RESUMEN
BackgroundSerological surveys have been the gold standard to estimate the numbers of SARS-CoV-2 infections, epidemic dynamics, and disease severity throughout the pandemic. Serological assays are known to have decaying sensitivity with time that can strongly bias their results, but there is a lack of guidelines to account for this phenomenon. AimAssess the sensitivity decay of seroassays for detecting infections, its dependence on assay characteristics, and provide a simple tool to correct for this phenomenon. MethodsWe performed a systematic review and meta-analysis of SARS-CoV-2 serology studies. We included studies testing previously diagnosed individuals, without any SARS-CoV-2 vaccines, and excluded studies of cohorts highly unrepresentative of the general population (e.g. hospitalised patients). ResultsOf the 488 screened studies, 76 studies reporting on 50 different seroassays were included in the analysis. Sensitivity decay depends strongly on the antigen and the analytic technique used by the assay, with average sensitivities ranging between 26% and 98% at 6 months after infection, depending on assay characteristics. We find that a third of the included assays depart significantly from manufacturer specifications after 6 months. ConclusionsSeroassay sensitivity decay depends on assay characteristics, and for some types of assays it can make manufacturer specifications highly unreliable. We provide a tool to correct for this phenomenon, and to assess the risk of decay for a given assay. This can be used to design better serosurveys, and quantify systematic biases in the existing serology literature.
RESUMEN
IntroductionThe impact of COVID-19 vaccination on disease in the community has been limited, as a result of both SARS-CoV-2 Variants of Concern that partially escape vaccine-induced immunity. We sought to characterise symptoms and viral loads over the course of COVID-19 infection in otherwise-healthy vaccinated adults, representative of the general population, to assess whether current self-isolation guidance remains justified. MethodsIn a prospective, observational cohort study, healthy vaccinated UK adults who reported a positive PCR or lateral flow test, self-swabbed on alternate days until day 10. We compared symptoms and viral kinetics between infections caused by VOCs Delta and Omicron (sub-variants BA.1 and BA.2) and investigated applicability of UK NHS isolation guidelines to these newer VOCs. Results373 infection episodes were reported among 349 participants. Across VOCs, symptom duration was similar, however symptom profiles differed significantly among infections caused by Delta, Omicron BA.1 and BA.2. Anosmia was reported in <10% of participants with BA.1 and BA.2, compared to 42% with Delta infection, coryza fatigue and myalgia predominated. Most notably, viral load trajectories and peaks did not differ between Delta, BA.1 and BA.2, irrespective of symptom severity, VOC or vaccination status. ConclusionCOVID-19 isolation guidance should not differ based on symptom severity or febrile illness and must remain under review as new SARS-CoV-2 VOCs emerge and population immunity changes. Our study emphasises the ongoing transmission risk of Omicron sub-variants in vaccinated adults with mild symptoms that may extend beyond current isolation periods. summaryWe provide prospective characterisation of COVID-19 caused by Delta and Omicron BA.1 and BA.2 in healthy, vaccinated adults. A minority of adults report symptoms that would mandate self-isolation, despite having equally high viral shedding across VOCs that persisted beyond ten days.
RESUMEN
We estimate the potential remaining COVID-19 burden in 19 European countries by estimating the proportion of each countrys population that has acquired immunity to severe disease through infection or vaccination. Our results suggest that many European countries could still face a substantial burden of hospitalisations and deaths, particularly those with lower vaccination coverage, less historical transmission, and/or older populations. Continued non-pharmaceutical interventions and efforts to achieve high vaccination coverage are required in these countries to limit severe COVID-19 outcomes.
RESUMEN
BackgroundMany countries require incoming air travellers to quarantine on arrival and/or undergo testing to limit importation of SARS-CoV-2. MethodsWe developed mathematical models of SARS-CoV-2 viral load trajectories over the course of infection to assess the effectiveness of quarantine and testing strategies. We consider the utility of pre and post-flight Polymerase Chain Reaction (PCR) and lateral flow testing (LFT) to reduce transmission risk from infected arrivals and to reduce the duration of, or replace, quarantine. We also estimate the effect of each strategy relative to domestic incidence, and limits of achievable risk reduction, for 99 countries where flight data and case numbers are estimated. ResultsWe find that LFTs immediately pre-flight are more effective than PCR tests 3 days before departure in decreasing the number of departing infectious travellers. Pre-flight LFTs and post-flight quarantines, with tests to release, may prevent the majority of transmission from infectious arrivals while reducing the required duration of quarantine; a pre-flight LFT followed by 5 days in quarantine with a test to release would reduce the expected number of secondary cases generated by an infected traveller compared to symptomatic self-isolation alone, Rs, by 85% (95% UI: 74%, 96%) for PCR and 85% (95% UI: 70%, 96%) for LFT, even assuming imperfect adherence to quarantine (28% of individuals) and self-isolation following a positive test (86%). Under the same adherence assumptions, 5 days of daily LFT testing would reduce Rs by 91% (95% UI: 75%, 98%). ConclusionsStrategies aimed at reducing the risk of imported cases should be considered with respect to: domestic incidence, transmission, and susceptibility; measures in place to support quarantining travellers; and incidence of new variants of concern in travellers origin countries. Daily testing with LFTs for 5 days is comparable to 5 days of quarantine with a test on exit or 14 days with no test.
RESUMEN
To mitigate SARS-CoV-2 transmission risks from international travellers, many countries currently use a combination of up to 14 days of self-quarantine on arrival and testing for active infection. We used a simulation model of air travellers arriving to the UK from the EU or the USA and the timing of their stages of infection to evaluate the ability of these strategies to reduce the risk of seeding community transmission. We find that a quarantine period of 8 days on arrival with a PCR test on day 7 (with a 1-day delay for test results) can reduce the number of infectious arrivals released into the community by a median 94% compared to a no quarantine, no test scenario. This reduction is similar to that achieved by a 14-day quarantine period (median 99% reduction). Shorter quarantine periods still can prevent a substantial amount of transmission; all strategies in which travellers spend at least 5 days (the mean incubation period) in quarantine and have at least one negative test before release are highly effective (e.g. a test on day 5 with release on day 6 results in a median 88% reduction in transmission potential). Without intervention, the current high prevalence in the US (40 per 10,000) results in a higher expected number of infectious arrivals per week (up to 23) compared to the EU (up to 12), despite an estimated 8 times lower volume of travel in July 2020. Requiring a 14-day quarantine period likely results in less than 1 infectious traveller each entering the UK per week from the EU and the USA (97.5th percentile). We also find that on arrival the transmission risk is highest from pre-symptomatic travellers; quarantine policies will shift this risk increasingly towards asymptomatic infections if eventually-symptomatic individuals self-isolate after the onset of symptoms. As passenger numbers recover, strategies to reduce the risk of re-introduction should be evaluated in the context of domestic SARS-CoV-2 incidence, preparedness to manage new outbreaks, and the economic and psychological impacts of quarantine.
RESUMEN
BackgroundCountries have restricted international arrivals to delay the spread of COVID-19. These measures carry a high economic and social cost. They may have little impact on COVID-19 epidemics if there are many more cases resulting from local transmission compared to imported cases. MethodsTo inform decisions about international travel restrictions, we compared the ratio of expected COVID-19 cases from international travel (assuming no travel restrictions) to the expected COVID-19 cases arising from internal spread on an average day in May 2020 in each country. COVID-19 prevalence and incidence were estimated using a modelling framework that adjusts reported cases for under-ascertainment and asymptomatic infections. FindingsWith May 2019 travel volumes, imported cases account for <10% of total incidence in 103 (95% credible interval: 76 - 130) out of 142 countries, and <1% in 48 (95% CrI: 9 - 95). If we assume that travel would decrease compared to May 2019 even in the absence of formal restrictions, then imported cases account for <10% of total incidence in 109-123 countries and <1% in 61-88 countries (depending on the assumptions about travel reductions). InterpretationWhile countries can expect infected travellers to arrive in the absence of travel restrictions, in most countries these imported cases likely contribute little to local COVID-19 epidemics. Stringent travel restrictions may have limited impact on epidemic dynamics except in countries with low COVID-19 incidence and large numbers of arrivals from other countries. FundingWellcome Trust, UK Department for International Development, European Commission, National Institute for Health Research, Medical Research Council, Bill & Melinda Gates Foundation Research in contextO_ST_ABSEvidence before this studyC_ST_ABSCountries are at different stages of COVID-19 epidemics, so many have implemented policies to minimise the risk of importing cases via international travel. Such policies include border closures, flight suspensions, quarantine and self-isolation on international arrivals. Searching PubMed and MedRxiv using the search: ("covid" OR "coronavirus" OR "SARS-CoV-2") AND ("travel" OR "restrictions" OR "flight" OR "flights" OR "border") from 1 January - 10 July 2020 returned 118 and 84 studies respectively, of which 39 were relevant to our study. These studies either concentrated in detail on the risk of importation to specific countries or used a single epidemiological or travel dataset to estimate risk. Most of them focused on the risk of COVID-19 introduction from China or other countries with cases earlier in 2020. No study combined country-specific travel data, prevalence estimates and incidence estimates to assess the global risk of importation relative to current local transmission within countries. Added value of this studyWe combined data on airline passengers and flight frequencies with estimates of COVID-19 prevalence and incidence (adjusted for underreporting and asymptomatic cases), to estimate the risk of imported cases, relative to the level of local transmission in each country. This allows decision makers to determine where travel restriction policies make large contributions to slowing local transmission, and where they have very little overall effect. Implications of all the available evidenceIn most countries, imported cases would make a relatively small contribution to local transmission, so travel restrictions would have very little effect on epidemics. Countries where travel restrictions would have a large effect on local transmission are those with strong travel links to countries with high COVID-19 prevalence and/or countries which have successfully managed to control their local outbreaks.
RESUMEN
BackgroundAsymptomatic or subclinical SARS-CoV-2 infections are often unreported, which means that confirmed case counts may not accurately reflect underlying epidemic dynamics. Understanding the level of ascertainment (the ratio of confirmed symptomatic cases to the true number of symptomatic individuals) and undetected epidemic progression is crucial to informing COVID-19 response planning, including the introduction and relaxation of control measures. Estimating case ascertainment over time allows for accurate estimates of specific outcomes such as seroprevalence, which is essential for planning control measures. MethodsUsing reported data on COVID-19 cases and fatalities globally, we estimated the proportion of symptomatic cases (i.e. any person with any of fever >= 37.5{degrees}C, cough, shortness of breath, sudden onset of anosmia, ageusia or dysgeusia illness) that were reported in 210 countries and territories, given those countries had experienced more than ten deaths. We used published estimates of the case fatality ratio (CFR) as an assumed baseline. We then calculated the ratio of this baseline CFR to an estimated local delay-adjusted CFR to estimate the level of under-ascertainment in a particular location. We then fit a Bayesian Gaussian process model to estimate the temporal pattern of under-ascertainment. ResultsWe estimate that, during March 2020, the median percentage of symptomatic cases detected across the 84 countries which experienced more than ten deaths ranged from 2.38% (Bangladesh) to 99.6% (Chile). Across the ten countries with the highest number of total confirmed cases as of 6th July 2020, we estimated that the peak number of symptomatic cases ranged from 1.4 times (Chile) to 17.8 times (France) larger than reported. Comparing our model with national and regional seroprevalence data where available, we find that our estimates are consistent with observed values. Finally, we estimated seroprevalence for each country. Despite low case detection in some countries, our results that adjust for this still suggest that all countries have had only a small fraction of their populations infected as of July 2020. ConclusionsWe found substantial under-ascertainment of symptomatic cases, particularly at the peak of the first wave of the SARS-CoV-2 pandemic, in many countries. Reported case counts will therefore likely underestimate the rate of outbreak growth initially and underestimate the decline in the later stages of an epidemic. Although there was considerable under-reporting in many locations, our estimates were consistent with emerging serological data, suggesting that the proportion of each countrys population infected with SARS-CoV-2 worldwide is generally low. FundingWellcome Trust, Bill & Melinda Gates Foundation, DFID, NIHR, GCRF, ARC.
RESUMEN
BackgroundThe health impact of COVID-19 may differ in African settings as compared to countries in Europe or China due to demographic, epidemiological, environmental and socio-economic factors. We evaluated strategies to reduce SARS-CoV-2 burden in African countries, so as to support decisions that balance minimising mortality, protecting health services and safeguarding livelihoods. MethodsWe used a Susceptible-Exposed-Infectious-Recovered mathematical model, stratified by age, to predict the evolution of COVID-19 epidemics in three countries representing a range of age distributions in Africa (from oldest to youngest average age: Mauritius, Nigeria and Niger), under various effectiveness assumptions for combinations of different non-pharmaceutical interventions: self-isolation of symptomatic people, physical distancing, and shielding (physical isolation) of the high-risk population. We adapted model parameters to better represent uncertainty about what might be expected in African populations, in particular by shifting the distribution of severity risk towards younger ages and increasing the case-fatality ratio. ResultsWe predicted median clinical attack rates over the first 12 months of 17% (Niger) to 39% (Mauritius), peaking at 2-4 months, if epidemics were unmitigated. Self-isolation while symptomatic had a maximum impact of about 30% on reducing severe cases, while the impact of physical distancing varied widely depending on percent contact reduction and R0. The effect of shielding high-risk people, e.g. by rehousing them in physical isolation, was sensitive mainly to residual contact with low-risk people, and to a lesser extent to contact among shielded individuals. Response strategies incorporating self-isolation of symptomatic individuals, moderate physical distancing and high uptake of shielding reduced predicted peak bed demand by 46% to 54% and mortality by 60% to 75%. Lockdowns delayed epidemics by about 3 months. Estimates were sensitive to differences in age-specific social mixing patterns, as published in the literature. DiscussionIn African settings, as elsewhere, current evidence suggests large COVID-19 epidemics are expected. However, African countries have fewer means to suppress transmission and manage cases. We found that self-isolation of symptomatic persons and general physical distancing are unlikely to avert very large epidemics, unless distancing takes the form of stringent lockdown measures. However, both interventions help to mitigate the epidemic. Shielding of high-risk individuals can reduce health service demand and, even more markedly, mortality if it features high uptake and low contact of shielded and unshielded people, with no increase in contact among shielded people. Strategies combining self-isolation, moderate physical distancing and shielding will probably achieve substantial reductions in mortality in African countries. Temporary lockdowns, where socioeconomically acceptable, can help gain crucial time for planning and expanding health service capacity.
RESUMEN
BackgroundTo contain the spread of COVID-19, a cordon sanitaire was put in place in Wuhan prior to the Lunar New Year, on 23 January 2020, restricting travel to other parts of China. We assess the efficacy of the cordon sanitaire to delay the introduction and onset of local transmission of COVID-19 in other major cities in mainland China. MethodsWe estimated the number of infected travellers from Wuhan to other major cities in mainland China from November 2019 to March 2020 using previously estimated COVID-19 prevalence in Wuhan and publicly available mobility data. We focused on Beijing, Chongqing, Hangzhou, and Shenzhen as four representative major cities to identify the potential independent contribution of the cordon sanitaire and holiday travel. To do this, we simulated outbreaks generated by infected arrivals in these destination cities using stochastic branching processes. We also modelled the effect of the cordon sanitaire in combination with reduced transmissibility scenarios representing the effect of local non-pharmaceutical interventions. FindingsIn the four cities, given the potentially high prevalence of COVID-19 in Wuhan between Dec 2019 and early Jan 2020, local transmission may have been seeded as early as 2 - 8 January 2020. By the time the cordon sanitaire was imposed, simulated case counts were likely in the hundreds. The cordon sanitaire alone did not substantially affect the epidemic progression in these cities, although it may have had some effect in smaller cities. InterpretationOur results indicate that the cordon sanitaire may not have prevented COVID-19 spread in major Chinese cities; local non-pharmaceutical interventions were likely more important for this. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSIn late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected in Wuhan, China. In response to the outbreak, authorities enacted a cordon sanitaire in order to limit spread. Several studies have sought to determine the efficacy of the policy; a search of PubMed for "coronavirus AND (travel restrictions OR travel ban OR shutdown OR cordon sanitaire) AND (Wuhan OR China)" returned 24 results. However other studies have relied on reported cases to determine efficacy, which are likely subject to reporting and testing biases. Early outbreak dynamics are also subject to a significant degree of stochastic uncertainty due to small numbers of cases. Added value of this studyHere we use publicly-available mobility data and a stochastic branching process model to evaluate the efficacy of the cordon sanitaire to limiting the spread of COVID-19 from Wuhan to other cities in mainland China, while accounting for underreporting and uncertainty. We find that although travel restrictions led to a significant decrease in the number of individuals leaving Wuhan during the busy post-Lunar New Year holiday travel period, local transmission was likely already established in major cities. Thus, the travel restrictions likely did not affect the epidemic trajectory substantially in these cities. Implications of all the available evidenceA cordon sanitaire around the epicentre alone may not be able to reduce COVID-19 incidence when implemented after local transmission has occurred in highly connected neighbors. Local non-pharmaceutical interventions to reduce transmissibility (e.g., school and workplace closures) may have contributed more to the observed decrease in incidence in mainland China.
RESUMEN
Adjusting for delay from confirmation-to-death, we estimated case and infection fatality ratios (CFR, IFR) for COVID-19 on the Diamond Princess ship as 2.3% (0.75%-5.3%) and 1.2% (0.38-2.7%). Comparing deaths onboard with expected deaths based on naive CFR estimates using China data, we estimate IFR and CFR in China to be 0.5% (95% CI: 0.2-1.2%) and 1.1% (95% CI: 0.3-2.4%) respectively. AimTo estimate the infection and case fatality ratio of COVID-19, using data from passengers of the Diamond Princess cruise ship while correcting for delays between confirmation-and-death, and age-structure of the population.
RESUMEN
BackgroundAn outbreak of the novel coronavirus SARS-CoV-2 has led to 46,997 confirmed cases as of 13th February 2020. Understanding the early transmission dynamics of the infection and evaluating the effectiveness of control measures is crucial for assessing the potential for sustained transmission to occur in new areas. MethodsWe combined a stochastic transmission model with data on cases of novel coronavirus disease (COVID-19) in Wuhan and international cases that originated in Wuhan to estimate how transmission had varied over time during January and February 2020. Based on these estimates, we then calculated the probability that newly introduced cases might generate outbreaks in other areas. FindingsWe estimated that the median daily reproduction number, Rt, declined from 2.35 (95% CI: 1.15-4.77) one week before travel restrictions were introduced on 23rd January to 1.05 (95% CI: 0.413-2.39) one week after. Based on our estimates of Rt,we calculated that in locations with similar transmission potential as Wuhan in early January, once there are at least four independently introduced cases, there is a more than 50% chance the infection will establish within that population. InterpretationOur results show that COVID-19 transmission likely declined in Wuhan during late January 2020, coinciding with the introduction of control measures. As more cases arrive in international locations with similar transmission potential to Wuhan pre-control, it is likely many chains of transmission will fail to establish initially, but may still cause new outbreaks eventually. FundingWellcome Trust (206250/Z/17/Z, 210758/Z/18/Z), HDR UK (MR/S003975/1), Gates Foundation (INV-003174), NIHR (16/137/109)
RESUMEN
BackgroundTo assess the viability of isolation and contact tracing to control onwards transmission from imported cases of 2019-nCoV. MethodsWe developed a stochastic transmission model, parameterised to the 2019-nCoV outbreak. We used the model to quantify the potential effectiveness of contact tracing and isolation of cases at controlling a 2019 nCoV-like pathogen. We considered scenarios that varied in: the number of initial cases; the basic reproduction number R0; the delay from symptom onset to isolation; the probability contacts were traced; the proportion of transmission that occurred before symptom onset, and the proportion of subclinical infections. We assumed isolation prevented all further transmission in the model. Outbreaks were deemed controlled if transmission ended within 12 weeks or before 5000 cases in total. We measured the success of controlling outbreaks using isolation and contact tracing, and quantified the weekly maximum number of cases traced to measure feasibility of public health effort. FindingsWhile simulated outbreaks starting with only 5 initial cases, R0 of 1.5 and little transmission before symptom onset could be controlled even with low contact tracing probability, the prospects of controlling an outbreak dramatically dropped with the number of initial cases, with higher R0, and with more transmission before symptom onset. Across different initial numbers of cases, the majority of scenarios with an R0 of 1.5 were controllable with under 50% of contacts successfully traced. For R0 of 2.5 and 3.5, more than 70% and 90% of contacts respectively had to be traced to control the majority of outbreaks. The delay between symptom onset and isolation played the largest role in determining whether an outbreak was controllable for lower values of R0. For higher values of R0 and a large initial number of cases, contact tracing and isolation was only potentially feasible when less than 1% of transmission occurred before symptom onset. InterpretationWe found that in most scenarios contact tracing and case isolation alone is unlikely to control a new outbreak of 2019-nCov within three months. The probability of control decreases with longer delays from symptom onset to isolation, fewer cases ascertained by contact tracing, and increasing transmission before symptoms. This model can be modified to reflect updated transmission characteristics and more specific definitions of outbreak control to assess the potential success of local response efforts. FundingWellcome Trust, Global Challenges Research Fund, and HDR UK. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSContact tracing and isolation of cases is a commonly used intervention for controlling infectious disease outbreaks. This intervention can be effective, but may require intensive public health effort and cooperation to effectively reach and monitor all contacts. When the pathogen has infectiousness before symptom onset, control of outbreaks using contact tracing and isolation is more challenging. Added value of this studyThis study uses a mathematical model to assess the feasibility of contact tracing and case isolation to control outbreaks of 2019-nCov, a newly emerged pathogen. We used disease transmission characteristics specific to the pathogen and therefore give the best available evidence if contact tracing and isolation can achieve control of outbreaks. Implications of all the available evidenceContact tracing and isolation may not contain outbreaks of 2019-nCoV unless very high levels of contact tracing are achieved. Even in this case, if there is asymptomatic transmission, or a high fraction of transmission before onset of symptoms, this strategy may not achieve control within three months.
