The SARS-CoV-2 virus changes over time, leading to different versions, or variants. Throughout the global pandemic, two variants in particular, Delta and Omicron, became dominant at different times, causing significant waves of infection worldwide. Each had a distinct profile in how it spread, the type of illness it caused, and how it interacted with the human immune system.
Differences in Transmission and Spread
A primary distinction between the Delta and Omicron variants was their transmissibility. Omicron spread far more easily than Delta, allowing it to quickly become the dominant circulating variant across the globe. This difference can be illustrated by their basic reproduction number (R0), which estimates how many people one infected person is likely to infect in a population with no immunity. While Delta’s R0 was estimated to be between 5 and 9, Omicron’s R0 was estimated to be as high as 10.
The reason for Omicron’s heightened transmissibility lies in its genetic makeup. The variant featured a large number of mutations on its spike protein, which the virus uses to enter human cells. Omicron had approximately 30 mutations on its spike protein, with about 15 located in the receptor-binding domain (RBD). This is the part of the spike that latches onto the ACE2 receptor on human cells. In contrast, the Delta variant had only around nine spike protein mutations and just two in the RBD.
These extensive changes, including specific mutations like Q498R and Q493R, enhanced the Omicron spike protein’s ability to bind to human cells. This stronger attachment made the process of infection more efficient, contributing to a transmission rate roughly 3.2 times higher than that of Delta. This transmission advantage meant that once Omicron was introduced into a population, it could outcompete and displace the Delta variant, leading to its rapid global takeover in late 2021 and early 2022.
Variations in Disease Severity and Symptoms
The clinical presentation and severity of illness caused by Delta and Omicron also showed clear differences. Data indicated that infection with the Omicron variant was less likely to lead to severe disease compared to the Delta variant. This was reflected in public health metrics such as hospitalizations, intensive care unit (ICU) admissions, and mortality. Multiple studies found that the risk of severe outcomes was considerably lower with Omicron.
A large-scale analysis from England revealed that the risk of hospital admission with Omicron was 59% lower than with Delta, and the risk of death was 69% lower. A separate meta-analysis of 42 studies supported these findings, calculating a 56% lower risk of hospitalization and a 61% lower risk of death for Omicron cases.
The profile of common symptoms also diverged between the two variants. Delta infections were more frequently associated with the loss of taste and smell. Omicron, by contrast, produced symptoms more characteristic of an upper respiratory infection, similar to a common cold. The most frequently reported symptoms for Omicron included sore throat, runny nose, sneezing, and headache.
This reduction in severity with Omicron was not uniform across all age groups. The most significant decrease in hospitalization risk was observed in adults, with individuals aged 60-69 experiencing a 75% lower risk with Omicron compared to Delta. For very young children, however, the difference in hospitalization risk between the two variants was not statistically significant, though the overall risk of severe disease in children remained very low for both.
Immune Response and Vaccine Effectiveness
The immune system’s response to Delta and Omicron was another area of significant divergence. Omicron demonstrated a capacity for “immune escape,” meaning it was more adept than Delta at evading the antibodies produced by the body. This led to a higher number of breakthrough infections in vaccinated individuals and a greater likelihood of reinfection in those who had already recovered from COVID-19.
Studies showed that the risk of being reinfected was over five times higher with Omicron than it was during the Delta wave, indicating that natural immunity from a prior strain offered less protection. This was largely due to the extensive mutations on Omicron’s spike protein, the primary target of antibodies. Because of these changes, antibodies generated against previous variants or the original virus struggled to recognize and neutralize Omicron effectively.
This challenge was also reflected in vaccine effectiveness against symptomatic infection. While two doses of an mRNA vaccine were about 90% effective at preventing a symptomatic Delta infection shortly after the second dose, that effectiveness dropped to around 65% against Omicron. Furthermore, protection against an Omicron infection waned much more quickly in the months following vaccination.
Despite the drop in protection against infection, an aspect of immunity remained largely intact. Protection against severe disease, hospitalization, and death was substantially preserved for both variants in vaccinated individuals. While the antibody response, which prevents the virus from taking hold, was diminished against Omicron, the T-cell response was not as affected. This deeper layer of the immune system is responsible for identifying and clearing infected cells, thereby preventing the infection from progressing to a more serious illness.