Table of Contents
Study population
Studied patients were COVID-19 suspected cases and their contacts tested through the Institut Pasteur de Dakar (IPD) labs during the pandemic in all Senegalese regions. It was a prospective study between March 2, 2020, and May 31, 2021. Suspected cases were identified through the alert system set up by the Ministry of Health or from physicians at health care centres according to the Senegalese surveillance protocol. In this study, the deaths recorded are those patients who were diagnosed at the Pasteur Institute in Dakar, hospitalised in treatment centres and whose death was documented by the Ministry of Health.
Case definitions and inclusion criteria
WHO case definitions for suspected, confirmed, and contact cases of COVID-19 disease were used14. A suspected case was a patient with: (i) acute respiratory illness (fever and at least one sign/symptom of respiratory disease, e.g., cough, shortness of breath), and a history of travel to or residence in a location reporting community transmission of COVID-19 disease during the 14 days prior to symptoms onset, or (ii) an acute respiratory illness and has been in contact with a confirmed or suspected COVID-19 case in the last 14 days prior to symptoms onset, or (iii) severe acute respiratory illness (fever and at least one sign/symptom of respiratory disease, e.g., cough, shortness of breath; and requiring hospitalization) and in the absence of an alternative diagnosis that fully explains the clinical presentation14.
COVID-19 PCR test
Oro- and/or naso-pharyngeal swabs specimens were collected from suspected patients or persons in contact with confirmed cases, stored at 4–8 °C, and transported to the IPD within 24 h of collection for testing. A nasopharyngeal swab sample was tested by a real-time RT-PCR test specific to SARS-CoV-2. Following testing, at least two aliquots of each received sample were also stored at − 80 °C for the purpose of biobanking or in case there is a need for additional testing.
Contact tracing, investigation and data collection method
Contact tracing and patient investigation were carried out by field epidemiologists from the IPD and the health districts. Medical follow-up of patients was in charge of the district of residency of patients. Medical care was administered at treatment centres or patients’ residences depending on the severity of the symptoms. Information was recorded on standardized investigation forms with an identification number and sent to IPD with their corresponding biological samples for SARS-CoV-2 PCR testing. The information collected was socio-demographic (age, sex, occupation, location), epidemiological (date of sample, date of onset of symptoms, geographical district, potential sources of infection/exposure, travel history, number of close contacts), clinical (body temperature, symptoms such as cough, sore throat, headache, arthralgia, myalgia, nasal discharge, nasal congestion, anosmia, ageusia, breathing difficulty, nausea/vomiting and diarrhea) and the presence of one or more comorbidities (diabetes, asthma, high blood pressure, and other cardiovascular diseases). Different strategies as specified below were adopted to investigate and trace contact cases.
Strategy 1 (March 2, 2020–June 30, 2020)
From the beginning of the pandemic to the end of June 2020, all suspected cases and their contacts were being systematically tested. Socio-demographic information was collected through an investigation form. The suspected case was followed for 14 days and sampled at regular intervals of three days. Thus, if a sample is positive during this period, a case-contact investigation form is established. All persons in contact with the positive case are identified and followed up. All positive patients were admitted to treatment centres. This first strategy needed substantial financial and human resources and was the main cause of overcrowding in treatment centres.
Strategy 2 (July 1, 2020–October 31, 2020)
A second strategy starting in July 2020, was to test only people at risk (i.e., contacts with advanced age and/or with comorbidities like diabetes, hypertension, or cardiovascular diseases) and symptomatic contacts. For asymptomatic cases staying at home, a follow-up is done by phone calls. However, if they became symptomatic, a sample was taken and a case-contact investigation was done.
Transmission clusters identification
We define a transmission cluster as a group of epidemiologically linked individuals with at least two positive members, one having transmitted the virus to the other. An individual identification number (ID) was assigned for each patient. Transmission clusters or networks include a starting node representing the index case linked with its contact cases. Among the contact cases, the positives will also be linked to their contacts (second generation of contacts) and so on until the end of the cluster. The degree of a transmission cluster was defined by its number of generations. A transmission cluster was considered non-active if no samples were received over a period of 15 days. Otherwise, the cluster was considered to be still active.
Analysis of transmission clusters
The main characteristics of a transmission cluster were summarized using indicators such as the number of contacts per index case, the number of SARS-CoV-2 infected contacts per index case, the maximum generations of secondary infection, the number of members, the number of infected members, the sex ratio and the duration from the first to the last identified member. Clusters that crossed many regions as well as deepest clusters (i.e., clusters with maximum number of generations) are presented in detail in supplemental materials.
Super-spreaders identification
If we consider q as the 99th percentile from the distribution of the number of infected contacts per index, a super-spreader is defined as any infected individual who transmits the virus to more than q people as done in previous studies15.
Symptom-scoring
Clinical symptoms are binary variables (coded 1/0 for Yes/No). Some are more associated with severity and thus with death. Then, for more equitability, we weighted each symptom according to its association with death. We constructed a continuous variable named “symptom-score” that summarize all clinical symptoms of an individual using multiple correspondence analysis (MCA). MCA is an extension of the correspondence analysis method, which enables analysis of the pattern of relationships of several categorical independent variables. The technique converts frequency data into a multi-dimensional graphical format such that each category of a variable is plotted at a certain distance from another category of another variable. The closer the distinct variable categories are to each other on the graph, the more associated they are. Then, the closer the “yes” modality of a symptom variable is to the "died" modality of the survival variable, the more this symptom is associated with death and therefore with severity. The inverse of the distance represents a quantitative value, used as partial score for that symptom. Thus, higher partial scores are assigned to symptoms closest to the “died” outcome. These partial scores were calculated from clinical data shared by the treatment centres including 1356 patients with data on the symptom list described above and on the survival variable. These generated scores were used on patients from the contact tracing dataset. The final “symptom-score” variable is obtained by summing the partial clinical symptom scores for each patient.
Linear regression was used to check for correlation between the degree of transmission of clusters and their percentage of asymptomatic members.
All analyses were performed by using R (www.r-project.org/) statistical software version 4.0.216. Drawing of transmission clusters was performed using the “epicontacts” R package17.
Ethics approval
This study was conducted using surveillance data collected via the TERANGA platform developed at IPD. Therefore, no ethical approval was needed.
