1.4 Monitoring and surveillance
On April 27, a nationwide seroprevalence study (ENE-COVID) was launched. The study aims to estimate the population’s level of exposure to the virus, and whether the population has developed protective antibody titers (that is, rapid antibody testing plus ELISA techniques will be used).
To that purpose, a sample of 36,000 households has been randomly selected to assure geographic representativeness at province level, which implies testing between 60,000 and 90,000 individuals. Participation requires consent and all the members within a household will be tested so as to elicit intra-familial exposure during confinement. The study will consist of three waves, with a time lag of 21 days, to assess the evolution of the epidemic during the last days of the lockdown and first weeks of the de- escalation measures.
Regional health authorities will be responsible for deployment. Primary care professionals, specifically nursing staff, will be in charge of the epidemiological survey and sample extractions that will be carried out either at home or in the primary care centres (https://www.isciii.es/Noticias/Noticias/Paginas/Noticias/ComienzoENECOVIDEstudioSeroprevalencia.aspx; https://www.mscbs.gob.es/en/gabinete/notasPrensa.do?metodo=detalle&id=4882).
On May 9, the Ministry of Health published new guidelines for diagnosis, surveillance and control of COVID-19 during the transition period with a view to ensure early detection of new cases and contacts (https://www.mscbs.gob.es/profesionales/saludPublica/ccayes/alertasActual/nCov-China/documentos/COVID19_Estrategia_vigilancia_y_control_e_indicadores.pdf, Order 404/2020 https://boe.es/diario_boe/txt.php?id=BOE-A-2020-4933).
So, the definitions have been updated as well as the decision making on testing, as follows:
Suspected cases will be people with acute respiratory infection irrespective of its severity that may present fever, coughing or short of breath, or other atypical symptoms such as: sore throat, anosmia, ageusia, muscular pain, diarrhoea or headache. All suspected cases will be tested using PCR (or any other appropriate technique) within the first 24 hours. Any suspected case will be isolated until the PCR result and their contacts will be traced.
Confirmed cases with an active infection will be (a) those cases with or without clinical symptoms but positive PCR (note that any other appropriate diagnostic molecular technique is also acceptable); or (b) cases with negative PCR but with clinical symptomatology and tested positive for IgM by serological test (note that rapid antibody detection tests are not suitable).
Probable Covid-19 cases will be: (a) those with acute respiratory infection with clinical symptoms and radiological signs compatible with COVID-19 and negative PCR or (b) those suspected cases with inconclusive PCR results.
Discarded cases will be defined as those suspected cases with negative PCR or negative IgM in those cases with strong clinical suspicion of COVID-19 and negative PCR.
Cases with a solved infection will be asymptomatic patients that reported symptoms 14 or more days ago who test positive in an antibody serological test (note that this is irrespective of whether patients were not tested or tested negative in the past).
In terms of monitoring, information on suspected and confirmed cases from primary care, public and private hospitals and occupational hazard prevention departments have to report to the regional epidemiological surveillance services on a daily basis.
Tracing workers (mainly, within primary care and public health services) will track down people who were closer than 2 meters and for more than 15 minutes to suspected or confirmed cases, in the two days before symptoms onset or positive testing. In any case, carers will, in all circumstances, be considered as contacts. Contacts will be prescribed a 14-day quarantine, starting the day when the last contact took place.
Along the transition period, regional authorities could implement screening studies such as: serological surveys in vulnerable and highly exposed populations (e.g. healthcare workers, nursing home personnel), PCR screening in patients prior to a surgical intervention or to an admission, and pooling testing in low-incidence contexts. The results of these screening strategies will be reported to the Ministry of Health (ESTRATEGIA DE DIAGNÓSTICO, VIGILANCIA Y CONTROL EN LA FASE DE TRANSICIÓN DE LA PANDEMIA DE COVID-19INDICADORES DE SEGUIMIENTO https://www.mscbs.gob.es/profesionales/saludPublica/ccayes/alertasActual/nCov-China/documentos/COVID19_Estrategia_vigilancia_y_control_e_indicadores.pdf).
On May 13, the Institute for Health Carlos III released the preliminary results of the first wave of the nationwide seroprevalence study (ENE-COVID) on 60,983 voluntary participants. Overall, 5% of the Spanish population (95% CI: 4.7%-5.4%) has been found to show IgG antibodies against SARS-Cov2 in the rapid antibody test. Notably, there has been a ten-fold difference across geographic areas, ranging from 1.1% prevalence in the autonomous city of Ceuta to 11.3% in the autonomous community of Madrid. Notably, the prevalence has been found higher in the more populated cities - more than 100,000 inhabitants-, with an IgG prevalence of 6.4% (95%CI: 5.8%-7.1%). The survey was carried out between April 27 and May 11, starting off the 7th week after lockdown (https://www.lamoncloa.gob.es/serviciosdeprensa/notasprensa/sanidad14/Documents/2020/130520-ENE-COVID_Informe1.pdf).
On June 5, the Institute for Health Carlos III and the Ministry of Health released the results of the second wave of the nationwide seroprevalence study (ENE-COVID), carried out from May 18 to June 1. Prevalence of IgG against SARS-Cov2 resulted in 5.2% (95% CI: 4.9-5.5), slightly higher than the 5% estimated on the first wave. As stated before, there were wide variations across territories, from 0.5% in the autonomous city of Ceuta to 14.7% in the province of Soria.
80.5% of the participants who had declared having a positive PCR more than two weeks before presented IgG antibodies, while 0.8% of those participants being IgG negative in the first wave resulted positive in the second one, standing out the provinces of Ávila, Valladolid and Palencia, with a sero-conversion rate close to 2% and Madrid, Soria and Segovia, with a 1.5% rate. On a different line, 2.8% of the participants that did not refer to any symptoms were IgG positive, so that 33% of the infections were referred to as asymptomatic.
The number of participants increased up to 63,564, and 95% of people participating in the first wave agreed to take part in this second one. Note that these results are based on IgG band in the rapid antibody test. Data on ELISA testing on the same population are not available yet (https://www.mscbs.gob.es/gabinetePrensa/notaPrensa/pdf/04.06040620204922437.pdf; https://portalcne.isciii.es/enecovid19/).
As COVID-19 is deemed an urgent notifiable disease, regional public health authorities will keep updating surveillance and monitoring data once the state of alarm expires. In addition, the implementation of the surveillance protocols agreed in the Interterritorial Council will be mandatory all over the territory (Royal Decree 21/2020 https://boe.es/diario_boe/txt.php?id=BOE-A-2020-5895).
On July 6, the Carlos III Health Institute and the Ministry of Health released the results of the third and last wave of the nationwide seroprevalence study (ENE-COVID), carried out from June 8 to June 22. Prevalence of IgG against SARS-Cov2 resulted in 5.2% (95%CI: 4.9-5.5), exactly the same as in the second wave and slightly higher than the 5% estimated in the first wave. As observed before, prevalence was similar in men and women and lower in children under 10 years old. Likewise, the study keeps showing wide variations across territories, with provinces presenting a prevalence slightly higher than 11% (Soria 14.4%, Segovia 12.4%, Cuenca 11.4%, Madrid 11.7%), whereas some others show a prevalence close to 1% (autonomous city of Ceuta 0.7%, Huelva 1.2%, Balearic Islands 1.4%, Lugo and Tarragona 1.5%).
The seroconversion rate (that is, the rate of detecting IgG in participants testing negative in the prior wave) was 0.7% (95%CI: 0.6-0.8). In turn, 14.4% (95%CI: 12.7-16.3%) of those participants who tested positive in round 2 became negative in round 3.
In addition, from 2.5% to 2.8% of the participants that did not refer to any symptoms were IgG positive, meaning that about a third of seropositive participants were asymptomatic (32.7%) (95%CI: 30.2–35.4).
This third wave results are based on 68,296 participants (77% of the total contacted people), out of which 54,858 took part in the three waves (https://www.mscbs.gob.es/gabinetePrensa/notaPrensa/pdf/INFOR060720134446500.pdf, https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31483-5/fulltext).
The National Centre of Epidemiology has published a report on the epidemiological situation in Spain from May 11 to July 17, just after the implementation of the Strategy for diagnosis, surveillance and control in the transition period (see details on this Strategy above). Along this period, a total of 25,628 confirmed cases were reported, 95% of them using PCR testing. 8.5% out of those cases were hospitalised, 0.6% admitted to an ICU and 0.8% died (until May 10, 38.4% of cases had been hospitalised, 3.9% admitted to an ICU, and 8.2% died). Importantly, only 45% of all the cases had reported any compatible symptoms with COVID-19. Note that since May 11, criteria for PRC testing includes those having an acute respiratory infection, having symptoms compatible with COVID-19 or being exposed to a COVID-19 case.
Although the overall declining trend, there are outbreaks all over the country mostly affecting people aged 15 to 59 (66% of the cases). Those new cases are having a small impact on hospitalisations, ICU admissions and the death toll (https://www.isciii.es/QueHacemos/Servicios/VigilanciaSaludPublicaRENAVE/EnfermedadesTransmisibles/Documents/INFORMES/Informes%20COVID-19/Informe%20n%C2%BA%2033.%20An%C3%A1lisis%20de%20los%20casos%20de%20COVID-19%20hasta%20el%2010%20de%20mayo%20en%20Espa%C3%B1a%20a%2029%20de%20mayo%20de%202020.pdf;https://www.isciii.es/QueHacemos/Servicios/VigilanciaSaludPublicaRENAVE/EnfermedadesTransmisibles/Documents/INFORMES/Informes%20COVID-19/Informe%20n%C2%BA%2035.%20Situaci%C3%B3n%20de%20COVID-19%20en%20Espa%C3%B1a%20a%2017%20de%20julio%20de%202020.pdf).
As of July 31, and after successfully passing the pilot test, the app RadarCOVID to alert about COVID-19 contagions and trace contacts is at the disposal of the regional health authorities. This app uses terminals’ bluetooth to send out and receive anonymous identifiers, in that way that, if two mobile phones have been close (2 meters or less) for at least 15 minutes, both store the anonymous identifier sent out by the other mobile. Then, if a user tests positive for COVID-19, he could decide giving consent to the regional health system to notify all his contacts, who would receive in their mobiles a warning about a potential contagion. RadarCOVID follows all the standards on user’s privacy as recommended by the European Commission, so no user can be identified or located as data is not registered anywhere.
The app will be fully available for those autonomous communities that wish so by September 15, but, if needed, some regions could have a first functional version by mid-August. In any case, the use of the app as well as communicating a possible contagion would be voluntary (https://www.lamoncloa.gob.es/serviciosdeprensa/notasprensa/asuntos-economicos/Paginas/2020/030820-app-covid.aspx; https://radarcovid.gob.es/estadisticas/codigos-entregados-a-casos-confirmados ).
The app will be fully available for those autonomous communities that so wish by September 15, but, if needed, some regions could have a first functional version by mid-August. In any case, the use of the app as well as communicating a possible contagion would be voluntary (https://www.lamoncloa.gob.es/serviciosdeprensa/notasprensa/asuntos-economicos/Paginas/2020/030820-app-covid.aspx).
Once an individual tests positive from a PCR test, the medical authorities will issue a code that is provided to the patient, who is recommended to introduce it in the app. When this code is entered voluntarily into the app, a notification will be sent to all those considered at risk (that is, those picked up by the app as spending at least 15 minutes within two metres from the individual) as well as instructions on how to proceed. Contact-tracing procedures have been updated at regional level to guide decisions on those contacts identified throughout the app. Since August 20, some regions started off piloting the app; at the time of writing (4th September), the app is operative in 12 Autonomous Communities and it has more than 3.4 million downloads.
On August 27, the Ministry of Defence offered up to 2,000 Armed Force personnel to reinforce tracing capacity if required by the regions. These soldiers have received special training to carry out effective contact tracing, obtain information to discriminate potential contacts of risk, calculate the quarantine time depending on the epidemiological survey and provide support to those traced individuals
On September 9, the Interterritorial Council agreed on carrying out three new waves of the nationwide seroprevalence study ENE-COVID in October 2020, February and June 2021, to expand the knowledge of the pandemic evolution. They also agreed on conducting the screening in the asymptomatic population under criteria of the health public services and on sharing the results in the Interterritorial Council (https://www.mscbs.gob.es/gabinete/notasPrensa.do?id=5048).
On September 25, guidelines for diagnosis, surveillance and control of COVID-19 were updated regarding quarantine duration. Specifically, asymptomatic cases will have to isolate 10 days since the test and they will be monitored until their epidemiological discharge in the way decided by each region. Likewise, close contacts of confirmed cases will have to be quarantined for ten days since the last contact. If possible, they should be tested 10 days after the contact, but every region can follow their own guidelines. In addition, symptomatic cases not requiring hospitalisation (managed by primary care) have to be isolated at home (or another suitable facility) for at least 10 days since the beginning of the symptoms and be free of them for at least three days. Once passed the quarantine period, they do not have to be tested again in order to get back to normal life except if they are health or social care workers. In that case, they would need a test ensuring they are not infectious anymore (https://www.mscbs.gob.es/gabinete/notasPrensa.do?id=5057; https://www.mscbs.gob.es/profesionales/saludPublica/ccayes/alertasActual/nCov/documentos/COVID19_Estrategia_vigilancia_y_control_e_indicadores.pdf).
On October 22, the Interterritorial Council agreed on a document (included in the early response plan approved in July 16) for a coordinated response to the Covid-19 pandemic. This document provides a common framework for the analysis of the evolution of the pandemic as well as for the decision-making process; thus, the document sets up common criteria for risk assessment and suggests actions according to the risk level.
Risk assessment will be based on indicators describing the epidemiological situation (7 or 14-day cumulative number of COVID-19 cases per 100 000 inhabitants, weekly positivity of diagnostic tests or weekly number of cases that were contacts of a confirmed case) and the healthcare capacity (hospital beds occupancy, ICU beds occupancy). This group of indicators are accompanied by other local contextual information as features of the territory (population density, mobility, vulnerability of the exposed population and the possibility of rapid-adoption of preventive and control measures).
Indicators should be interpreted as a group (altogether), evaluating the trend and velocity. As a result, a 5-alert level system with different compliance thresholds will be used to characterize the situation as normal, low-risk, high-risk, very-high risk and extreme-risk to recommend policy action.
Finally, the document suggests actions for alert-levels 1 to 3. In those territories in alert level 4, besides the actions corresponding to level 3, exceptional measures that could require the state of alarm, emergency or siege, could be established. The autonomous communities will decide which measures (and when) will be taken and inform the Ministry of Health before their implementation. In a coordinated way, the Ministry will review the epidemiological situation to assess, maintain or modify the alert level and the implemented measures (https://www.mscbs.gob.es/gabinetePrensa/notaPrensa/pdf/Actua221020184719091.pdf#page=7&zoom=auto,-24,531).
On December 15, the Carlos III Health Institute and the Ministry of Health released the results of the fourth wave of the nationwide seroprevalence study (ENE-COVID), carried out from November 16 to November 29. The fourth wave is based on 51,409 participants, that is, 54.7% of the total eligible participants and three out of four of the participants in the previous waves. Children under 10, young adults as well as people older than 80 are under represented in this wave. The reported results are preliminary as they referred to the IgG rapid antibody test (ELISA testing results are not yet available). The seroconversion rate, that is the rate of participants testing IgG positive now but testing negative in the first phase, was 3.8% (IC 95%: 3.5-4.1).
According to the survey, 9.9% (IC95%: 9.4-10.4) of Spanish population shows titles of SARS-CoV2 IgG antibodies. As observed before, prevalence is similar in men and women and persists a high geographic variability. While some provinces, such as Coruña or Lugo in Galicia or Canary Islands have a prevalence around 4%, Madrid and neighbouring areas show figures higher than 15%.
Healthcare workers (16.8%) and female caregivers (16.3%) showed the highest prevalence among active workers. Prevalence was higher in cities larger than 100,000 inhabitants (up to 11.6%).
Finally, 3.3% of the participants that did not refer any symptoms were IgG positive. Anosmia was the most frequent symptom among IgG positive cases (43%) (https://portalcne.isciii.es/enecovid19/informes/informe_cuarta_ronda.pdf).
On January 22, the Conference on Alerts and Preparedness and Response Plans (Ponencia de Alertas y Planes de Preparación y Respuesta) published a protocol to include SARS-CoV-2 genome sequencing into the SARS-CoV-2 surveillance.
The document defines the procedure to follow to identify and monitor the different SARS-CoV2 varieties in Spain as well as methodology to include this information in the Spanish epidemiological surveillance system (SiViEs). In pursuing this aim, a network of laboratories coordinated by the Ministry of Health and the National Centre of Microbiology has to be set up in the upcoming weeks (https://www.mscbs.gob.es/profesionales/saludPublica/ccayes/alertasActual/nCov/documentos/Integracion_de_la_secuenciacion_genomica-en_la_vigilancia_del_SARS-CoV-2.pdf).
Case definition has evolved in response to the evolution of the outbreak but has always followed protocols proposed by WHO, which was updated by the ECDC on February 24th to include the outbreaks in South Korea, Iran, Singapore, Japan and four provinces in northern Italy. After this update of the case definition, the Conference on Alert Preparedness and Response Plans, a task force within the Inter-territorial Council for the SNS, decided to modify the case definition in Spain to include all those people with symptoms of acute respiratory infection that could have been or maintained contact with people from those risk areas during the last 14 days. Later, on February 26, the Inter-territorial Council of the National Health System decided to widen the definition, whereby “possible cases” include persons with atypical pneumonias (or of unknown origin) and severe symptoms.
In the current scenario of sustained widespread community transmission of SARS-CoV-2, infection cases are classified as:
● Confirmed case: a case fulfilling the laboratory testing criteria - consisting of a positive screening rt-PCR plus and an additional confirmatory rt-PCR. In addition, for all confirmed cases with an atypical clinical course or which are especially severe, samples are to be sent to the National Laboratory Centre in Majadahonda (Madrid) for further testing.
● Probable case: a case with inconclusive laboratory results testing SARS-CoV-2. These cases have to be sent to the National Laboratory Centre in Majadahonda for confirmation.
● Discarded case: a case with negative laboratory results testing SARS-CoV-2.
● Possible case: a case with clinical signs of acute mild respiratory infection without criteria to proceed to laboratory testing.
When it comes to contact tracing, standard mechanisms were implemented after the detection of the first imported cases on January 31, in La Gomera (https://www.dsn.gob.es/es/actualidad/sala-prensa/coronavirus-covid-19-23-febrero-2020). The contact tracing protocol classifies “close contacts” or as possible, probable or confirmed cases, as follows:
● Any person who has provided care while the case presented active symptoms; this includes, health workers who had not used the appropriate protective measures, family members or other people having close contact with the case;
● Spouses, or family members and persons who stayed at the same place, at a distance of less than 2 meters and for a period of at least 15 minutes, while the patient presented active symptoms.
In the specific case of health workers, the occupational risk prevention services are in charge of establishing the mechanisms for the investigation and follow-up of close contacts within the field of its competences, in coordination with public health authorities.
The monitoring and management of health professionals is established in a specific procedure (Procedure for preventing risks - PROCEDIMIENTO DE ACTUACIÓN PARA LOS SERVICIOS DE PREVENCIÓN DE RIESGOS LABORALES FRENTE A LA EXPOSICIÓN AL SARS-CoV-2, 26 de marzo de 2020, https://www.mscbs.gob.es/en/profesionales/saludPublica/ccayes/alertasActual/nCov-China/documentos/PrevencionRRLL_COVID-19.pdf).
Contacts are not actively followed up or tested, but they are instructed to quarantine at home for 14 days. The health authorities may assess individual situations that require other types of recommendations. If, during the 14 days after exposure, the contact develops symptoms and the clinical situation allows it, they are required to proceed with immediate home self-isolation and contact the COVID-19 available resources (basically, phone helplines) as set out in the protocols of each Autonomous Community (see also section 1.3).
All confirmed cases are immediately communicated to the public health authorities in each Autonomous Community, who then will notify the Ministry of Health using SiVIES (an on-line platform). In turn, the Centre for the Coordination of Health Alerts and Emergencies (CCAES, in Spanish) provides the information to the National Centre for Epidemiology (CNE) in the Carlos III Health Institute (ISCIII), which processes and delivers aggregated information and statistics to national response organizations and international organizations, according to established procedures.
The COVID-19 surveillance and monitoring systems are developing and evolving in accordance with the evolution of the scenarios and strategies implemented by the National Epidemiological Surveillance Network (National Epidemiological Surveillance Network: https://www.isciii.es/QueHacemos/Servicios/VigilanciaSaludPublicaRENAVE/Paginas/default.aspx).
On 27 March, the Secretary of Digitalization and Artificial Intelligence (a body of the Ministry of Economic Affairs) was ordered to develop an app to support the management of the COVID-19 crisis. Using this app, citizens are able to self-assess their health status and how likely it is for them to suffer from a COVID-19 infection, as well as receive advice and recommendations about how to proceed depending on the results of this assessment (Order SND/297/2020 https://www.boe.es/buscar/doc.php?id=BOE-A-2020-4162). Since April 7, the app is available and covers the population living in those Autonomous Communities that have not developed their own information and monitoring applications (that is, Cantabria, Canarias, Castilla-La Mancha, Extremadura and the Balearic Islands). Similar web or mobile apps are available for the population in other Autonomous Communities, such as Andalucía, Madrid, Aragón, Cataluña or País Vasco (https://www.boe.es/buscar/doc.php?id=BOE-A-2020-4829).
The same Order regulates the use of anonymised and aggregated data provided by mobile operators in order to analyse the population movements prior and during the lockdown, with a view to identify hotspots and improve the management and coordination of health care resources (Order SND/297/2020 https://www.boe.es/buscar/doc.php?id=BOE-A-2020-4162). On April 20, the National Institute of Statistics published the main results of the data analysis on population movements at https://www.ine.es/covid/covid_movilidad.htm.
In the following weeks, a seroprevalence study will be launched. This study aims to estimate the current prevalence of the infection as well as the level of acquired immunization at population level, so as to guide future public health measures, such as “exit policies”. This study, which covers 62,400 individuals, will provide representativeness at province level (10 April https://www.lamoncloa.gob.es/consejodeministros/ruedas/Paginas/rpcm10042020.aspx). Recently, the Interterritorial Council of the Spanish Health System has decided that the epidemiological survey and the collection of biological samples will be carried out by the primary care workforce https://www.mscbs.gob.es/en/gabinete/notasPrensa.do?metodo=detalle&id=4874).
On April 16, the Ministry of Health updated the information required in the monitoring of cases by including a specific definition of ‘epidemiological discharge’, which captures any confirmed case of COVID-19 with a hospital discharge after treatment completion or primary care episode discharge after the termination of the follow-up (Order SND 352/2020 https://boe.es/diario_boe/txt.php?id=BOE-A-2020-4493).