Most of the 215 patients included were females aged 18–59. Seventy-eight of the patients had been hospitalised during the COVID-19 acute phase and the main long COVID symptoms reported were fatigue, dyspnoea, and muscle weakness. Among the hospitalised patients, the mean levels of triglycerides and ferritin were higher than those in the non-hospitalised group. In patients with a shorter period of long COVID, most quantitative laboratory tests, especially HbA1c and ferritin levels, were altered. Furthermore, BMI and HbA1c levels were higher in patients with more than six symptoms. Female sex, hospitalisation, and a high BMI were associated with more symptoms. Finally, triglyceride levels were correlated with FBG and ferritin levels in the worst long COVID outcomes.
The most commonly reported long COVID symptoms in recent studies are fatigue, dyspnoea, chest pain, and muscle weakness, among other non-specific manifestations [1, 8]. This study demonstrated a similar profile of involvement, with fatigue being the most frequent symptom. In addition, most of the affected population consisted of women aged approximately 50 years, in agreement with several recent investigations [7,11−13].
Patients who had been hospitalised during the COVID-19 acute phase showed abnormal levels of triglycerides and ferritin. Although there is evidence that hospitalisation during the onset of symptoms is a risk factor for long COVID susceptibility and severity [14, 15], it is unclear whether hospitalisation is directly responsible for the abnormality in the markers mentioned above and how this interaction occurs considering the vast multi-organ pathophysiology of long COVID. However, the non-specific harmful effects of hospitalisation certainly influence the long-term alterations in these markers, as demonstrated in the current study.
Our results suggest that patients with a shorter period of COVID symptoms have a higher risk of complications associated with metabolic health since significant alterations were observed in HbA1c and ferritin levels, in addition to several minor alterations in other studied markers in these patients. This might be explained by the temporal proximity to the acute involvement of COVID-19 since even though the patient is still presenting with long COVID symptoms, most of the laboratory markers investigated here showed normalisation in their mean levels in more extended periods of long COVID. This supposed benign evolution can be related to evidence that the number of symptoms tends to decrease over time [15–17], although when comparing patients with up to three months and with more than one year of long COVID, we could not observe a significant difference in the number of simultaneous symptoms reported.
It was shown here that BMI measures suggestive of obesity and abnormalities in triglycerides, HbA1c, and ferritin were related to worse clinical scenarios, such as previous acute hospitalisation and presentation of more symptoms, indicating a worse long-term COVID involvement, in agreement with other studies [4, 18, 19]. Alterations in these markers suggest that patients with long COVID may be more likely to develop clinical complications related to MS. It has been hypothesised that acute inflammation driven by SARS-CoV-2 infection could dysregulate metabolic pathways, such as impairment of insulin signalling, which could lead to abnormalities in cardiometabolic homeostasis [10, 20].
The lack of a control group is a limitation of this study. A control group would allow for a comparison between patients with and without prolonged symptoms. Additionally, evaluating screening clinical and laboratory markers may not be enough to detail all the particularities of metabolic health, considering the complexity of long COVID. On the other hand, monitoring markers involved in metabolism that are widely available certainly enhances our understanding of the metabolic profile of patients with long COVID. To the best of our knowledge, this is the first study to demonstrate possible metabolic changes in patients with up to 21 months of long COVID, highlighting MS-related markers while linking these metabolic abnormalities to the clinical context of long COVID.
This study presents interesting clues regarding the relationship between long COVID and metabolic health-related markers. Knowing the clinical and laboratory profile of patients with long COVID by presenting population patterns could provide useful insight into possible risk patterns and markers and help to better manage these patients. The findings presented here, together with other evidence [4, 8, 19], may provide a basis for more robust and detailed investigations in the future.
In conclusion, this study has examined how the metabolic profile is affected in patients with long COVID, illustrating how common markers in clinical practice, especially those involved in glycaemic and lipid metabolism, relate to the course of the disease. Our main findings indicate that abnormal triglyceride, HbA1c, BMI, and ferritin levels are related to worse long COVID presentations, such as hospitalisation in the acute phase and more concomitant symptoms. These results suggest that patients with long COVID may be more likely to develop clinical complications related to MS. Therefore, it is recommended that health systems be prepared to receive an increasing number of patients affected by conditions related to MS, given the influence of long COVID. It is also suggested that further investigations, especially regarding cellular metabolic mechanisms shared by MS and long COVID, be conducted in case symptoms persist. Finally, cohort studies that follow patients with long COVID for an extended period are advisable and could provide a better understanding of how the metabolic profile develops in these patients.