Healthcare Worker Study Cohort Study: mRNA Boosters Not Adequately Controlling Omicron COVID-19 Surges
Swedish researchers affiliated with the preeminent academic medical center Karolinska Institutet studied breakthrough infections in triple vaccinated healthcare workers (HCW) both with and without non-Omicron COVID-19 infection during a four-week stretch between January to February 2022. This was a time when Omicron first presented in Sweden, specifically, a time when BA.1, BA.1.1. and BA.2 predominated in Stockholm, Sweden’s capital and largest city. The study supported a comparison of breakthrough infections across the three Omicron sublineages. Analyzing serum antibody levels, protection against infection, and viral RNA trajectories, the study outputs evidence of a high cumulative incidence in breakthrough infections across the Omicron sublineages. What was indicative of infectivity? Viral RNA trajectories measured at week five after the initial COVID-19 vaccine booster dose. The study authors point out that greater post-booster serum antibody titers indicated a protective role against infection, thus reducing the effect of viral load, independent of mucosal spike-specific IgA titers. Based on the results of this real-world study, the authors question the association of detection of vaccine-induced serum antibody levels and Omicron risk protection. The study herein demonstrates a high viral load in triple-vaccinated healthcare workers, indicating substantial rates of breakthrough infections with the current mRNA COVID-19 vaccines associated with Pfizer-BioNTech and Moderna. The study authors report that based on this observational data, albeit with limitations, booster doses are not controlling the surge in cases.
With the surge of infection caused by Omicron (B.1.1.529) even in populations with high vaccine uptake, the implementation of mRNA booster doses (third shot) appears to have reduced more severe COVID-19, yet was far less effective at stopping viral transmission during this period. The study team sought to better quantify the dynamic—after all, vaccine-induced serological responses correlate well to risk of infection with the ancestral virus and pre-Omicron variants of concern---so they applied to the Omicron infection.
The Swedish team organized this study because little data has been collected as to the characteristics from serum antibody titer correlation to protection, viral abundance and clearance of Omicron infection in vaccinated persons.
Drilling into the data associated with 368 triple vaccinated healthcare workers, the study team presented 4-week twice-weekly SARS-CoV-2 qPCR screening output meaning spike-specific IgG levels, neutralization titers and mucosal spike-specific IgA levels from study start and samples at two weeks.
The authors report 81 (cumulative incidence 22%) BA.1, BA.1.1, and BA.2 infections were detected. Evident protection against infection were high serum antibody titers (p < 0.0) which linked to reduced viral load (p < 0.01) as well as time to clearance (p < 0.05).
While pre-Omicron COVID-19 infection was independently associated to increase protection against Omicron, the Swedish study authors report this was “largely mediated by mucosal spike specific IgA responses (nested models lr test p = 0.02 and 0.008).
With only 10% of infected study subjects remaining asymptomatic through the course of their infection, the study team report that “high levels of vaccine-induced spike-specific WT antibodies are linked to increased protection against infection and to reduced viral load if infected, and suggest that the additional protection offered by pre-omicron SARS-CoV-2 infection largely is mediated by mucosal spike-specific IgA.”
With acknowledged limitations and a sharing of the data, the study team identified possible immune correlates of protection from infection while attempting to shine a light on the kinetics of COVID-19 Omicron shedding in the vaccinated, critical data necessary to better understand just how to “guide infection control measures and vaccination policy.”
The net result of this study isn’t great from the standpoint of the mRNA vaccines serving as neutralizing vaccine products. On the contrary, the data from this study involving Swedish healthcare workers evidence a “high incidence of Omicron infection in a recently triple vaccinated healthcare worker cohort.”
Known of course as “breakthrough infections,” they are associated with high viral load, which the study authors suggest is “likely” contributing to the global surges in SARS-CoV-2 infections. The results aren’t promising given the “very high cumulative incidence” of infections despite the recent booster push in Sweden.
One possible takeaway: The study authors question the very relation associated with detection of vaccine induced serum antibody levels and Omicron risk prediction. How might this study result impact the COVID-19 vaccination policy in the United States and elsewhere?
Two Ph.D. students helped lead this study with the oversight of seasoned physician-scientists from both Karolinska Institutet, Uppsala University and Linköping University.
The trial site location
The healthcare workers were associated with Danderyd Hospital, one of Sweden’s largest emergency hospitals offering university affiliated healthcare distributed across twelve operational areas. Annually, the hospital receives approximately 90,000 emergency patients, 429,000 outpatient visits and 50,000 inpatient visits, and performs 6,300 deliveries. In collaboration with the Karolinska Institutet (KIDS), education and research are conducted around the most common public diseases. Annually, roughly 2,000 students from 100 different institutions of higher learning are welcomed in about 30 different educational programs. The hospital was founded in 1922, as Stockholm County's central hospital in Mörby and was renamed in 1964 to Danderyd Hospital. Danderyd’s Sjukhus AB is a wholly owned company within Region Stockholm and has around 4,500 employees.
Ulrika Marking, Ph.D. student Karolinska Institutet Danderyd Hospital
Sebastian Havervall, Ph.D. student, Karolinska Institutet Danderyd Hospital
Charlotte Thålin, Karolinska Institutet Danderyd Hospital
Mikael Åberg, Uppsala University, Department of Medical Sciences, Clinical Chemistry & SciLifeLab
Jonas Klingström, Karolinska Institutet, Center for Infectious Medicine, Department of Medicine Huddinge; Linköping University, Division of Molecular Medicine and Virology, Department of Biomedical and Clinical Sciences