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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
Original article / research
Full Version
Hybrid Immunity in SARS-CoV-2: Are Antibody Responses Similar in all Infected and AZD1222 Vaccinated Persons?
Correspondence Address :
Dr. Sajitha Musthafa,
Assistant Professor, Department of Pulmonary Medicine, Government Medical College, Kottayam-686008, Kerala, India.
E-mail: drsajitham@gmail.com
Introduction: There is a diversity in population regarding the number and doses of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines and past infection status and the antibody titres may be different across various groups. The antibody titres determined in the same time-frame after the immune evoking event may give clues regarding the prioritisation for boosters and factors causing variability in titres.
Aim: To compare and assess the Immunoglobulin G (IgG) anti-spike (S) antibody titres among the Healthcare Workers (HCWs) with history of Adenovirus vector based vaccine AZD1222 (Covishield) and infections, in different orders.
Materials and Methods: An observational cross-sectional cohort study was conducted in a tertiary care centre during November 2021 to December 2021. The antibody titres of a healthy cohort of HCWs (n=178) who were either double-vaccinated with no history of SARS-CoV-2 infection or vaccinated but along with a history of SARS-CoV-2 infection were determined six weeks after the last event (infection/vaccination). They were grouped based on the order of vaccination (V) and infection (I).
Results: The major groups were group 1 (V+V), group 2 (I+V+V), group 3 (V+ V+ I) and group 4 (V+I+V). The highest titres of Anti-S IgG antibody observed in vaccinated with breakthrough infection group 3-V+V+I (n=71) {20662(10853-34744)}. The group with double vaccination but with no history of infection {group 1-V+V (N=49)} had the lowest titres - {2395(844.4-7443)}. The hybrid immunity group (those who had infection which was followed by vaccination) group 2 (I+V+V) had titres 4241 (2220-7373) and group 4 (V+I+V) had titres 6542 (3772-11700) which were lower than those with breakthrough infection.
Conclusion: Anti-S antibody titres are highest among vaccinated with breakthrough infections and lowest in those with two doses of vaccines but no history of previous confirmed infections and booster doses may be prioritised for the second group. The timing of previous infection can also be a criterion for further booster doses.
Anti-spike antibody, Anti-S titres, Breakthrough infections, Heathcare workers
Even after two years there are difficulties encountered in the fight against SARS-CoV-2 virus. There is non uniformity in vaccine distribution in low-income countries. The variants of concern like delta and omicron continue to cause deaths and there are still unmitigated concerns regarding emergence of new variants. Vaccination remains the greatest armour against SARS-CoV-2 pandemic. Even though the Variant of Concern (VoC) like delta and omicron made their way, vaccination provided the defence against severe infections and played a great role in reducing mortality (1). It has been shown that previously infected people have greater protection against reinfection (2). On the other hand the immunity starts waning after few months hence the choice of population who need booster doses and timing of booster depends on the antibody titres of the population (3),(4).
Since vaccination was rolled out when the epidemic was raging in waves of varying intensity, there is a diversity in population regarding the number of doses of vaccine and past infection status and the order of these events. There is a knowledge gap regarding the protective antibody titres in this diverse population. Several studies have shown that neutralising antibody titre is a good indicator of vaccine efficacy against SARS-CoV-2 reinfection and can dictate need for further booster doses (5),(6),(7). Neutralising antibody titres are readily not available and a more practical immune correlate of protection like anti-S-IgG titre can also be used as a surrogate for protection against reinfection (2),(8),(9). There is evidence that a single dose of messenger Ribonucleic Acid (mRNA) vaccine (Pfizer or Moderna) after a documented SARS-CoV-2 infection produces a robust antibody response that is superior to the antibody response generated by natural infection alone (5),(10),(11). There have not been studies comparing the antibody response in AZD12222 (Covishield vaccination) in double vaccinated with no history of natural infection and vaccinated individuals who had breakthrough infections (infections after vaccination) (12) and individuals who had infections first and then got vaccinated (hybrid immunity) (11),(13).
Hence the present study was aimed to assess and compare the IgG Anti S antibody titres among the HCWs with history of two doses of adenovirus vector based vaccination (AZD1222) and infections in different orders.
This observational cross-sectional cohort study was conducted in a tertiary care centre during November 2021 to December 2021. Healthy HCWs who had received two doses of AZD1222 (Covishield) vaccine were included in the study. History of molecular confirmed COVID (confirmed covid infection), the symptoms during the infection and co-morbidities were elicited using a structured proforma after getting consent. Study was carried out at the Government Medical College, Kerala, India, after Institutional Ethical Committee (IEC) approval (IEC No: 115/2021, IRB, Govt Medical College, Kerala) and informed consent obtained from all participants.
Inclusion criteria: HCWs with age >18 years having history of two doses of vaccination with Covishield with or without history of molecular confirmed SARS-CoV-2 infection. The last immune evoking incident (infection or vaccination) was six to eight weeks prior to the time of sera collection.
Exclusion criteria: Vaccination with any other vaccine and history of Moderate and Severe COVID-19 infection as per World Health Organisation (WHO) criteria at the time of study (3).
Sample size calculation: Sample size was calculated for comparison of two means using the formula N=(Zα/2+Zβ)2×2×σ2/d2. Based on the study conducted by Shenoy P et al., (13), it was found to be less than 10 in each group. So considering attrition a minimum of 20 individuals in each category was considered.
The persons satisfying inclusion criteria were grouped based on the number and order of vaccination and infection. The four major groups identified were (1) double vaccinated with no history of previous confirmed infection (V+V), (2) individuals who had both doses of vaccination after confirmed infection-hybrid group (I+V+V) (3) double vaccinated individuals with breakthrough infections (infections after two stipulated doses of vaccine) (V+V+I). (4) Individuals who were infected between 2 doses of vaccine {V+I+V}.
The sera was collected four to six weeks after the last event (infection/vaccination). The demographic details, history of co-morbidities, symptoms during COVID infection were noted.
Antibody assay: IgG-Receptor Binding Domain (RBD) antibodies against the S1 subunit of the spike protein of SARS-CoV-2 (12) was assessed using SARS-CoV 2 IgG @ Quant (Abbott, Ireland) Chemiluminescent microparticle immunoassay (CMIA) (14). SARS-CoV-2 IgG 2 Quant assay (CE marked) was performed in all groups on the Abbot Architect 12000 platform in accordance with the manufacturer’s package insert. In this antibody CMIA test, the SARS-CoV-2 antigen coated paramagnetic microparticles bind to the IgG antibodies that attach to the virus spike protein in human serum and plasma sample. The result in chemiluminescence in Relative Light Units (RLU) following the addition of antihuman IgG acridinium labelled conjugate in comparison with IgG 2 calibrator indicates the strength of response which reflects the quantity of IgG present and is represented as Arbitrary Units (AU). Fifty Arbitrary units/millilitre (50 AU/mL) and above is considered positive. This quantitative measurement is helpful to evaluate an individuals humoural response.
Statistical Analysis
All intragroup comparisons of antibody titres were done by independent samples t-test after log transformations of antibody levels. Data are expressed as Mean and Standard Deviation (SD) or median and Interquartile Range (IQR) based on Shapiro-Wilk test for normality. Statistical analysis was carried out using the Statistical Package for the Social Sciences (SPSS) software (IBM SPSS Statistics for Windows, Version 25.0) with a p-value of <0.05 as statistically significant, all reported values were two sided.
A total of 178 persons were recruited in the study and anti-S antibody titres estimated. Eleven persons who were included initially and found to have only single vaccination later on detailed enquiry (6), I+V(5) and were excluded from final analysis. A total of 167 belonged to the four groups, group 1 double vaccinated with no history of previous confirmed infection V+V (n=49), (2) individuals who had both doses of vaccination after confirmed infection – group 2 I+V+V (n=30), (3) double vaccinated individuals with breakthrough infections (infections after two stipulated doses of vaccine) V+V+I (n=71) and (4) individuals who were infected between two doses of vaccine group 4 V+I+V (n=17). They were included in the final analysis.
There was no association between antibody levels and age in the four groups. The mean age was comparable across various groups. The co-morbidities observed were hypertension in five persons, diabetes in four, asthma in two, coronary artery disease in one and hypothyroidism in one person (Table/Fig 1). Fever was the commonest symptom during the infection in three groups (I+V+V- 40%; V+V+I - 39.44% & V+I+V - 58.82%) (Table/Fig 2).
Antibody levels across various groups: The antibody levels were found to be highest among the double vaccinated group with breakthrough infections V+V+I (20662(10853-34744)} compared to all other groups which was statistically significant (Table/Fig 3). The levels were lowest among vaccination alone group (V+V) {2395(844.4-7443)}. The hybrid groups with infection followed double vaccination had titres I+V+V{4241(2220-7373) and V+I+V{6542(3772-11700} which were lower than those with breakthrough infections.
In subgroup analysis of the V+V+I group that had breakthrough infections, anti-spike antibody titres were maximum with the V+V+I group and significantly high compared to all other groups. Duration between date of last vaccine dose and breakthrough infection showed no association.
The study compared the antibody titres across the various subgroups (depending on the doses of vaccines and order of vaccination and infection) measured at a uniform timeframe after the last immune activation (infection or immunisation). It shows that anti-S IgG titres were highest in the group who had breakthrough infections (V+V+I) after the stipulated two doses of vaccination compared to vaccination alone group (V+V) or the group with infection initially followed by vaccination (I+V+V). The vaccinated group with no history of infections (V+V) had the lowest titres compared to the groups with history of vaccination and infection in whichever order. Not withstanding the chance of them having a previously undetected/ asymptomatic infection, this group with history of no previous confirmed infections had the lowest titres. With further evidence in waning of immunity prioritisation of booster/augmentation doses maybe done for persons without previous confirmed infections in low income countries (15),(16).
The breakthrough infections (infections after both doses of vaccination) generate better antibody titres due to exposure to an array of antigens (11). Hence infection, like vaccination is a potent immune evoking event. This was shown by neutralisation assays in previous studies also (9). There was no association between the antibody titres and duration from last dose of vaccination to the infection in this group on subgroup analysis. There is ample evidence by previous studies that, a single dose of mRNA vaccines Pfizer/BioNtech or Moderna mount robust immune response in previously infected individuals (6),(8),(9),(17),(18). A study in Acute inflammatory rheumatoid disease patients in India with AZD12222 also showed that hybrid immunity is superior to vaccine alone induced immunity (10).
There are very few studies comparing the titres obtained after breakthrough infections (V+V+I) and titres obtained after vaccination following an earlier infection (I+V+V). A study by Bates TA et al., assessed the humoural response between vaccinated alone, breakthrough infections and hybrid immunity (vaccinations after infection) with antibody titres and neutralisation assays, showed that infections before or after vaccination significantly improves neutralisation responses (12). In this study there was no significant differences between the break through infection group and hybrid immunity group. This study by Bates TA et al., showed 8.5-and 15.7-fold improvements against the Delta variant for the breakthrough and hybrid immune groups, respectively, compared with two vaccine doses alone group (12). Earlier studies suggested that Delta variant neutralising titers improved by 6- to 12-fold after booster vaccination eight months after a second dose (19). Hence, in fully vaccinated individuals magnitude of improvement in natural infection is similar to that of booster doses.
In the present study, comparison done between the two groups I+V+V group 2 and V+V+I group 3 at a uniform time frame after the last immune response showed statistically significant high titres in V+V+I group. Compared to vaccine alone (V+V) group 1 they had very high titres. A neutralisation assay study done on AZD1222 recipients with history of COVID-19 infection and breakthrough infection also revealed similar results with high neutralising antibody levels in breakthrough infections (20),(21).
Booster/augmentation doses are being rolled out in India now for those who are already vaccinated with two doses. They are given for individuals with history of two doses of vaccination and nine months after the date of last vaccination (22). The infections are not considered as an immune provoking event and vaccinations can be done after three months of last documented infection in India. The vaccine roadmap by WHO-Strategic Advisory Group of Experts on Immunization (SAGE) is awaiting further studies in hybrid immunity to determine the importance of infection in deciding timing and number of booster doses (23). Considering that a large population had infections and are having already robust titres, booster doses may be needed only at a later time after the last infection in the population with history of breakthrough infections. Prior infection can be considered as a criterion similar to the last vaccine dose for further vaccination. This would lead to effective utilisation of vaccines in low income countries where vaccine procurement maybe a problem.
Limitation(s)
A small sample size, lack of neutralisation assays were the limitations of the study. The study needs follow-up with further assays to assess rate of waning and effects of reinfections.
Anti-S antibody titres after AZD1222 were highest among vaccinated with breakthrough infections and lowest in those with two doses of vaccines but no history of previous confirmed infections and booster doses may be prioritised for the second group. The timing of previous infection can also be a criterion for further booster doses. The strengths of the study are comparison across the groups with different orders of vaccines and infection at a uniform time frame and a fairly uniform study group (young, frontline HCWs).
DOI: 10.7860/JCDR/2022/57766.16694
Date of Submission: May 13, 2022
Date of Peer Review: May 26, 2022
Date of Acceptance: Jul 21, 2022
Date of Publishing: Aug 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
PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: May 20, 2022
• Manual Googling: Jul 12, 2022
• iThenticate Software: Jul 27, 2022 (6%)
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