Long COVID exhibits clinically distinct phenotypes at 3-6 months post-SARS-CoV-2 infection: results from the P4O2 consortium.

BACKGROUND: Four months after SARS-CoV-2 infection, 22%-50% of COVID-19 patients still experience complaints. Long COVID is a heterogeneous disease and finding subtypes could aid in optimising and developing treatment for the individual patient. METHODS: Data were collected from 95 patients in the P4O2 COVID-19 cohort at 3-6 months after infection. Unsupervised hierarchical clustering was performed on patient characteristics, characteristics from acute SARS-CoV-2 infection, long COVID symptom data, lung function and questionnaires describing the impact and severity of long COVID. To assess robustness, partitioning around medoids was used as alternative clustering. RESULTS: Three distinct clusters of patients with long COVID were revealed. Cluster 1 (44%) represented predominantly female patients (93%) with pre-existing asthma and suffered from a median of four symptom categories, including fatigue and respiratory and neurological symptoms. They showed a milder SARS-CoV-2 infection. Cluster 2 (38%) consisted of predominantly male patients (83%) with cardiovascular disease (CVD) and suffered from a median of three symptom categories, most commonly respiratory and neurological symptoms. This cluster also showed a significantly lower forced expiratory volume within 1 s and diffusion capacity of the lung for carbon monoxide. Cluster 3 (18%) was predominantly male (88%) with pre-existing CVD and diabetes. This cluster showed the mildest long COVID, and suffered from symptoms in a median of one symptom category. CONCLUSIONS: Long COVID patients can be clustered into three distinct phenotypes based on their clinical presentation and easily obtainable information. These clusters show distinction in patient characteristics, lung function, long COVID severity and acute SARS-CoV-2 infection severity. This clustering can help in selecting the most beneficial monitoring and/or treatment strategies for patients suffering from long COVID. Follow-up research is needed to reveal the underlying molecular mechanisms implicated in the different phenotypes and determine the efficacy of treatment.

Precision Medicine for More Oxygen (P4O2)-Study Design and First Results of the Long COVID-19 Extension.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has led to the death of almost 7 million people, however, with a cumulative incidence of 0.76 billion, most people survive COVID-19. Several studies indicate that the acute phase of COVID-19 may be followed by persistent symptoms including fatigue, dyspnea, headache, musculoskeletal symptoms, and pulmonary functional-and radiological abnormalities. However, the impact of COVID-19 on long-term health outcomes remains to be elucidated. Aims: The Precision Medicine for more Oxygen (P4O2) consortium COVID-19 extension aims to identify long COVID patients that are at risk for developing chronic lung disease and furthermore, to identify treatable traits and innovative personalized therapeutic strategies for prevention and treatment. This study aims to describe the study design and first results of the P4O2 COVID-19 cohort. Methods: The P4O2 COVID-19 study is a prospective multicenter cohort study that includes nested personalized counseling intervention trial. Patients, aged 40-65 years, were recruited from outpatient post-COVID clinics from five hospitals in The Netherlands. During study visits at 3-6 and 12-18 months post-COVID-19, data from medical records, pulmonary function tests, chest computed tomography scans and biological samples were collected and questionnaires were administered. Furthermore, exposome data was collected at the patient's home and state-of-the-art imaging techniques as well as multi-omics analyses will be performed on collected data. Results: 95 long COVID patients were enrolled between May 2021 and September 2022. The current study showed persistence of clinical symptoms and signs of pulmonary function test/radiological abnormalities in post-COVID patients at 3-6 months post-COVID. The most commonly reported symptoms included respiratory symptoms (78.9%), neurological symptoms (68.4%) and fatigue (67.4%). Female sex and infection with the Delta, compared with the Beta, SARS-CoV-2 variant were significantly associated with more persisting symptom categories. Conclusions: The P4O2 COVID-19 study contributes to our understanding of the long-term health impacts of COVID-19. Furthermore, P4O2 COVID-19 can lead to the identification of different phenotypes of long COVID patients, for example those that are at risk for developing chronic lung disease. Understanding the mechanisms behind the different phenotypes and identifying these patients at an early stage can help to develop and optimize prevention and treatment strategies.

The migration pattern and initial stability of the Optimys short stem in total hip arthroplasty: a prospective 2-year follow-up study of 33 patients with RSA.

BACKGROUND AND PURPOSE: The consensus that bone stock preservation and optimal restoration of offset and leg length is important in total hip arthroplasty is now widespread, especially for young and active patients. Short stems seem promising in this aspect, though implant stability is still of concern. This study looked at the migration pattern of the Optimys short stem through RSA analysis. PATIENTS AND METHODS: 40 patients were included. RSA images were made directly postoperatively (within 5 days), at 6 weeks and at 3, 6, 12 and 24 months. Double examinations were made for precision measurement. HOOS and pain scores were obtained preoperatively and at 2 years. 4 patients were excluded due to protocol violation and 1 patient was excluded for RSA analysis with a CN number >110. 2 patients were lost to follow-up after 3 and 6 months (n = 1 lost, n = 1 deep infection, respectively). RESULTS: Mean age was 60 years with a mean BMI of 27. RSA analysis of 34 patients showed a significant initial median proximodistal translation (subsidence) of 0.21 mm (IQR 0.64-0.06) and anteversion-retroversion rotation of 0.59° (IQR 0.01-1.34) at 6 weeks, after which the stem stabilises and showed no further significant movement. Median migration in other directions was small. 4 patients had an initial subsidence of >2 mm, all showed secondary stabilisation. HOOS outcomes were satisfactory, with the domain symptoms and pain showing a median score of 95/100 at 2 years. CONCLUSIONS: After initial migration the Optimys achieves secondary stabilisation, suggesting low risk on long-term aseptic loosening. CLINICAL TRIALS REGISTRATION: NL47055.048.13.