’re relatively mild symptoms were recorded.
The test measures blood levels of a protein in the virus that causes COVID-19. High protein levels were strongly correlated with an increased need for respiratory support five days later, regardless of the severity of the patient’s illness when the test was performed, the researchers found. People with high scores also had to be hospitalized significantly longer than those with lower scores.
The results suggest that the virus may continue to replicate in a subset of hospitalized patients and that these patients could benefit from antiviral treatments such as monoclonal antibodies or remdesivir. Such antiviral treatments are now mainly used in outpatient settings after previous clinical trials showed that inpatients were not benefiting from them.
The way we’ve been thinking about COVID-19 is that antiviral drugs are most helpful early in an illness to stop viral replication before a person actually gets sick. When a person is sick enough to be hospitalized, the inflammatory response to the virus appears to be causing many of their clinical symptoms. Some have suggested it is time to end antiviral drug testing in the sickest patients hospitalized with COVID-19. But this study suggests that a subset of patients may benefit from antiviral therapies even after hospitalization.”
Angela Rogers, MD, associate professor of pulmonary and critical care medicine
Rogers is the lead author of the study, which was published online Aug. 30 in Annals of Internal Medicine. She led an international group of researchers in analyzing the results of a large, multi-center clinical trial of antiviral therapies in hospitalized COVID-19 patients, dubbed the ACTIV-3 or TICO trial (Therapeutics for Inpatients with COVID-19). becomes.
Testing of antivirals
The ACTIV-3 study was designed to test five antiviral drugs versus a placebo in hospitalized COVID-19 patients. Rogers and her colleagues studied more than 2,500 people hospitalized for COVID-19 in multiple locations in the United States, Europe, Asia and Africa between August 2020 and mid-November 2021 — a period that marked the rise of the Delta variant of the virus spanned the globe. Few patients were vaccinated.
Blood samples from patients were tested for the presence of the telltale protein from the nucleocapsid, or outer envelope, of the SARS-CoV-2 virus that causes COVID-19 at the time of their enrollment in the study. 95% of the participants had detectable levels of this protein, called N protein. 57% of them had levels of at least 1,000 nanograms per liter (a nanogram is one billionth of a gram). On average, people with levels above 1,000 ng/L at the time of sample collection were sicker than people with lower blood N-protein levels.
At first glance, the results may seem obvious – more virus could indicate a higher infection load or that the immune system cannot control the infection. However, the researchers highlighted some important subtleties when they compared relative N-protein levels in 1,085 patients randomly assigned to receive placebo treatment with their symptoms five days after sample collection.
“At any disease severity level, people with higher protein or antigen levels had a significantly higher risk of worsening,” Rogers said. “People with high antigen levels but who were able to breathe without oxygen when they enrolled in the study were five times more likely to require oxygen supplementation five days later than those with lower antigen levels.”
Among the 257 people in the placebo group who did not initially require oxygen, 26% of those with N-protein levels of at least 1,000 ng/L had achieved oxygen requirement five days later. That’s compared to just 6% of people who had lower scores.
More N-protein, longer hospital stay
Viral protein levels also correlated with the length of time a patient was hospitalized, the researchers found. Patients with lower levels had a median hospital stay of four days, but those with levels above 1000 ng/L were hospitalized for a median of seven days. The difference was more pronounced in the group that required non-invasive ventilation or high-flow nasal cannulas (both deliver more oxygen to the lungs than normal breathing). Of these patients, 42% with levels above 1,000 ng/L were discharged by day 28 of their hospital stay, compared with 73% for those with lower levels.
“All of the patients in the study were ill enough to be hospitalized,” Rogers said. “We know from previous studies that COVID-19 patients with higher antigen levels are more likely to die. But the lingering question was: Is that because they’re just sicker to begin with? Now we know that is not the case. Even patients with relatively mild symptoms do worse when plasma antigen levels are high.”
The researchers also found that men in the study tended to have higher blood N-protein levels than women at all stages of disease severity, even after accounting for differences in rates of high blood pressure, heart disease and other possible confounding factors.
“That’s really interesting and we don’t know why that is,” Rogers said. “There is still so much research to be done.”
The ACTIV-3 trial is still ongoing, but five of the six antiviral drugs studied by the group performed no better than placebo; Many of these drugs have been effective in the outpatient setting. This new study suggests that hospitalized patients are not uniform and that a precision medicine approach is needed for inpatient COVID-19 studies.
“Clinical trials of antivirals are very likely to fail if half the people you enroll already have low levels of the virus and can’t benefit from it,” Rogers said. “But some hospitalized patients with ongoing viral replication may benefit from these treatments.” Developing a point-of-care version of the test that could quickly identify patients with elevated viral levels could help physicians triage their treatment and target inclusion in future ones enable antiviral studies targeting the SARS-CoV-2 virus, Rogers believes.
Researchers from around the world who are part of the ACTIV-3/TICO study group are co-authors of the study.
The study was funded by the US program Operation Warp Speed; the National Institutes of Health (Grants 1OT2HL156812 and 75N91019D00024); Leidos Biomedical Research Inc. for the Insight Network; the Research Triangle Institute for the Prevention and Early Treatment of Acute Lung Injury Network; the Cardiothoracic Surgical Trials Network; and grants from the governments of Denmark, Australia, the United Kingdom and Singapore.
#onetime #test #predicts #hospitalized #COVID19 #patients #develop #worsening #study #finds
Leave a Comment