We implemented a long-term stratified follow-up path that adhered to the international proposed clinical guidance for the assessment and management of COVID-19 patients 7,8,34,35, in the context of the limited availability of resources and the operational pressure faced by hospitals during the pandemic. This project was part of a broad set of strategies and paths implemented within the Healthcare Trust of the Autonomous Province of Trento for reorganizing care and managing patients at a distance, including routine services and the continuation of care after hospital discharge 36, as well assessing the impact of pandemic burden and related change in practice 37. In our study, we targeted the same cohort of patients (excluding six patients with multiple admissions) to investigate in-hospital outcomes during the COVID-19 pandemic 38.
Overall, in our study any long COVID symptoms were reported at 6 months in 27.0% of patients and at 12 months in 24.4%, but we noted an increased number of different symptoms at 12 months. Alterations in the mMRC scale were reported in almost 20.5% of patients at 6 months and in 14.5% of patients at 12 months. The frequency of neurocognitive symptoms increased from 5.4–10.0% from the 6-month to the 12-month timepoints. At both 6 and 12 months, neurocognitive symptoms were markedly more common in patients who had been treated with mechanical ventilation during hospital admission. Furthermore, patients who had been treated with tracheal intubation in comparison to HFNC or NIV and who had received no therapy or low-flow oxygen reported a significantly higher prevalence of experiencing any symptom and having dyspnea at 12 months.
Published studies investigating the highly heterogeneous and poorly understood post-COVID-19 syndrome show the relevance of medical and psychological sequelae for several months after active infection, with more than 50 long-term effects of COVID-19 having been reported 39. Pooled prevalence data show that the 10 most prevalent symptoms are fatigue, shortness of breath, muscle pain, joint pain, headache, cough, chest pain, altered smell, altered taste, and diarrhea 40. The increasingly evident long-term neurological effects include the impact of the virus on cognition, autonomic function, and mental wellbeing 41. Patients with long COVID present with prolonged multisystem involvement and significant disability 13. The development of long COVID symptoms may be linked to symptomatic COVID-19 infection, hospitalization (with mechanical ventilation being required), severity of illness, and sex (women may have a higher incidence) 42–44. However, any patient with COVID-19 may develop long COVID, regardless of the severity of their infection and the intensity of the treatment they received 43.
The few published prospective studies using a 12-month timepoint providing an overview of the clinical symptoms and quality of life of adult patients show that, although decreasing over time, a meaningful portion of patients still report persistent symptoms one year after infection 20,22−25. Overall, our findings are in line with such results, although with a lower proportion of patients experiencing persistent symptoms, with a meaningful proportion of patients of experiencing dyspnea and patterns of neurologic symptoms. Clinical impairment can persist at least until one year after COVID-19 symptom onset and reduce patients’ quality of life significantly 22. The persistence of neuropsychiatric long COVID symptoms (which can reduce quality of life significantly) one year after COVID-19 symptom onset may be partially explained by the influence of the extended pandemic situation and consequent psychological impact 22.
Our findings seem consistent with the literature showing the persistence of chest imaging manifestations months after hospitalization for COVID-19 pneumonia 12,45−47 and the persistence (although decreasing over time) of pulmonary alterations up to 12 months later 21,25. However, we did not find any association between lung structural abnormalities and the severity of the disease during hospital stay. Lung imaging patterns at 12 months may be associated with lung diffusion impairment, although further studies are needed to explore the effect of these persistent abnormalities on physical function and quality of life 25.In our study, we found a decreased detection of IgG antibodies in SARS-CoV-2-infected patients, dropping from 95.3% at six months to 85.7% at 12 months. The detectability of antibodies 1 year after infection, although with different temporal trends and magnitudes, seems to confirm the findings of other studies that have carried out comparable long-term follow-ups 48–50. The relationship between the antibody level and protection against COVID-19 is still unclear; however, the one-year follow-up data show that patients who have recovered from COVID-19 have a very low risk of reinfection. Natural immunity to SARS-CoV-2 appears to confer a protective effect for at least a year 51. The rate of full vaccine coverage at 12 months seem to mirror the progress of the Italian vaccination campaign, which is still underway at the timeframe of the writing, reflecting the need of specific logistic organization 52–54.
All in all, our study shows the high clinical burden of long COVID-19 12 months after acute infection and affirms the importance of understanding the natural course of long COVID as a long-term chronic condition with symptoms persisting beyond 12 months after the onset of illness. Identifying patients at major risk of sequelae from the early post-acute phase; setting up appropriate and patient-centered pathways supported by online support tools; and the implementation of surveillance systems and specialized multidisciplinary care, including rehabilitation, are critical in order to understand and treat patients suffering from long COVID 40,55−58.
The development and implementation of clinical guidelines 59 as well as use of tools and methods for Health Technology Assessment 60,61 in order to evaluate the effects of decisions and actions related to resource allocation, models of care, professional practice, drugs, and medical devices in response to the complex and evolving challenges of long COVID may enable value-based decisions to be made 62.