Refining "Long-COVID" by a Prospective Multimodal Evaluation of Patients with Long-Term Symptoms Attributed to SARS-CoV-2 Infection.

INTRODUCTION: COVID-19 long-haulers, also decribed as having "long-COVID" or post-acute COVID-19 syndrome, represent 10% of COVID-19 patients and remain understudied. METHODS: In this prospective study, we recruited 30 consecutive patients seeking medical help for persistent symptoms (> 30 days) attributed to COVID-19. All reported a viral illness compatible with COVID-19. The patients underwent a multi-modal evaluation, including clinical, psychologic, virologic and specific immunologic assays and were followed longitudinally. A group of 17 convalescent COVID-19 individuals without persistent symptoms were included as a comparison group. RESULTS: The median age was 40 [interquartile range: 35-54] years and 18 (60%) were female. At a median time of 152 [102-164] days after symptom onset, fever, cough and dyspnea were less frequently reported compared with the initial presentation, but paresthesia and burning pain emerged in 18 (60%) and 13 (43%) patients, respectively. The clinical examination was unremarkable in all patients, although the median fatigue and pain visual analog scales were 7 [5-8] and 5 [2-6], respectively. Extensive biologic studies were unremarkable, and multiplex cytokines and ultra-sensitive interferon-α2 measurements were similar between long-haulers and convalescent COVID-19 individuals without persistent symptoms. Using SARS-CoV-2 serology and IFN-γ ELISPOT, we found evidence of a previous SARS-CoV-2 infection in 50% (15/30) of patients, with evidence of a lack of immune response, or a waning immune response, in two patients. Finally, psychiatric evaluation showed that 11 (36.7%), 13 (43.3%) and 9 (30%) patients had a positive screening for anxiety, depression and post-traumatic stress disorder, respectively. CONCLUSIONS: Half of patients seeking medical help for post-acute COVID-19 syndrome lack SARS-CoV-2 immunity. The presence of SARS-CoV-2 immunity, or not, had no consequence on the clinical or biologic characteristics of post-acute COVID-19 syndrome patients, all of whom reported severe fatigue, altered quality of life and psychologic distress.

A big-data approach to producing descriptive anthropometric references: a feasibility and validation study of paediatric growth charts.

BACKGROUND: Both national and WHO growth charts have been found to be poorly calibrated with the physical growth of children in many countries. We aimed to generate new national growth charts for French children in the context of huge datasets of physical growth measurements routinely collected by office-based health practitioners. METHODS: We recruited 32 randomly sampled primary care paediatricians and ten volunteer general practitioners from across the French metropolitan territory who used the same electronic medical records software, from which we extracted all physical growth data for the paediatric patients, with anonymisation. We included measurements from all children born from Jan 1, 1990, and aged 1 month to 18 years by Feb 8, 2018, with birthweight greater than 2500 g, to which an automated process of data cleaning developed to detect and delete measurement or transcription errors was applied. Growth charts for weight and height were derived by using generalised additive models for location, scale, and shape with the Box-Cox power exponential distribution. We compared the new charts to WHO growth charts and existing French national growth charts, and validated our charts using growth data from recent national cross-sectional surveys. FINDINGS: After data cleaning, we included 1 458 468 height and 1 690 340 weight measurements from 238 102 children. When compared with the existing French national and WHO growth charts, all height SD and weight percentile curves for the new growth charts were distinctly above those for the existing French national growth charts, as early as age 1 month, with an average difference of -0·75 SD for height and -0·50 SD for weight for both sexes. Comparison with national cross-sectional surveys showed satisfactory calibration, with generally good fit for children aged 5-6 years and 10-11 years in height and weight and small differences at age 14-15 years. INTERPRETATION: We successfully produced calibrated paediatric growth charts by using a novel big-data approach applied to data routinely collected in clinical practice that could be used in many fields other than anthropometry. FUNDING: The French Ministry of Health; Laboratoires Guigoz-General Pediatrics section of the French Society of Pediatrics-Pediatric Epidemiological Research Group; and the French Association for Ambulatory Pediatrics.

Priority target conditions for algorithms for monitoring children's growth: Interdisciplinary consensus.

BACKGROUND: Growth monitoring of apparently healthy children aims at early detection of serious conditions through the use of both clinical expertise and algorithms that define abnormal growth. Optimization of growth monitoring requires standardization of the definition of abnormal growth, and the selection of the priority target conditions is a prerequisite of such standardization. OBJECTIVE: To obtain a consensus about the priority target conditions for algorithms monitoring children's growth. METHODS: We applied a formal consensus method with a modified version of the RAND/UCLA method, based on three phases (preparatory, literature review, and rating), with the participation of expert advisory groups from the relevant professional medical societies (ranging from primary care providers to hospital subspecialists) as well as parent associations. We asked experts in the pilot (n = 11), reading (n = 8) and rating (n = 60) groups to complete the list of diagnostic classification of the European Society for Paediatric Endocrinology and then to select the conditions meeting the four predefined criteria of an ideal type of priority target condition. RESULTS: Strong agreement was obtained for the 8 conditions selected by the experts among the 133 possible: celiac disease, Crohn disease, craniopharyngioma, juvenile nephronophthisis, Turner syndrome, growth hormone deficiency with pituitary stalk interruption syndrome, infantile cystinosis, and hypothalamic-optochiasmatic astrocytoma (in decreasing order of agreement). CONCLUSION: This national consensus can be used to evaluate the algorithms currently suggested for growth monitoring. The method used for this national consensus could be re-used to obtain an international consensus.

Internet use for information seeking in clinical practice: a cross-sectional survey among French general practitioners.

BACKGROUND: Medical information needs regarding patient care are particularly large for general practitioners (GPs). The Internet seems to be a relevant but underused tool to seek medical information. OBJECTIVE: We aimed to describe the characteristics of the French GPs using the Internet for information seeking, to identify the barriers to its use and the factors that could facilitate it. METHOD: We conducted a cross-sectional survey among GPs currently practicing in France, using an online questionnaire, in July 2009. We analysed the answers of 721 respondents. RESULTS: Most of the respondents used the Internet to seek information. They were significantly younger, worked in group practice, had Internet training and had Internet access at the practice. The main barriers were related to the physician (lack of knowledge or specific skills), to the practice conditions (lack of time, concerns about relationship with patient, financial non-recognition) and to the information (information overload, quality concerns, low relevance, language barrier). Practitioners wanted more reliable and more relevant documents for daily practice. Websites with already selected resources could increase the GPs use of the Internet for medical information seeking. CONCLUSION: The reported obstacles were largely common with those previously described in other countries, except the language barrier and the financial non-recognition. Even if the generalization of our results to all French GPs should be cautious, the study provided better insights into the obstacles to the Internet use to seek clinical information in family practice and the factors that could facilitate it.

Refining long-COVID by a prospective multimodal evaluation of patients with long-term symptoms related to SARS-CoV-2 infection

BackgroundCOVID-19 long-haulers or "long-COVID" represent 10% of COVID-19 patients and remain understudied. MethodsIn this prospective study, we recruited 30 consecutive patients seeking medical help for persistent symptoms (> 30 days) attributed to COVID-19. All reported a viral illness compatible with COVID-19. The patients underwent a multi-modal evaluation including clinical, psychological, virological, specific immunological assays and were followed longitudinally. ResultsThe median age was 40 [interquartile range: 35-54] and 18 (60%) were female. After a median time of 152 [102-164] days after symptom onset, fever, cough and dyspnea were less frequently reported as compared with the initial presentation, but paresthesia and burning pain emerged in 18 (60%) and 13 (43%) patients, respectively. The clinical examination was unremarkable in all patients although the median fatigue and pain visual analogic scales were 7 [5-8] and 5 [2-6], respectively. Extensive biological studies were unremarkable, as were multiplex cytokine and ultra-sensitive interferon-a2 measurements. At this time, nasopharyngeal swab and stool RT-PCR were negative for all tested patients. Using SARS-CoV-2 serology and IFN-{gamma} ELISPOT, we found evidence of a previous SARS-CoV-2 infection in 50% (15/30) of patients, with objective evidence of lack or waning of immune response in two. Finally, psychiatric evaluation showed that 11 (36.7%), 13 (43.3%) and 9 (30%) patients had a positive screening for anxiety, depression and post-traumatic stress disorder, respectively. ConclusionsHalf of patients seeking medical help for long-COVID lack SARS-CoV-2 immunity. The presence of SARS-CoV-2 immunity did not cluster clinically or biologically long haulers, who reported severe fatigue, altered quality of life, and exhibited psychological distress. Key pointsO_LIAmong 30 consecutive patients reporting persistent symptoms (median 6 months) self-attributed to COVID-19, pain, fatigue and disability were reported in virtually all patients. C_LIO_LIMore than one third of patients suffer from psychological disorders such as anxiety, depression and/or post-traumatic stress disorder, regardless of SARS-CoV-2 immunity. C_LIO_LIAt the time of evaluation, only 50% of patients had cellular and/or humoral sign of a past SARS-CoV-2, and serology positivity varied depending of the kit used. C_LIO_LIExhaustive clinical, biological and immunological evaluations failed to find an alternative diagnosis, or to identify specific cytokine signature including type I interferon. C_LI