Omicron infection should be taken more seriously: study

The idea that the omicron subvariant of COVID-19 causes mild infection depends on just what it’s being compared to, experts say.

It is less lethal than the delta variant, but—for the unvaccinated—it’s just as lethal as the original iterations of SARS-CoV-2 or the alpha variant that followed right on their heels, according to a study in Clinical Infectious Diseases.

Researchers with Johns Hopkins University concluded that “severe outcomes were less common in vaccinated inpatients, with no difference between Delta and Omicron infections.”

The study found that comparing omicron to delta doesn’t take into account just how severe the variants that came before delta were. “Using stricter criteria for cohort entry to exclude asymptomatic SARS-CoV-2 infection, we found a 0.72-fold risk of severe disease for patients with Omicron compared to Delta, but no significant difference compared to ancestral lineages,” the study said.

Vaccinated patients or patients who’d been infected by SARS-CoV-2 in the past were less than half as likely as the unvaccinated to suffer severe disease in the delta and omicron eras.

“We found that vaccinated patients requiring hospitalization were older and had more comorbidities,” the study said. “Vaccines remain largely effective in preventing COVID-19 related mortality and population-based surveillance continues to show >5- fold protection against hospitalization.”

Corresponding author Matthew Robinson, M.D., of the division of infectious diseases at Johns Hopkins University School of Medicine, tells Fierce Healthcare that “I think that a year ago, no one was quite sure how severe Omicron would be. We were concerned that although the risk of hospitalization was less for Omicron, because so many patients were hospitalized that there would still be many patients at risk for severe disease which could overwhelm intensive care units.”

It’s important to compare the risk of severe disease between different COVID-19 variants, because most of the evidence for understanding the disease had been collected before the arrival of delta.

“The perception that healthy persons hospitalized for COVID19 are unlikely to require ICU-level care formed early in the pandemic underestimated their risk after Delta variant emergence,” the study said. “As it is infeasible to reevaluate every COVID-19 therapeutic each time a new variant emerges, data comparing severe disease risk by variant is necessary for clinicians to regauge the risks and benefits of COVID-19 therapeutics.”

The data were collected from an examination of electronic medical records for patients who were admitted to five hospitals in Maryland and Washington, D.C., from Sept. 1, 2020, to May 7, 2022, within two weeks of a COVID-19 diagnosis. The patients exhibited symptoms that included abnormally rapid breathing rate or heart rate, low oxygen levels or fever. Their EMRs contained information derived from viral whole-genome sequencing.

The data tracked 3,369 unvaccinated patients and 1,230 patients who’d either been vaccinated or had tested positive for COVID in the past. Vaccinated patients were older and had more underlying illnesses than the unvaccinated. Vaccination status meant that the patients had received either two doses of the Pfizer/BioNTech or Moderna vaccines or one dose of the Johnson and Johnson vaccine.

“Among patients without history of SARS-CoV-2 vaccination or prior infection, 977 (29%) developed severe disease or death within 28 days of hospitalization (median time to event 0.45 days, IQR 0.07-2.35) including 583 (29%) ancestral, 66 (33%) Alpha, 179 (33%) Delta, 140 (26%) Omicron, and 9 (27%) other variant group infections,” the study said. “By 28-days of follow-up, almost all patients were discharged or developed severe disease; only 12 (<1%) patients remained hospitalized without having developed severe disease.”

Study authors argued their research “undercuts public perception that Omicron is a mild disease.”

Q&A With Matthew Robinson, M.D.

Fierce Healthcare: Why you and your coauthors chose this particular topic?

Matthew Robinson: One year ago, we witnessed a surge in COVID-19 cases along with an abrupt transition from Delta variant being the most commonly circulating SARS-CoV-2 lineage to Omicron variant. As hospitals were starting to fill up, the public and clinicians such as myself were very interested to know whether patients hospitalized with Omicron infections were likely to fare similarly to patients with Delta infections or if Omicron variant was truly less severe.

Matthew Robinson
Matthew Robinson, M.D. (Johns Hopkins University School of Medicine)

FH: It seems that you may have had concerns that the possible lethality of the Omicron variant might be underestimated. Did you think that was the case among providers? The CDC? The public? Or all three?

MR: When the Omicron surge hit last winter, we were concerned that the severity of Omicron might have been underestimated, especially when only comparing Omicron severity to Delta variant as Delta variant was more severe than the originally circulating ancestral lineages which had caused millions of deaths…. Multiple studies have since shown that the risk of hospitalization and death for Omicron is less than for Delta which is encouraging, and I think the basis for providers, the CDC, and the public to adjust their risk posture towards COVID-19. Luckily, the combination of increasing population level immunity, availability of therapies such as nirmatrelvir/ritonavir, and decreased severity of Omicron has kept most patients with COVID-19 out of the hospital. Once hospitalized though, I do think that there is a lack of awareness regarding the potential for severe disease with Omicron, especially for those without immunity from vaccination or prior infection.

FH: Is the CDC doing enough, in your opinion, to dispel the notion that Omicron is mild? Do you worry that this might continue to be the attitude even as newer sub-subvariants such as BQ.1, BQ.1.1. and XBB increase their presence in the U.S. and seem to demonstrate an evasiveness to antibodies created by vaccines and/or prior infection that we haven’t seen before?

MR: I think that the CDC is appropriately trying to encourage vaccination with the latest bivalent boosters in time to reduce severe disease, especially among higher risk older populations. These efforts have included preparing recently released evidence showing the efficacy of bivalent boosters to reduce hospitalization. I think that now more than three years into the pandemic, the public is fatigued from hearing ever more warnings about COVID-19 and may be generally uninterested in new challenges presented by the most recent Omicron sub-variants to emerge.

FH: What’s the main thing that you want providers in hospitals to take away from your study?

MR: Patients hospitalized with COVID-19, even in the era of Omicron, can still become severely ill, especially if they lack immunity. This message at this point may be most relevant for hospital providers in China as they face a large wave of simultaneous infections in a population with limited vaccine uptake and prior COVD-19 exposure. They should be aware that even though Omicron may be less likely to land patients in the hospital, those patients who do require hospitalization and are unvaccinated may face a similar risk of severe illness to the initial waves of COVID-19.

FH: Your study wasn’t written for the public, but do you hope that it might also find something useful?

MR: I would hope that the public will find some of this useful. The intent is not to scare people into thinking that if they get an Omicron infection that they are at a similarly high risk of severe illness or death compared to earlier in the pandemic. However, I hope that it may serve as a reminder to vulnerable patients to remain up to date on vaccination and take preventive efforts during periods of peak SARS-CoV-2 transmission as there remains a risk for severe disease or death if their case of COVID-19 is severe enough to require hospitalization.