COVID-19 that occurs after vaccination carries a much lower risk of serious illness


Scientists have developed several vaccines to prevent infection with coronavirus 2 (SARS-CoV-2), the causative agent of the ongoing coronavirus 2019 (COVID-19) pandemic. Previous studies have shown that although vaccine-induced immunity declines over time, vaccine efficacy (VE) against severe COVID-19 persists for prolonged periods.

Study: Protection of Two and Three Doses of an mRNA Vaccine Against Severe Outcomes Among Adults Hospitalized with COVID-19 - VISION Network, August 2021 to March 2022. Image credit: Prostock-studio/

Stady: Protection of two and three doses of an mRNA vaccine against severe outcomes among hospitalized adults with COVID-19 – VISION Network, August 2021 to March 2022. Image credit: Prostock-studio /


Several studies indicated that COVID-19 vaccines were less effective in preventing severe disease in the elderly and immunocompromised patients. However, the COVID-19 vaccine has reduced the severity of illness among patients hospitalized with SARS-CoV-2 infection.

Fully vaccinated people who were hospitalized with symptoms of COVID-19 were less likely to need mechanical ventilation, enter an intensive care unit (ICU), or die compared to unvaccinated individuals. However, there is still a lack of studies evaluating the relationship between booster vaccination for COVID-19 and disease severity using large samples infected with different variants of SARS-CoV-2.

about studying

newly Journal of Infectious Diseases The study investigates the impact of the COVID-19 vaccine on severe infections requiring hospitalization. The researchers also explored remaining confounding factors using the COVID-19 negative controls and the difference in differences method.

The VISION Network is a collaboration of healthcare systems and research centers in the United States that provide vaccination, as well as medical and laboratory records. Patients over 18 years of age without any immunological diseases who were hospitalized for more than 24 hours with a COVID-19-like illness (CLI) between August 19, 2021, and March 28, 2022, were included in the study cohort. All relevant information for these patients was available on the VISION Network websites.

A test-negative control group included patients who had negative molecular screening results for COVID-19 within 14 days before and 72 hours after hospital admission. This study included individuals who were fully vaccinated with two doses of the COVID-19 mRNA vaccine and those who received a booster or third dose. Unvaccinated individuals were also included for comparative analysis.

All eligible participants who were fully vaccinated with two COVID-19 mRNA vaccines were divided into two groups. These groups included the ‘two doses recently’ group, which included individuals who received their second vaccine dose less than 150 days before the indicator date, and the ‘two doses apart’ group which included individuals who received their second vaccine dose 150 or more days before the indicator date. Contents.

To investigate the severity of illness due to COVID-19, ICU admissions, death in hospital, and length of hospitalization were considered.


A total of 27,149 individuals were hospitalized for COVID-19, and 59.2% and 40.8% of them were hospitalized during the SARS-CoV-2 Delta and Omicron periods, respectively. These participants were included in the test-positive cohort. It was observed that 75% of the individuals in the hospital were not vaccinated.

Compared to the vaccinated group, the unvaccinated individuals were significantly younger. Typically, the younger age group is less likely to have underlying comorbidities, such as diabetes and cardiovascular disease.

A higher attenuation in disease severity prevailed among those who received the booster vaccine than among those who completed the two-dose vaccine regimen. This may be due to the weakened immunity induced by the vaccine, which was restored after the booster dose.

Consistent with previous studies, the COVID-19 mRNA vaccine showed lower efficacy against severe infections caused by the Omicron variant compared to the Delta variant.

In most cases, less protection against severe disease has been observed in modern two-dose vaccines than in patients vaccinated with two or three booster doses. This may be due to an unknown factor that was not taken into account during the analysis.

The negative control group helped to identify potential residual confounding factors after controlling for medical comorbidities and demographic factors, such as gender, ethnicity, urbanization, and age. Finally, a difference-of-differences approach was applied to adjust for unmeasured factors, with all results indicating that vaccination reduces disease severity.


The current study has several limitations, including considering COVID-19 tests performed in medical settings and those conducted at home or in public health sectors were ignored. Therefore, a large number of COVID-19 patients were not included in this study.

In addition, information related to the prevention and treatment of COVID-19, such as antiviral drugs and monoclonal antibodies, was not considered. It is worth noting that these interventions will influence the course of the disease for the individual.

The difference-by-difference approach did not consider reasons for hospitalization between vaccinated and unvaccinated patients. The full spectrum of clinical symptoms was not investigated between the vaccinated and unvaccinated groups; Therefore, the role of vaccines in reducing meaningful outcomes cannot be determined.


Individuals vaccinated with COVID-19 were closely associated with lower rates of ICU admissions and in-hospital deaths during the predominance of the Delta and Omicron variants. However, no such association was found in unvaccinated individuals.

All the evidence supported the fact that the COVID-19 vaccine reduces the severity of illness in hospitalized patients. However, future research related to the mitigation of COVID-19 will require more comprehensive data from a prospective study design rather than electronic health record data.

Journal reference:

  • DeSilva, BM, Mithcell, PK, Klein, NP, et al. (2023) Protection of two and three doses of mRNA vaccine against acute outcomes among adults hospitalized with COVID-19 – VISION Network, August 2021 to March 2022. Journal of Infectious Diseases 227(8); 961-969. doi: 10.1093/infdis/jiac458


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