|Year : 2021 | Volume
| Issue : 1 | Page : 5-10
Severe acute respiratory syndrome coronavirus 2 immunoglobulin G antibody: Seroprevalence among contacts of COVID-19 cases
Om Prakash1, Bhavin Solanki2, Jay Kirtikumar Sheth3, Mina Kadam4, Sheetal Vyas5, Serosurveillance Research Team*6
1 Deputy Municipal Commissioner, AMC, Ahmedabad, Gujarat, India
2 Medical Officer of Health, AMC, Ahmedabad, Gujarat, India
3 Associate Professor, Community Medicine, AMC MET Medical College, Ahmedabad, Gujarat, India
4 Professor & Head, Microbiology, AMC MET Medical College, Ahmedabad, Gujarat, India
5 Professor & Head, Community Medicine, AMC MET Medical College, Ahmedabad, Gujarat, India
|Date of Submission||13-Oct-2020|
|Date of Decision||01-Nov-2020|
|Date of Acceptance||22-Dec-2020|
|Date of Web Publication||20-Mar-2021|
Jay Kirtikumar Sheth
Department of Community Medicine, AMC MET Medical College, Maninagar, Ahmedabad, Gujarat
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Multiple serosurveillance studies have focused on the presence of antibodies against severe acute respiratory syndrome coronavirus 2 in the general population and confirmed cases. However, seroprevalence of immunoglobulin G (IgG) among contacts of confirmed cases can add further value to the scientific findings. Objectives: The objective is to estimate COVID-19 seropositivity among contacts of COVID-19 cases and to compare the seropositivity between types of contact for the assessment of differential risk and transmission dynamics. Methods: Large scale population-based serosurveillance on contacts of COVID-19 cases was carried out during the second half of August 2020 in Ahmedabad using the COVID-Kavach. The seropositivity among contacts was estimated and correlated-compared with type of contact and other demographic factors. Results: With 1268 positive for IgG antibodies from 3973 samples, the seropositivity against COVID-19 among contacts of cases in Ahmedabad was 31.92% (95% confidence interval 30.48%–33.38%). The seropositivity among family contacts was significantly higher (39.36%) as compared to other contacts (28.72%) (Z = 6.60, P < 0.01). This trend is seen across all age groups and both the sex groups. The seropositivity has increasing trend with increasing age and is significantly higher among females (35.11%) than males (28.95%) (Z = 4.16, P < 0.01). Conclusion: Seropositivity of 31.92% among contacts indicates that a large proportion of contacts have already acquired immunity on account of their contact with the case. Higher seropositivity among family contacts justifies the risk categorization and testing strategy adopted for the contacts of the cases. This also reaffirms the need for contact tracing strategy for controlling the inevitable spread of pandemic.
Keywords: Contact of cases, COVID-19, family contact, immunoglobulin G antibody, serosurveillance, severe acute respiratory syndrome coronavirus 2
|How to cite this article:|
Prakash O, Solanki B, Sheth JK, Kadam M, Vyas S, Serosurveillance Research Team*. Severe acute respiratory syndrome coronavirus 2 immunoglobulin G antibody: Seroprevalence among contacts of COVID-19 cases. Indian J Public Health 2021;65:5-10
|How to cite this URL:|
Prakash O, Solanki B, Sheth JK, Kadam M, Vyas S, Serosurveillance Research Team*. Severe acute respiratory syndrome coronavirus 2 immunoglobulin G antibody: Seroprevalence among contacts of COVID-19 cases. Indian J Public Health [serial online] 2021 [cited 2021 Jun 21];65:5-10. Available from: https://www.ijph.in/text.asp?2021/65/1/5/311512
FNx01Serosurveillance Research Team
Aparajita Shukla, Professor & Head, Community Medicine;
Jayshri Pethani, Professor & Head, Microbiology, NHL Municipal Medical
Sanket Patel, Assistant Health Officer, Ahmedabad Municipal Corporation;
Mayank Patel, Assistant Professor Statistics, Community Medicine, AMC MET Medical College, Ahmedabad, Gujarat, India
| Introduction|| |
COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), spread across the world during 2020., Being a new virus, the scientific community was not much aware of its natural history and immune response following the viral infection. Since the SARS-CoV2 was a novel virus, the presence of antibodies against SARS-CoV2 may be considered as an evidence of immunity. This indirect estimation is crucial in assessing the true extent of SARS-CoV-2 spread within the population. For a newly identified agent, the WHO has also suggested monitoring of seroprevalence. Since such surveys also uncover the asymptomatic, subclinical transmission, it helps in understanding the disease dynamics in a better way and to plan an appropriate public health response. Through antibody-based serologic testing, we can minimize the biases of referral and selective testing affecting laboratory-based surveillance, generate evidence on the role of asymptomatic infection in driving transmission and estimate the extent of infection.
During the pandemic of COVID-19, multiple serosurveillance studies have focused on the presence of antibodies against SARS-CoV2 in the general population and confirmed cases.,, Studies to find the presence of immunoglobulin G (IgG) antibodies among contacts of confirmed cases can add further value to the scientific finding. The study of seropositivity among contacts, and their comparison with seropositivity among general population as well as cases can give better insight into the transmission dynamics and risk of disease transmission.
The “WHO” has defined contact of a confirmed case of COVID-19. Considering the risk of acquiring the infection, contacts are generally categorized into high-risk contact and low-risk contact. While other high-risk contacts require careful assessment, family contacts are usually considered as “high risk contacts” as they have more likely to have close contact for longer duration without mask or appropriate personal protective equipment. Hence, for operational feasibility of categorizing the contact, we categorized the contacts into “Family contacts” and “other contacts” for the purpose of the study. We carried out a serosurvey among contact of cases, keeping the estimation of seroprevalence as our primary objective. The present study also allowed us to check our secondary objective of comparing the seropositivity between the two types of contact and to confirm the differential risk and transmission dynamics.
| Materials and Methods|| |
The Indian Council of Medical Research (ICMR) had issued directives for conducting IgG antibody-based serosurveys to monitor the pandemic, understand its progression and to take appropriate corrective public health measures. The primary purpose was to understand the proportion of population exposed to SARS-CoV-2. Ahmedabad Municipal Corporation, from the state of Gujarat, India, had already completed one large scale population-based serosurveillance for IgG antibodies against SARS-CoV-2 Virus with an average positivity of 17.61% at the end of June 2020. A repeat population-based serosurvey was planned to study the COVID-19 seropositivity in the second half of August 2020. The population-based stratified sampling was used to calculate the ward/Urban Primary Health Centre (UPHC) wise required sample for the general population category. Along with population-based serosurvey, contacts of confirm cases of COVID-19 were also covered separately. Additional sample size for the “contacts of case” category was decided as at least 30% of the general population sample targets. Thus, the sample size of contacts was also based on population proportion and it was not related to the reported COVID-19 cases. These contacts were further categorized into two types of contacts: family contacts and other contacts.
“Covid Kavach” (Anti-SARS CoV-2 IgG Antibody Detection capture ELISA) kits developed and manufactured by Zydus Diagnostics, validated by the National Institute of Virology, Pune, India, and approved for use by the ICMR were used for the purpose of this study. As per the validation reports, this kit has a sensitivity of 92.37% and a specificity of 97.9%. So, with very high level of sensitivity and specificity, the results received through this testing kit is quite reliable and ICMR has permitted its use for serosurveillance of SARS-CoV-2. The manufacturer reported no cross-reactivity with other viruses in the serum from real-time polymerase chain reaction confirmed patients of various other infections. Testing procedures were followed as per the manufacturer's instructions. To reduce the sample rejection rate, Serum Separation Transport Tube-Gel Vacutee was used for the collection of blood samples.
There are 75 UPHCs within 48 wards, across 7 zones in Ahmedabad city. Contacts of COVID-19 cases were selected from these 75 UPHCs which are functional units for the COVID-19 management in the field area. Contacts, by definition, include all individual, irrespective of age, sex, etc., who is a confirmed “contact” of a COVID-19 case (any individual who is recorded as contact and followed up as a part of contact tracing activity). If an old contact of a case turns out to be positive later on (but, before the enrollment in our study), then he/she is enrolled only as a “case” and not as a “contact.” Based on the presence or absence of a confirmed case of COVID-19 in their family, they were recorded as a family contact or other contact. At the UPHC, contacts were selected from the available contacts within the UPHC field area without any exception. An effort was made to cover a wide variety of people of different age groups from both the gender and from different localities within the field area of the UPHC. However, so far as possible, an effort was specifically made to cover at least 10% of contacts for <18 years and >60 years.
The study was carried out after the ethical approval. A written informed consent was taken from all the participants before enrollment. In case of contacts from minor age group, an assent with informed written consent of their parents/guardian was taken for the purpose of the study. Strict confidentiality was ensured at all the levels. For the purpose of testing and standardization, only those laboratories with national level accreditation and state of the art facilities and equipment were approved for testing the samples of the present study.
Microsoft Excel and Epi-Info was used for the purpose of data management. In-depth analysis of the data was carried out with focus on the type of contact and other demographic factors. Simple proportions and appropriate statistical tests were used wherever required. As an ethical obligation, the results were shared with the concerned local authorities. We herewith share the findings of our results for the detailed insight by the scientific community.
| Results|| |
A total of 3986 serum samples were collected from the contacts, from which, 13 samples were rejected by the laboratories due to various reasons. Results were thus available for 3973 contacts. From these results, 2667 (67.13%) were negative and 38 (0.96%) had indeterminate results. Thus, a total of 1268 results were positive for the antibodies against COVID-19 giving an overall positivity of about 31.92% (95% confidence interval [CI] 30.48%–33.38%).
Detailed analysis of contacts [Table 1] shows that there were 1914 female and 2059 male contacts. A total of 672 samples were positive among female giving a positivity rate of 35.11% (95% CI 33.00%–37.28%) whereas 596 samples were positive among male giving a positivity of 28.95% (95% CI 27.03%–30.94%) This difference between two gender groups is statistically significant (Z = 4.16, P < 0.01). Seroprevalence was also analyzed for the types of contact [Table 2]. The overall seropositivity among family contact was 39.36% (95% CI 36.63%–42.16%) and among other contacts, it was 28.72% (95% CI 27.06%–30.43%). This difference was also statistically significant (Z = 6.60, P < 0.01).
|Table 2: Age-sex wise percentage seropositivity according to type of contact|
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Among the family contacts, 470 were seropositive giving a positivity of 39.36% (95% CI 36.63%–42.16%). Among family contacts, females have slightly higher positivity (39.79%) than males (38.85%) and this difference was statistically not significant (Z = 0.33, P = 0.74). Among the other contacts, 798 were seropositive giving a positivity of 28.72% (95% CI 27.06%–30.43%). Among other contacts, females have higher positivity (32.67%) than males (25.44%) and this difference was statistically significant (Z = 4.19, P < 0.01). The comparison of seropositivity in both the gender groups and types of contact [Table 1] shows that females have higher seropositivity than males and the other contacts have lower positivity as compared to family contacts.
The age distribution of the contacts of cases typically follows age-heaping bias at 5 years' gap (data not shown, only grouped data shown in data table) as the age of the enrolled individuals were not verified with any official document. The age of the contacts ranged from 2 years to 92 years with a mode of 30 years, median of 35 years and an average of 37.51 ± 15.90 years. Among the contacts, the mean age of females is 38.11 ± 15.76 years, whereas the mean age of males is 36·95 ± 16.01 years. Considering the seropositive, the mean age for females is 39.78 ± 16.04 years where as that of male is 38.03 ± 17.04 years.
The age group-wise analysis of positivity with type of contacts [Figure 1] shows that the age group-wise lowest positivity is for 20–29 years. Children have slightly higher positivity as compared to young adults. For adults, the seropositivity among contacts has increasing trend as the age increases. When the positivity among contact is further bifurcated into family contacts and other contacts, the same trend is seen for both the types of contacts and the positivity for family contacts is seen higher than that of other contacts for all the age groups.
When the age groups are compared with the sex groups [Figure 2], it shows that the positivity from 20 to 80 years increases with increasing age and females have higher positivity than male. However, on the extremes of age, male children and elderly females have higher positivity.
| Discussion|| |
Although the scientific community is aware of the general immune response after any viral infection, and has some insight into the seropositivity for COVID-19, there is very little information about the immune response among contacts of COVID-19 cases., The present study on the seropositivity among contacts is probably one of the first few serological studies from India, exclusively covering the contacts of COVID-19 cases with a large sample of contacts.
Seropositive contacts are those who have developed antibodies against the agent – SARS-CoV2 on account of their exposure to the confirmed case of COVID-19 and these seropositive contacts gives an idea about infected but undetected proportion of general population, who might have contributed to the ongoing disease transmission. At the same time, these are more crucial in transmission dynamics as they are not identified as clinical or subclinical cases.
Based on our findings with an average seropositivity of 31.92% (95%CI 30.48%–33.38%) among contacts, it can be said that about a third of total contacts have already been seropositive without themselves being identified as a confirmed case. The positivity among family contacts is higher (39.36%) as compared to other contacts (28.72%). This indirectly justifies the risk categorization of family contacts as high-risk contacts and validates the strategy adopted for these contacts.
Since, convenience sampling was followed for the selection of contacts and the sampling was not related to COVID-19 cases, the proportion of family contacts and other contacts are unrelated. However still, the selection of higher number of other contacts than the family contact supports the fact that generally high number of casual other contacts are recorded for a confirmed case in contrast to limited number of family contacts during the process of contact tracing.
The seropositivity is significantly higher among females for other contacts and total contacts but it is statistically not significant for the family contacts. This suggests that the higher risk among family contacts affects both the gender groups equally. Statistically significant higher seropositivity among females for other contacts, require in-depth analysis to know the reasons behind this difference. The larger proportion of other contacts in the total sample seems to be affecting the difference seen in the total contacts.
The statistic of mode < median < mean also indicates that the distribution had many young adults as compared to elderly and the mean is deviated on the right due to higher values of comparatively small number of elderly contacts with age more than double of the mean age. Children have slightly higher positivity as compared to young adults with lowest positivity. This can be explained by the higher susceptibility and lower compliance of preventive measures required for a contact, which leads to subsequent seroconversion. For adults, the seropositivity increases with increasing age, and is true for both the types of the contacts. Low sensitivity of the diagnostic test along with large number of asymptomatic contacts might be the overall reason for this high level of seropositivity. Such asymptomatic individuals are more commonly the young adults than the elderly contacts. Even when such contacts are symptomatic, the symptoms are more likely to be mild and for shorter duration among the young adults than the elderly. This difference in symptoms among the contacts may be the reason behind the higher seroconversion among elderly with increasing trend in positivity with increasing age.
Considering all the contacts, young male children and elderly females have higher positivity. The possible reasons (such as higher playfulness and poor compliance to quarantine principles by young male children) behind the difference among both the sex groups for childhood and adolescent age groups need to be explored further. For elderly, the difference may be due to higher load of household activities by elderly female (particularly in traditional Indian culture) as compared to elderly male contacts during the quarantine, which increases the risk during exposure and affects subsequent seropositivity.
The present study gives a rough estimate of contacts who might have already acquired immunity on account of their contact with a case, and with these numbers, it justifies the national strategy to test all the high-risk contacts and symptomatic low-risk contacts. If contacts are not identified by contact tracing and kept in quarantine (with subsequent testing when indicated) then the ongoing transmission could be exponential. Hence, this study also reaffirms the need for contact tracing strategy for controlling the inevitable spread of pandemic. The results have highlighted scope for further research to generate greater evidences regarding risk dynamics and the COVID-19 transmission.
| Conclusion|| |
Higher positivity among family contacts, justifies the risk categorization and testing strategy adopted for the contacts of the cases. Overall seropositivity of 31.92% among contacts gives an indirect estimate of the proportion of contacts who have already acquired immunity on account of their contact. This also reaffirms the need for contact tracing strategy for controlling the inevitable spread of pandemic. The results have highlighted scope for further research to generate greater evidences regarding risk dynamics and the COVID-19 transmission.
We are extremely thankful to respected Dr. Rajiv Kumar Gupta, IAS (Additional Chief Secretary, Government of Gujarat) and Mr. Mukesh Kumar, IAS (Municipal Commissioner, Ahmedabad) for their whole hearted support. This study would not have been possible without the financial support from the authorities of Ahmedabad Municipal Corporation. We acknowledge the full support from the field level health care workers (Corona warriors) who put in great efforts to perform their duties as well as sample collection after informed written consent particularly in a COVID-19 pandemic situation. All the Zonal Deputy Health Officers, Deputy Health Officer (Epidemic), Assistant Health Officers and Medical officers of the Urban Primary Health Centers extended full support in conducting the serosurveillance. We are thankful to all the medical and paramedical support staff posted at the laboratories for their contribution in timely testing of the samples with accuracy and quality. Finally, we are indebted to all the participants including health care workers whose willingness and support has generated the much desired data for the study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]