|Year : 2021 | Volume
| Issue : 2 | Page : 48-53
Severe acute respiratory syndrome coronavirus-2 IgG antibodies among health-care workers in a tertiary care hospital in Delhi India
Mala Chhabra, Stuti Kansra Arora, Anuradha Shulania, Sanjeet Panesar, Ankit Kumar Chauhan, Kriti Ganguly, Arvind Achra, Kirti Nirmal, Nandini Duggal
Department of Microbiology, Dr Ram Manohar Lohia Hospital and Atal Bihari Vajpayee, Institute of Medical Sciences, New Delhi, India
|Date of Submission||17-Jun-2021|
|Date of Decision||19-Oct-2021|
|Date of Acceptance||19-Oct-2021|
|Date of Web Publication||1-Feb-2022|
Dr. Mala Chhabra
Consultant ,Department of Microbiology,Dr RML Hospital and ABVIMS, New Delhi
Source of Support: None, Conflict of Interest: None
Introduction: COVID-19 is a novel viral disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that was first detected in Wuhan, China, in December 2019. Hospital health care workers (HCW's) are the frontline workforce for clinical care of cases and they are exposed to a higher risk of acquiring the disease than the general population. Thus, this study was planned with the aim to detect the presence of IgG antibody against SARS-CoV2 among the HCW's.
Materials and Methods: This retrospective study was carried out from June to August 2020 among the HCW's of a tertiary care hospital in New Delhi. Information on demography, risk factors and COVID-19 infection was obtained on predesigned pro forma and the blood sample was collected in the plain vial for the detection of COVID 19 IgG antibodies, targeting recombinant Spike 2 protein and nucleoprotein, using the Indian Council of Medical Research approved enzyme-linked immunosorbent assays kit.
Results: Eight hundred HCWs voluntarily participated in the study. The seroconversion rate among the HCW's enrolled in our study was found to be 16.75%. They were divided into three groups on the basis of reverse transcription-polymerase chain reaction (RT PCR) test done for SARS-CoV2 genes since 30 January 2020. In Group I, who were RT PCR positive, 34 (70.8%) were found to be seroconverted. In Group II who were RT PCR negative, 12.09% had IgG antibodies. Group III comprised 529 HCW's, who never got themselves tested for RT PCR, of these 13.8% had developed IgG antibodies. The most common symptom was found to be cough, fever, bodyache, loss of taste and loss of smell. The odds ratio amongst seroconverted and nonseroconverted HCW's was found to be significant in all the symptoms except for nasal discharge and sore throat. Among the significant symptoms the odds ratio was observed to be 16.09 and 12.99 for loss of taste and loss of smell, respectively, and was observed to be highly significant (P < 0.001). Only 1.5% had moderate and severe infection and the rest had mild infection or were asymptomatic. Seroconversion rate among the asymptomatic HCWs was found to be 10.84%.
Conclusion: Serology plays an important role in understanding the pandemic COVID-19 by identifying the individuals who have been infected and seroconverted, infected but not seroconverted, infected and remained asymptomatic or who never got themselves tested but showed the presence of IgG antibodies.
Keywords: Health care worker, severe acute respiratory syndrome coronavirus-2 IgG serology, seroconversion
|How to cite this article:|
Chhabra M, Arora SK, Shulania A, Panesar S, Chauhan AK, Ganguly K, Achra A, Nirmal K, Duggal N. Severe acute respiratory syndrome coronavirus-2 IgG antibodies among health-care workers in a tertiary care hospital in Delhi India. J Patient Saf Infect Control 2021;9:48-53
|How to cite this URL:|
Chhabra M, Arora SK, Shulania A, Panesar S, Chauhan AK, Ganguly K, Achra A, Nirmal K, Duggal N. Severe acute respiratory syndrome coronavirus-2 IgG antibodies among health-care workers in a tertiary care hospital in Delhi India. J Patient Saf Infect Control [serial online] 2021 [cited 2022 Jun 30];9:48-53. Available from: https://www.jpsiconline.com/text.asp?2021/9/2/48/337089
| Introduction|| |
COVID-19 a novel viral disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), was first detected in Wuhan, China, in December 2019. Given the alarming levels of spread, the severity of disease, and the number of affected countries, the World Health Organisation declared COVID-19 as a pandemic on March 11, 2020. India reported the first case of SARS CoV-2 on 30th January 2020. The clinical syndrome caused by SARS-CoV-2 ranges from very mild symptoms to severe pneumonia, acute respiratory distress syndrome and death. However, several reports show that many individuals might carry the virus without presenting any symptoms for several weeks.,, Thus, the exact number of individuals who have been infected by SARS-CoV-2 remains unknown.
The role of the serological assay in this setting of acute pandemic ranges from as an adjunct to molecular testing >14 days post symptoms onset, when the molecular test is negative or when molecular tests are persistently positive. Further, the use of serological assays could be in the community surveys-including asymptomatic infections, evaluation of immune response after infection, identifying convalescent plasma donors and evaluation of antibody response postvaccination.,,,,
Hospital health-care workers (HCW's) are the frontline workforce for clinical care of suspected and confirmed COVID-19 cases. Consequently, they are exposed to a higher risk of acquiring the disease than the general population and, if infected, pose a risk to vulnerable patients and fellow HCWs. Monitoring the prevalence of infection in HCW's is useful to assess the level of exposure among hospital personnel and identify the high-risk areas.,
Our hospital was among the first nodal centres identified for COVID 19 for both in-patient and out-patient services, which included screening center for sample collection, ward and intensive care unit (ICU) for the management of COVID19 patients and laboratory for doing RT–PCR for the diagnosis of COVID19 involving the significant number of HCW's. Ministry of Health and Family Welfare (MoHFW) issued an advisory for the serological survey of HCW's. Thus, this study was planned with the aim to detect the presence of IgG antibodies against SARS-CoV2 among the HCWs.
| Materials and Methods|| |
This retrospective study was carried out from June to August 2020 among the HCW's of a tertiary hospital in New Delhi.
Ethical clearance was obtained from the institutional ethical committee (No-440 [89/2020 IEC/ABVIMS RMLH] 256/2020) dated 06/11/2020.
A pro forma was designed which included demographic details like resisdence in containment zone, designation, mode of transport to the hospital, risk factors like duty in COVID 19 area and appropriate use of personal protective equipment (PPE). In addition, information was obtained on potential signs and symptoms of COVID 19 like fever, cough, sore throat, nasal discharge, body ache, nausea, diarrhea, abdominal pain, loss of smell and loss of taste, the result of the RT-PCR COVID-19 test done anytime after 30 January 2020 and grading of disease as mild, moderate, severe and asymptomatic. Eight hundred HCW's voluntarily filled the pro forma and gave the sample for the COVID-19 IgG antibody test. All the samples for serology testing were collected at least after 2 weeks of the onset of symptoms if any. 3–4 ml of blood sample was collected in plain vial and serum was separated. COVID 19 IgG antibodies were detected using the Indian Council of Medical Research approved ErbaLisa COVID-19 IgG Antibody Detection enzyme-linked immunosorbent assays (ELISA) kit, by Erba Mannheim, as per manufacturers instruction. IgG antibody results were interpreted as 'Detected' when the antibody index was calculated to be >1.1; 'positive' when the antibody index was between 0.9 and 1.1 and 'Not Detectable' when the antibody index was <0.9. Seroconverted HCWs included both whose antibodies were in the detectable range and borderline positive.
| Results|| |
Eight hundred HCW's including doctors (37.62%), nurses (20.5%), Laboratory staff (10.37%), Administrative staff (7.75%), Sanitary attendant (11%), Security staff (9.75%) and others (3%) such as multipurpose workers, ward attendants, etc., voluntarily participated in the study [Table 1].
Out of 800 HCW's, 17 reported breach in PPE. Of these, SARS-CoV2 genes were detected in 11 (64.7%).
Sample of 800 HCWs was processed for COVID 19 IgG antibodies by ELISA, Of these 98 (12.25%) had antibodies in the detectable range with antibody index >1.1, while 36 (4.5%) were borderline positive with antibody index ranging between 0.9 and 1.1. Thus, 134 (16.75%) HCWs were considered sero positive for IgG antibodies against SARS-CoV2. IgG SARS-CoV 2 antibodies were not detected in 666 (83.25%) [Table 2].
|Table 2: Health-care workers tested for severe acute respiratory syndrome coronavirus 2 immunoglobulin G antibody|
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For analysis of results, we divided the HCWs into three groups based on the reverse transcription-polymerase chain reaction (RT PCR) for SARS-CoV2 [Table 2] Group I included 48 (6%) HCW's who tested positive for SARS-CoV2 genes, Group II included 223 (27.87%) who tested negative for SARS-CoV2 genes and Group III included 529 (66.13%) HCW's who never got themselves tested for SARS-CoV2 genes by RT PCR [Table 2].
Out of 48 COVID 19 RT PCR-positive HCWs, only 34 (70.8%) developed IgG antibody to SARS CoV2 [Group I, [Table 2]]. Of these 34 seropositives, only 01 (2.08%) had severe infection that required admission in ICU, 11 (22.91%) had moderate infection, while 17 (35.41%) had mild infection. Asymptomatic infection was reported in 05 (10.41%) [Table 3].
|Table 3: Correlation of immunoglobulin G with polymerase chain reaction status|
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As shown in [Table 2] (Group II), out of 223 COVID 19 RT PCR negative, 27 (12.09%) demonstrated the presence of IgG antibodies to SARS CoV2. Of these 20 (8.96%) had mild symptoms of fever, cough, cold sore throat body ache, loss of smell and taste that did not require admission and 07 (3.13%) were asymptomatic [Table 3].
Group III [Table 2] comprised 529 HCW's who did not get themselves tested for COVID 19 RT PCR since 30 January 2020. Of these, 73 (13.79%) showed the presence of IgG antibodies to SARS CoV 2. Out of 73 seropositives, 64 (12.66%) were asymptomatic and only 09 (1.7%) had mild symptoms [Table 3].
The most common symptom present among seroconverted HCWs was cough 53 (39.55%) bodyache 47 (35%) followed by fever 40 (29.85%) while cough 173 (25.97%) and sore throat 166 (24.9%) was the most common symptom among the seronegative HCWs. Only one HCW had severe infection which required admission to ICU. No mortality was reported among the HCW's enrolled in the study.
| Discussion|| |
Out of 800 HCWs of our hospital included in this study, 134 (16.75%) were found to be positive for IgG to SARS CoV 2. The study by Basteiro et al. reported 9.3% seroprevalence among HCW of a Spanish reference hospital. Another study by Schmidt et al. reported the seroprevalence to be 2.7% among the staff of Spanish clinics. Seroconversion rate in HCW's of our study was lower than the community serosurvey of Delhi for July 2020 and August 2020 which was reported to be 23.48% and 29.1%, respectively. Lower prevalence of COVID 19 infection among the HCWs of the hospital could be due to high awareness of risk factors, availability of PPE, high standards of infection prevention, risk assessment and screening and isolation of symptomatic staff, along with contact tracing and quarantine facility in a tertiary care hospital.
The 800 HCWs, 17 reported breach in PPE. Out of these, the SARS-CoV2 gene was detected in 11 (64.7%) and these, 8 (72.7%) had mild infection and 3 (27.3%) reported moderate infection. Hence, breech in PPE was a high-risk factor. Another study by Khalil et al. has also reported a higher percentage of COVID-19 positivity in HCW who reported breech in PPE.,
In our study, we considered RT PCR as the gold standard test for the diagnosis of COVID 19 infection. The first group comprised of48 HCWs, who were RT PCR positive 30 January 2020. Amongst the cases with mild infection (n = 22) only 17 (35.41%) were found to be serconverted. Asymptomatic infection was reported in 14 and only 5 (10.41%) had seroconverted [Table 3]. The odds of seroconversion was significantly high in PCR positive group than the other two groups (P < 0.001) which is statistically significant [Table 2]. According to a study done by Marklund et al. 9.4% of patients with mild symptoms did not develop detectable IgG antibodies. In our study, 10.41% of persons, with mild symptoms did not seroconvert. Reasons for IgG not being detected could be due to delayed antibody production or rapid decay of antibodies in persons with mild illness. This could also be due to the limitation of kit used, viz antibody levels developed below the detection limit of the kit or use of single antigenic target in the kit. Lippi et al. reported in a study that in patients with mild or asymptomatic infection low or undetectable levels of antibodies develops after COVID 19 infection.,,,, Seronegative patients should be further tested by neutralisation assays which is considered the gold standard for serology.
In the second group, of 223 HCW's who tested PCR negative, 27 (12.09%) [Table 2]. HCWs had seroconverted while rest 196 (87.89%) were negative for IgG antibodies. Of these 27, 20 (8.96%) HCWs had mild symptoms of fever, cough, cold sore throat body ache, loss of smell and taste that did not require admission and 7 (3.13%) were asymptomatic [Table 3]. Positive IgG without confirmation of disease by PCR test could be due to time of collection of sample for PCR with reference to the onset of disease, that is, if the person got themselves tested in very early or late phase of disease, the PCR test may be negative. Other reasons could be, improper collection of samples or poor maintenance of cold chain which may have led to false-negative PCR results. The positive results of the IgG antibody test also could be false-positive due to cross-reactivity to other commonly circulating coronaviruses and due to autoimmune diseases.
In the third group who never got themselves tested for RT PCR since 30 January 2020, 529 were screened for the presence of IgG antibodies. Of these 73 (13.8%) had developed IgG antibodies and the rest 456 (86.2%) were negative [Table 2]. Out of those who tested positive for IgG only 9 (1.7%) had mild symptoms and 64 (12.09%) were asymptomatic [Table 3]. This could be because as they were asymptomatic hence unaware that they were harbouring infection and thus never got themselves tested.
The most common symptom present in our HCWs (both seroconverted and non-seroconverted) was cough. Our findings correlate well with the study done by Wesley et al. Study by Carfi et al. found fatigue followed by cough and dyspnoea to be the most common symptom during acute COVID 19 infection. According to another study done by Grant et al. fever was the most common symptom followed by cough. On using the test of significance for comparison of symptoms of seroconverted and non-seroconverted group, a significant difference was observed in all the mentioned symptoms (fever, cough, bodyache, nausea, diarrhoea, abdominal pain, loss of smell, loss of taste) except for sore throat and nasal discharge. Among the significant symptoms the odds ratio was observed to be 16.09 and 12.99 for loss of taste and loss of smell, respectively, which was highly significant (P < 0.001). Whereas, the odds ratio for the remaining signs and symptoms ranging from 1 to 4 [Table 4]. Hence during the pandemic, a person who presents with recent onset of loss of taste and loss of smell may be strongly suspected of having of COVID19 infection. A study done by Callejon-Leblic also predicted a strong association of loss of smell and loss of taste in COVID 19-positive cases.
Current evidence suggests that seroconversion occurs approximately within 2 weeks after symptoms onset. Literature suggests that the detection of IgM and IgA detect recent infection in comparison to IgG. Varying sensitivities and specificities have been reported for assays detecting IgM, IgA, IgG or total antibodies. In comparison to various classes of antibodies, IgG is anticipated to play a major role in monitoring serological response due its longer-lasting response.,, However, there is insufficient evidence to support any one specific immunoglobulin isotype better than the other in assay selection. In our study, we have used Ig G based ELISA kits as they were available and also recommended by MoHFW.
An additional consideration in assay selection is the antigenic target. Most of the available assay targets either spike glycoprotein (S) or nucleocapsid protein (N) of SARS-CoV 2. The S protein consists of two subunits, the N-terminal S1 unit which contains the receptor-binding domain and the C-terminal S2 subunit. Kit used in our study is ELISA-based IgG detection kit, targeting recombinant spike 2 protein and Nucleoprotein. Current evidence is insufficient to prove that assays which employ specific antigens to capture antibodies show a greater correlation to antibody neutralisation activity than others. Neutralisation assay still remains to be the gold standard test in serology.,,, This may be the limitation in our study as we used IgG-based ELISA kit, as the performance of neutralisation assay needs viral culture and BSL 4 facility which was not available at our institute. Another lacunae in our study is, we could not collect the second sample, especially in borderline cases as it was a retrospective study.
Testing principles for SARS-CoV-2 serological assays range from chemiluminescent immunoassays (CLIA), ELISA, rapid diagnostic test Lateral flow assay (LFA), etc., Varying clinical specificities and sensitivities have been reported across CLIA, ELISA, LFA methods due to variable test validation protocol and variation in manufacturer's instructions., A thorough analysis of expression of T-cell surface markers should also be analysed, which are still under study and evolving day by day which will determine naïve, effector (activated or exhausted) and memory T-cells.As it is the novel disease we have calculated the antibody index, as reference values/cut-off values and units are still under study. Many aspects of serology of this novel disease are still evolving as currently there is insufficient evidence supporting any specific immunoglobulin assay, antigenic target and cell-mediated response and its detection.
| Conclusion|| |
Serology plays an important role in understanding the pandemic COVID-19 by identifying the individuals who have been infected and seroconverted, infected but not seroconverted, infected and remained asymptomatic or not got themselves tested but still seroconverted. Seroconversion rate among the HCWs of our hospital was found to be 16.75%. Lower prevalence among the HCW may be due to infection control practices and appropriate use PPE. The odds of seroconversion are significantly high in PCR positive group than other two groups (P < 0.001) which is statistically significant. Only 1.5% (12/800) had severe and moderate infection and 98.5% (788/800) HCWs had mild infection or were asymptomatic. Seroconversion rate among the asymptomatic HCWs was found to be 10.84% (76/701) by IgG ELISA. Serological aspect of COVID-19 is still evolving and studies need to be conducted to find out the most efficient assay, target antigen and immunoglobulin subclass to detect the antibodies against SARS CoV-2.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]