The impact of SARS-CoV-2 variants on clinical trajectory and outcome

Even as countries around the world open up, allowing the latest variant of the novel coronavirus to spread, a new report shows that things have not changed much since the virus first emerged.

Study: Impact of SARS-CoV-2 variants on inpatient clinical outcome. Image Credit: Alina Troeva/Shutterstock

Introduction

In December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported, spreading rapidly worldwide to cause horrifyingly high numbers of casualties and overwhelming hospitals with its ferocity and extensive transmission. As the first wave died down, scientists predicted future, perhaps worse, surges.

However, when the first severe variant of the virus was reported, dubbed the Alpha variant by the World Health Organization (WHO), it's even higher propensity to spread led to its being determined to be a variant of concern. Since then, multiple variants have emerged, some with immune evasion capabilities in addition to, or instead of, increased transmissibility. The latest is the Omicron, which has been found to be even more infectious than the preceding Delta variant of concern.

The Delta variant was shockingly devastating in its clinical severity compared to the ancestral variant. In contrast, "mild" was the word used most commonly to describe the illness caused by Omicron. Both are more infectious than the wild-type variant of the virus.

With both of these variants in circulation, there were more than 150,000 daily hospitalizations in mid-January 2022, which set a new record. Both Alpha and Delta were associated with increased hospitalizations, but even more, Delta appears to be linked to worse outcomes following hospitalization, according to some studies.

Conversely, Omicron has been reported to be milder in terms of severe disease, hospitalization, and death, compared to Delta. The current study, published on the medRxiv* preprint server, describes the results of examining a patient database to understand just how Omicron affected the clinical outcome.

What did the study show?

The study included over 6,500 adults hospitalized within two weeks of their diagnosis with COVID-19, within a period starting September 1, 2020, extending January 20, 2022. Of these, almost 90% had one or more abnormal vital signs, including low oxygen levels in 80%, oxygen supplementation required in two-thirds, rapid breathing in half the patients, and fever or a rapid pulse in over a third.

Of the ~500 study days, a single variant accounted for 95% or more of infections on 285 days. Of these, the ancestral variants dominated for 139 days, with 124 Delta-dominated and 22 Omicron-dominated days. Only a fifth of patients had whole-genome sequencing (WGS) data, with over half the patients being allotted a variant based on the dominant variant of that day.

The inferred variant agreed with the WGS variant in 96% of cases when only one variant was dominant. Omicron made up 87% of infections confirmed by WGS during the Omicron-dominant period and 81% of severe infections.

Unvaccinated patients tended to be younger, at a median age of 62 years, vs. 69 years for vaccinated patients. The former was also healthier than those with a history of vaccination or prior COVID-19. In addition, Black patients made up a higher proportion of Alpha, Delta, and Omicron infections compared to ancestral variant infections, at 63%, 42%, and 46%, respectively, vs. 31%.

Unvaccinated cohort

In the unvaccinated cohort, ancestral variant infections affected more older patients compared to other groups. Hypoxia was less common with the Omicron variant compared to ancestral or Delta. In contrast, Omicron and ancestral variants were associated with lower levels of C-reactive protein, an inflammatory marker, compared to Delta.

They found that 28% of unvaccinated patients became severely ill or died within two weeks of hospitalization, including 27% with ancestral variant infection, ~31% each for Alpha and Delta, and a quarter each for Omicron or other variants. One in seven patients in this cohort were mechanically ventilated or died within 21 days of hospitalization.

Of the deaths, about a tenth each occurred among those infected by ancestral or Delta variants, and another tenth among those with other variants except Alpha or Omicron, which claimed ~5% each. The median time to death was ten days.

The risk of severe disease or death within the two-week period of hospitalization was comparable for the ancestral and Omicron variants, at 0.26 and 0.28, respectively, vs. 0.31 and 0.35 for Alpha and Delta, respectively. The risk was 34% higher with Delta vs. ancestral but was equivalent for ancestral or Omicron variants. Omicron carried a 22% lower risk compared to Delta.

Oxygen levels were lower by 22 for Delta compared to ancestral variants.

 Vaccinated cohort

Of the 800 vaccinated/previously infected patients, only 17 with ancestral or Alpha or other variants. While over 60% had Omicron, 34% had Delta. About a quarter of the patients who developed severe infection or died had Delta, and just over a fifth had Omicron infection.

The risk of severe disease or death within 14 days of hospitalization was cut in half among the Omicron/Delta patients with prior infection or vaccination, compared to unvaccinated inpatients. However, there was no difference in the risk between these two variants in this group, with 11% of patients with severe outcomes within two weeks having either of these two variants.

What are the implications?

The study shows that Delta is associated with a higher risk of severe outcomes compared to the earlier lineages among unvaccinated patients. The risk of Omicron-associated severe disease or death was lower in this cohort, compared to Delta, but comparable to ancestral lineages.

However, severe breakthrough infection or repeated infection among vaccinated patients did not vary by Omicron or Delta lineage. The risk was only half of that in the unvaccinated cohort, despite the higher age and increased number of comorbidities in the vaccinated cohort.

The implication is that unvaccinated individuals remain at just as high risk of severe outcomes as at the beginning of the pandemic, though Omicron is widely considered a mild variant. This picture, to be accurate, comes from the fact that Omicron-infected outpatients were hospitalized at 0.7-0.8-fold lower rates than Delta patients, and the risk of oxygen supplementation or severe disease was 0.7-fold less in the former group. However, this ignores the extreme severity of Delta compared to the ancestral lineages.

In fact, whereas healthy young adults were at a very low level of risk for intensive care unit admission during the first phase of the pandemic, that changed after Delta emerged. Comparing the risk for severe outcomes between variants gives us a true picture of the actual clinical severity of each variant.

Thus, the conclusion is that the risk of severe disease with Omicron is 0-22-fold lower than with Delta but almost identical to that of the ancestral lineages among unvaccinated patients.

Vaccines remain largely effective in preventing COVID-19 related hospitalization and death, even after the emergence of Delta and Omicron variants. Most importantly, population-based surveillance shows a striking 16-fold greater risk of hospitalization for unvaccinated individuals compared to the vaccinated."

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.