Next Article in Journal
Novel Therapeutic Advances in β-Thalassemia
Next Article in Special Issue
Plant-Based Phytochemical Screening by Targeting Main Protease of SARS-CoV-2 to Design Effective Potent Inhibitors
Previous Article in Journal
Research on the Mechanisms of Plant Enrichment and Detoxification of Cadmium
Previous Article in Special Issue
Associations between the Severity of the Post-Acute COVID-19 Syndrome and Echocardiographic Abnormalities in Previously Healthy Outpatients Following Infection with SARS-CoV-2
 
 
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Opinion

Coronavirus Disease 2019 (COVID-19) Crisis: Losing Our Immunity When We Need It the Most

1
Functional Genomics Laboratory, Endocrinology and Nephrology Axis, CHU de Québec-Université Laval Research Center, Québec, QC G1V 4G2, Canada
2
Department of Molecular Medicine, Faculty of Medicine, Laval University, Québec, QC G1V 0A6, Canada
*
Author to whom correspondence should be addressed.
Biology 2021, 10(6), 545; https://doi.org/10.3390/biology10060545
Received: 20 April 2021 / Revised: 2 June 2021 / Accepted: 15 June 2021 / Published: 18 June 2021
(This article belongs to the Special Issue Coronavirus Disease 2019 (COVID-19))

Abstract

:

Simple Summary

With the current coronavirus disease 2019 (COVID-19) crisis, humans have developed new habits and adapted to a novel socioeconomic reality. Indeed, measures including confinement and lockdown have led to mental health problems, economic crisis, and social isolation, among other consequences. These consequences, along with hand washing, sanitization, and face masks, would reduce our immunity against infections, including COVID-19. Such reduced immunity could impact not only our vulnerability to diseases but also the efficacy of vaccines that carry the biggest hope to putting an end to this COVID-19 pandemic. Thus, there is a need to review these approaches and optimize measures taken to limit the spread of COVID-19 by taking into consideration the possible impact of these measures on our immunity to fight COVID-19.

Abstract

The ongoing coronavirus disease 2019 (COVID-19) crisis has led to a new socioeconomic reality with the acquisition of novel habits. Measures imposed by governments and health authorities such as confinement and lockdown have had important consequences, including mental health problems, economic crisis, and social isolation. Combined with newly acquired habits such as hand washing, sanitization, and face masks, these have all directly and indirectly led to reduced immunity. Such effects on the immune system not only impact the epidemiological profile with respect to COVID-19 and other infectious diseases but also limit the efficacy of the ongoing anti-COVID-19 vaccination campaign. Therefore, there is a need to review these approaches and optimize measures towards better population immunity, which is much needed during such an epidemic.

The ongoing coronavirus disease 2019 (COVID-19) crisis [1], as well as the measures imposed by governments, public health recommendations, the emergence of new variants, and the delay in vaccination campaigns, has put a greater spotlight on the importance of population immunity during the critical phase of this rapidly evolving pandemic. In this paper, we focus on the hypothesis that the measures taken during the pandemic and the socioeconomic situation caused by this crisis are reducing immunity at a period when we need it the most.
One of the most important risk factors for immunity problems is obesity, which negatively impacts immunity [2,3]. We believe that the measures imposed to limit the spread of COVID-19, including home confinement, curfew, closed gymnasiums, and work from home recommendations, result in sedentary behaviors [4], which would lead to an obesity pandemic [5]. As we have previously suggested, obesity also increases the vulnerability of patients recovering from COVID-19 as it can lead to an impaired regeneration homeostasis [6] and impact the development of immune cells.
The other measures characterizing this crisis are the periodic hand washing and sanitizing along with physical distancing. Both of these reduce our contact with different infections and pathogenic agents. Contact with pathogens, in a similar way to vaccines, stimulates the immune system [7,8] and increases its performance. However, with such limited interaction with the environment compared to that before the start of the COVID-19 crisis, less pathogens are detected by the immune system. This could limit its functional interaction as described by the hygiene hypothesis [9], especially within the context of the COVID-19 crisis [10] and the impact on the microbiome [11]. This is also of particular importance given the close link between the microbiome and immunity [12,13] as well as the link between microbiota composition and mental health, including anxiety and depression [14,15], during this COVID-19 outbreak as per the opinions of Venema et al. and Janda et al. and supported by the research of Yeoh et al. [16,17,18].
The hard economic situation caused by this COVID-19 crisis [19] has also made a contribution. For instance, many individuals have lost their jobs [20], and food insecurity has worsened [21] due to price inflation in the markets [22]. Therefore, the grocery options for individuals with limited income is more inclined towards unhealthy choices, including high-fat, high-sugar, and high-salt foods, which are more affordable but have an impact on immunity [23], including the microbiome [24,25], and further worsen obesity. In addition, the poor nutritive value of such an unhealthy diet limits the intake of nutrients like vitamins and therefore impacts the production of antibodies [26], among other immune functions [27]. In addition, diets also impact the microbiota [28,29] and therefore mental health and immunity.
Another consequence of the ongoing COVID-19 crisis is the impact on mental health [30,31] due to psychological stress, disturbed sleeping, and reduced social interaction, which can lead to problems including depression, anxiety, distress, and panic disorder [32,33,34]. These mental health issues during the COVID-19 crisis, along with the impact on immunity [35], could also increase the usage/intake of products such as drugs, alcohol, and tobacco [36,37] with consequent effect on immunity, as has been reported for alcohol consumption [38,39], tobacco [40,41], and drugs [42]. Within this context, it is worth highlighting the importance of pets as companions in reducing the discomfort caused by social isolation, with resulting benefits for both mental health (depression, anxiety, and stress) and physical activity [43], especially as they do not cause transmission of the COVID-19 virus [44].
Moreover, with the lockdown, some individuals may delay receiving the medical care they need or reduce the frequency of visits to these services [45,46], especially given most healthcare facilities would have reduced their regular services so that they could focus their energy on treating COVID-19 cases. This also has a significant impact on general health, including immunity.

Conclusions

The consequences of this multifactorial reduced immunity (Figure 1) can not only increase the risk of developing a severe case of COVID-19 [47] and other infectious diseases [48,49] but also limit the efficacy of vaccines [50].
However, to what extent the effects on immunity due to the issues discussed in this paper (obesity, stress, mental health, hygiene hypothesis, etc.) impact the immune system compared to primary and secondary immunodeficiencies would depend on many factors, including the duration of exposure (which would be the period of the COVID-19 crisis), the severity of these factors, and individual physiological and pathological profiles. Other factors that could have an important influence include medication and the available medical care, which could worsen or improve the immunological outcome. Within this context, our theory indicates that these elements will have an immediate impact on immunity and vaccine effectiveness (pertinent to the current outcomes in this pandemic) as well as potential long-term effects that could persist in the future. Indeed, whereas factors such as disturbed microbiota and mental health problems [51] can be reversed following a healthy lifestyle and/or therapies, which will then improve immunity, other factors such as obesity can turn into a chronic status [52] with long-lasting consequences [53], including on immunity.
Therefore, it is urgent to find innovative solutions beyond home confinement and lockdown to get over this health crisis. Among the most efficient approaches would be to increase the physical activity of the population because exercise has been shown to improve immunity, including in the context of COVID-19 [54,55,56]. This could reduce the incidence of COVID-19 and improve vaccine efficacy. Importantly, the negative effects of this crisis on immunity described herein suggest the need to speed up the vaccination process before the effect of the vaccines is reduced, especially due to the emerging variants.

Author Contributions

A.G. designed the manuscript structure and wrote it. A.G., M.Y., and J.S.-A. discussed the content and exchanged ideas and suggestions (concepts to add, the figure, references selection, etc.) throughout the writing process, edited and critically revised the paper. J.S.-A. gave the final approval for the version to be published. All authors have read and agreed to the published version of the manuscript.

Funding

This work received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Acknowledgments

Abdelaziz Ghanemi received a scholarship under the Merit Scholarship Program for foreign students from the Ministry of Education and Higher Education of Quebec, Canada. The Fonds de recherche du Québec—Nature et technologies (FRQNT) is responsible for managing the program (Bourses d’excellence pour étudiants étrangers du Ministère de l’Éducation et de l’Enseignement supérieur du Québec, Le Fonds de recherche du Québec—Nature et technologies (FRQNT) est responsable de la gestion du programme). The figure was created using images from https://mindthegraph.com/ (accessed on 19 April 2021).

Conflicts of Interest

The authors declare that there is no conflict of interest. This paper does not take any position for or against any decision of a political or economic nature.

References

  1. Sohrabi, C.; Alsafi, Z.; O’Neill, N.; Khan, M.; Kerwan, A.; Al-Jabir, A.; Iosifidis, C.; Agha, R. World Health Organization declares global emergency: A review of the 2019 novel coronavirus (COVID-19). Int. J. Surg. 2020, 76, 71–76. [Google Scholar] [CrossRef]
  2. Milner, J.J.; Beck, M.A. The impact of obesity on the immune response to infection. Proc. Nutr. Soc. 2012, 71, 298–306. [Google Scholar] [CrossRef] [PubMed][Green Version]
  3. Andersen, C.J.; Murphy, K.E.; Fernandez, M.L. Impact of Obesity and Metabolic Syndrome on Immunity. Adv. Nutr. 2016, 7, 66–75. [Google Scholar] [CrossRef] [PubMed][Green Version]
  4. McDowell, C.P.; Herring, M.P.; Lansing, J.; Brower, C.; Meyer, J.D. Working From Home and Job Loss Due to the COVID-19 Pandemic Are Associated With Greater Time in Sedentary Behaviors. Front. Public Health 2020, 8, 597619. [Google Scholar] [CrossRef] [PubMed]
  5. Ghanemi, A.; Yoshioka, M.; St-Amand, J. Will an obesity pandemic replace the coronavirus disease-2019 (COVID-19) pandemic? Med. Hypotheses 2020, 144, 110042. [Google Scholar] [CrossRef] [PubMed]
  6. Ghanemi, A.; Yoshioka, M.; St-Amand, J. Regeneration during Obesity: An Impaired Homeostasis. Animals 2020, 10, 2344. [Google Scholar] [CrossRef]
  7. Akira, S.; Uematsu, S.; Takeuchi, O. Pathogen recognition and innate immunity. Cell 2006, 124, 783–801. [Google Scholar] [CrossRef][Green Version]
  8. Medzhitov, R. Recognition of microorganisms and activation of the immune response. Nature 2007, 449, 819–826. [Google Scholar] [CrossRef] [PubMed]
  9. Alexandre-Silva, G.M.; Brito-Souza, P.A.; Oliveira, A.C.S.; Cerni, F.A.; Zottich, U.; Pucca, M.B. The hygiene hypothesis at a glance: Early exposures, immune mechanism and novel therapies. Acta Trop. 2018, 188, 16–26. [Google Scholar] [CrossRef]
  10. Sehrawat, S.; Rouse, B.T. Does the hygiene hypothesis apply to COVID-19 susceptibility? Microbes Infect. 2020, 22, 400–402. [Google Scholar] [CrossRef]
  11. Finlay, B.B.; Amato, K.R.; Azad, M.; Blaser, M.J.; Bosch, T.C.G.; Chu, H.; Dominguez-Bello, M.G.; Ehrlich, S.D.; Elinav, E.; Geva-Zatorsky, N.; et al. The hygiene hypothesis, the COVID pandemic, and consequences for the human microbiome. Proc. Natl. Acad. Sci. USA 2021, 118. [Google Scholar] [CrossRef]
  12. Thaiss, C.A.; Zmora, N.; Levy, M.; Elinav, E. The microbiome and innate immunity. Nature 2016, 535, 65–74. [Google Scholar] [CrossRef]
  13. Sadler, R.; Singh, V.; Benakis, C.; Garzetti, D.; Brea, D.; Stecher, B.; Anrather, J.; Liesz, A. Microbiota differences between commercial breeders impacts the post-stroke immune response. Brain Behav. Immun. 2017, 66, 23–30. [Google Scholar] [CrossRef]
  14. Rieder, R.; Wisniewski, P.J.; Alderman, B.L.; Campbell, S.C. Microbes and mental health: A review. Brain Behav. Immun. 2017, 66, 9–17. [Google Scholar] [CrossRef] [PubMed]
  15. Dinan, T.G.; Cryan, J.F. The Microbiome-Gut-Brain Axis in Health and Disease. Gastroentero. Clin. N. Am. 2017, 46, 77–89. [Google Scholar] [CrossRef] [PubMed][Green Version]
  16. Venema, K. Foreword—The importance of a healthy microbiota in the era of COVID-19. Benef. Microbes 2021, 12, 1–3. [Google Scholar] [CrossRef] [PubMed]
  17. Janda, L.; Mihalčin, M.; Šťastná, M. Is a healthy microbiome responsible for lower mortality in COVID-19? Biologia 2021, 76, 819–829. [Google Scholar] [CrossRef] [PubMed]
  18. Yeoh, Y.K.; Zuo, T.; Lui, G.C.; Zhang, F.; Liu, Q.; Li, A.Y.; Chung, A.C.; Cheung, C.P.; Tso, E.Y.; Fung, K.S.; et al. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut 2021, 70, 698–706. [Google Scholar] [CrossRef]
  19. Gupta, M.; Abdelmaksoud, A.; Jafferany, M.; Lotti, T.; Sadoughifar, R.; Goldust, M. COVID-19 and economy. Dermatol. Ther. 2020, 33, e13329. [Google Scholar] [CrossRef] [PubMed]
  20. Crayne, M.P. The traumatic impact of job loss and job search in the aftermath of COVID-19. Psychol. Trauma 2020, 12, S180–S182. [Google Scholar] [CrossRef]
  21. Niles, M.T.; Bertmann, F.; Belarmino, E.H.; Wentworth, T.; Biehl, E.; Neff, R. The Early Food Insecurity Impacts of COVID-19. Nutrients 2020, 12, 96. [Google Scholar] [CrossRef] [PubMed]
  22. Singh, S.; Nourozi, S.; Acharya, L.; Thapa, S. Estimating the potential effects of COVID-19 pandemic on food commodity prices and nutrition security in Nepal. J. Nutr. Sci. 2020, 9, e51. [Google Scholar] [CrossRef] [PubMed]
  23. Myles, I.A. Fast food fever: Reviewing the impacts of the Western diet on immunity. Nutr. J. 2014, 13, 61. [Google Scholar] [CrossRef][Green Version]
  24. Agus, A.; Denizot, J.; Thévenot, J.; Martinez-Medina, M.; Massier, S.; Sauvanet, P.; Bernalier-Donadille, A.; Denis, S.; Hofman, P.; Bonnet, R.; et al. Western diet induces a shift in microbiota composition enhancing susceptibility to Adherent-Invasive E. coli infection and intestinal inflammation. Sci. Rep. 2016, 6, 19032. [Google Scholar] [CrossRef][Green Version]
  25. Yang, W.; Cong, Y. Gut microbiota-derived metabolites in the regulation of host immune responses and immune-related inflammatory diseases. Cell Mol. Immunol. 2021. [Google Scholar] [CrossRef]
  26. Axelrod, A.E.; Pruzansky, J. The Role of the Vitamins in Antibody Production. In Vitamins & Hormones; Harris, R.S., Marrian, G.F., Thimann, K.V., Eds.; Academic Press: Cambridge, MA, USA, 1955; Volume 13, pp. 1–27. [Google Scholar]
  27. Wintergerst, E.S.; Maggini, S.; Hornig, D.H. Contribution of selected vitamins and trace elements to immune function. Ann. Nutr. Metab. 2007, 51, 301–323. [Google Scholar] [CrossRef][Green Version]
  28. Conlon, M.A.; Bird, A.R. The Impact of Diet and Lifestyle on Gut Microbiota and Human Health. Nutrients 2015, 7, 17–44. [Google Scholar] [CrossRef] [PubMed]
  29. Chassaing, B.; Vijay-Kumar, M.; Gewirtz, A.T. How diet can impact gut microbiota to promote or endanger health. Curr. Opin. Gastroenterol. 2017, 33, 417–421. [Google Scholar] [CrossRef]
  30. Li, S.; Wang, Y.; Xue, J.; Zhao, N.; Zhu, T. The Impact of COVID-19 Epidemic Declaration on Psychological Consequences: A Study on Active Weibo Users. Int. J. Environ. Res. Public Health 2020, 17, 2032. [Google Scholar] [CrossRef][Green Version]
  31. Shigemura, J.; Ursano, R.J.; Morganstein, J.C.; Kurosawa, M.; Benedek, D.M. Public responses to the novel 2019 coronavirus (2019-nCoV) in Japan: Mental health consequences and target populations. Psychiatry Clin. Neurosci. 2020, 74, 281–282. [Google Scholar] [CrossRef]
  32. Ettman, C.K.; Abdalla, S.M.; Cohen, G.H.; Sampson, L.; Vivier, P.M.; Galea, S. Prevalence of Depression Symptoms in US Adults Before and During the COVID-19 Pandemic. JAMA Netw. Open 2020, 3, e2019686. [Google Scholar] [CrossRef]
  33. Sher, L. COVID-19, anxiety, sleep disturbances and suicide. Sleep Med. 2020, 70, 124. [Google Scholar] [CrossRef]
  34. Qiu, J.; Shen, B.; Zhao, M.; Wang, Z.; Xie, B.; Xu, Y. A nationwide survey of psychological distress among Chinese people in the COVID-19 epidemic: Implications and policy recommendations. Gen. Psychiatr. 2020, 33, e100213. [Google Scholar] [CrossRef] [PubMed][Green Version]
  35. Vasile, C. Mental health and immunity (Review). Exp. Ther. Med. 2020, 20, 211. [Google Scholar] [CrossRef] [PubMed]
  36. Jane-Llopis, E.; Matytsina, I. Mental health and alcohol, drugs and tobacco: A review of the comorbidity between mental disorders and the use of alcohol, tobacco and illicit drugs. Drug Alcohol Rev. 2006, 25, 515–536. [Google Scholar] [CrossRef] [PubMed]
  37. Tran, T.D.; Hammarberg, K.; Kirkman, M.; Nguyen, H.T.M.; Fisher, J. Alcohol use and mental health status during the first months of COVID-19 pandemic in Australia. J. Affect. Disord. 2020, 277, 810–813. [Google Scholar] [CrossRef] [PubMed]
  38. Pasala, S.; Barr, T.; Messaoudi, I. Impact of Alcohol Abuse on the Adaptive Immune System. Alcohol Res. 2015, 37, 185–197. [Google Scholar]
  39. Szabo, G.; Saha, B. Alcohol’s Effect on Host Defense. Alcohol Res. 2015, 37, 159–170. [Google Scholar]
  40. Johnson, J.D.; Houchens, D.P.; Kluwe, W.M.; Craig, D.K.; Fisher, G.L. Effects of Mainstream and Environmental Tobacco Smoke on the Immune System in Animals and Humans: A Review. Crit. Rev. Toxicol. 1990, 20, 369–395. [Google Scholar] [CrossRef]
  41. Arnson, Y.; Shoenfeld, Y.; Amital, H. Effects of tobacco smoke on immunity, inflammation and autoimmunity. J. Autoimmun. 2010, 34, J258–J265. [Google Scholar] [CrossRef]
  42. Cabral, G.A.; Dove Pettit, D.A. Drugs and immunity: Cannabinoids and their role in decreased resistance to infectious disease. J. Neuroimmunol. 1998, 83, 116–123. [Google Scholar] [CrossRef]
  43. Morgan, L.; Protopopova, A.; Birkler, R.I.D.; Itin-Shwartz, B.; Sutton, G.A.; Gamliel, A.; Yakobson, B.; Raz, T. Human–dog relationships during the COVID-19 pandemic: Booming dog adoption during social isolation. Humanit. Soc. Sci. Commun. 2020, 7, 155. [Google Scholar] [CrossRef]
  44. Costagliola, A.; Liguori, G.; d’Angelo, D.; Costa, C.; Ciani, F.; Giordano, A. Do Animals Play a Role in the Transmission of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)? A Commentary. Animals 2020, 11, 16. [Google Scholar] [CrossRef]
  45. Ahmed, S.; Ajisola, M.; Azeem, K.; Bakibinga, P.; Chen, Y.F.; Choudhury, N.N.; Fayehun, O.; Griffiths, F.; Harris, B.; Kibe, P.; et al. Impact of the societal response to COVID-19 on access to healthcare for non-COVID-19 health issues in slum communities of Bangladesh, Kenya, Nigeria and Pakistan: Results of pre-COVID and COVID-19 lockdown stakeholder engagements. BMJ Glob. Health 2020, 5. [Google Scholar] [CrossRef] [PubMed]
  46. Murewanhema, G.; Makurumidze, R. Essential health services delivery in Zimbabwe during the COVID-19 pandemic: Perspectives and recommendations. Pan Afr. Med. J. 2020, 35, 143. [Google Scholar] [CrossRef]
  47. Shields, A.M.; Burns, S.O.; Savic, S.; Richter, A.G. COVID-19 in patients with primary and secondary immunodeficiency: The United Kingdom experience. J. Allergy Clin. Immunol. 2021, 147, 870–875.e871. [Google Scholar] [CrossRef]
  48. Cohen, J.I. Primary Immunodeficiencies Associated with EBV Disease. Curr. Top. Microbiol. Immunol. 2015, 390, 241–265. [Google Scholar] [CrossRef]
  49. Chinen, J.; Shearer, W.T. Secondary immunodeficiencies, including HIV infection. J. Allergy Clin. Immunol. 2010, 125, S195–S203. [Google Scholar] [CrossRef] [PubMed]
  50. Bonilla, F.A. Update: Vaccines in primary immunodeficiency. J. Allergy Clin. Immunol. 2018, 141, 474–481. [Google Scholar] [CrossRef] [PubMed][Green Version]
  51. Minihan, E.; Gavin, B.; Kelly, B.D.; McNicholas, F. COVID-19, mental health and psychological first aid. Ir. J. Psychol. Med. 2020, 37, 259–263. [Google Scholar] [CrossRef]
  52. Ghanemi, A.; St-Amand, J. Redefining obesity toward classifying as a disease. Eur. J. Intern. Med. 2018, 55, 20–22. [Google Scholar] [CrossRef] [PubMed]
  53. Ghanemi, A.; Yoshioka, M.; St-Amand, J. Broken Energy Homeostasis and Obesity Pathogenesis: The Surrounding Concepts. J. Clin. Med. 2018, 7, 453. [Google Scholar] [CrossRef] [PubMed][Green Version]
  54. Abdelbasset, W.K. Stay Home: Role of Physical Exercise Training in Elderly Individuals’ Ability to Face the COVID-19 Infection. J. Immunol. Res. 2020, 2020, 8375096. [Google Scholar] [CrossRef]
  55. Ranasinghe, C.; Ozemek, C.; Arena, R. Exercise and well-being during COVID 19—Time to boost your immunity. Expert Rev. Anti-Infect. Ther. 2020, 18, 1195–1200. [Google Scholar] [CrossRef] [PubMed]
  56. Shahrbanian, S.; Alikhani, S.; Ahmadi Kakavandi, M.; Hackney, A.C. Physical Activity for Improving the Immune System of Older Adults During the COVID-19 Pandemic. Altern Ther. Health Med. 2020, 26, 117–125. [Google Scholar]
Figure 1. COVID-19 crisis measures lead to reduced immunity via diverse factors that could impact both COVID-19 morbidities and vaccines efficacy.
Figure 1. COVID-19 crisis measures lead to reduced immunity via diverse factors that could impact both COVID-19 morbidities and vaccines efficacy.
Biology 10 00545 g001
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Ghanemi, A.; Yoshioka, M.; St-Amand, J. Coronavirus Disease 2019 (COVID-19) Crisis: Losing Our Immunity When We Need It the Most. Biology 2021, 10, 545. https://doi.org/10.3390/biology10060545

AMA Style

Ghanemi A, Yoshioka M, St-Amand J. Coronavirus Disease 2019 (COVID-19) Crisis: Losing Our Immunity When We Need It the Most. Biology. 2021; 10(6):545. https://doi.org/10.3390/biology10060545

Chicago/Turabian Style

Ghanemi, Abdelaziz, Mayumi Yoshioka, and Jonny St-Amand. 2021. "Coronavirus Disease 2019 (COVID-19) Crisis: Losing Our Immunity When We Need It the Most" Biology 10, no. 6: 545. https://doi.org/10.3390/biology10060545

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop