A Contact Tracing Prospective Cohort Retrieving Epidemiological Facts on SARS-CoV-2 Transmission Aspects: A Serological Analysis in an Iranian Community
Reza Vazirinejad1, Parvin Khalili2*, Abdollah Jafarzadeh3, Ziba Shabani4, Ahmad Jamalizadeh5, Batool Rezaei6, Hassan Ahmadinia7, Mohammad-taghi Rezayati8, Mohammad Ebrahimian9, Gholamreza Mehralinasab10, Azam Bagherizadeh9, Shima Bazaz9, Erfan Vazirinejad11
1. Professor, Dept. of Epidemiology, School of Public Health, Social Determinants of Health Research Centre, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
2. Assistant Prof., Dept. of Epidemiology, School of Public Health, Social Determinants of Health Research Centre, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
3. Professor, Dept. of Immunology, Kerman University of Medical Sciences, Kerman, Iran.
4. Assistant Prof., Dept. of Infection Diseases, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
5. General Physician, Health System Research Centre, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
6. BSc in Midwifery, Health System Research Centre, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
7. Assistant Prof., Dept. of Epidemiology and Biostatistics, School of Public Health, Social Determinants of Health Research Centre, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
8. BSc in Laboratory Sciences, Dept. of Immunology, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
9. BSc in Laboratory Sciences, Pathobiological Laboratory, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
10. BSc in Disease Control, Health System Research Centre, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
11. Medical Student, Medical School, University of Pecs Medical School, Pecs, Hungary.
* Corresponding author: Parvin Khalili, E-mail: parvinkhalili61@yahoo.com
Abstract
Background: The spread of the novel coronavirus seems mysterious enough to make us double-check the indices being used to predict its transmission. In this study, serological analysis was performed to assess some metric and epidemiological aspects of the infection and its transmissibility among people in contact with SARA-CoV-2 patients.
Material and Methods: A total of 453 contacts of 40 COVID-19 patients entered this contact tracing prospective cohort study. Accordingly, SARS-CoV-2 patients were diagnosed by the real-time polymerase chain reaction testing of nasopharyngeal samples. The infectiousness history was detected by the serological testing of IgG and IgM. Trained expert team completed two questionnaires, and blood samples were taken by experts in a laboratory. Data were analyzed using SPSS V21.0 and R software.
Results: The mean ages of the SARS-CoV-2 patients and the contacts were 53.0±18.2 and 30.8±19.3 years, respectively. The overall R0 of the infection was 2.58. Household and non-household secondary attack rates (SAR) were 20% (95%CI; 12.7–27.3) and 11.3% (95%CI; 6.1-16.5), respectively. The transmission probability of each contact was 0.0205, and the serial interval was 6.4±4.6 (95% CI; 5.2–7.6) days. The SAR was higher among the contacts who were exposed to asymptomatic primary cases (28%, 95%CI; 10-46%) than (13.8%, 95%CI; 9.4-18.2) among those exposed to symptomatic patients.
Conclusions: It is concluded that the herd immunity of 60 to 65% is needed in human communities, based on the amount of R0 estimated in our survey. The findings demonstrated the amount of the reduction in infection R0, which is predicted based on both clinical and public health interventions.
Keywords: SARS-CoV-2, Serology, Transmission, Iran.
Introduction
Over one year has passed from the date when the first case of the new coronavirus (SARS-CoV-2) infection was reported in Wuhan, China. The first World Health Organization (WHO) report for COVID-19 was issued on January 21, 2020 [1]. As of that date, the disease is in the form of a pandemic, and almost all countries around the world are entangled with it. In Iran, a total of 1,558,159 COVID-19 patients and 59,341 deaths were reported due to the infection by February 19, 2021, indicating a case fatality rate of 3.8% [2]. A study reported the prevalence of antibody seropositivity in the Kerman Province at 8.2% by the end of April 2020 [3]. However, no specific prevalence or incidence has been reported in the Rafsanjan County (the area of the present study) in the Kerman Province.
In the early weeks of the infection, there were concerns about some major aspects of the disease transmission. For instance, it was predicted that asymptomatic transmission would not be a serious concern in the case of the novel coronavirus [4]. Besides, it was reported that “the extent to which asymptomatic and subclinical patients could pass on the virus still remained unclear” [4]. Although many epidemiological investigations have been conducted in the last several months, there are not enough findings to provide accurate evidence to policy makers to answer all related questions. Pollock and Lancaster claimed that the transmission rate among those people in contact with an asymptomatic infected person (the secondary attack rate) might be 3-25 times lower than that among people in contact with symptomatic patients. In other words, people with symptomatic infections are more contagious than people with asymptomatic infections [5]. However, people in the community would have more and closer contacts with asymptomatic patients than with symptomatic ones because of the isolation of symptomatic patients and the fear of infection transmission in the community. This means that the claim made by Pollock and Lancaster should be investigated more cautiously.
Similar to other infections, every detail about transmissibility of the novel coronavirus can play a crucial role in developing programs for controlling the spread of the infection. Household contacts and visits between people are closer than outdoor contacts and visits, with the transmission probability being clearly different. Besides, the type and duration of contacts and visits are important, which should be taken into account. Accurate contact tracing data should be collected to provide the most precise information on human-to-human transmissibility of the infectious agent. The household secondary attack rate (SAR) of SARS-CoV-2 was measured in few studies, such as in that of Jing et al [6].
Winter and Hegde stated that in the case of infectious pathogens, for the purpose of contact tracing in highly dense populations, serological analysis can be useful [7]. However, cross-reactivity of serological tests with other viral pathogens is criticized. Serological analysis along with contact tracing are effective in estimating the proportion of asymptomatic infectors in a population [7]. According to Buitrago-Garcia et al, the overall proportion of people who were infected with COVID-19 without any symptoms throughout the infection was 20% (95% CI; 17-25) [8].
Serological testing can have a crucial role in identifying convalescent cases or people with the milder disease, who might have been missed by other surveillance methods [9].
Bi et al reported some metric measures for COVID-19 transmission, including R0 and SAR among a group of patients and their contacts [10]. In the present contact tracing prospective cohort, serological analysis was performed to obtain more accurate data to assess some metric and epidemiological measures of the infection and its transmissibility among people in contact with SARA-CoV-2 patients.
Materials and Methods
In this prospective cohort study, all COVID-19 patients whose disease was confirmed by the RT-PCR test from March 1, 2020 to April 30, 2020, (Rafsanjan County, Kerman Province, Southeastern Iran) were invited (n = 48 primary cases). Accordingly, a time period of about three months was considered for each primary case (each COVID-19 patient), and all people in contact with the patient (indoors and outdoors) in this period were identified and invited to assist us with the survey. The three-month time period started from the date of the patient's infection with COVID-19. The date for each patient was calculated based on the date of the first COVID-19 symptom minus the mean duration of the SARS-CoV-2 incubation period (14-21 days). In addition, the termination date of the three-month time period was calculated based on the recovery date of the primary case plus the duration of the convalescent period. Since there was no duration reported for the COVID-19 convalescent period, we considered a duration of three to four weeks. In other words, a three-month duration was estimated for the starting date of the disease to the end of the patient’s infectiousness period for each primary case. Besides, all people in contact with this group of COVID-19 patients during the three-month period were invited (n = 453). The inclusion criteria of this study included confirmed RT-PCR results and patients’ willingness to participate in the study. On the other hand, the exclusion criteria included unwillingness to help with the survey and being unable to give contacts' details. The Ethics Committee of Rafsanjan University of Medical Sciences approved the current study before data collection (Ethics code: IR.RUMS.REC.1399.001). In addition, all methods were followed in accordance with ethical principles and regulations introduced by the Declaration of Helsinki.
Two checklists were used to register the data collected from the COVID-19 patients and their contacts in two phases. In the first phase, demographic characteristics of the patients (n = 48), including age, gender, occupation, nationality, educational status, marital status, living place, family size, weight, height, smoking, addiction, travel history, destination, and its date were recorded. In addition, information on their medical status, including the first COVID-19 symptom and its start date, the list of all COVID-19 symptoms, the duration of COVID-19 symptoms, the COVID-19 diagnosis date, the date of admission to the hospital, the date of recovery or death, severity of the disease, the date of the contact with a COVID-19 patient, and comorbidities were recorded by protected trained experts when they were admitted to the hospital and after receiving informed written consent from the patients or their relatives. Besides, some extra questions were asked from the patients about their contacts in three time periods. These time periods included (1) the time before the first symptom of COVID-19 (at least for two weeks based on the COVID-19 incubation period), (2) the duration from the first symptom onset and admission to the hospital, and (3) the duration from the patients’ admission to the data collection time.
In the second phase, the research team traced all people listed as contacts of each COVID-19 patient (n = 40, of whom eight individuals were excluded for their opposition) from the infection time until the end of their infectiousness period. At most, a three-month period was considered for this duration. Besides, all contacts who were visited by each patient during this period were invited (the mean number of the contacts for each patient was 11.32, and the overall number of the contacts was 453). The contacts were visited in their place of residence by protected trained experts. Besides, the participants were briefed on the details of the methods and objectives of the study. In addition, written informed consent was obtained from those who were willing to assist us with the study before data collection. In the case of the contacts being less than 18 years old, we received written informed consent from their parents.
Further to the demographic data that included age, gender, occupation, nationality, educational status, marital status, living place, family size, weight, height, smoking, addiction, travel history, and the type of kinship to the COVID-19 patients, some details of exposure to the COVID-19 patients were collected from the contacts. Further, the contacts were referred to the reference laboratory after recording their data in a face-to-face interview. This study was performed in accordance with the guidelines for reporting observational studies in epidemiology (STROBE). Fig. 1 shows the flowchart for recruiting the SARS-CoV-2 patients and their contacts in this study.
Trained experts recorded the data on COVID-19 patients and their contacts on two separate checklists. In the case of the contacts, some details of the diseases that the participants might suffer from, such as comorbidities, including hypertension, cardiovascular disease, respiratory diseases, diabetes, cancer, and the like were collected. Besides, they were asked about specific items, including the date of their visits of the COVID-19 patients, duration (minutes), place (“indoors at home”, “indoors outside home”, such as in a shop or on a bus, and “outdoors”), type (“close”, such as kissing and/or hugging, “not close, not far”, such as shaking hands or having food together, and “far”, such as visiting at a distance over 2 meters and/or for less than 2 minutes), and the number of visits. In the last section of the contacts’ checklist, some questions were asked about the symptoms of the disease, including the date of the first symptom, duration of the symptom, and date of the admission to the hospital (in case of admission).
Furthermore, all contacts were given a letter that referred them to the medical school's laboratory, and a 5cc vein blood sample was taken from the top of their forearms. The blood sample was used to measure CBC, ESR, CRP, IgG, and IgM. In addition, serological tests were performed to assess the level of specific IgG and IgM antibodies. The laboratory results were given to the participants for free. A member of the research team was asked to consult those participants whose laboratory results showed the need for further medical attention (the consultant was an infection disease specialist).
In the present study, a primary confirmed case was a symptomatic or an asymptomatic case with the positive detection of SARS-CoV-2 nucleic acid by the Real-time Polymerase Chain Reaction (RT-PCR). To this end, specimens taken from respiratory excretions, or viral genes highly homologous to SARS-CoV-2 were used by the sequencing method. In the contact tracing phase, an individual with the serology test results of IgG and IgM ≥ 1, with or without clinical symptoms, was defined as the secondary case. The serum levels of anti-SARS-CoV-2 IgM/IgG were detected using commercial as well as Iran Food and Drug Administration-approved ELISA kits (Pishtaz-tab, Tehran, Iran). According to the manufacturer's guidelines, the sensitivity and specificity of the ELISA kits were 79.4 and 99.4% for IgM a well as 94.1 and 98.3% for IgG, respectively.