Hybrid immunity improves the immune response after fourth Covid-19 vaccine dose in individuals with medical conditions predisposing to severe Covid-19 (preprint)

BackgroundData on Covid-19 booster vaccinations and subsequent infections on immune responses in the immunocompromised is limited. We studied antibody responses after the fourth dose and subsequent breakthrough infection to define patient groups benefiting most from boosters. MethodsIn Finland, fourth vaccine (booster) doses were first recommended for severely immunocompromised individuals, whom we invited to participate in 2022. We assessed spike protein specific IgG antibody levels and neutralizing antibodies (NAb) against the ancestral and Omicron BA.1 strains one month after the fourth dose from 488 adult participants and compared to the levels of 35 healthy controls after 3 doses. We used Bayesian generalized linear modelling to assess factors explaining antibody concentrations after the fourth dose. We assessed vaccine-induced and hybrid immunity six months after the last vaccine dose. ResultsChronic kidney disease (CKD) and immunosuppressive therapy (IT) were identified as factors explaining sub-optimal antibody responses. The proportion of participants with a normal antibody response and NAbs were significantly lower in CKD patients as compared to controls. By the 6-month sampling one third of the participants became infected, which enhanced antibody levels notably in most immunocompromised participants. ConclusionsImpaired antibody responses, especially NAbs against the Omicron lineage, predict limited protection in individuals with CKD, and highlight the need for alternative pharmaceutical preventive strategies. Vaccination strategies should take into account development of robust hybrid immunity responses also among the immunocompromised.

Predictors of hospitalisation and death due to SARS-CoV-2 infection in Finland: a population-based register study with implications to vaccinations (preprint)

Abstract Introduction. The aim of this study was to investigate how age and underlying medical conditions affect the risk of severe outcomes following SARS-CoV-2 infection and how they should be weighed while prioritising vaccinations against COVID-19. Methods. This population-based register study includes all SARS-CoV-2 PCR-test-positive cases until 24 Feb 2021, based on the Finnish National Infectious Diseases Register. The cases were linked to other registers to identify presence of comorbidities and severe outcomes (hospitalisation, intensive care treatment, death). The odds of severe outcomes were compared in those with and without the pre-specified comorbidities using logistic regression. Furthermore, population-based rates were compared between those with a given comorbidity and those without any of the specified comorbidities using negative binomial regression. Results. Age and various comorbidities were found to be predictors of severe COVID-19. Compared to 60-69-year-olds, the odds ratio (OR) of death was 7.1 for 70-79-year-olds, 26.7 for 80-89-year-olds, and 55.8 for 90-year-olds and over. Among the 20-69-year-olds, chronic renal disease (OR 9.4), malignant neoplasms (5.8), hematologic malignancy (5.6), chronic pulmonary disease (5.4), and cerebral palsy or other paralytic syndromes (4.6) were strongly associated with COVID-19 mortality; severe disorders of the immune system (8.0), organ or stem cell transplant (7.2), chronic renal disease (6.7), and diseases of myoneural junction and muscle (5.5) were strongly associated with COVID-19 hospitalisation. Type 2 diabetes and asthma, two very common comorbidities, were associated with all three outcomes, with ORs from 2.1 to 4.3. The population-based rate of SARS-CoV-2 infection decreased with age. Taking the 60-69-year-olds as reference, the rate ratio was highest (3.0) for 20-29-year-olds but under 1 for 70-79-year-olds and 80-89-year-olds. Conclusion. Comorbidities predispose for severe COVID-19 among younger ages. In vaccine prioritisation both the risk of infection and the risk of severe outcomes, if infected, should be combined.