F1000Research F1000Research 2046-1402 F1000 Research Limited London, UK 10.12688/f1000research.42122.1 Brief Report Articles Temporal development of research publications on SARS-CoV-2 and COVID-19

[version 1; peer review: 1 approved, 1 approved with reservations]

 Kang Jonghoon Conceptualization Data Curation Formal Analysis Investigation Methodology Project Administration Supervision Validation Visualization Writing – Original Draft Preparation Writing – Review & Editing https://orcid.org/0000-0001-5594-6141 a 1 Kang Erin Data Curation Formal Analysis Investigation Validation Writing – Original Draft Preparation 2 Cowan Matthew L. Conceptualization Data Curation Methodology Writing – Original Draft Preparation Writing – Review & Editing 1 Orozco Manuel Writing – Original Draft Preparation Writing – Review & Editing 3 Biology, Valdosta State University, Valdosta, Georgia, 31698, USA James S. Rickards High School, Tallahassee, Florida, 32301, USA Medicine, Philadelphia College of Osteopathic Medicine, Suwanee, Georgia, 30024, USA jkang@valdosta.edu

No competing interests were disclosed.

 12 4 2021 2021 10 283 31 3 2021 Copyright: © 2021 Kang J et al. 2021 This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The coronavirus disease 2019 (COVID-19) pandemic has affected daily life throughout the world. The scientific community has globally responded to the pandemic with research on an unprecedented scale to help prevent disease spread and terminate the pandemic, resulting in a proliferation of scientific publications. In this article, the temporal trend of research on COVID-19 is analyzed to describe its development and inform a prediction of its future. Four other viruses are included in the analysis as negative or positive controls to illustrate that the concerns of the general public and/or the interest of the scientific community are major driving forces in the development of research. Our analysis predicts that COVID-19 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will be major topics of research until at least 2025. We discuss the implications of our analysis for three sectors of community: researchers, epidemiologists, and young students.

 COVID-19 SARS-CoV-2 HCV HIV Ebola Zika PubMed Scientometrics The author(s) declared that no grants were involved in supporting this work. Introduction

The recent outbreak of coronavirus disease 2019 (COVID-19) has imposed an unprecedented and devastating burden on the world, 1 including a serious encumbrance to health care systems. 2 Collectively the scientific community has responded to the pandemic by researching the spread of the disease and its causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in order to understand and terminate the pandemic. These efforts have resulted in a vast amount of publications. We believe it would be worthwhile to analyze the trend of the publications in order to predict the future of research in this area.

We have previously demonstrated that the number of publications may be a reliable quantitative measure of the magnitude of research activity of a biological or biomedical science. 3 In conjunction with regression analysis, the method of assessing research activity of a biological or biomedical discipline based on the number of publications in the field has been found to be effective in the prognostication of the future of biomedical fields by extrapolation of the best fit equation. 4 The method has successfully been applied to various fields such as food sciences, 5 epigenetics, 6 metabolomics, 7 and environmental sciences. 8

In this paper, we apply the method mentioned above to COVID-19 research to quantitatively describe the temporal development of the research and predict its future. We also include four other viruses in the study; hepatitis C virus (HCV) and HIV as negative controls without any apparent outbreaks in the period from January to November, 2020, and Ebola virus disease (EVD) and Zika virus (ZIKV) as positive controls of epidemiological outbreak during the period of examination from January 2014 to November 2020.

 Methods

To quantitatively investigate the trend of research related to the five viruses (SARS-CoV-2, HCV, HIV, EVD, and ZIKV), we searched the PubMed database on December 23, 2020. Our search strategy was as follows for the different viruses: (The superscripts a and b in the search phrases represent month and year, respectively.)

SARS-CoV-2: (((COVID [Title/Abstract]) OR (COVID-19[Title/Abstract])) OR (SARS-CoV-2[Title/Abstract])) AND ((“2020/M a”[Date - Publication]: “2020/M a”[Date - Publication]))

HCV: (((HCV [Title/Abstract]) OR (“hepatitis C virus”[Title/Abstract])) AND (virus [Text Word])) AND ((“2020/M a”[Date - Publication]: “2020/M a”[Date - Publication]))

HIV: (((HIV [Title/Abstract]) OR (“human immunodeficiency virus”[Title/Abstract])) AND (virus [Text Word])) AND ((“2020/M a”[Date - Publication]: “2020/M a”[Date - Publication]))

Ebola: ((Ebola [Title/Abstract]) AND (virus [Text Word])) AND ((“Y b/M a”[Date - Publication]: “Y b/M a”[Date - Publication]))

Zika: ((ZIKA [Title/Abstract]) AND (virus [Text Word])) AND ((“Y b/M a”[Date - Publication]: “Y b/M a”[Date - Publication]))

The number of publications on each virus was manually recorded on a monthly basis for eleven months for SARS-CoV-2, HCV, and HIV from January to November 2020, and for eighty three months for EVD and ZIKV from January 2014 to November 2020 for further investigation of data. Subsequent nonlinear regression analysis of the PubMed search results was conducted to obtain equation of best fit using SigmaPlot (version 11; Systat Software, Inc., San Jose, CA).

 Results

We retrieved monthly publication numbers of the five viruses from the Pubmed database, and obtained the best fitting equation for each virus. Our results are summarized in Figure 1 and Table 1. We identified that temporal dynamics of publications related to the five viruses exhibit four characteristics. Number of research publications related to five viruses.

The solid line in each graph represents the best fit. The corresponding year in the panel B is presented above the x-axis. SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.

Fitting parameters ( <italic toggle="yes">a</italic>, <italic toggle="yes">b</italic>, and <italic toggle="yes">c</italic>) and associated standard errors (SE) and the squared Pearson correlation coefficients ( <italic toggle="yes">R</italic> <sup>2</sup>).
Equation Virus a ± SE b ± SE c ± SE R 2
Eq. ( 1) SARS-CoV-2 12900 ± 370 0.67 ± 0.12 4.1 ± 0.14 0.9803
Ebola 150 ± 65 1.8 ± 0.87 9.5 ± 1.9 0.8345
Zika 220 ± 3.9 0.96 ± 0.088 25.8 ± 0.1 0.9916
Eq. ( 2) Ebola 150 ± 8.7 0.013 ± 0.001 0.5522
Zika 300 ± 22 0.01 ± 0.001 0.5466

First, a sigmoidal equation ( Equation 1) was found to be the best quantitative description of the publication trend of COVID-19 research: f 1 x = a 1 + exp c − x b

The value of each parameter is listed in Table 1. The mathematical meaning of each parameter can be found in our previous publication. 4 In brief, the parameter “ a” represents an asymptotic maximum value of the function, “ b” is related to the shape of the function, and “ c” is the year when the value of the function is half of the asymptotic maximum value. 4 The sigmoidal kinetics observed in the research trend of COVID-19 ( Figure 1) is congruent with other areas of research such as bioinformatics, epigenetics, food sciences, and environmental sciences. 4– 7

Second, there was no significant correlation between the temporal point and the number of research publications on HCV and HIV during the time period examined from January to Novmber 2020 ( p = 0.240 for HCV, and p = 0.367 for HIV) ( Figure 1). This can be attributed to the absence of any significant outbreaks of HCV or HIV during the time period; while these viruses are important in a biomedical sense, 10, 11 those viruses have likely been endemic. 12, 13

Third, two examples of outbreaks in the decade of 2010, EVD 14 and ZIKV, 15 exhibit biphasic kinetics in the publication trend ( Figure 1). The phase of sharp increase in number of publications, which overlaps with the time of each outbreak, also follows sigmoidal kinetics ( Equation 1 and Table 1) as does COVID-19. The second phase, a decreasing phase, shows a slow and gradual decline that can be described by an exponential decay function ( Equation 2): f 2 x = a × exp − bx

Fourth, the exponential nature of the decay kinetics may be valuable for the prediction of the future of COVID-19 research. In the case of EVD, the publication number started to decrease, when x = 11 ( Figure 1), where the publication number is 123 (see underlying data 9 ) corresponding to 82% of the asymptotic maximum value of 150 ( Table 1). Zika research started to decrease, when x = 33 ( Figure 1), where the publication number is 222 (see underlying data 9 ) corresponding to 101% of its asymptotic maximum value of 219 ( Table 1). As of June, 2020, COVID-19 research reached 95% of its asymptotic maximum value of 12900 ( Figure 1): 12288/12900 = 0.95 (underlying data 9 and Table 1). The quantitative comparison between SARS-CoV-2 and the two viruses suggests that the case of ZIKV is a more appropriate model for the prediction of COVID-19 research. Despite the apparent similarity of the research trend between SARS-CoV-2 and ZIKV, one should note that there is a substantial difference in the asymptotic maximum value ( a in Equation 1) between these two areas of research: SARS-CoV-2 has an almost 60 times (≅ 12900/220) larger value of a than ZIKV ( Table 1).

 Discussion

The results of our research have implications for three sectors of the global community. One is for the scientific community in that research on COVID-19 is predicted to be active for a long time, even after commencing a downward trend. According to our mathematical model of the research on ZIKV, it will take COVID-19 research approximately 5 years (65.8 months) to reach half of its maximum value: f 2(98.8) = f 1(33)/2 and 98.8 – 33 = 65.8. While it is not certain when the publications on COVID-19 will start to decline, we expect that it will remain a major topic of research until at least 2025. This prediction may serve as a guide in planning research on COVID-19. The second implication of our results is for researchers in epidemiology as the method introduced in this paper can be easily applied to other epidemics and pandemics. The third implication is for young students. Our analysis of the ongoing research on COVID-19 should show them that science is a valuable way of contributing to humanity by providing solutions for public concerns such as COVID-19.

 Data availability Underlying data

Figshare: Number of PubMed-indexed articles related to five viruses; SARS-CoV-2, HCV, HIV, Ebola, and Zika. https://doi.org/10.6084/m9.figshare.12958361.v3 9

This project contains the following underlying data:

covid_figshare_kang.csv (spreadsheet of the number of research publications found relating to five viruses).

Data are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication).

 Acknowledgments

We would like to thank Kathi Canese, a Program Manager for the support department of PubMed, for the valuable advice in the search of PubMed.

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Competing interests: No competing interests were disclosed.

 1 12 2021 Copyright: © 2021 Nassar M 2021 This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. recommendation approve-with-reservations

Dear Authors

Thank you so much for your great effort. This is an interesting topic. Here are some opportunities for improvement:

Please justify the selection of the four viruses compared to COVID-19. I propose to make a comparison table with similarities and differences.

Please comment on why this article did not include other databases like Medline or Embase.

Please mention other factors affecting that affect the number of publications (direct and indirect).

Please comment on changes to the journals' publication policies, time, APC, indexing, etc.

Please comment on the global quarantine, governmental closure, and the negative impact on developed and developing countries' economic and social aspects.

I suggest commenting on the trend or theme 1 of research development of the diagnosis, prevention, COVID-19 complication, treatment, vaccination, COVID-19 vaccine-induced complications[ref2] , 3 , 4 , COVID-19 variants, COVID-19 vaccination booster dose.

There are many publications as case reports, case series, descriptive, case-control, RCT, meta-analysis, and umbrella review. For each phase and with other comorbidities 5 , 6 ,[ref7] , 8 . NB: All citations are my own papers and for guidance. You do not need to cite them.

Please create a limitation section and mention these factors as a study limitation. At least try to mention these factors as limitations in the study.

I suggest creating a diagram to demonstrate the evolution of COVID-19 research.

Is the work clearly and accurately presented and does it cite the current literature?

Partly

If applicable, is the statistical analysis and its interpretation appropriate?

I cannot comment. A qualified statistician is required.

Are all the source data underlying the results available to ensure full reproducibility?

Yes

Is the study design appropriate and is the work technically sound?

Partly

Are the conclusions drawn adequately supported by the results?

Yes

Are sufficient details of methods and analysis provided to allow replication by others?

Yes

Reviewer Expertise:

Clinical research, COVID-19, Cardiovascular Diabetes, and Organ transplantation.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

References : Current systematic reviews and meta-analyses of COVID-19. World J Virol .2021;10(4) : 10.5501/wjv.v10.i4.182 182-208 34367933 10.5501/wjv.v10.i4.182 : COVID-19 vaccine induced rhabdomyolysis: Case report with literature review. Diabetes Metab Syndr .15(4) : 10.1016/j.dsx.2021.06.007 102170 34186348 10.1016/j.dsx.2021.06.007 : COVID-19 vaccine-induced myocarditis: Case report with literature review. Diabetes Metab Syndr .15(5) : 10.1016/j.dsx.2021.102205 102205 34293552 10.1016/j.dsx.2021.102205 : Bullous drug eruption after second dose of mRNA-1273 (Moderna) COVID-19 vaccine: Case report. Journal of Infection and Public Health .2021;14(10) : 10.1016/j.jiph.2021.06.021 1392-1394 10.1016/j.jiph.2021.06.021 : COVID-19 Mortality in Transplant Recipients. Int J Organ Transplant Med .2020;11(4) :145-162 33335696 : Diabetes mellitus and Coronavirus Disease (Covid-19) Associated Mucormycosis (CAM): A wake-up call from Egypt. Diabetes Metab Syndr .15(5) : 10.1016/j.dsx.2021.102195 102195 34314921 10.1016/j.dsx.2021.102195 : Liver transplantation during global COVID-19 pandemic. World J Clin Cases .2021;9(23) : 10.12998/wjcc.v9.i23.6608 6608-6623 34447809 10.12998/wjcc.v9.i23.6608 : Coronavirus disease 2019 and renal transplantation. World J Clin Cases .2021;9(27) : 10.12998/wjcc.v9.i27.7986 7986-7997 34621855 10.12998/wjcc.v9.i27.7986 Kang Jonghoon Valdosta State University, USA

Competing interests: No competing interests were disclosed.

 16 4 2022

Dear Dr Nassar,

Than you for your thoughtful comments (in plain fonts) on our paper. Here, we respond to your comments (in bold font).

Please justify the selection of the four viruses compared to COVID-19. I propose to make a comparison table with similarities and differences.

Justification for the selection of the four viruses is comparison of COVID-19 to a negative control group (HCV and HIV) without any recent breaks and to a positive control group (EVD and ZIKV) with recent breaks. We selected those viruses based on our familiarity with them. We have included a comparison table (Table 1) in the revision.

Please comment on why this article did not include other databases like Medline or Embase.

We have included our justification for the selection of PubMed in our study in Discussion.

Please mention other factors affecting that affect the number of publications (direct and indirect).

Surely public interests are one of the factors affecting the number of publications as noted in our paper. However, we are not aware of any other factors for sure, even though there must be various factors. For example, we expect that the number of researchers and number of journals in a particular field will affect the number of publications in the field. It will be of great interest recognizing those factors in future research.

Please comment on changes to the journals' publication policies, time, APC, indexing, etc.

Those factors must play a role in the trend of publications. However, we do not have any explanation for the point.

Please comment on the global quarantine, governmental closure, and the negative impact on developed and developing countries' economic and social aspects.

Thank you for the additional guidance. However, the nature of this paper is to forecast the number of publications in the future by analyzing the trends and not related to the global quarantine, governmental closure, and the negative impact on developed and developing countries' economic and social aspects. That is not to say these areas are any less important but we are chiefly concerned with the mathematical nature of the trends we saw from our gathering of publication counts on PubMed.

I suggest commenting on the trend or theme1 of research development of the diagnosis, prevention, COVID-19 complication, treatment, vaccination, COVID-19 vaccine-induced complications[ref2],3,4, COVID-19 variants, COVID-19 vaccination booster dose.

There are many publications as case reports, case series, descriptive, case-control, RCT, meta-analysis, and umbrella review. For each phase and with other comorbidities5,6,[ref7],8. NB: All citations are my own papers and for guidance. You do not need to cite them.

Please create a limitation section and mention these factors as a study limitation. At least try to mention these factors as limitations in the study.

I suggest creating a diagram to demonstrate the evolution of COVID-19 research.

References

1. Nassar M, Nso N, Alfishawy M, Novikov A, et al.: Current systematic reviews and meta-analyses of COVID-19.World J Virol. 2021; 10 (4): 182-208 PubMed Abstract | Publisher Full Text

2. Nassar M, Chung H, Dhayaparan Y, Nyein A, et al.: COVID-19 vaccine induced rhabdomyolysis: Case report with literature review.Diabetes Metab Syndr. 15 (4): 102170 PubMed Abstract | Publisher Full Text

3. Nassar M, Nso N, Gonzalez C, Lakhdar S, et al.: COVID-19 vaccine-induced myocarditis: Case report with literature review.Diabetes Metab Syndr. 15 (5): 102205 PubMed Abstract | Publisher Full Text

4. Kong J, Cuevas-Castillo F, Nassar M, Lei C, et al.: Bullous drug eruption after second dose of mRNA-1273 (Moderna) COVID-19 vaccine: Case report. Journal of Infection and Public Health. 2021; 14 (10): 1392-1394 Publisher Full Text

5. Alfishawy M, Elbendary A, Mohamed M, Nassar M: COVID-19 Mortality in Transplant Recipients.Int J Organ Transplant Med. 2020; 11 (4): 145-162 PubMed Abstract

6. Alfishawy M, Elbendary A, Younes A, Negm A, et al.: Diabetes mellitus and Coronavirus Disease (Covid-19) Associated Mucormycosis (CAM): A wake-up call from Egypt.Diabetes Metab Syndr. 15 (5): 102195 PubMed Abstract | Publisher Full Text

7. Alfishawy M, Nso N, Nassar M, Ariyaratnam J, et al.: Liver transplantation during global COVID-19 pandemic.World J Clin Cases. 2021; 9 (23): 6608-6623 PubMed Abstract | Publisher Full Text

8. Nassar M, Nso N, Ariyaratnam J, Sandhu J, et al.: Coronavirus disease 2019 and renal transplantation.World J Clin Cases. 2021; 9 (27): 7986-7997 PubMed Abstract | Publisher Full Text

Thank you for the additional guidance. However, given the nature of this publication is a brief report we feel it would not be necessary to overburden the scope of the paper itself with this addition of the perceived diagram. Brief Reports are small, often preliminary studies, descriptions of unexpected and perhaps unexplained observations or lab protocols that can be described in a short report with a few illustrations (figures/tables), or even a single figure. https://f1000research.com/for-authors/article-guidelines/brief-report.

While qualitative investigation on the evolution of COVID-19 research is beyond the scope of our research, your suggestion of including a limitation section is deemed valuable for our research, and we discussed limitation of our approach in the revised edition. We also included two of the references you suggested in our revision. Thank you for suggesting the references.

10.5256/f1000research.45188.r97764 Reviewer response for version 1 Abenavoli Ludovico 1 Referee https://orcid.org/0000-0002-5922-1524 Department of Health Sciences, Magna Graecia University, Catanzaro, Italy

Competing interests: No competing interests were disclosed.

 27 10 2021 Copyright: © 2021 Abenavoli L 2021 This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. recommendation approve

General comments:

I read with interest this article. It provides data on the scientific production during the pandemic, with regards to 2020. The background is solid, the results have been discussed, and the conclusion supported the data.

Minor point:

I suggest to report the data stratified for original articles, review, brief report and letter to the editor related to COVID-19 topic.

Is the work clearly and accurately presented and does it cite the current literature?

Yes

If applicable, is the statistical analysis and its interpretation appropriate?

Yes

Are all the source data underlying the results available to ensure full reproducibility?

Yes

Is the study design appropriate and is the work technically sound?

Yes

Are the conclusions drawn adequately supported by the results?

Yes

Are sufficient details of methods and analysis provided to allow replication by others?

Yes

Reviewer Expertise:

Epidemiology of COVID-19, COVID-19 clinical aspects, COVID-19 research trends

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

Kang Jonghoon Valdosta State University, USA

Competing interests: No competing interests were disclosed.

 16 4 2022

Dear Dr. Abenavoli

We appreciate your time and effort for reviewing our paper. In the revised manuscript, we have included the data you suggested. We believe the added data will enhance the quality of our work and thank you for the suggestions.