What do we know about risk factors for severe COVID-19 and how could this knowledge help us: nationwide retrospective cohort studies in Estonia?

Tatjana Meister, Anneli Uusküla, Tatjana Meister

Keywords: COVID-19, epidemiology, risk factors, severe COVID-19

Background:

The risk of severe COVID-19 is not completely defunct although most of the world population has acquired some kind of immunity against COVID-19: vaccine-induced, natural, or hybrid.

Research questions:

What are severe COVID-19 risk factors in unvaccinated and vaccinated individuals?

Method:

We conducted two retrospective cohort studies aimed at identifying severe COVID-19 risk factors among 184,132 SARS-CoV-2-vaccinated individuals (Jan 19, 2021–Feb 9, 2022) and a historical cohort of 66,295 unvaccinated individuals (Feb 26, 2020–Feb 28, 2021) in Estonia.

Results:

The incidence rate (IR) of severe COVID-19 defined as COVID-19-related hospitalization was 0.093 (95% CI 0.084⎼0.104 per 10,000 person-days) among vaccinated individuals, and 15.9 (95% CI 15.5–16.4 per 10,000 person-days) for those in the historical cohort from the pre-vaccination era. COVID-19 hospitalization rate among vaccinated individuals with breakthrough infection was at least five times lower than in the historical cohort of unvaccinated individuals (1,2% vs 6,9%, p<0.0001).
Older age and impaired renal homeostasis were the strongest risk factors for COVID-19-related hospitalization in both cohorts. The other risk factors were male sex, cancer, liver disease, cardiovascular, and cerebrovascular disease.
The majority (70%) of individuals in the pre-vaccination era hospitalized for COVID-19 had no preexisting death risk modifying comorbid conditions (Charlson Comorbidity Index, CCI = 0). In contrast, most vaccinated individuals with severe breakthrough infections had multiple comorbidities (60%, with CCI=1-3)
COVID-19-related hospitalization was delayed for at least six months for those vaccinated against COVID-19, and the booster conferred substantial (up to 81%) protection against hospitalization.

Conclusions:

The prevention paradox should be considered when planning the rollout of preventive strategies in case of future pandemics.
Considering the essential role of family physicians in identifying people at higher risk, analyzing changes in risk factors over time is an essential component in planning protective measures for the most vulnerable populations.

Points for discussion:

Vaccination strategies in post pandemic era

Risk group vs mass vaccination strategies

The role of chronic renal disease in the pathogenesis of COVID-19

#41