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IntroductionVery little is known about possible clinical sequelae that may persist after resolution of the acute Coronavirus Disease 2019 (COVID-19). A recent longitudinal cohort from Italy including 143 patients recovered after hospitalisation with COVID-19 reported that 87% had at least one ongoing symptom at 60 day follow-up. Early indications suggest that patients with COVID-19 may need even more psychological support than typical ICU patients. The assessment of risk factors for longer term consequences requires a longitudinal study linked to data on pre-existing conditions and care received during the acute phase of illness. Methods and analysisThis is an international open-access prospective, observational multi-site study. It will enrol patients following a diagnosis of COVID-19. Tier 1 is developed for following up patients day 28 post-discharge, additionally at 3 to 6 months intervals. This module can be used to identify sub-sets of patients experiencing specific symptomatology or syndromes for further follow up. A Tier 2 module will be developed for in-clinic, in-depth follow up. The primary aim is to characterise physical consequences in patients post-COVID-19. Secondary aim includes estimating the frequency of and risk factors for post-COVID-19 medical sequalae, psychosocial consequences and post-COVID-19 mortality. A subset of patients will have sampling to characterize longer term antibody, innate and cell-mediated immune responses to SARS-CoV-2. Ethics and disseminationThis collaborative, open-access study aims to characterize the frequency of and risk factors for long-term consequences and characterise the immune response over time in patients following a diagnosis of COVID-19 and facilitate standardized and longitudinal data collection globally. The outcomes of this study will inform strategies to prevent long term consequences; inform clinical management, direct rehabilitation, and inform public health management to reduce overall morbidity and improve outcomes of COVID-19. Article summaryO_ST_ABSStrengths and limitations of this studyC_ST_ABSO_LIAs an international prospective, observational study we provide open-access standardised tools that can be adapted by any site interested in following up patients with COVID-19, for independent or combined analysis, to forward knowledge into short and long term consequences of COVID-19. C_LIO_LIThis study aims to inform strategies to prevent longer term sequalae; inform clinical management, rehabilitation, and public health management strategies to reduce morbidity and improve outcomes. C_LIO_LIThe protocol will be used for a sub-set of patients, already included in the existing cohort of more than 85,973 individuals hospitalized with confirmed COVID-19 infection across 42 countries (as of 20 July 2020), using the ISARIC/WHO standardized Core- or RAPID Case Report Forms (CRFs). C_LIO_LIThe data will be linked with data on pre-existing comorbidities, presentation, clinical care and treatments documented in the existing cohort already documented using the ISARIC/WHO standardized Core- or RAPID CRFs. C_LIO_LIThe data collection tool is developed to facilitate wide dissemination and uptake, by enabling patient self-assessment, however, follow up of patients requires consent and resources, which might limit the uptake and bias the data towards countries /sites with capacity to follow up patients over time. C_LI
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Accuracy of diagnostic tests is essential for suspected cases of Coronavirus Disease 2019 (COVID-19). This study aimed to assess the sensitivity, specificity and positive and negative predictive value (PPV and NPV) of molecular and serological tests for the diagnosis of SARS-CoV-2 infection. A total of 346 consenting, adult patients were enrolled at the emergency room of IRCCS Sacro Cuore Don Calabria Hospital, Negrar, Italy. We evaluated three RT-PCR methods including six different gene targets; five serologic rapid diagnostic tests (RDT); one ELISA test. The final classification of infected/not infected patients was performed using Latent Class Analysis in combination with clinical re-assessment of incongruous cases and was the basis for the main analysis of accuracy. Of 346 patients consecutively enrolled, 85 (24.6%) were classified as infected. The molecular test with the highest sensitivity, specificity, PPV and NPV was RQ-SARS-nCoV-2 with 91.8% (C.I. 83.8-96.6), 100% (C.I. 98.6-100.0), 100.0% (C.I. 95.4-100.0) and 97.4% (C.I. 94.7-98.9) respectively, followed by CDC 2019-nCoV with 76.2% (C.I. 65.7-84.8), 99.6% (C.I. 97.9-100.0), 98.5% (C.I. 91.7-100.0) and 92.9% (C.I. 89.2-95.6) and by in-house test targeting E-RdRp with 61.2% (C.I. 50.0-71.6), 99.6% (C.I. 97.9-100.0), 98.1% (C.I. 89.9-100.0) and 88.7% (C.I. 84.6-92.1). The analyses on single gene targets found the highest sensitivity for S and RdRp of the RQ-SARS-nCoV-2 (both with sensitivity 94.1%, C.I. 86.8-98.1). The in-house RdRp had the lowest sensitivity (62.4%, C.I. 51.2-72.6). The specificity ranged from 99.2% (C.I. 97.3-99.9) for in-house RdRp and N2 to 95.0% (C.I. 91.6-97.3) for E. The PPV ranged from 97.1% (C.I. 89.8-99.6) of N2 to 85.4% (C.I. 76.3-92.00) of E, and the NPV from 98.1% (C.I. 95.5-99.4) of gene S to 89.0% (C.I. 84.8-92.4) of in-house RdRp. All serological tests had <50% sensitivity and low PPV and NPV. One RDT (VivaDiag IgM) had high specificity (98.5%, with PPV 84.0%), but poor sensitivity (24.7%). Molecular tests for SARS-CoV-2 infection showed excellent specificity, but significant differences in sensitivity. As expected, serological tests have limited utility in a clinical context.
