Persistent Symptoms in Adult Patients 1 Year After Coronavirus Disease 2019 (COVID-19): A Prospective Cohort Study

Jessica Seeßle, Tim Waterboer, Theresa Hippchen, Julia Simon, Marietta Kirchner, Adeline Lim, Barbara Müller, Uta Merle, Jessica Seeßle, Tim Waterboer, Theresa Hippchen, Julia Simon, Marietta Kirchner, Adeline Lim, Barbara Müller, Uta Merle

Abstract

Background: Long COVID is defined as the persistence of symptoms beyond 3 months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To better understand the long-term course and etiology of symptoms we analyzed a cohort of patients with COVID-19 prospectively.

Methods: Patients were included at 5 months after acute COVID-19 in this prospective, noninterventional, follow-up study. Patients followed until 12 months after COVID-19 symptom onset (n = 96; 32.3% hospitalized, 55.2% females) were included in this analysis of symptoms, quality of life (based on an SF-12 survey), laboratory parameters including antinuclear antibodies (ANAs), and SARS-CoV-2 antibody levels.

Results: At month 12, only 22.9% of patients were completely free of symptoms and the most frequent symptoms were reduced exercise capacity (56.3%), fatigue (53.1%), dyspnea (37.5%), and problems with concentration (39.6%), finding words (32.3%), and sleeping (26.0%). Females showed significantly more neurocognitive symptoms than males. ANA titers were ≥1:160 in 43.6% of patients at 12 months post-COVID-19 symptom onset, and neurocognitive symptom frequency was significantly higher in the group with an ANA titer ≥1:160 versus <1:160. Compared with patients without symptoms, patients with ≥1 long-COVID symptom at 12 months did not differ significantly with respect to their SARS-CoV-2 antibody levels but had a significantly reduced physical and mental life quality compared with patients without symptoms.

Conclusions: Neurocognitive long-COVID symptoms can persist ≥1 year after COVID-19 symptom onset and reduce life quality significantly. Several neurocognitive symptoms were associated with ANA titer elevations. This may indicate autoimmunity as a cofactor in etiology of long COVID.

Keywords: ANA titers; coronavirus disease 2019 (COVID-19); life quality; long COVID.

© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Figures

Figure 1.
Figure 1.
Distribution of ANA titers within study group at acute COVID-19 and 5 and 12 months post–symptom onset of COVID-19 presented in percentage of the total cohort (n = 96). Abbreviations: ANA, antinuclear antibody; COVID-19, coronavirus disease 2019.
Figure 2.
Figure 2.
Frequencies of symptoms (%) in the study cohort at acute COVID-19, as well as at 5, 9, and 12 months post–COVID-19 symptom onset. P values for the group differences between 5- and 12-month time points are based on McNemar test for dependent samples. Symptoms with significant differences are marked with an asterisk (*P < .05). Abbreviations: COVID-19, coronavirus disease 2019; n.d., not determined.
Figure 3.
Figure 3.
Frequencies of symptoms (%) among the study population presented as a heatmap for the time of acute COVID-19 and at 5 and 12 months post–symptom onset. Symptom frequencies are stratified by disease severity (mild/moderate and severe/critical disease), gender (male and female), age (

Figure 4.

The PCS and MCS assessed…

Figure 4.

The PCS and MCS assessed by the SF-12 questionnaire for the study population…

Figure 4.
The PCS and MCS assessed by the SF-12 questionnaire for the study population subgrouped for patients with at least 1 symptom or no symptoms at 12 months post–COVID-19 symptom onset. Data are presented as medians and interquartile ranges, and P values for the group differences are based on the Mann-Whitney U test for independent samples. Significant differences are marked with an asterisk (*P < .05, **P < .01). Abbreviations: COVID-19, coronavirus disease 2019; MCS, Mental Component Scale; PCS, Physical Component Scale; SF-12, 12-item Short Form Survey.
Figure 4.
Figure 4.
The PCS and MCS assessed by the SF-12 questionnaire for the study population subgrouped for patients with at least 1 symptom or no symptoms at 12 months post–COVID-19 symptom onset. Data are presented as medians and interquartile ranges, and P values for the group differences are based on the Mann-Whitney U test for independent samples. Significant differences are marked with an asterisk (*P < .05, **P < .01). Abbreviations: COVID-19, coronavirus disease 2019; MCS, Mental Component Scale; PCS, Physical Component Scale; SF-12, 12-item Short Form Survey.

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