Risk Factor, Immune

Response and Clinical of

Severe COVID-19
Prof. NASRONUDIN, MD., PhD, Internist., Infectiologist, FINASIM
DIRECTOR OF UNIVERSITAS AIRLANGGA TEACHING HOSPITAL.
PRESIDENT OF INDONESIAN STATE UNIVERSITY HOSPITAL ASSOCIATION
25 NOVEMBER 2021
COVID-19 AND NCD RISK FACTOR
OBESITY

CANCER SMOKING

RESPIRATORY DISEASE
CARDIOVASCULAR
DISEASE

PHYSICAL
ALCOHOL
INACTIVITY

DIABETES POLUTION
COVID-19 AND NCD RISK FACTOR
 IMMUNE RESPONSES INDUCE BY COVID-
19 INFECTION
Clinically, the immune responses induced by SARS-CoV-2 infection are two
phased. During the incubation and non-severe and severe stages

However, when a protective immune response is impaired, virus

will propagate and massive destruction of the affected tissues will
occur, especially in organs that have high ACE2 expression, such
as intestine and kidney.

The damaged cells induce innate inflammation in the lungs that is largely
mediated by proinflammatory macrophages and granulocytes

Source ; Singh N, Suthar B, Mehta A, Pandey A (2020) Immune Response Towards COVID-19: A Review on
Host Body. J Infect Dis Diagn.5.134. DOI: 10.35248/2576-389X.5.134
FACTORS THAT INFLUENCE DISEASE SEVERITY
Genetic factors impacting the immune response to SARS-CoV-2
• The Clinical observation that otherwise healthy young individuals are among fatal cases
suggested that host genetics might contribute to disease susceptibility and severity

Age inflammaging, and COVID-19

• Age is the major clinical risk factor for severe, critical, and fatal COVID-19

Comorbid Factors

• Obesity, Diabetes, Cardiovascular Disease, Respiratory Disease, Cancer,

Smoking, Alcoholic,

Source : Schultze. Cell 184, April1, 2021

IMMUNE RESPONSE TO
COVID-19
 Components of the SARS-CoV-2 virus: neutralizing
antibodies bind to viral proteins

Antibodies to other components may

not effectively neutralize the virus

Neutralizing antibody
hypothesis: the
antibody changes the
viral spike protein
and prevents entry of
the virus via the ACE2
receptor into a
targeted cell

** Some T cells in healthy (uninfected) Antibodies that attach differently

persons (possibly due to prior exposure may not effectively neutralize the
to other coronaviruses) have also been virus
found to cross-react with the SARS-
CoV-2 viral spike protein. The
importance of this finding for immunity
or vaccine design is as yet unknown. Sources for hypothesis (5 June 2020) and image (16 July 2020)
 SARS-CoV-2 tropism, infection, and
alarming the innate immune system

Source : Cell 184, April 1, 2021

 SARS-CoV-2 tropism, infection, and
alarming the innate immune system

Source : Cell 184, April 1, 2021

The adaptive response: T cells (start day 6 - 8)
T cells (cellular response)
• recognize cells that are infected with a specific virus
and rapidly increase in number to tackle the
infection
• types of T cells :
➢ CD8+ cytotoxic T cells kill the cells in which the virus is multiplying
and help to slow down or stop the infection.
➢ CD4+ helper T cells bring in other cells of the immune system
and stimulate B-Cells to produce antibodies specific to that
virus.
Source : WHO. What We Know About COVID-19
Immune Response, 02 August 2020
 CD8+ T cell destruction of virus-infected cells

TCR : T cell receptor; MHC: major histocompatibility complex For further information, see source: Wikimedia Commons
 The adaptive response: B cells (start day 6-8)
B CELLS (Antibody response)
• produce antibodies that are specific to that virus
• IgM antibodies are produced first and disappear after a few weeks.
• IgG antibodies are produced at the same time or 2-3 days later, and titres (levels) usually remain for months or years

MEMORY CELLS
• Once the infection is over, the T cells and B cells decline in number, but some cells will remain (memory cells)
• Memory cells respond rapidly if they come in contact with the same virus again, killing the virus and accelerating an
antibody response

CRITICAL ASPECTS OF ANTIBODIES (Abs)

• Quality: do the Abs neutralize the virus (block it entering cells and multiplying)?
• Abs develop against different proteins that are part of a virus. Abs against one type of viral protein might neutralize the
virus, while others might not.
• Quantity: how many antibodies are produced (titre)?

CRITICAL ASPECTS OF VIRAL PROTEINS (Antigens)

• Antigen stability: Viruses may mutate over time. Viral proteins may change so much that antibodies produced against
the virus won’t recognize the antigens if they meet again later. (The importance of this phenomenon is not yet known
for COVID-19)
Source : WHO. What We Know About COVID-19
Immune Response, 02 August 2020
 SARSCoV-2 lapse/evade
the protective immune
pathways and increasing
the inflammatory
activities.

Source : Anju Kaushal. “Immune Response and Pathogenesis of

COVID-19 and The Strategies for Developing Target Drugs". Acta
Scientific Microbiology 3.9 (2020).: 92-102
Proposed host immune responses during SARS-CoV-2 Infection

Source ; Singh N, Suthar B, Mehta A, Pandey A (2020) Immune Response Towards COVID-19: A Review on Host Body. J Infect Dis
Diagn.5.134. DOI: 10.35248/2576-389X.5.134
CYTOKINE
STORM
 SARSCoV-2 entry through ACE-2 receptors activates
neutrophils and macrophage to produce cytokines. MHC-Antigens on APC help to
reduce the T cells activation

Source : Anju Kaushal. “Immune Response and Pathogenesis of COVID-19 and The Strategies for Developing Target Drugs". Acta Scientific Microbiology
3.9 (2020).: 92-102
POSSIBLE MECHANISM OF CYTOKINE STORMS IN COVID-19

Source : Cytokine storm syndrome in COVID-19/ Y.M. Gao et al, 2020

18
PHATOGENESIS OF CSS

Source : Cytokine storm syndrome in COVID-19/ Y.M. Gao et al, 2020 19

Pathophysiology and treatment of cytokine storm in COVID-19

Source : Theranostic, 2021

Clinical of Severe COVID-19
 Soluble
mediators
during the
disease
course of
COVID-19
Source : Cell 184, April 1, 2021
CARDIOVASCULAR LUNGS
SYSTEM
BLOOD AND
CIRCULATORY
SYSTEM

What are the longer-

term immunological
health consequences
of COVID-19
infection?
OTHER
FATIGUE

NEUROLOGY
SYSTEM

Source : British Society for Immunology, 13 August 2020

 SUMMARY OF
CURRENT
KNOWLEDGE,
OUTLOOK,
AND OPEN
QUESTION

Source : Schultze. Cell 184, April1, 2021

‘Herd immunity’ in the context of COVID-19
• Herd immunity is the indirect protection of individuals from an
infectious disease when a high proportion of a population is
immune (usually through vaccination). Persons who haven’t been
infected, or who haven’t had a good immune response, are
protected because there are enough immune people around them
to slow or stop person-to-person transmission.

• Many countries are testing for COVID-19 antibodies in the

population1 or in specific groups2
• Fewer than 10% of the general population have detectable COVID-19
antibodies (excepting in a few high intensity transmission sites or in
specific small groups).

• Worldwide most people remain susceptible to COVID-19 infection

1 Selected seroprevalence studies can be found here and here.
2 Unity Studies: Early Investigation Protocols: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/early-investigations
Shutterstock, 2020
Shutterstock, 2020
SUMMARY OF POST-ACUTE COVID-19 / COVID-19 LONG
HAULERS BY ORGAN SYSTEM

NEUROPSYCHIATRIC

DERMATOLOGIC AUDITORY

PULMONARY
POST
ACCUTE
ENDOCRINE COVID-19
BY ORGAN
SYSTEM

CARDIOVASCULAR
RENAL

GASTROINTESTINAL
HEMATOLOGIC AND
HAPATOBILIARY

Source : Nature Medicine, 2021. Modified : Nasronudin, 2021

THANKYOU