Background Long COVID is defined as the persistence of symptoms beyond 3 months after SARS-CoV-2 infection. To better understand the long-term course and etiology of symptoms we analyzed a cohort of COVID-19 patients prospectively. Methods Patients were included at 5 months after acute COVID-19 in this prospective, non-interventional follow-up study. Patients followed until 12 months after COVID-19 symptom onset (n=96, 32.3% hospitalised, 55.2% females) were included in this analysis of symptoms, quality of life (based on a SF-12 survey), laboratory parameters including antinuclear antibodies (ANA), 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%), dyspnoea (37.5%), concentration problems (39.6%), problems finding words (32.3%), and sleeping problems (26.0%). Females showed significantly more neurocognitive symptoms than males. ANA titres 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 titre ≥1:160 compared to <1:160. Compared to patients without symptoms, patients with at least one 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 to patients without symptoms. Conclusions Neurocognitive long COVID symptoms can persist at least for one year after COVID-19 symptom onset, and reduce life quality significantly. Several neurocognitive symptoms were associated with ANA titre elevations. This may indicate autoimmunity as cofactor in aetiology of long COVID.

Infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses an enormous challenge to health care systems throughout the world. Without causal treatment, identification of modifiable prognostic factors may help to improve outcomes. To explore possible associations of vitamin D (VitD) status with disease severity and survival, we studied 185 patients diagnosed with coronavirus disease 2019 (COVID-19) and treated at our center. VitD status at first presentation was assessed retrospectively using accredited laboratory methods. VitD deficiency was defined as serum total 25-hydroxyvitamin D level < 12 ng/mL (<30 nM). Primary endpoint was severe course of disease (i.e., need for invasive mechanical ventilation and/or death, IMV/D). Within a median observation period of 66 days (range 2–92), 23 patients required IMV. A total of 28 patients had IMV/D, including 16 deaths. Ninety-three (50%) patients required hospitalization (inpatient subgroup). A total of 41 (22%) patients were VitD deficient. When adjusted for age, gender, and comorbidities, VitD deficiency was associated with higher risk of IMV/D and death (HR 6.12, 95% CI 2.79–13.42, p < 0.001 and HR 14.73, 95% CI 4.16–52.19, p < 0.001, respectively). Similar correlations were observed in the inpatient subgroup. Our study demonstrates an association between VitD deficiency and severity/mortality of COVID-19, highlighting the need for interventional studies on VitD supplementation in SARS-CoV-2 infected individuals.

Iron metabolism might play a crucial role in cytokine release syndrome in COVID-19 patients. Therefore, we assessed iron metabolism markers in COVID-19 patients for their ability to predict disease severity. COVID-19 patients referred to the Heidelberg University Hospital were retrospectively analyzed. Patients were divided into outpatients (cohort A, n = 204), inpatients (cohort B, n = 81), and outpatients later admitted to hospital because of health deterioration (cohort C, n = 23). Iron metabolism parameters were severely altered in patients of cohort B and C compared to cohort A. In multivariate regression analysis including age, gender, CRP and iron-related parameters only serum iron and ferritin were significantly associated with hospitalization. ROC analysis revealed an AUC for serum iron of 0.894 and an iron concentration <6 μmol/l as the best cutoff-point predicting hospitalization with a sensitivity of 94.7% and a specificity of 67.9%. When stratifying inpatients in a low- and high oxygen demand group serum iron levels differed significantly between these two groups and showed a high negative correlation with the inflammatory parameters IL-6, procalcitonin, and CRP. Unexpectedly, serum iron levels poorly correlate with hepcidin. We conclude that measurement of serum iron can help predicting the severity of COVID-19. The differences in serum iron availability observed between the low and high oxygen demand group suggest that disturbed iron metabolism likely plays a causal role in the pathophysiology leading to lung injury.