In response to an invitation from Benha University, in this presentation, Prof. Mohamed Labib Salem, Prof. of Immunology, Faculty of Science, Tanta University, Egypt, presents entitled "Immune Responses To The Pandemic New Coronavirus (COVID-19)". في هذه المحاضرة يقدم يا.د. محمد لبيب سالم أستاذ علم المناعة بكلية العلوم جامعة طنطا مصر محاضرة عن فيروس كورونا والمناعة

1. Immune Responses To The
Pandemic New Coronavirus
Dr. Mohamed Labib Salem, PhD
Prof. of Immunology
Immunology & Biotechnology Unit
Zoology Department, Faculty of Science
Director, Center of Excellence in Cancer
Research, Tanta University, Egypt
Benha University, 27 September 2010

2. Talk outlines
1.Historical Pandemic outbreaks
2.Basics of Coronavirus and COVID-19
3.Immune Responses to the new
Coronavirus
4.Anti-Coronavirus treatments
5.My contribution

3. OUTBREAK
10 OF THE WORST
PANDEMICS IN HISTORY

5. Death Toll of the 10 historically
pandemic infection (~272 million)
1. ANTONINE PLAGUE (165 AD) 5m
2. PLAGUE OF JUSTINIAN (541-542) 25m
3. THE BLACK DEATH (1346-1353) 75-200m
4. THIRD CHOLERA PANDEMIC (1852–1860) 1m
5. FLU PANDEMIC (1889-1890) 1m
6. SIXTH CHOLERA PANDEMIC (1910-1911) 800,000+
7. FLU PANDEMIC (1918-1920) 20-50m
8. ASIAN FLU (1956-1958) 2m
9. FLU PANDEMIC (1968) 1m
10.HIV/AIDS PANDEMIC (2005-2012) 36m
11.SARS-Con-2 (2019-2020) 962,631

6. ANTONINE
PLAGUE
(165
AD)

7. The bubonic plague was caused by
the bacterium Yersinia pestis.

8. 2019-nCoV

9. https://fb.watch/1FdLD4XaFW/
https://www.worldometers.info/coronavirus/

10. Reported Cases and Deaths by Country
by Nov. 9, 2020

11. Reported Cases and Deaths by Country
by Nov. 9, 2020

12. • SARS-Cov-2 is a new strain of
coronavirus that hasn't been
previously identified in humans.
• First originated in Wuhan, China
and spread around the world
(Ongoing pandemic)
• Up to 22 September 2020, more
than 31 million confirmed cases
have been reported across 188
countries
SARS-CoV-2 and COVID-19
COVID-19
is the diseases
caused by the
virus

13. How did novel Coronavirus infect people?
2- To infect new hosts
the virus’s genes
undergo mutations
that alter its surface
proteins, allowing
them to latch onto the
cells of new species.
3- In the case of SARS, the virus jumped from bats to civet cats before gaining the ability to
infect humans in the case of MERS, camels served as the intermediate host.
5- Researchers have
found the novel
coronavirus likely
originated in bats and
then transferred to
human through
pangolin as an
intermediate host.
4- Coronaviruses can
also jump directly to
humans without
mutating or passing
through and
intermediate
species.
1- Proteins on the
outer shell of the
virus allow to latch
onto cells in the
hosts respiratory
tract. The proteins
shapes are
determined by the
virus’s genes.

14. Coronaviruses (CoV) family: first identified as human pathogens in the 1960s
Outbreak Virus type Deaths
2003 severe acute respiratory syndrome outbreak. SARS-CoV 774
2012 Middle East respiratory syndrome coronavirus
outbreak
MERS-CoV Over 400
2015 Middle East respiratory syndrome coronavirus
outbreak
MERS-CoV 36
2018 Middle East respiratory syndrome coronavirus
outbreak
MERS-CoV 41
2019–20 coronavirus outbreak SARS-CoV2 31,900,000
till now*
History of Coronaviruses Outbreaks

15. European Centre for Disease Prevention and Control, 2020
Human
Coronavirus
Taxonomy

16. WHO Coronavirus Disease (COVID-19) Dashboard, 2020
Total Number of Cases Worldwide
Up to September 2020

17. The mortality rate has ranged between 2%
and about 3.4%
Mortality Rate Worldwide Up to September 2020
WHO Coronavirus Disease (COVID-19) Dashboard, 2020

18. Mortality Rate in Egypt Up to September 2020
Worldometer
-
www.worldometers.info

19. Structure of Coronavirus

20. Virus binding, internalization to epithelial cells, and its
replication
Allergy, Volume: 75, Issue: 7, Pages: 1564-1581, First published: 12 May 2020, DOI: (10.1111/all.14364)

21. Spike proteins on the
surface of the SARS-
CoV-2 virus bound to
neuropilin-1 and thus
can invade nerve
cells as it does through
ACE2.
Neuropilin-1 can be an
alternate gateway
related to abrogate
pain.

22. Symptoms
of
COVID-19

23. Different clinical phases of COVID‐19
Allergy, Volume: 75, Issue: 7, Pages: 1564-1581, First published: 12 May 2020, DOI: (10.1111/all.14364)

24. Albumin
C‐reactive protein (CRP)
Erythrocyte sedimentation rate (ESR)
Alanine transaminase (ALT)
Aspartate aminotransferase (AST)
Lactate dehydrogenase (LDH)
Serum amyloid A (SAA)
Cardiac troponin I (cTnI)
Prothrombin time (PT)
Activated partial thromboplastin time (APTT)
Serum amyloid A (SAA)
Activated partial thromboplastin time (APTT)
Cardiac troponin I (cTnI)
COVID-19 associates with increases in the acute‐phase
responses but with leukepenia & decreases in albumin
Fibrinogen (FIB)
Procalcitonin (PCT)
Interleukin 6 (IL‐6)
Urea nitrogen (BUN)
Creatinine (CRN)
Ferritin
Fibrinogen (FIB)
D‐dimer
Ferritin
Fibrinogen (FIB)
D‐dimer
Prothrombin time (PT)
Lymphocytes

25. Immunologic changes COVID‐19
T‐cell responses Lymphopenia in severe cases (<20%). Initial lymphopenia is predictive of severe
disease.
CD8
+
T cells Severe lymphopenia (<5%) is observed in CD8
+
T cells and can be a predictor of
severe disease.
Th1‐Th2 responses Normal antiviral immunity requires a CD4 and CD8 Th1 response. Severe disease
shows a systemic severe inflammatory response with a cytokine storm. Cytokine
storm response is mainly Th1 and inflammatory. It can also have a major role in
inflammasome activation.
Eosinophils Decreased circulating eosinophil numbers in 50%‐80% of the hospitalized
patients.
Specific antibody levels In the acute phase, virus‐specific IgM increases followed by virus‐specific IgG
during convalescence.
Cytokine storm Innate and adaptive cytokines are released in high amounts linked to severe
disease.
Acute‐phase reactants High in severe cases. Initially high values are predictive of severe disease.
Summary of immunologic characteristics of COVID-19

26. Blood lymphocyte
percentage
1st time point
10‐12 d after
symptom onset
2nd time point
17‐19 d after
symptom onset
20%
< Mild/Moderate Recovering
5% - 20% Severe Risky
Less than 5% Severe Critically ill
The percentage of lymphocytes is decisive for
prognosis at the first and secon visits

27. + − − Proposed immunologic period of infection before the symptoms develop
Early days of infection before detectable antibody response
Antibody assay may have given false‐negative results
+ + − Early stage of infection approximately 5‐7 d after the beginning of symptoms
+ + + Active phase of infection
+ − + Late phase or recurrent infection
IgM ELISA is false‐negative
− + − Early stage of infection
IgG may be false‐negative
RT‐PCR result may be false‐negative
−
-
−
+
+
+
Past infection
Recovered PCR‐negative patients
Cross‐reactivity with other coronaviruses
Recovery stage of infection
Early infection with false‐negative RT‐PCR
Proposed immunologic crieria for the diagnosis of the
stage of the disease
PCR IgM IgG Clinical significance

28. COVID-19 and
Immune Responses

29. Phases of Anti-viral Immune Responses

30. Anti-viral Cytotoxic CD8+ T cells Response

31. Specific antibody response to
SARS‐CoV‐2
Allergy, Volume: 75, Issue: 7, Pages: 1564-1581, First published: 12 May 2020, DOI: (10.1111/all.14364)

32. COVID-19 clinical and
Immunological spectrum
Clinical stages of
COID-19
Protective
immunity
and
inflammatory
spectra
Frontiers
in
Immunology

33. Allergy, Volume: 75, Issue: 7, Pages: 1564-1581, First published: 12 May 2020, DOI: (10.1111/all.14364)
2
3
2.1
2.2
2.3
2.2
2.3
3
3
2.3
Events of Anti-viral Immune Responses
4
1

34. Immune evasion strategies of SARS‐CoV‐2
Targeting TLR3/7 in lung cells
SARS infects airway
epithelial cells and
suppresses the activation
of TRAF3/6, limiting
activation of NFκB and
IRF3 and 7, thereby
suppressing early
production of anti-viral
cytokines IFNs , IL-1, IL-6,
TNF-α

35. Mf express very
low levels of ACE2.
They are not
heavily infected
but are highly
stimulated through
Ag/immune
complexes.
Immune evasion strategies of SARS‐CoV‐2:
Role of tissue Mf

36. Immune evasion strategies of SARS‐CoV‐2:
Role of blood-born monocytes and Mf
Cell produce
significant
amounts of pro-
inflammatory
cytokines which
recruit additional
innate and
adaptive immune
cells and cause
additional tissue
damage.

37. Pathogenesis
of
severe
COVID‐19
Allergy,
Volume:
75,
Issue:
7,
Pages:
1564-1581,
First
published:
12
May
2020,
DOI:
(10.1111/all.14364)

38. COVID-19: the role of excessive cytokine release and potential ACE2 down-regulation in promoting hypercoagulable state associated with severe illness, 2020
Dysregulated immunity in Severe COVID-19

39. Inflammatory mechanisms in immune
complex vasculitis

40. Distinct response to high‐ and low‐dose
virus exposure and infection
Allergy, Volume: 75, Issue: 7, Pages: 1564-1581, First published: 12 May 2020, DOI: (10.1111/all.14364)

41. Allergy, Volume: 75, Issue: 7, Pages: 1564-1581, First published: 12 May 2020, DOI: (10.1111/all.14364)
Ideal immune response to
SARS‐CoV‐2 infection or a vaccine

42. Treatment
Approaches for
COVIDS-19

43. Potential therapeutics targets in COID-19
1
2
7
6
3
4
5

44. NO clinically
proven
therapeutic
regimen to
prevent and
eradicate
SARS-CoV-2
infection
Treatment
Approaches
COVID-19:
the
role
of
excessive
cytokine
release
and
potential
ACE2
down-regulation
in
promoting
hypercoagulable
state
associated
with
severe
illness,
2020

45. Antiviral
drugs

46. Principal
of
Vaccine
Manufacture

47. (https://www.who.int/topics/vaccines/en/).
Towards effective COVID-19 vaccines: Updates, perspectives and challenges, 2020 Summary of strategy types for COVID-19 vaccine development.
Vaccine Development against Coronavirus

48. Platform Type of Vaccine Developer Status
Non-Replicating Viral Vector ChAdOx1-S University of Oxford/AstraZeneca
Phase 1/2: PACTR202006922165132
2020-001072-15
Phase 2: 2020-001228-32
Phase 3: ISRCTN89951424
Inactivated Inactivated Sinovac
Phase 1/2:
NCT04383574
NCT04352608
Phase 3: NCT04456595
Inactivated Inactivated
Wuhan Institute of Biological
Products/Sinopharm
Phase 1/2: ChiCTR2000031809
Phase 3: ChiCTR2000034780
Inactivated Inactivated
Beijing Institute of Biological
Products/Sinopharm
Phase 1/2: ChiCTR2000032459
Phase 3: ChiCTR2000034780
RNA LNP-encapsulated mRNA Moderna/NIAID
Phase 1: NCT04283461
Phase 2: NCT04405076
Phase 3: NCT04470427
RNA 3 LNP-mRNAs BioNTech/Fosun Pharma/Pfizer
Phase 1/2: 2020-001038-36
ChiCTR2000034825
Phase 3: NCT04368728
Non-Replicating Viral Vector Adenovirus Type 5 Vector
CanSino Biological Inc./Beijing Institute
of Biotechnology
Phase 1: ChiCTR2000030906
Phase 2: ChiCTR2000031781
Protein Subunit
Adjuvanted recombinant protein (RBD-
Dimer)
Anhui Zhifei Longcom
Biopharmaceutical/Institute of
Microbiology, Chinese Academy of
Sciences
Phase 1: NCT04445194
Phase 2: NCT04466085
24 Vaccine Clinical Trials

49. DNA DNA plasmid vaccine with electroporation
Inovio Pharmaceuticals/International
Vaccine Institute
Phase 1/2: NCT04447781
NCT04336410
DNA DNA plasmid vaccine + Adjuvant Osaka University/AnGes/Takara Bio Phase 1/2: NCT04463472
DNA DNA plasmid vaccine Cadila Healthcare Limited Phase 1/2: CTRI/2020/07/026352
DNA DNA Vaccine (GX-19) Genexine Consortium Phase 1/2: NCT04445389
Inactivated Whole-Virion Inactivated Bharat Biotech NA
Protein Subunit
Full length recombinant SARS CoV-2
glycoprotein NPs vaccine adjuvanted with
Matrix M
Novavax Phase 1/2: NCT04368988
Protein Subunit RBD-based Kentucky Bioprocessing, Inc Phase 1/2: NCT04473690
RNA mRNA Arcturus/Duke-NUS Phase 1/2: NCT04480957
Non-Replicating Viral Vector Adeno-based Gamaleya Research Institute Phase 1: NCT04436471 NCT04437875
Protein Subunit
Native like Trimeric subunit Spike Protein
vaccine
Clover Biopharmaceuticals
Inc./GSK/Dynavax
Phase 1: NCT04405908
Protein Subunit
Recombinant spike protein with Advax™
adjuvant
Vaxine Pty Ltd./Medytox Phase 1: NCT04453852
Protein Subunit
Molecular clamp stabilized Spike protein
with MF59 adjuvant
University of Queensland/CSL/Seqirus Phase 1: ACTRN12620000674932p
RNA LNP-nCoVsaRNA Imperial College London Phase 1: ISRCTN17072692
RNA mRNA Curevac Phase 1: NCT04449276
RNA mRNA
People’s Liberation Army (PLA)
Academy of Military Sciences/Walvax
Biotech.
Phase 1: ChiCTR2000034112
VLP
Plant-derived VLP adjuvanted with GSK or
Dynavax adjs.
Medicago Inc. Phase 1: NCT04450004
Protein Subunit S-2P protein + CpG 1018
Medigen Vaccine Biologics
Corporation/NIAID/Dynavax
Phase 1: NCT04487210
Platform Type of Vaccine Developer Status

52. The basic idea behind this
“Herd Immunity” is to let
people at low risk socialize
and naturally become
infected with the virus,
while Vulnerable people
will maintain social
distancing and continue to
shelter. This “Natural herd
immunity” will minimize
harm from virus while
protecting the economy.
Another way to get to herd immunity
is through mass vaccinations, as we
have done with measles, smallpox
and largely with polio.

53. https://covid-101.org/science/what-is-convalescent-plasma-treatment-for-covid-19/
Convalescent Plasma Therapy

54. Continuous blood purification:
Is an essential technology to control
inflammatory factors, cytokine storm, electrolyte
imbalance, and acid-base balance for severe
COVID-19 patient
Auxiliary Blood Purification Treatment

55. Boost your Immune System
The 5S
• Super Diet (Natural rich of 5 colors)
• Sleep (Enough and regular sleep)
• Sport (Enough exercise)
• Sugar (little)
• Salt (little)
• Sadness (little)

56. The greatest risk of COVID-19 infection is exposure. While exercise may not prevent us
from becoming infected if exposed, it is likely that keeping active will boost our immune
system to help minimize the deleterious effects of the virus, ameliorate our symptoms,
expedite our recovery times and lower the likelihood that we can infect others.

57. The 4 Directions Medicine Wheel
How Indigenous
Communities in
Canada
Organized an
Exemplary Public
Health Response
to COVID

58. My Contribution
to Coronavirus
• Publication
• Science Communication

64. Dr. Mohamed Labib Salem
Prof. of Immunology
Faculty of Science, Tanta University
mohamedlabibsalem@yahoo.com