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COVID-19 was milder and potentially less transmissible among people who got infected with a Delta or Omicron variant within about 5 months after their second or third dose of an mRNA vaccine, a prospective routine surveillance study found.

Among more than 1,100 frontline and essential workers, those who received a second mRNA vaccine dose in the 14 to 149 days prior to developing infection from the Delta variant had a significantly lower risk of experiencing symptoms than unvaccinated individuals (77.8% vs 96.1%; OR 0.13, 95% CI 0.0-0.6), reported Ashley Fowlkes, ScD, MPH, of the CDC in Atlanta, and colleagues in the HEROES-RECOVER Network.

Getting a third (booster) dose within 7-149 days prior to a Delta infection was associated with an average of about 6 fewer symptomatic days (10.2 vs 16.4 days) and 93% lower odds of experiencing fever or chills (38.5% vs 84.9%), both statistically significant advantages over no vaccination, the authors wrote in .

When it came to Omicron infections, a third vaccine dose 7-149 days prior to infection was associated with a higher likelihood of symptomatic infection compared with unvaccinated individuals (88.4% vs 79.4%; OR 2.0, 95% CI 1.1-3.5), an "unexpected" finding the researchers said was difficult to interpret due to an inability to adjust for certain potential confounders.

Despite that, for those with symptomatic Omicron cases, a booster dose 7-149 days prior to infection was linked to a lower risk for experiencing fever or chills (OR 0.25, 95% CI 0.1-0.5) or seeking medical care (OR 0.45, 95% CI 0.2-0.9) versus no vaccination.

"Only participants with a breakthrough infection after dose three showed consistent signs of vaccine attenuation of COVID-19," Fowlkes and coauthors noted. "It is possible that the recall of immunologic memory that reduces viral replication and accelerates elimination of virally infected cells that may underlie vaccine attenuation of disease wanes with time."

Those who received a second vaccine dose at 14-149 days prior to infection with a Delta or Omicron variant had lower mean viral loads on quantitative RT-PCR testing compared with the unvaccinated.

Vaccination was also linked to lower viral viability in the two groups with this measured -- Delta variant infections and unvaccinated individuals with the origin virus. The mean plaque forming units (PFU) of presumably infectious virus was lower for those who received their second vaccine dose at least 150 days prior to a breakthrough infection (4.1 PFU/mL) or their third dose within 7-149 days prior to a breakthrough infection (3.1 PFU/mL), when compared with the unvaccinated group (4.8 PFU/mL).

"Although viral RNA shedding cannot be directly attributable to transmission, the relatively high viral load of Omicron infections together with the higher frequency of asymptomatic infection supports previous studies suggesting an association with increased transmission, particularly during the first 3 to 5 days when viral load peaked," the researchers noted.

For those unvaccinated, Omicron infections were 5.6-fold (95% CI 1.6-19.6) more likely to be asymptomatic than were Delta infections.

"This study is consistent with other studies showing that the COVID-19 vaccines work," commented John P. Cooke, MD, PhD, of Houston Methodist Academic Institute in Texas, who was not involved in the research. "This study shows that even if you do get infected, you won't be quite as ill, as those that were unvaccinated."

Previous studies have had mixed findings on the attenuation of symptoms, symptom duration, and RNA viral shedding with COVID-19 vaccines, Fowlkes' group noted. However, waning vaccine-induced immunity, virologic feature changes, more variant-specific immune evasion, or a multifactorial combination may be to blame, the authors suggested.

For this study, Fowlkes and colleagues examined data on 1,199 essential and frontline workers with a confirmed SARS-CoV-2 infection across six states (Arizona, Minnesota, Texas, Florida, Oregon, and Utah) from Dec. 14, 2020, to April 19, 2022. Follow-up extended until May 9, 2022. Those included were from the HEROES-RECOVER Network of first responders, healthcare workers, and teachers, along with others who work at least 20 weekly hours in a job that regularly brings them within 3 feet of others.

For their initial vaccination, 62% received Pfizer-BioNTech and 37% got Moderna, with all getting the same brand for both shots. However, 5.5% received a different mRNA vaccine brand for the third dose.

Median age was 41, and 59.5% of participants were women. Nearly three-quarters were white and 19.3% were Hispanic. Over one-quarter had at least one chronic condition. At the time of infection, 29% were unvaccinated, 6% had received their second dose 14-149 days prior, 31% had received their second dose 150 days or more prior to infection, and 33% received their third dose 7-149 days prior.

Among all infections, 62% were the Omicron variant, 24% were Delta, and 14% were the original strain.

In line with clinical experience, "COVID-19 symptoms associated with Omicron appeared to be milder and of a shorter duration than COVID-19 associated with Delta by many indicators," the researchers noted.

Other study limitations included reliance on self-collected mid-turbinate nasal swabs for analysis of virologic features, problems culturing Omicron virus for viability analysis, and the relatively low proportion of non-white participants.

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