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

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.

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.

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.

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 (<60 and ≥60 years) and ANA titer (<1:160 vs ≥ 1:160). Gray fields with a cross indicate that this parameter was not analyzed at that specific time point. Abbreviations: ANA, antinuclear antibody; COVID-19, coronavirus disease 2019.

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.