RESUMO
Cross-reactivity to SARS-CoV-2 from previous exposure to endemic coronaviruses (eHCoV) is gaining increasing attention as a possible driver of both protection against infection and severity of COVID-19 disease. Here, we use a stochastic individual-based model to show that heterogeneities in individual exposure histories to endemic coronaviruses are able to explain observed age patterns of hospitalisation due to COVID-19 in EU/EEA countries and the UK, provided there is (i) a decrease in cross-protection to SARS-CoV-2 with the number of eHCoV exposures and (ii) an increase in potential disease severity with number of eHCoV exposures or as a result of immune senescence. We also show that variation in health care capacity and testing efforts is compatible with country-specific differences in hospitalisation rates. Our findings call for further research on the role of cross-reactivity to endemic coronaviruses and highlight potential challenges arising from heterogeneous health care capacity and testing.
RESUMO
BackgroundThe progression and geographical distribution of SARS coronavirus 2 (SARS-CoV-2) infection in the UK and elsewhere is unknown because typically only symptomatic individuals are diagnosed. We performed a serological study of blood donors in Scotland between the 17th of March and the 18th of May to detect neutralising antibodies to SARS-CoV-2 as a marker of past infection and epidemic progression. AimTo determine if sera from blood bank donors can be used to track the emergence and progression of the SARS-CoV-2 epidemic. MethodsA pseudotyped SARS-CoV-2 virus microneutralisation assay was used to detect neutralising antibodies to SARS-CoV-2. The study group comprised samples from 3,500 blood donors collected in Scotland between the 17th of March and 19th of May, 2020. Controls were collected from 100 donors in Scotland during 2019. ResultsAll samples collected on the 17th March, 2020 (n=500) were negative in the pseudotyped SARS-CoV-2 virus microneutralisation assay. Neutralising antibodies were detected in 6/500 donors from the 23th-26th of March. The number of samples containing neutralising antibodies did not significantly rise after the 5th-6th April until the end of the study on the 18th of May. We find that infections are concentrated in certain postcodes indicating that outbreaks of infection are extremely localised. In contrast, other areas remain comparatively untouched by the epidemic. ConclusionThese data indicate that sero-surveys of blood banks can serve as a useful tool for tracking the emergence and progression of an epidemic like the current SARS-CoV-2 outbreak.
RESUMO
The spread of a novel pathogenic infectious agent eliciting protective immunity is typically characterised by three distinct phases: (I) an initial phase of slow accumulation of new infections (often undetectable), (II) a second phase of rapid growth in cases of infection, disease and death, and (III) an eventual slow down of transmission due to the depletion of susceptible individuals, typically leading to the termination of the (first) epidemic wave. Before the implementation of control measures (e.g. social distancing, travel bans, etc) and under the assumption that infection elicits protective immunity, epidemiological theory indicates that the ongoing epidemic of SARS-CoV-2 will conform to this pattern. Here, we calibrate a susceptible-infected-recovered (SIR) model to data on cumulative reported SARS-CoV-2 associated deaths from the United Kingdom (UK) and Italy under the assumption that such deaths are well reported events that occur only in a vulnerable fraction of the population. We focus on model solutions which take into consideration previous estimates of critical epidemiological parameters such as the basic reproduction number (R0), probability of death in the vulnerable fraction of the population, infectious period and time from infection to death, with the intention of exploring the sensitivity of the system to the actual fraction of the population vulnerable to severe disease and death. Our simulations are in agreement with other studies that the current epidemic wave in the UK and Italy in the absence of interventions should have an approximate duration of 2-3 months, with numbers of deaths lagging behind in time relative to overall infections. Importantly, the results we present here suggest the ongoing epidemics in the UK and Italy started at least a month before the first reported death and have already led to the accumulation of significant levels of herd immunity in both countries. There is an inverse relationship between the proportion currently immune and the fraction of the population vulnerable to severe disease. This relationship can be used to determine how many people will require hospitalisation (and possibly die) in the coming weeks if we are able to accurately determine current levels of herd immunity. There is thus an urgent need for investment in technologies such as virus (or viral pseudotype) neutralization assays and other robust assays which provide reliable read-outs of protective immunity, and for the provision of open access to valuable data sources such as blood banks and paired samples of acute and convalescent sera from confirmed cases of SARS-CoV-2 to validate these. Urgent development and assessment of such tests should be followed by rapid implementation at scale to provide real-time data. These data will be critical to the proper assessment of the effects of social distancing and other measures currently being adopted to slow down the case incidence and for informing future policy direction. Disclaimer(a) This material is not final and is subject to be updated any time. (b) Code used will be made available as soon as possible. (c) Contact for press enquiries: Cairbre Sugrue, cairbre@sugruecomms.com, +44 (0)7502 203 769.
