Document Type : Review Article
Authors
1 ATMP Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR,Tehran, Iran
2 Department of Cellular and Molecular Tehran Medical Sciences Branch,lslamic Azad University, Tehran, Iran
10.22034/pmj.2021.244730
Abstract
Severe Acute Respiratory Syndrome
Coronavirus 2 (SARS-CoV-2), is a severe infection with respiratory and systemic
manifestations. This infectious disease has a complex course and manifests itself with
various clinical presentations, ranging from asymptomatic infection to a severe clinical
course. These variations in severity have raised the question of whether the genetic or
epigenetic variations have a role in COVID-19 susceptibility or severity, and that these
factors can be used to predict the disease course. A whole-genome sequencing performed
on 95 samples of SARS-CoV-2 identified 116 unique mutations, most of which were
missense and synonymous. Moreover, some studies have reported a relationship between
the COVID-19 severity and the genes ACE and TMPRSS2. The present review provides
an overview of different genes that have been found to be implicated or related to the
susceptibility to COVID-19 or its severity.
Keywords
1. Abraham EP, Chain E. An enzyme from bacteria able to destroy
penicillin. Nature. 1940 Dec;146(3713):837-.
2. Aldred KJ, Kerns RJ, Osheroff N. Mechanism of quinolone
action and resistance. Biochemistry. 2014 Mar 18;53(10):1565-
74.
3. Allen HK, Moe LA, Rodbumrer J, Gaarder A, Handelsman
J. Functional metagenomics reveals diverse β-lactamases in a
remote Alaskan soil. The ISME journal. 2009 Feb;3(2):243-51.
4. Costelloe C, Metcalfe C, Lovering A, Mant D, Hay AD.
Effect of antibiotic prescribing in primary care on antimicrobial
resistance in individual patients: systematic review and meta-
analysis. Bmj. 2010 May 18;340.
5. Benveniste R, Davies J. Aminoglycoside antibiotic-inactivating
enzymes in actinomycetes similar to those present in clinical
isolates of antibiotic-resistant bacteria. Proceedings of the
National Academy of Sciences. 1973 Aug 1;70(8):2276-80.
6. Fernández L, Hancock RE. Adaptive and mutational resistance:
role of porins and efflux pumps in drug resistance. Clinical
microbiology reviews. 2012 Oct;25(4):661-81.
7. Leclercq R. Mechanisms of resistance to macrolides and lincosamides: nature of the resistance elements and their clinical
implications. Clinical Infectious Diseases. 2002 Feb 15;34(4):482-
92.
8. Holmes AH, Moore LS, Sundsfjord A, Steinbakk M, Regmi S,
Karkey A, Guerin PJ, Piddock LJ. Understanding the mechanisms
and drivers of antimicrobial resistance. The Lancet. 2016 Jan
9;387(10014):176-87.
9. Miller WR, Munita JM, Arias CA. Mechanisms of antibiotic
resistance in enterococci. Expert review of anti-infective therapy.
2014 Oct 1;12(10):1221-36.
10. Nikaido H, Pagès JM. Broad-specificity efflux pumps and their
role in multidrug resistance of Gram-negative bacteria. FEMS
microbiology reviews. 2012 Mar 1;36(2):340-63.
11. Demple B, Amabile-Cuevas CF. ‘Multiple resistance mediated
by individual genetic loci. Multiple drug resistant bacteria.
Horizon Scientific Press, Wymondham, UK. 2003:61-80.
12. D’Costa VM, King CE, Kalan L, Morar M, Sung WW, Schwarz
C, Froese D, Zazula G, Calmels F, Debruyne R, Golding GB.
Antibiotic resistance is ancient. Nature. 2011 Sep;477(7365):457-
61.
13. da SILVA KC, KNÖBL T, Moreno AM. Antimicrobial
resistance in veterinary medicine. Braz. j. vet. res. anim. sci.
2013;50(3):171-83.
14. Nisha AR. Antibiotic residues-a global health hazard.
Veterinary world. 2008 Dec 1;1(12):375.
15. Hao H, Cheng G, Iqbal Z, Ai X, Hussain HI, Huang L, Dai
M, Wang Y, Liu Z, Yuan Z. Benefits and risks of antimicrobial
use in food-producing animals. Frontiers in microbiology. 2014
Jun 12;5:288.
16. Weinstein RA. Controlling antimicrobial resistance in
hospitals: infection control and use of antibiotics. Emerging
infectious diseases. 2001 Mar;7(2):188.
17. Aarestrup FM. Occurrence of glycopeptide resistance among
Enterococcus faecium isolates from conventional and ecological
poultry farms. Microbial Drug Resistance. 1995;1(3):255-7.
18. Aarestrup FM, Jensen NE. Development of penicillin
resistance among Staphylococcus aureus isolated from bovine
mastitis in Denmark and other countries. Microbial Drug
Resistance. 1998;4(3):247-56.
19. Adrian PV, Thomson CJ, Klugman KP, Amyes SG. New gene
cassettes for trimethoprim resistance, dfr13, and streptomycin-
spectinomycin resistance, aadA4, inserted on a class 1 integron.
Antimicrobial agents and chemotherapy. 2000 Feb 1;44(2):355-
61.
20. Allen HK, Donato J, Wang HH, Cloud-Hansen KA, Davies
J, Handelsman J. Call of the wild: antibiotic resistance genes
in natural environments. Nature Reviews Microbiology. 2010
Apr;8(4):251-9.
21. DiazGranados CA, Zimmer SM, Mitchel K, Jernigan
JA. Comparison of mortality associated with vancomycin-
resistant and vancomycin-susceptible enterococcal bloodstream
infections: a meta-analysis. Clinical infectious diseases. 2005 Aug
1;41(3):327-33.
22. Nannini EC, Singh KV, Arias CA, Murray BE. In vivo
effects of cefazolin, daptomycin, and nafcillin in experimental
endocarditis with a methicillin-susceptible Staphylococcus aureus
strain showing an inoculum effect against cefazolin. Antimicrobial
agents and chemotherapy. 2013 Sep;57(9):4276-81.
23. Thomas CM, Nielsen KM. Mechanisms of, and barriers
to, horizontal gene transfer between bacteria. Nature reviews
microbiology. 2005 Sep;3(9):711-21.
24. Hollenbeck BL, Rice LB. Intrinsic and acquired resistance
mechanisms in enterococcus. Virulence. 2012 Aug 15;3(5):421-
569.
25. Abraham EP, Chain E. An enzyme from bacteria able to
destroy penicillin. Nature. 1940 Dec;146(3713):837-.
26. Bush K, Jacoby GA. Updated functional classification of
β-lactamases. Antimicrobial agents and chemotherapy. 2010
Mar;54(3):969-76.
27. Sirot D, Sirot J, Labia R, Morand A, Courvalin P, Darfeuille-
Michaud A, Perroux R, Cluzel R. Transferable resistance to
third-generation cephalosporins in clinical isolates of Klebsiella
pneumoniae: identification of CTX-1, a novel β-lactamase.
Journal of Antimicrobial Chemotherapy. 1987 Sep 1;20(3):323-
34.
28. Jacobs C, Frère JM, Normark S. Cytosolic intermediates
for cell wall biosynthesis and degradation control inducible
β-lactam resistance in gram-negative bacteria. Cell. 1997 Mar
21;88(6):823-32.
29. Pagès JM, James CE, Winterhalter M. The porin and the
permeating antibiotic: a selective diffusion barrier in Gram-
negative bacteria. Nature Reviews Microbiology. 2008
Dec;6(12):893-903.
30. Hasdemir UO, Chevalier J, Nordmann P, Pagès JM. Detection
and prevalence of active drug efflux mechanism in various
multidrug-resistant Klebsiella pneumoniae strains from Turkey.
Journal of clinical microbiology. 2004 Jun;42(6):2701-6.
31. Adachi H, Ishiguro M, Imajoh S, Ohta T, Matsuzawa H.
Active-site residues of the transpeptidase domain of penicillin-
binding protein 2 from Escherichia coli: similarity in catalytic
mechanism to class A. beta.-lactamases. Biochemistry. 1992
Jan;31(2):430-7.
32. Alekshun MN, Levy SB. The mar regulon: multiple resistance
to antibiotics and other toxic chemicals. Trends in microbiology.
1999 Oct 1;7(10):410-3.
33. Alonso A, Sanchez P, Martínez JL. Stenotrophomonas
maltophilia D457R contains a cluster of genes from gram-positive
bacteria involved in antibiotic and heavy metal resistance.
Antimicrobial agents and chemotherapy. 2000 Jul 1;44(7):1778-
82.
34. Benveniste R, Davies J. Aminoglycoside antibiotic-
inactivating enzymes in actinomycetes similar to those present in
clinical isolates of antibiotic-resistant bacteria. Proceedings of the
National Academy of Sciences. 1973 Aug 1;70(8):2276-80.
35. Aminov RI, Garrigues-Jeanjean N, Mackie RI. Molecular
ecology of tetracycline resistance: development and validation
of primers for detection of tetracycline resistance genes encoding
ribosomal protection proteins. Applied and environmental
microbiology. 2001 Jan 1;67(1):22-32.
36. Atkinson BA, Abu-Al-Jaibat A, LeBlanc DJ. Antibiotic
resistance among enterococci isolated from clinical specimens
between 1953 and 1954. Antimicrobial agents and
chemotherapy. 1997 Jul;41(7):1598-600.
37. Batt AL, Snow DD, Aga DS. Occurrence of sulfonamide
antimicrobials in private water wells in Washington County,
Idaho, USA. Chemosphere. 2006 Sep 1;64(11):1963-71.
38. McMurry L, Petrucci RE, Levy SB. Active efflux of
tetracycline encoded by four genetically different tetracycline
resistance determinants in Escherichia coli. Proceedings of the
national academy of sciences. 1980 Jul 1;77(7):3974-7.
39. Dönhöfer A, Franckenberg S, Wickles S, Berninghausen O,
Beckmann R, Wilson DN. Structural basis for TetM-mediated
tetracycline resistance. Proceedings of the National Academy of
Sciences. 2012 Oct 16;109(42):16900-5.
40. Aldred KJ, Kerns RJ, Osheroff N. Mechanism of quinolone
action and resistance. Biochemistry. 2014 Mar 18;53(10):1565-74.
41. Bayer AS, Schneider T, Sahl HG. Mechanisms of daptomycin
resistance in Staphylococcus aureus: role of the cell membrane
and cell wall. Annals of the New York Academy of Sciences. 2013
Jan;1277(1):139.
42. Howden BP, Davies JK, Johnson PD, Stinear TP, Grayson
ML. Reduced vancomycin susceptibility in Staphylococcus
aureus, including vancomycin-intermediate and heterogeneous
vancomycin-intermediate strains: resistance mechanisms,
laboratory detection, and clinical implications. Clinical
microbiology reviews. 2010 Jan;23(1):99-139.
43. Watanabe Y, Cui L, Katayama Y, Kozue K, Hiramatsu K.
Impact of rpoB mutations on reduced vancomycin susceptibility
in Staphylococcus aureus. Journal of Clinical Microbiology. 2011
Jul;49(7):2680-4.
44. Tran TT, Panesso D, Mishra NN, Mileykovskaya E, Guan Z,
Munita JM, Reyes J, Diaz L, Weinstock GM, Murray BE, Shamoo
Y. Daptomycin-resistant Enterococcus faecalis diverts the
antibiotic molecule from the division septum and remodels cell
membrane phospholipids. MBio. 2013 Jul 23;4(4):e00281-13.
45. Silver S, Phung LT. Bacterial heavy metal resistance: new
surprises. Annual review of microbiology. 1996 Oct;50(1):753-
89.
46. Witte W. Medical consequences of antibiotic use in agriculture.
47. Davies J. Inactivation of antibiotics and the dissemination of
resistance genes. Science. 1994 Apr 15;264(5157):375-82.
penicillin. Nature. 1940 Dec;146(3713):837-.
2. Aldred KJ, Kerns RJ, Osheroff N. Mechanism of quinolone
action and resistance. Biochemistry. 2014 Mar 18;53(10):1565-
74.
3. Allen HK, Moe LA, Rodbumrer J, Gaarder A, Handelsman
J. Functional metagenomics reveals diverse β-lactamases in a
remote Alaskan soil. The ISME journal. 2009 Feb;3(2):243-51.
4. Costelloe C, Metcalfe C, Lovering A, Mant D, Hay AD.
Effect of antibiotic prescribing in primary care on antimicrobial
resistance in individual patients: systematic review and meta-
analysis. Bmj. 2010 May 18;340.
5. Benveniste R, Davies J. Aminoglycoside antibiotic-inactivating
enzymes in actinomycetes similar to those present in clinical
isolates of antibiotic-resistant bacteria. Proceedings of the
National Academy of Sciences. 1973 Aug 1;70(8):2276-80.
6. Fernández L, Hancock RE. Adaptive and mutational resistance:
role of porins and efflux pumps in drug resistance. Clinical
microbiology reviews. 2012 Oct;25(4):661-81.
7. Leclercq R. Mechanisms of resistance to macrolides and lincosamides: nature of the resistance elements and their clinical
implications. Clinical Infectious Diseases. 2002 Feb 15;34(4):482-
92.
8. Holmes AH, Moore LS, Sundsfjord A, Steinbakk M, Regmi S,
Karkey A, Guerin PJ, Piddock LJ. Understanding the mechanisms
and drivers of antimicrobial resistance. The Lancet. 2016 Jan
9;387(10014):176-87.
9. Miller WR, Munita JM, Arias CA. Mechanisms of antibiotic
resistance in enterococci. Expert review of anti-infective therapy.
2014 Oct 1;12(10):1221-36.
10. Nikaido H, Pagès JM. Broad-specificity efflux pumps and their
role in multidrug resistance of Gram-negative bacteria. FEMS
microbiology reviews. 2012 Mar 1;36(2):340-63.
11. Demple B, Amabile-Cuevas CF. ‘Multiple resistance mediated
by individual genetic loci. Multiple drug resistant bacteria.
Horizon Scientific Press, Wymondham, UK. 2003:61-80.
12. D’Costa VM, King CE, Kalan L, Morar M, Sung WW, Schwarz
C, Froese D, Zazula G, Calmels F, Debruyne R, Golding GB.
Antibiotic resistance is ancient. Nature. 2011 Sep;477(7365):457-
61.
13. da SILVA KC, KNÖBL T, Moreno AM. Antimicrobial
resistance in veterinary medicine. Braz. j. vet. res. anim. sci.
2013;50(3):171-83.
14. Nisha AR. Antibiotic residues-a global health hazard.
Veterinary world. 2008 Dec 1;1(12):375.
15. Hao H, Cheng G, Iqbal Z, Ai X, Hussain HI, Huang L, Dai
M, Wang Y, Liu Z, Yuan Z. Benefits and risks of antimicrobial
use in food-producing animals. Frontiers in microbiology. 2014
Jun 12;5:288.
16. Weinstein RA. Controlling antimicrobial resistance in
hospitals: infection control and use of antibiotics. Emerging
infectious diseases. 2001 Mar;7(2):188.
17. Aarestrup FM. Occurrence of glycopeptide resistance among
Enterococcus faecium isolates from conventional and ecological
poultry farms. Microbial Drug Resistance. 1995;1(3):255-7.
18. Aarestrup FM, Jensen NE. Development of penicillin
resistance among Staphylococcus aureus isolated from bovine
mastitis in Denmark and other countries. Microbial Drug
Resistance. 1998;4(3):247-56.
19. Adrian PV, Thomson CJ, Klugman KP, Amyes SG. New gene
cassettes for trimethoprim resistance, dfr13, and streptomycin-
spectinomycin resistance, aadA4, inserted on a class 1 integron.
Antimicrobial agents and chemotherapy. 2000 Feb 1;44(2):355-
61.
20. Allen HK, Donato J, Wang HH, Cloud-Hansen KA, Davies
J, Handelsman J. Call of the wild: antibiotic resistance genes
in natural environments. Nature Reviews Microbiology. 2010
Apr;8(4):251-9.
21. DiazGranados CA, Zimmer SM, Mitchel K, Jernigan
JA. Comparison of mortality associated with vancomycin-
resistant and vancomycin-susceptible enterococcal bloodstream
infections: a meta-analysis. Clinical infectious diseases. 2005 Aug
1;41(3):327-33.
22. Nannini EC, Singh KV, Arias CA, Murray BE. In vivo
effects of cefazolin, daptomycin, and nafcillin in experimental
endocarditis with a methicillin-susceptible Staphylococcus aureus
strain showing an inoculum effect against cefazolin. Antimicrobial
agents and chemotherapy. 2013 Sep;57(9):4276-81.
23. Thomas CM, Nielsen KM. Mechanisms of, and barriers
to, horizontal gene transfer between bacteria. Nature reviews
microbiology. 2005 Sep;3(9):711-21.
24. Hollenbeck BL, Rice LB. Intrinsic and acquired resistance
mechanisms in enterococcus. Virulence. 2012 Aug 15;3(5):421-
569.
25. Abraham EP, Chain E. An enzyme from bacteria able to
destroy penicillin. Nature. 1940 Dec;146(3713):837-.
26. Bush K, Jacoby GA. Updated functional classification of
β-lactamases. Antimicrobial agents and chemotherapy. 2010
Mar;54(3):969-76.
27. Sirot D, Sirot J, Labia R, Morand A, Courvalin P, Darfeuille-
Michaud A, Perroux R, Cluzel R. Transferable resistance to
third-generation cephalosporins in clinical isolates of Klebsiella
pneumoniae: identification of CTX-1, a novel β-lactamase.
Journal of Antimicrobial Chemotherapy. 1987 Sep 1;20(3):323-
34.
28. Jacobs C, Frère JM, Normark S. Cytosolic intermediates
for cell wall biosynthesis and degradation control inducible
β-lactam resistance in gram-negative bacteria. Cell. 1997 Mar
21;88(6):823-32.
29. Pagès JM, James CE, Winterhalter M. The porin and the
permeating antibiotic: a selective diffusion barrier in Gram-
negative bacteria. Nature Reviews Microbiology. 2008
Dec;6(12):893-903.
30. Hasdemir UO, Chevalier J, Nordmann P, Pagès JM. Detection
and prevalence of active drug efflux mechanism in various
multidrug-resistant Klebsiella pneumoniae strains from Turkey.
Journal of clinical microbiology. 2004 Jun;42(6):2701-6.
31. Adachi H, Ishiguro M, Imajoh S, Ohta T, Matsuzawa H.
Active-site residues of the transpeptidase domain of penicillin-
binding protein 2 from Escherichia coli: similarity in catalytic
mechanism to class A. beta.-lactamases. Biochemistry. 1992
Jan;31(2):430-7.
32. Alekshun MN, Levy SB. The mar regulon: multiple resistance
to antibiotics and other toxic chemicals. Trends in microbiology.
1999 Oct 1;7(10):410-3.
33. Alonso A, Sanchez P, Martínez JL. Stenotrophomonas
maltophilia D457R contains a cluster of genes from gram-positive
bacteria involved in antibiotic and heavy metal resistance.
Antimicrobial agents and chemotherapy. 2000 Jul 1;44(7):1778-
82.
34. Benveniste R, Davies J. Aminoglycoside antibiotic-
inactivating enzymes in actinomycetes similar to those present in
clinical isolates of antibiotic-resistant bacteria. Proceedings of the
National Academy of Sciences. 1973 Aug 1;70(8):2276-80.
35. Aminov RI, Garrigues-Jeanjean N, Mackie RI. Molecular
ecology of tetracycline resistance: development and validation
of primers for detection of tetracycline resistance genes encoding
ribosomal protection proteins. Applied and environmental
microbiology. 2001 Jan 1;67(1):22-32.
36. Atkinson BA, Abu-Al-Jaibat A, LeBlanc DJ. Antibiotic
resistance among enterococci isolated from clinical specimens
between 1953 and 1954. Antimicrobial agents and
chemotherapy. 1997 Jul;41(7):1598-600.
37. Batt AL, Snow DD, Aga DS. Occurrence of sulfonamide
antimicrobials in private water wells in Washington County,
Idaho, USA. Chemosphere. 2006 Sep 1;64(11):1963-71.
38. McMurry L, Petrucci RE, Levy SB. Active efflux of
tetracycline encoded by four genetically different tetracycline
resistance determinants in Escherichia coli. Proceedings of the
national academy of sciences. 1980 Jul 1;77(7):3974-7.
39. Dönhöfer A, Franckenberg S, Wickles S, Berninghausen O,
Beckmann R, Wilson DN. Structural basis for TetM-mediated
tetracycline resistance. Proceedings of the National Academy of
Sciences. 2012 Oct 16;109(42):16900-5.
40. Aldred KJ, Kerns RJ, Osheroff N. Mechanism of quinolone
action and resistance. Biochemistry. 2014 Mar 18;53(10):1565-74.
41. Bayer AS, Schneider T, Sahl HG. Mechanisms of daptomycin
resistance in Staphylococcus aureus: role of the cell membrane
and cell wall. Annals of the New York Academy of Sciences. 2013
Jan;1277(1):139.
42. Howden BP, Davies JK, Johnson PD, Stinear TP, Grayson
ML. Reduced vancomycin susceptibility in Staphylococcus
aureus, including vancomycin-intermediate and heterogeneous
vancomycin-intermediate strains: resistance mechanisms,
laboratory detection, and clinical implications. Clinical
microbiology reviews. 2010 Jan;23(1):99-139.
43. Watanabe Y, Cui L, Katayama Y, Kozue K, Hiramatsu K.
Impact of rpoB mutations on reduced vancomycin susceptibility
in Staphylococcus aureus. Journal of Clinical Microbiology. 2011
Jul;49(7):2680-4.
44. Tran TT, Panesso D, Mishra NN, Mileykovskaya E, Guan Z,
Munita JM, Reyes J, Diaz L, Weinstock GM, Murray BE, Shamoo
Y. Daptomycin-resistant Enterococcus faecalis diverts the
antibiotic molecule from the division septum and remodels cell
membrane phospholipids. MBio. 2013 Jul 23;4(4):e00281-13.
45. Silver S, Phung LT. Bacterial heavy metal resistance: new
surprises. Annual review of microbiology. 1996 Oct;50(1):753-
89.
46. Witte W. Medical consequences of antibiotic use in agriculture.
47. Davies J. Inactivation of antibiotics and the dissemination of
resistance genes. Science. 1994 Apr 15;264(5157):375-82.
)