Background Reports of Guillain-Barre Syndrome (GBS) have emerged during the Coronavirus Disease 2019 (COVID-19) pandemic. This epidemiological and cohort study sought to investigate any causative association between COVID-19 infection and GBS. Methods The epidemiology of GBS cases reported via the UK National Immunoglobulin Database were studied from 2016-2019 and compared to cases reported during the COVID-19 pandemic. For the cohort study, members of the British Peripheral Nerve Society reported all cases of GBS during the pandemic. The clinical features, investigation findings and outcomes of COVID-19 (definite or probable) and non-COVID-19 associated GBS cases were compared. Results The UK GBS incidence from 2016-2019 was 1.65-1.88 per 100,000 people per year. GBS and COVID-19 incidence varied between regions and did not correlate (r = 0.06, 95% CI -0.56 to 0.63, p=0.86). GBS incidence fell between March and May 2020 compared to the same months of 2016-2019. Forty-seven GBS cases were included in the cohort study (13 definite, 12 probable COVID-19 and 22 non-COVID-19). There were no significant differences in the pattern of weakness, time to nadir, neurophysiology, CSF findings or outcome. Intubation was more frequent in the COVID-19+ve cohort (7/13, 54% vs 5/22, 23% in COVID negative) thought to be related directly to COVID-19 pulmonary involvement. Conclusions This study finds no epidemiological or phenotypic clues of SARS-CoV-2 being causative of GBS. GBS incidence has fallen during the pandemic which may be the influence of lockdown measures reducing transmission of GBS inducing pathogens such as Campylobacter jejuni and respiratory viruses.
Human and animal studies on antibody-mediated neuropathy implicate complement in pathogenesis. In animal models complement inhibition is therapeutically beneficial. The monoclonal antibody, eculizumab (Soliris™, Alexion Pharmaceuticals, Cheshire, CT), prevents cleavage of C5 and thus inhibits terminal complement activation. In an open label study, 13 multifocal motor neuropathy patients received eculizumab for 14 weeks, 10 of whom were concomitantly receiving intravenous immunoglobulin. The primary outcome was safety of eculizumab, and the secondary outcomes included change in intravenous immunoglobulin (IVIg) dosing frequency, performance, and electrophysiological parameters. Adverse events were minor during the study. Nine of 10 patients on IVIg maintenance continued to require IVIg. IVIg dosing interval was not different between the run-in and the treatment period. There were improvements in patient-rated subjective scores and selected clinical and electrophysiological measurements. Overall, a small treatment effect occurred in some patients that appeared supplementary to and independent of the IVIg treatment effect, and occurred more frequently in patients with higher baseline motor function.
Determining the level of social distancing, quantified here as the reduction in daily number of social contacts per person, i.e. the daily contact rate, needed to maintain control of the COVID-19 epidemic and not exceed acute bed capacity in case of future epidemic waves, is important for future planning of relaxing of strict social distancing measures. This work uses mathematical modelling to simulate the levels of COVID-19 in North East London (NEL) and inform the level of social distancing necessary to protect the public and the healthcare demand from future COVID-19 waves. We used a Susceptible-Exposed-Infected-Removed (SEIR) model describing the transmission of SARS-CoV-2 in NEL, calibrated to data on hospitalised patients with confirmed COVID-19, hospital discharges and in-hospital deaths in NEL during the first epidemic wave. To account for the uncertainty in both the infectiousness period and the proportion of symptomatic infection, we simulated nine scenarios for different combinations of infectiousness period (1, 3 and 5 days) and proportion of symptomatic infection (70%, 50% and 25% of all infections). Across all scenarios, the calibrated model was used to assess the risk of occurrence and predict the strength and timing of a second COVID-19 wave under varying levels of daily contact rate from July 04, 2020. Specifically, the daily contact rate required to suppress the epidemic and prevent a resurgence of COVID-19 cases, and the daily contact rate required to stay within the acute bed capacity of the NEL system without any additional intervention measures after July 2020, were determined across the nine different scenarios. Our results caution against a full relaxing of the lockdown later in 2020, predicting that a return to pre-COVID-19 levels of social contact from July 04, 2020, would induce a second wave up to eight times the original wave. With different levels of ongoing social distancing, future resurgence can be avoided, or the strength of the resurgence can be mitigated. Keeping the daily contact rate lower than 5 or 6, depending on scenarios, can prevent an increase in the number of COVID-19 cases, could keep the effective reproduction number Re below 1 and a secondary COVID-19 wave may be avoided in NEL. A daily contact rate between 6 and 7, across scenarios, is likely to increase Re above 1 and result in a secondary COVID-19 wave with significantly increased COVID-19 cases and associated deaths, but with demand for hospital-based care remaining within the bed capacity of the NEL health and care system. In contrast, an increase in daily contact rate above 8 to 9, depending on scenarios, will likely exceed the acute bed capacity in NEL and may potentially require additional lockdowns. This scenario is associated with significantly increased COVID-19 cases and deaths, and acute COVID-19 care demand is likely to require significant scaling down of the usual operation of the health and care system and should be avoided. Our findings suggest that to avoid future COVID-19 waves and to stay within the acute bed capacity of the NEL health and care system, maintaining social distancing in NEL is advised with a view to limiting the average number of social interactions in the population. Increasing the level of social interaction beyond the limits described in this work could result in future COVID-19 waves that will likely exceed the acute bed capacity in the system, and depending on the strength of the resurgence may require additional lockdown measures.
Background It is important that population cohorts at increased risk of hospitalisation and death following a COVID‐19 infection are identified and protected. Objectives We identified risk factors associated with increased risk of hospitalisation, intensive care unit (ICU) admission and mortality in inner North East London (NEL) during the first UK COVID‐19 wave. Methods Multivariate logistic regression analysis on linked primary and secondary care data from people aged 16 or older with confirmed COVID‐19 infection between 01/02/2020 and 30/06/2020 determined odds ratios (OR), 95% confidence intervals (CI) and P ‐values for the association between demographic, deprivation and clinical factors with COVID‐19 hospitalisation, ICU admission and mortality. Results Over the study period, 1781 people were diagnosed with COVID‐19, of whom 1195 (67%) were hospitalised, 152 (9%) admitted to ICU and 400 (23%) died. Results confirm previously identified risk factors: being male, or of Black or Asian ethnicity, or aged over 50. Obesity, type 2 diabetes and chronic kidney disease (CKD) increased the risk of hospitalisation. Obesity increased the risk of being admitted to ICU. Underlying CKD, stroke and dementia increased the risk of death. Having learning disabilities was strongly associated with increased risk of death (OR = 4.75, 95% CI = [1.91, 11.84], P = .001). Having three or four co‐morbidities increased the risk of hospitalisation (OR = 2.34, 95% CI = [1.55, 3.54], P < .001; OR = 2.40, 95% CI = [1.55, 3.73], P < .001 respectively) and death (OR = 2.61, 95% CI = [1.59, 4.28], P < .001; OR = 4.07, 95% CI = [2.48, 6.69], P < .001 respectively). Conclusions We confirm that age, sex, ethnicity, obesity, CKD and diabetes are important determinants of risk of COVID‐19 hospitalisation or death. For the first time, we also identify people with learning disabilities and multi‐morbidity as additional patient cohorts that need to be actively protected during COVID‐19 waves.
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