Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Mohan Z Mani

"Thank you very much for having published my article in record time.I would like to compliment you and your entire staff for your promptness, courtesy, and willingness to be customer friendly, which is quite unusual.I was given your reference by a colleague in pathology,and was able to directly phone your editorial office for clarifications.I would particularly like to thank the publication managers and the Assistant Editor who were following up my article. I would also like to thank you for adjusting the money I paid initially into payment for my modified article,and refunding the balance.
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Dr Mohan Z Mani,
Professor & Head,
Department of Dermatolgy,
Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Original article / research
Year : 2022 | Month : February | Volume : 16 | Issue : 2 | Page : DC25 - DC29 Full Version

Dynamics of SARS-CoV-2 Antibody Response in a Longitudinal Cohort of Healthcare Workers from India


Published: February 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/51855.16011
Sonam Singla, Vyoma Singh, Smita Sarma, Charu Yadav, Kamini Vinayak, Teena Wadhwa, Renu Saxena, Yatin Mehta

1. Senior Resident, Department of Microbiology, Medanta- The Medicity, Gurugram, Haryana, India. 2. Associate Consultant, Department of Microbiology, Medanta- The Medicity, Gurugram, Haryana, India. 3. Associate Director and Head, Department of Microbiology, Medanta- The Medicity, Gurugram, Haryana, India. 4. Attending Consultant, Department of Biochemistry, Medanta- The Medicity, Gurugram, Haryana, India. 5. Lab Manager, Department of Biochemistry, Medanta- The Medicity, Gurugram, Haryana, India. 6. Senior Consultant, Department of Microbiology, Medanta- The Medicity, Gurugram, Haryana, India. 7. Director, Department of Lab Medicine, Medanta- The Medicity, Gurugram, Haryana, India. 8. Chairman, Department of Anaesthesia and Critical Care, Medanta- The Medicity, Gurugram, Haryana, India.

Correspondence Address :
Dr. Smita Sarma,
Associate Director and Head, Department of Microbiology, Medanta- The Medicity,
Sector 38, Gurugram, Haryana, India.
E-mail: sarma.smita@rediffmail.com

Abstract

Introduction: Coronavirus Disease 2019 (COVID-19) pandemic has affected healthcare systems worldwide. Healthcare Workers (HCWs) form one of the most at-risk population groups for acquiring infection. Trend analysis of anti Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antibody titres in vaccination naïve HCWs will give an insight into the role of natural protective immunity against reinfection.

Aim: To understand the dynamics of anti SARS-CoV-2 antibody response and its protective role against reinfection in a cohort of HCWs.

Materials and Methods: This observational longitudinal cohort study was conducted in a tertiary care hospital in Gurugram, Haryana, North India from June to December 2020. The study was approved by the Institutional Ethics Committee. Serum specimens from 230 HCWs were tested for anti-spike protein Immunogloublin G (IgG) antibodies by chemiluminescence immunoassay. The HCWs with positive antibody status and previous Polymerase Chain Reaction (PCR) confirmed infection (n=47) were followed-up over 180 days for serial antibody titres at four visits, each at a gap of 30-45 days. Participants were classified into asymptomatic (n=18), mild (n=17) and moderate (n=12) disease categories based on severity of previous COVID-19
illness. SPSS version 22.0 was used for statistical analysis. Intergroup comparison of means was done using Kruskal-Wallis test and Chi-square test. The p<0.05 was considered statistically significant.

Results: Positivity rate for anti SARS-CoV-2 IgG antibodies was 25.7%. Seroconversion rate was 90.74% in HCWs with history of previous Real Time-Polymerase Chain Reaction (RT-PCR) confirmed COVID-19 infection. Incidence of infection in seronegative group (n=171) was 12.96 per 10,000 person days while in seropositive group, it was 1.29 per 10,000 person days. Risk ratio for infection (baseline seronegative vs baseline seropositive) was determined to be 8.12 [95% Confidence Interval (CI) 1.068-61.755]. Incidence of PCR confirmed SARS-CoV-2 reinfection was inversely associated with antibody titres (p=0.018). Antibody response trend showed a peak in mean titres in the 46-90 days period followed by steep decline till 135 days and a gradual waning till 180 days.

Conclusion: Significant postinfection immunity is offered by even low to moderate amounts of antibodies and this occurs regardless of whether a seropositive HCW had previous asymptomatic or symptomatic infection. These findings have significant implications in establishing the protective role of anti-spike protein antibodies against subsequent infection.

Keywords

Coronavirus disease 2019, Immunity, Immunogobulin G, Severe acute respiratory syndrome coronavirus 2, Serial titres

Coronaviruses are a group of enveloped positive-sense single stranded RNA viruses constituting the subfamily Orthocoronaviridae within the Nidovirales order. They are further divided into four genera: Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus (1). In December 2019, a novel betacoronavirus causing severe acute respiratory syndrome emerged in Wuhan, China (2). The virus, designated as SARS-CoV-2, unleashed a pandemic which has wreaked havoc on healthcare systems across the world. Globally, as of 9th August 2021, there have been 202,608,306 confirmed cases of COVID-19, including 4,293,591 deaths, reported by the World Health Organisation (WHO) (3).

The reasons for immunity to seasonal human coronaviruses being short in duration have not been fully elucidated. Reinfections have been observed with three of the four seasonal human coronaviruses (i.e., 229E, NL63, and OC43). Antibodies to SARS-CoV-2 and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) were detectable until two years after infection but were reduced when re-testing was done within three years (4),(5). Large populations have demonstrated antibodies to the SARS-CoV-2 virus due to previous infection and speculations are that we are slowly inching towards ‘herd immunity’ (6),(7),(8). With the advent of several subsequent waves of the pandemic and emergence of new variants of the virus in several countries, communities are not only at a greater risk of infection but also reinfections (9),(10),(11),(12),(13). Despite there being widespread media reports and several observations made by clinicians with respect to a surge in reinfection cases in the past year, the number of published studies validating the same are far and few in between (14),(15),(16),(17). Existing knowledge on SARS-CoV-2 immune memory is limited (18),(19). Filling the gaps in our understanding of immune response has implications for the future course of the pandemic, the safety of frontline HCWs and the success of vaccination programs. Longitudinal studies to gain an insight into temporal kinetics of antibody responses in asymptomatic, mildly symptomatic, and severely ill populations are the need of the hour.

There are hardly any cohort studies published from India that have investigated serial antibody titres in HCWs and their role in the protection against subsequent infections, although few have recently shed light on their duration and correlation with severity of infection (20). The present study was conducted with the aim to perform a temporal analysis of anti SARS-CoV-2 IgG titres in a cohort of HCWs so as to understand the dynamics of antibody response, duration and magnitude of protection afforded, and association of disease severity with these parameters.

Material and Methods

An observational longitudinal cohort study was conducted to analyse the trend of antibody response in HCWs over a follow-up period of six months from June 2020-December 2020. The study was conducted at Medanta- The Medicity, Gurugram, Haryana, a 1250-bedded tertiary care centre in North India. There was no predefined sample size; participants volunteered for enrollment. Informed consent was obtained from all participants and Ethics Committee approval was duly taken {vide letter no. MICR-1136/2020 (Academic)}. The study was conducted in accordance with the Helsinki Declaration of 1975 and registered with the Clinical Trials Registry- India (CTRI/2020/07/026837).

Inclusion and Exclusion criteria: A total of 230 HCWs were included in the study. Serum specimens were collected from the study subjects and tested for antibodies to SARS-CoV-2. Furthermore, serial serum samples were collected only from individuals with previous RT-PCR confirmed SARS-CoV-2 infection (n=47) at four separate visits viz., first sample collected at (15-45) days after testing PCR positive (Day-0), second sample was collected between 46-90 days, third sample was collected between 91-135 days and fourth sample was collected between 136-180 days. Individuals who did not report having had PCR-confirmed infection were not included in the longitudinal cohort. However, they were tested for the presence of baseline antibodies.

Study Procedure

Antibody titres and the duration of their persistence were associated with severity of previous COVID-19 illness. The medical records of the participants were classified into asymptomatic (n=18), mild disease (n=17) and moderate disease (n=12) categories based on the severity of previous COVID-19 illness as per the Ministry of Health and Family Welfare- Government of India guidelines (21). None of the HCWs reported symptoms which qualified them as having had severe disease.

The individuals who were categorised as having had asymptomatic infection, were high risk contacts of confirmed SARS-CoV-2 PCR positive cases and were tested as part of the institutional COVID-19 contact tracing protocol.

The LIAISON® Immunodiagnostic Anti-SARS-CoV-2 assay for IgG detection was used. The test was performed on LIAISON® XL Analyser (DiaSorin S.p.A., Saluggia, Italy). It uses a Chemi-Luminescence Immunoassay (CLIA) technology for the determination of anti-S1 spike protein and anti-S2 spike protein specific IgG antibodies to SARS-CoV-2 (further referred to as anti SARS-CoV-2 antibodies) in human serum or plasma samples. Strict adherence to the analyser operator’s manual was ensured for proper assay performance. The analyser automatically calculates anti SARS-CoV-2 IgG antibody concentrations expressed as arbitrary units (AU/mL) and grades the results. Assay range is 3.8-400 AU/mL as per the manufacturer. Sample results were interpreted as follows: values of less than 12 AU/mL were negative, 12-15 AU/mL were considered equivocal and values greater than 15 AU/mL were positive.

In the following six months, disease outcome (COVID-19 infection) was documented whenever any HCW reported symptoms consistent with Influenza-Like Illness (ILI) and tested positive for SARS-CoV-2 by RT-PCR. Nasopharyngeal swabs were collected for this purpose and viral RNA extraction was done using Maxwell® RSC TNA kit on Maxwell® 16 instrument (Promega Corporation, Wisconsin, USA). For PCR, TaqPath TM COVID-19 CE-IVD RT-PCR Kit (Thermo Fisher Scientific Inc., Massachusetts, USA) was used with Quant StudioTM 5 Dx Real-Time PCR instrument (Applied Biosystems, California, USA) as per manufacturer’s instructions.

Statistical Analysis

Statistical analysis was done using SPSS version 22.0. Descriptive analysis of categorical variables was depicted as frequency (percentage) and quantitative variables were described as mean±SD (parametric data) and median (interquartile range) for non parametric data. Normality was assessed using Shapiro-Wilk test. Intergroup comparison of means was done using Kruskal Wallis test (for non parametric data), one-way ANOVA (for parametric data) and Chi-square test (for categorical variables). p<0.05 was considered statistically significant. Incidence rate was calculated as number of PCR positive infection per at-risk day according to baseline antibody status.

Results

A total of 230 healthcare workers were included in this longitudinal cohort study and underwent an assessment of baseline anti SARS-CoV-2 antibody titres. The gender-wise distribution of the study population comprised of 63.9% males (n=147) and 36.1% females (n=83). The number of participants who tested negative for baseline SARS-CoV-2 antibodies (henceforth, referred to as seronegative) was 171 (171/230=74.3%), while 59 (59/230=25.7%) were found to have antibodies above the cut-off value (henceforth referred to as seropositive).

Five HCWs had RT-PCR confirmed COVID-19 infection but did not have IgG antibodies even after 30 days had lapsed since the PCR test i.e., seroconversion did not occur. These individuals were not followed-up. Of the 59 baseline seropositive HCWs, 49 had previous history of COVID-19 infection in the one month preceding their enrollment in the study. Amongst these individuals, three were lost to follow-up. Ten seropositive HCWs (10/59=16.9%) had no history of ILI or PCR-confirmed SARS-CoV-2 infection. From these, one HCW was included in the follow-up group when he reported ILI symptoms three months later and was confirmed to have COVID-19 by RT-PCR. So, in essence, the longitudinal cohort (n=47) consisted of 46 seropositive HCWs who had a history of COVID-19, and one baseline seropositive HCW who was included midway into the study (Table/Fig 1).

Rest of the baseline seropositive HCWs did not report any symptoms of COVID-19 or tested positive for SARS-CoV-2 RT-PCR at any point of time in the follow-up period. Seroconversion rate for anti SARS-CoV-2 IgG antibodies amongst participants with history of COVID-19 was 90.74% (49/54) after atleast 30 days of testing positive by RT-PCR. Of the 171, baseline seronegative HCWs, 21 became symptomatic and tested positive by RT-PCR on follow-up. As mentioned earlier, only one person from the seropositive group had a subsequent PCR-confirmed infection. Incidence of PCR positive SARS-CoV-2 reinfection cases were inversely associated with baseline seronegative status i.e., titres below the cut-off threshold (p<0.05) (Table/Fig 2).

• Incidence in seronegative group: 21/16195 cases per person days=12.96 per 10,000 person days
• Incidence in seropositive group: =1/7743 cases per person days=1.29 per 10,000 person days
• Incidence rate ratio=Incidence in seropositive/Incidence in seronegative=1.29/12.96=0.099

Risk ratio for infection based on antibody status (baseline seronegative vs baseline seropositive) was determined to be 8.12 (95% CI 1.068-61.755). For PCR positive individuals it was 0.138 (95% confidence interval 0.019-1.004) while for those who were COVID-19 naïve, it was 1.121 (95% CI 1.05-1.196). This implies that seronegative HCWs were at eight time higher risk of getting infected with SARS-CoV-2 as compared to seropositive individuals. Incidence varied by calendar time and reflected a consistently higher incidence in the seronegative HCWs. A peak in cases was noted during August-September 2020 and expectedly coincided with the first wave of the pandemic in India which occurred post the relaxation of lockdown regulations from June 2020 onwards (Table/Fig 3).

The follow-up cohort of 47 HCWs were tested for anti SARS-CoV-2 IgG antibody titre at four follow-up visits viz., 1st sample was collected 15-45 days after testing PCR positive (day-0), 2nd sample was collected between 46-90 days, 3rd sample was collected between 91-135 days and 4th sample was collected between 136-180 days for only 14 HCWs as the rest were lost to follow-up for reasons like refusal to give further samples, job attrition etc. Mean age of this set of participants was 37±11 years. Mean follow-up duration was 124±31 days. The gender distribution consisted of 26 males and 21 females.

We compared antibody titres against the severity of past infection to assess the differences in immune responses in each category. We observed a positive relation between increases in the geometric mean titres of IgG for all four serial samples versus the severity of previous infection i.e., more was the severity of symptoms more was the antibody response (Table/Fig 4). Antibody response trend showed a peak in the mean titres in the 46-90 days period followed by a steep decline till 135 days and a gradual waning thereafter (Table/Fig 5). Notably, only two HCWs (from the asymptomatic HCW category) demonstrated complete seroconversion below the cut-off value of 15 AU/mL over the course of 180 days of follow-up.

Discussion

The SARS-CoV-2, a human betacoronavirus, first reported from Wuhan, China in December 2019, has emerged as the latest viral pneumonia pandemic engulfing more than 200 countries. The HCWs are a particularly high-risk group for infection due to constant exposure to the pathogen. A recent meta-analysis of 11 studies found that the proportion of HCWs who were SARS-CoV-2 positive among all COVID-19 patients were 10.1% (22). In India, a case-control study conducted by the Indian Council of Medical Research COVID-19 team analysed data of over 23,000 symptomatic HCWs and found the SARS-CoV-2 infection prevalence rate of 5% (23). Another report from Mumbai found the prevalence of COVID-19 amongst asymptomatic and previously symptomatic HCWs to be 4.3% and 70%, respectively (24). Most studies from India have focused solely on examining sero-prevalence of SARS-CoV-2 and epidemiological risk factors for infection in HCWs. A cohort study published from Chennai, India demonstrated an average duration of 104 days for persistence of IgG antibodies and a positive correlation with presence of symptoms. However, antibody levels of study subjects were tested on only one occasion (20).

A priori, we wanted to further investigate the role of protective immunity in a hospital setting. Hence, a longitudinal study to map the SARS-CoV-2 anti S1/S2 IgG antibody levels of study subjects at multiple occasions and their durability was planned in a cohort of HCWs. The observed seroconversion rate for IgG antibodies was expectedly above 90% after about 30 days of diagnosis of infection. In a report from China, serial samples from 63 patients were assessed, out of whom 97% sero converted for both IgM and IgG antibodies with median days of seroconversion after symptom onset being 13 days for both antibodies (25).

In another case-control report examining 77 samples to compare immune responses to the Receptor-Binding Domain (RBD) of the spike protein it was found that nine days after symptom onset, 98% of patients had a positive IgG response with a specificity of 100% (26). Zhao J et al., reported a sero conversion rate of 93.1% and 64.7% for IgM and IgG antibodies respectively. Seroconversion for IgG occurred after 14 days (27). In the present study, 45 HCWs of the follow-up cohort had consistently high values above the cut-off threshold till at least 180 days from day-0, while seroreversion occurred in only two individuals.

Similar observations were made in a multicentric longitudinal study conducted in India where no fall in anti-RBD IgG titers was reported after at least 10 weeks of follow-up. This is an ongoing project where more prospective data is yet to be published (28). In stark contrast to our data, a multicentric report from USA found that out of 156 HCWs who were tested for serial titers of SARS-CoV-2 antibodies at an interval of approximately 60 days, 146 (93.6%) had a decline in antibody levels, and 44 (28.2%) had a decline to levels below the threshold for positivity, thus showing complete seroreversion (29).

In the present cohort, mean antibody titres peaked between 46-90 days and there was biphasic decay thereafter. The antibody levels declined steeply during the time-gap between second and third samples followed by a slower rate of decay. A mathematical model has been proposed for analysing antibody kinetics by the utilisation of prior data from other coronaviruses. There searchers predict that antibody responses peak within 2-4 weeks after symptom onset, followed by rapid decay in the first 3-6 months and an estimated one-year period for 60% decay from the peak response (30). A comprehensive report on immune memory against SARS-CoV-2 was published where the dynamics of memory B cells, CD 8+ cells and CD 4+ cells was analysed over eight months. It was observed that immune memory persisted in most subjects for longer than five months after infection. The investigators also observed persistent anti-spike IgG antibodies from 20-240 days post symptom onset and a half-life of 140 days (31). In another report from China, it was found that anti nucleoprotein antibodies persisted till 194 days in in-patients (32). These findings are contrary to one of the reports on antibody durability, where half-life was found to be only 36 days in a cohort of community patients (33).

The present study reported that antibody titres increased proportionately with severity of previous infection. Similar findings have been reported in a cohort of 56 HCWs by Birch T et al., (34). Another study from Bangladesh reported that mildly symptomatic patients developed IgM and IgA responses by day 14 in 72% and 83% of individuals, respectively, while 95% of individuals developed IgG response, and rose to 100% by day 30. However, asymptomatic infected individuals with SARS-CoV-2 developed antibody responses significantly less frequently, with only 20% positive for IgA and 22% positive for IgM by day 14, and 45% positive for IgG by day 30 after infection (35).

Tan W et al., have also demonstrated that in a longitudinal cohort of 67 patients, IgM and IgG titres were significantly higher in patients with severe symptoms than those who had milder symptoms. Also, patients with weak IgG antibody response had a faster viral clearance versus patients with strong antibody response who had delayed viral clearance (36). In a bid to explain this phenomenon, researchers analysed anti-RBD antibodies of severely ill COVID-19 patients and demonstrated a unique serologic signature where increased IgG1 antibodies were seen with distinct post-translational modification (i.e., reduced fucosylation). This enhances Fc receptor (fragment crystallisable) binding and in turn augments effector functions of innate immunity including inflammatory cytokine production (37). Five HCWs who had prior history of COVID-19 but tested negative for baseline IgG antibodies may have seroconverted later. However, they were not followed-up for their subsequent antibody status. Interestingly, all of them had had an asymptomatic infection. Even low to moderate amounts of anti-spike protein antibodies seemed to offer significant postinfection immunity. The present study found the seronegative cohort to be at eight times higher risk for acquiring infection than those who had IgG antibodies. Furthermore, whether the HCW had a previous asymptomatic or symptomatic infection, it had no bearing on protective immunity as only one subsequent symptomatic reinfection was seen in the seropositive group. This finding is corroborated by very similar observations made by the researchers of Oxford University Hospitals. The study cohort comprised of 11,364 HCWs who tested negative for baseline antibody results and 1265 who tested positive for baseline antibody results. The latter group included 88 HCWs who seroconverted in the follow-up period. The incidence of SARS-CoV-2 infection was 1.09 per 10,000 days at risk amongst seronegative HCWs versus 0.13 per 10,000 days at risk for the seropositive group (adjusted incidence rate ratio, 0.11; 95% confidence interval, 0.03 to 0.44; p=0.002) (38).

Limitation(s)

A drawback in the evaluation of possible reinfections in the present study could have been that it was based solely on self-reporting of ILI symptoms by the HCWs and not screening by regular PCR tests. Nonetheless, the difference in number is gross and cannot be attributed to asymptomatic reinfections alone. Other limitations in the report may be that some individuals in the baseline seronegative group with previous COVID-19 illness may have had antibody levels that might still have been rising and hence, missed the signal threshold limit. The study cohort was derived from a convenience sample that consisted only of a limited number of HCWs, which might result in non representativeness. The follow-up duration was also limited to six months.

Conclusion

Data from reports including the present study are encouraging and indicate that immune memory has a role in preventing transmission of infection. Mass vaccination (and its success) remains a distant dream for several poor nations and large swathes of vulnerable populations across the world. As such, studies that analyse natural humoral and cellular immunity especially in high-risk groups like HCWs are imperative to assess the magnitude and duration of protection from reinfection, differences in asymptomatic and symptomatic disease, and the effect of herd immunity on disease transmission. Such sero-epidemiological research can be extrapolated to larger population groups and will go a long way in instituting robust public health interventions.

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DOI and Others

DOI: 10.7860/JCDR/2022/51855.16011

Date of Submission: Aug 10, 2021
Date of Peer Review: Oct 28, 2021
Date of Acceptance: Jan 09, 2022
Date of Publishing: Feb 01, 2022

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA

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