COVID-19 Sentinel Surveillance

1.0  BACKGROUND

1.1  The Global COVID-19 Pandemic

A novel coronavirus identified on 7th January 2020, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the cause of coronavirus disease (COVID-19)[1] detected in nearly all countries of the world. On 30th January 2020, the Director-General of the World Health Organization (WHO) declared the COVID-19 outbreak a public health emergency of international concern[2]. Less than two months later on 11 March 2020, concerned by the alarming levels of spread and severity of the disease, WHO declared COVID-19 a global pandemic[2]. The SARS-CoV-2 virus has spread rapidly across the globe, by the end of September 2020, there were more than 33 million cases and over one million deaths reported to the World Health Organization[3].

Efforts to control COVID-19 heavily rely on public health interventions such as wearing of masks, hand washing, social distancing, testing, contact tracing and quarantine[4]. The disease has demonstrated effective community spread in multiple settings, but the limited diagnostic capacity in many settings limits the extent to which the full disease spectrum of pre-symptomatic, asymptomatic and symptomatic infections can be assessed. As a result, the role of pre-symptomatic, asymptomatic infections in human-to-human transmission of COVID-19 virus is not fully understood. Globally and locally in Eswatini, significant efforts and resources have been directed towards an emergency response to the pandemic. It is critical that sentinel surveillance systems are established to track disease beyond the current emergency, and to continue background surveillance for new infections, allowing countries to readily and quickly identify and respond to new infections from within community’s and those imported from other countries or communities. Such sentinel surveillance systems and data would provide critical information on any sustained community spread of COVID-19.

1.2  The Eswatini COVID-19 Epidemic

The first case of COVID-19 in the Kingdom of Eswatini was confirmed  on 14th March 2020[5], and was an imported infection. Since then, the number of patients with COVID-19 has grown steadily, with widespread community transmission leading to more than 5,400 confirmed infections and more than 100 deaths by the end of September 2020[6]. A national state of emergency was announced by the Prime Minister on 17th March 2020[7].  Response strategies and disease mitigation measures have been implemented across multiple pillars as recommended by the WHO and Eswatini Ministry of Health (MOH)[8, 9]. The Government of the Kingdom of Eswatini (GKoE) through a collaborative process involving the Ministry of Health, WHO, other government sectors, development partners and stakeholders developed a contingency plan with multi-pillar strategies and activities. Through this multi-sectoral approach, the response to the pandemic has been a collaborative process covering response coordination, surveillance, rapid response teams, and case investigation, laboratory support, case management, infection prevention and control, port health, risk communication and community engagement, and operational support and logistics[9].

Surveillance and case investigation for COVID-19 in Eswatini currently includes screening in routine care, contact tracing, and active case finding[10].  Outbreak data are reported through daily situation reports with minimal indicators on the number of cases identified and number of deaths by age, gender and location[6, 11].  The 5,462 confirmed cases are 0.499% of the Eswatini population (or 499 cases per 100,000 population), representing a significant disease burden[6]. Two-thirds of the cases are in the age group 20-49 years, and 45% are located in Manzini, the most populous of the 4 regions of Eswatini. The current surveillance system is strategically identifying new cases in this outbreak phase but is limited in identifying previous infections through antibody testing, and not sustainably positioned to assess future outbreaks beyond the current emergency. The current surveillance system also has limitations in identifying asymptomatic infections: asymptomatic contacts are not prioritized for PCR testing due to limited resources. Additionally, there are challenges in quantifying contacts linked to index cases diagnosed.

1.3  Sentinel Surveillance Program Justification

For several years, the Ministry of Health through the Epidemiology Disease Control Unit (EDCU) has had a vision to establish sentinel surveillance for influenza-like illness (ILI) and similar illnesses, with a protocol developed in 2018[12]. However, this vision remained unfulfilled due to lack of resources and diagnostic lab capacity. The COVID-19 outbreak therefore occurred at a time when ILI was only monitored through reported symptoms, and hardly reported from health facilities through the weekly and monthly epi-bulletins. As the COVID-19 outbreak emerged, several factors limited Eswatini’s capacity to effectively conduct surveillance for COVID-19 and similar infections. With limited local laboratory testing for COVID-19 and sub-optimal linkages between laboratory and clinical data, there were challenges in having accurate estimates of the number of COVID-19 cases, their distribution and the characteristics of affected individuals. There is minimal integration of COVID-19 surveillance into health facility reporting structures, causing limitations in capturing of facility-level screening data, positive cases and case outcomes. Ports of entry (PoE) health structures need strengthening to provide real-time information on travelers, with robust measurement of screening procedures and screening outcomes.

Following the national emergency, multiple sectors of the economy e.g. border crossings and workplaces, social institutions e.g. churches and educational institutions e.g. schools, vocational centers and universities will re-open. This would be associated with increased movement and in-person contact, potentially leading to new and continuing COVID-19 infections. It is therefore important that sentinel surveillance activities include routine testing in health facilities, congregated settings such as schools, work places and churches. It is also imperative that all these surveillance data (from health facilities, PoE, contact tracing) are collected electronically, transmitted in real time, are merged and are analyzed in an integrated manner for real-time visualization. Such data dashboards will provide a comprehensive assessment of the status of COVID-19 and similar pandemics for immediate programmatic actions, to inform policies, guide resource allocation and shape the country’s response now and in the future.

Currently, Eswatini does not have a functional sentinel surveillance system for acute febrile illnesses (AFI), influenza-like illness (ILI) or severe acute respiratory infections (SARI). With this protocol, we propose the establishment of sentinel surveillance sites for detection of COVID-19, and in the process the development of a sustainable platform that can also be used for future surveillance of AFI, ILI, and. SARI. This sentinel surveillance protocol will promote the integration of sentinel surveillance into the existing health service system as recommended by CDC and WHO [13, 14] to create a consistent monitoring system, utilize diagnostic real-time reverse transcription polymerase chain reaction (rRT-PCR) technology, and create a laboratory sample archive for additional testing as such novel diseases evolve and treatments emerge. The Eswatini sentinel surveillance program for COVID-19 and similar illnesses sentinel surveillance will establish a robust continuous surveillance system with real-time reporting. Data from this program will provide information on exposure to COVID-19 and similar illnesses, risk factors and other epidemiological trends to inform prevention, care and treatment strategies. It will support COVID-19 national and regional planning by providing Eswatini-specific data, support laboratory and epidemiologic infrastructure for alert and response activities, and establish a mechanism to monitor outcomes of diagnosed cases through existing epidemiologic task force teams.

For integration and sustainability, this sentinel surveillance protocol will be based on the WHO  strategy for Integrated Disease Surveillance and Response (IDSR),[15], and the global surveillance standards for influenza [16].  This approach aligns with the International Health Regulations[17] for surveillance, reporting, notification, verification, response and collaboration activities for such public health events of international concern. We will implement the IDSR One-Health approach to promote collaboration between MOH and key local and international stakeholders to identify and mitigate public health risks at multiple levels.

1.4  Program Goal

Surveillance is the process of systematic collection, collation and analysis of data with prompt dissemination to those who need to know, for relevant action to be taken. A well-functioning disease surveillance system is sensitive enough to detect unusual events, monitor changes over time, and promote investigation and initiation of control and mitigation measures[18]. This collectively serves to provide information for planning, implementation, monitoring and evaluation of public health intervention programs.  Sentinel surveillance in particular targets specific conditions in specific groups, such as in a geographical area or population, and aims to generate early warning reports in order to promptly address outbreaks[18].

The goal of the surveillance program described in this protocol is to establish a robust sentinel surveillance system for real-time reporting of COVID-19 and similar illnesses. This sentinel surveillance system will rapidly detect emerging COVID-19 infections, examine epidemiological trends, monitor severity, intensity and progression of cases and outbreaks, and assess risk factors for outbreaks. The sentinel surveillance system will provide real-time data to inform clinical and public health prevention and care and treatment strategies. The sentinel surveillance system will also ensure country preparedness to conduct surveillance for emerging SARIs, ILIs and AFIs.

1.5  Program Objectives

The overall objective of the sentinel surveillance is to provide timely epidemiological and virologic data to better inform national prevention and control activities of COVID-19 and similar illnesses. The primary and secondary objectives for this sentinel surveillance program have been aligned with WHO objectives for influenza surveillance to generate data on when and where disease is occurring, determine disease severity and outcomes, and detect unique genetic characteristics of local viral strains [16]. The primary and secondary objectives also align with current WHO guidance to establish sentinel surveillance systems that can monitor geographic spread, disease intensity, risk factors, and genetic evolution of the virus [13, 19].

Primary Objectives

  1. Establish surveillance system: Establish a platform for sentinel surveillance for COVID-19 and similar illnesses e.g. SARIs, ILIs and AFIs
  2. Estimate disease: To measure COVID-19 infection (by laboratory PCR diagnosis) in a population of individuals 15 years and older attending sentinel surveillance sites by place, time, demographic and clinical characteristics
  3. Describe disease: Among those with COVID-19 infection (by laboratory PCR diagnosis): to estimate the fraction and trends of symptomatic versus asymptomatic or pre-symptomatic infections by demographic and clinical characteristics.
  4. Quantify contacts: To estimate the population of high- and low- risk contacts of diagnosed cases.
  5. Estimate antibody prevalence: To measure prevalence of COVID-19 antibodies in a population of individuals 15 years and older attending sentinel surveillance sites by place, time, demographic and clinical characteristics.

Secondary Objectives

  1. To determine risk factors for COVID-19 infection and similar illnesses
  2. Describe the seasonality and temporal peaks forCOVID-19 and similar illnesses
  3. Identify and characterize atypical or unusual outbreaks of COVID-19 and similar illnesses
  4. Identify new and circulating sub-types/strains
  5. Estimate morbidity and mortality associated with COVID-19 and similar illnesses
  6. Describe COVID-19 antibody levels and determine previous exposure to COVID-19 disease or vaccines
  7. Determine drug-susceptibility of COVID-19 and similar illnesses as treatments are identified
  8. Establish a sample archive for future repository testing as the disease and diagnostic technology evolve, and treatments emerge.

2.0  METHODS

2.1  Setting

The Kingdom of Eswatini is a landlocked lower-middle income country of 6.704 square miles, and shares borders with South Africa and Mozambique. Eswatini is divided into 4 administrative regions: Manzini, Hhohho, Lubombo, and Shiselweni. Each region has one regional hospital for in- and out-patient services and referral care, in addition to multiple lower-level hospitals, clinics and health centers. Eswatini has a local administration system along 59 geographical subareas called Tinkhundla. The estimated population of Eswatini in 2020 is 1,146,903, with most of the population in the two regions of Manzini (33%) and Hhohho 29% [20, 21]. The country has two international airports, 13 formal border crossings and numerous informal border crossings.

2.2   General Design

This will be a continuous year-round surveillance activity at selected sentinel surveillance sites with regional representation (Figure 1). In order to accommodate limited diagnostic capacity in Eswatini, a phased approach will be used to establish sentinel surveillance sites. The first phase of surveillance sites will include all four regional hospitals: each regional hospital in each region has the full spectrum of primary, secondary and tertiary care. The catchment area of these 4 regional hospitals is expected to cover the most populous administrative areas in each region, and two are within a 30 km radius of major formal border crossings.  Additional phases of this sentinel surveillance program, subject to availability of resources, would include ports of entry/border crossings, private health facilities, community clinics, as well as selected congregated settings such as schools, Eswatini correctional systems (police, army, prisons), churches and workplaces. Additional phases of this surveillance program will be dependent on observed disease outbreak patterns and availability of resources.

At selected sentinel surveillance sites, individuals 15 years and older will be selected consecutively until the target quota of surveillance participants with and without COVID-19 symptoms, by sex (male and female) and age -group (15-49 years and 50+ years) is reached. This will ensure demographic diversity and adequate representation by age and sex in the overall surveillance sample. Healthcare workers at the sentinel surveillance sites will work with designated surveillance officers to assess client symptoms and triage them according to presence or absence of COVID-19 symptoms.

Following verbal consent, a questionnaire assessing for additional symptoms, travel history, and history of COVID-19 disease or vaccine exposure and underlying medical conditions will be administered by the surveillance officer. Medical history data, e.g. HIV status, underlying chronic conditions, current medications will be abstracted from medical records. The surveillance officer will then collect nasopharyngeal swabs and blood sample regardless of symptoms i.e. from both individuals presenting with and without COVID-19 symptoms.

All nasopharyngeal swabs will be tested with PCR to diagnose COVID-19, using pooled testing when COVID-19 prevalence is low (<10%), and individual testing f or time periods with high COVID-19 e.g. among symptomatic individuals, or during an outbreak. When a pool is positive, each sample within the pool will be individually tested to determine which specimen(s) is/are positive. Individuals diagnosed with COVID-19 by PCR testing will be contacted to inform them of the results, refer them to Rapid Response Teams (RRTs) or designated health facilities for management, and elicit contacts.

Antibody testing on blood samples of individuals with and without COVID-19 symptoms will be conducted using rapid diagnostic tests (RDTs) and ELISA. These results will be used for surveillance purposes only and not returned to participants. An archive of plasma aliquots, dry blood spot (DBS) samples and nasopharyngeal swab extracts will be maintained for additional testing as COVID-19 diagnostic technology evolves and treatments emerge.

Figure 1: Surveillance Methods

SENTINEL SURVEILLANCE SITES Symptom assessment using a questionnaire: N = 4,160 (per quarter) Select a sentinel surveillance area within each sentinel surveillance site: Surveillance participant enrolment will be conducted at multiple surveillance areas in each surveillance site (i.e. in-patient services or outpatient clinic or HIV antiretroviral therapy (ART) clinic or non-communicable disease (NCD) clinic.  See Table 3 for target quotas.  Consecutive client selection: Clients will be consecutively selected for participation in the surveillance activity until the target quota of participants is met (See Table 3). The surveillance program will target inclusion of clients with and without COVID-19 symptoms (1:1 distribution), with target quotas to ensure adequate representation of females and males, and by age group (15-49 years vs 50+ years)- See Table 3.Service providers: All service providers in selected surveillance area will be included, estimated 40 providers per site per quarter

Individuals with symptoms from the screening questionnaire, N=2000 Individuals without COVID-19 symptoms from the screening questionnaire, N=2,000 Service providers, N=160 Data abstraction: underlying conditions, medicationSample collection: Collect blood sample and NP swabSample transportation: samples transported to Eswatini Health Laboratory Services (EHLS) using routine systems
ESWATINI HEALTH LABORATORY SERVICES (EHLS) COVID-19 diagnosis: PCR testing of NP swabs COVID-19 antibody prevalence: rapid antibody test and ELISA Sample archive: Nasopharyngeal swab extract, dried blood spots, plasma aliquots
Telephone follow-up At approximately 7-14 days after return of results, conduct phone follow-up to assess progression of symptoms and disease outcomes (i.e. 7-28 days after date of diagnosis) 
PCR positive: N~208 Return of results via telephone call. During the same call:Advise on linkages to MOH structures Assess progression of symptoms and disease outcomes since date of sample collection ( approximately day 1-7) Elicit contacts, provide contact list to MOH rapid response teams for follow-up
PCR negative: N~3952 Return of results via text message as per standard MOH practice