Dataset Information

Preexisting comorbidities shape the immune response associated with severe COVID-19.

ABSTRACT:

Background

Comorbidities are risk factors for development of severe coronavirus disease 2019 (COVID-19). However, the extent to which an underlying comorbidity influences the immune response to severe acute respiratory syndrome coronavirus 2 remains unknown.

Objective

Our aim was to investigate the complex interrelations of comorbidities, the immune response, and patient outcome in COVID-19.

Methods

We used high-throughput, high-dimensional, single-cell mapping of peripheral blood leukocytes and algorithm-guided analysis.

Results

We discovered characteristic immune signatures associated not only with severe COVID-19 but also with the underlying medical condition. Different factors of the metabolic syndrome (obesity, hypertension, and diabetes) affected distinct immune populations, thereby additively increasing the immunodysregulatory effect when present in a single patient. Patients with disorders affecting the lung or heart, together with factors of metabolic syndrome, were clustered together, whereas immune disorder and chronic kidney disease displayed a distinct immune profile in COVID-19. In particular, severe acute respiratory syndrome coronavirus 2-infected patients with preexisting chronic kidney disease were characterized by the highest number of altered immune signatures of both lymphoid and myeloid immune branches. This overall major immune dysregulation could be the underlying mechanism for the estimated odds ratio of 16.3 for development of severe COVID-19 in this burdened cohort.

Conclusion

The combinatorial systematic analysis of the immune signatures, comorbidities, and outcomes of patients with COVID-19 has provided the mechanistic immunologic underpinnings of comorbidity-driven patient risk and uncovered comorbidity-driven immune signatures.

SUBMITTER: Kreutmair S

PROVIDER: S-EPMC9212690 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

Preexisting comorbidities shape the immune response associated with severe COVID-19.

Kreutmair Stefanie S Kauffmann Manuel M Unger Susanne S Ingelfinger Florian F Núñez Nicolás Gonzalo NG Alberti Chiara C De Feo Donatella D Krishnarajah Sinduya S Friebel Ekaterina E Ulutekin Can C Babaei Sepideh S Gaborit Benjamin B Lutz Mirjam M Jurado Nicole Puertas NP Malek Nisar P NP Göpel Siri S Rosenberger Peter P Häberle Helene A HA Ayoub Ikram I Al-Hajj Sally S Claassen Manfred M Liblau Roland R Martin-Blondel Guillaume G Bitzer Michael M Roquilly Antoine A Becher Burkhard B

The Journal of allergy and clinical immunology 20220616 2

<h4>Background</h4>Comorbidities are risk factors for development of severe coronavirus disease 2019 (COVID-19). However, the extent to which an underlying comorbidity influences the immune response to severe acute respiratory syndrome coronavirus 2 remains unknown.<h4>Objective</h4>Our aim was to investigate the complex interrelations of comorbidities, the immune response, and patient outcome in COVID-19.<h4>Methods</h4>We used high-throughput, high-dimensional, single-cell mapping of periphera ...[more]

PMID: 35716951

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Project description:ImportanceEvidence indicates that preexisting neuropsychiatric conditions confer increased risks of severe outcomes from COVID-19 infection. It is unclear how this increased risk compares with risks associated with other severe acute respiratory infections (SARIs).ObjectiveTo determine whether preexisting diagnosis of and/or treatment for a neuropsychiatric condition is associated with severe outcomes from COVID-19 infection and other SARIs and whether any observed association is similar between the 2 outcomes.Design, setting, and participantsPrepandemic (2015-2020) and contemporary (2020-2021) longitudinal cohorts were derived from the QResearch database of English primary care records. Adjusted hazard ratios (HRs) with 99% CIs were estimated in April 2022 using flexible parametric survival models clustered by primary care clinic. This study included a population-based sample, including all adults in the database who had been registered with a primary care clinic for at least 1 year. Analysis of routinely collected primary care electronic medical records was performed.ExposuresDiagnosis of and/or medication for anxiety, mood, or psychotic disorders and diagnosis of dementia, depression, schizophrenia, or bipolar disorder.Main outcomes and measuresCOVID-19-related mortality, or hospital or intensive care unit admission; SARI-related mortality, or hospital or intensive care unit admission.ResultsThe prepandemic cohort comprised 11 134 789 adults (223 569 SARI cases [2.0%]) with a median (IQR) age of 42 (29-58) years, of which 5 644 525 (50.7%) were female. The contemporary cohort comprised 8 388 956 adults (58 203 severe COVID-19 cases [0.7%]) with a median (IQR) age of 48 (34-63) years, of which 4 207 192 were male (50.2%). Diagnosis and/or treatment for neuropsychiatric conditions other than dementia was associated with an increased likelihood of a severe outcome from SARI (anxiety diagnosis: HR, 1.16; 99% CI, 1.13-1.18; psychotic disorder diagnosis and treatment: HR, 2.56; 99% CI, 2.40-2.72) and COVID-19 (anxiety diagnosis: HR, 1.16; 99% CI, 1.12-1.20; psychotic disorder treatment: HR, 2.37; 99% CI, 2.20-2.55). The effect estimate for severe outcome with dementia was higher for those with COVID-19 than SARI (HR, 2.85; 99% CI, 2.71-3.00 vs HR, 2.13; 99% CI, 2.07-2.19).Conclusions and relevanceIn this longitudinal cohort study, UK patients with preexisting neuropsychiatric conditions and treatments were associated with similarly increased risks of severe outcome from COVID-19 infection and SARIs, except for dementia.

Dataset Information

Preexisting comorbidities shape the immune response associated with severe COVID-19.

Background

Objective

Methods

Results

Conclusion

Publications

Preexisting comorbidities shape the immune response associated with severe COVID-19.

Similar Datasets

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