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      Effective immunity and second waves: a dynamic causal modelling study

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          Abstract

          This technical report addresses a pressing issue in the trajectory of the coronavirus outbreak; namely, the rate at which effective immunity is lost following the first wave of the pandemic. This is a crucial epidemiological parameter that speaks to both the consequences of relaxing lockdown and the propensity for a second wave of infections. Using a dynamic causal model of reported cases and deaths from multiple countries, we evaluated the evidence models of progressively longer periods of immunity. The results speak to an effective population immunity of about three months that, under the model, defers any second wave for approximately six months in most countries. This may have implications for the window of opportunity for tracking and tracing, as well as for developing vaccination programmes, and other therapeutic interventions.

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China

            In December 2019, novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited.
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              Virological assessment of hospitalized patients with COVID-2019

              Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 20191,2. Initial outbreaks in China involved 13.8% of cases with severe courses, and 6.1% of cases with critical courses3. This severe presentation may result from the virus using a virus receptor that is expressed predominantly in the lung2,4; the same receptor tropism is thought to have determined the pathogenicity-but also aided in the control-of severe acute respiratory syndrome (SARS) in 20035. However, there are reports of cases of COVID-19 in which the patient shows mild upper respiratory tract symptoms, which suggests the potential for pre- or oligosymptomatic transmission6-8. There is an urgent need for information on virus replication, immunity and infectivity in specific sites of the body. Here we report a detailed virological analysis of nine cases of COVID-19 that provides proof of active virus replication in tissues of the upper respiratory tract. Pharyngeal virus shedding was very high during the first week of symptoms, with a peak at 7.11 × 108 RNA copies per throat swab on day 4. Infectious virus was readily isolated from samples derived from the throat or lung, but not from stool samples-in spite of high concentrations of virus RNA. Blood and urine samples never yielded virus. Active replication in the throat was confirmed by the presence of viral replicative RNA intermediates in the throat samples. We consistently detected sequence-distinct virus populations in throat and lung samples from one patient, proving independent replication. The shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (and by day 14 in all patients), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild illness of the upper respiratory tract. The confirmation of active virus replication in the upper respiratory tract has implications for the containment of COVID-19.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data CurationRole: Formal AnalysisRole: Funding AcquisitionRole: MethodologyRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – Original Draft Preparation
                Role: MethodologyRole: Writing – Review & Editing
                Role: MethodologyRole: Writing – Review & Editing
                Role: MethodologyRole: ValidationRole: Writing – Review & Editing
                Role: MethodologyRole: SoftwareRole: ValidationRole: Writing – Review & Editing
                Role: MethodologyRole: Writing – Review & Editing
                Role: MethodologyRole: Writing – Review & Editing
                Role: MethodologyRole: Writing – Review & Editing
                Role: MethodologyRole: Writing – Review & Editing
                Role: Writing – Review & Editing
                Role: MethodologyRole: Writing – Review & Editing
                Role: Writing – Review & Editing
                Role: Writing – Review & Editing
                Role: MethodologyRole: Writing – Review & Editing
                Journal
                Wellcome Open Res
                Wellcome Open Res
                Wellcome Open Res
                Wellcome Open Research
                F1000 Research Limited (London, UK )
                2398-502X
                30 September 2020
                2020
                30 September 2020
                : 5
                : 204
                Affiliations
                [1 ]The Wellcome Centre for Human Neuroimaging, University College London, London, UK
                [2 ]Turner Institute for Brain and Mental Health, Monash University, Clayton, VIC, 3800, Australia
                [3 ]Institut du Cerveau et de la Moelle épinière, INSERM UMRS 1127, Paris, France
                [4 ]Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark
                [5 ]London Mathematical Laboratory, Hammersmith, London, UK
                [6 ]UCL Ear Institute, University College London, London, UK
                [7 ]Centre for Neuroimaging Science, Department of Neuroimaging, IoPPN, King's College London, London, UK
                [8 ]UCL Institute for Global Health, Institute of Child Health, University College London, London, UK
                [9 ]UCL Division of Infection and Immunity, University College London, London, UK
                [1 ]School of Mathematical and Physical Sciences, Department of Mathematics, University of Sussex, Brighton, UK
                [1 ]School of Mathematical and Physical Sciences, Department of Mathematics, University of Sussex, Brighton, UK
                Monash University, Australia
                [1 ]Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA
                Author notes

                No competing interests were disclosed.

                Competing interests: No competing interests were disclosed.

                Competing interests: No competing interests were disclosed.

                Competing interests: No competing interests were disclosed.

                Competing interests: No competing interests were disclosed.

                Author information
                https://orcid.org/0000-0001-7984-8909
                https://orcid.org/0000-0001-5108-5743
                https://orcid.org/0000-0002-0779-9439
                https://orcid.org/0000-0002-4531-8616
                https://orcid.org/0000-0002-2736-2621
                https://orcid.org/0000-0001-8281-4611
                Article
                10.12688/wellcomeopenres.16253.2
                7549178
                33088924
                2358e754-cd65-45ec-bb36-88cabd5901b6
                Copyright: © 2020 Friston KJ et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 September 2020
                Funding
                Funded by: Medical Research Council
                Award ID: MR/R006504/1
                Funded by: Wellcome Trust
                Award ID: 203147
                Funded by: Wellcome Trust
                Award ID: 088130
                Funded by: Australian Research Council
                Award ID: DP200100757
                Award ID: DE170100128
                Funded by: Wellcome Trust
                Award ID: WT091681MA
                The Wellcome Centre for Human Neuroimaging is supported by core funding from Wellcome [203147]. A.R. is funded by the Australian Research Council (Refs: DE170100128 and DP200100757). A.J.B. is supported by a Wellcome Trust grant WT091681MA. CL is supported by an MRC Clinician Scientist award (MR/R006504/1).
                The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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