Departemen Ilmu Penyakit Dalam

Divisi Reumatologi
FK ULM-RSUD Ulin Banjarmasin
2020
INTRODUCTION

•Jan 2020, WHO officially term COVID-19

•Jun 2020, over 7.1M case confirmed globally
•3-7% mortality rate, 20% develop to severe

PATHOGENESIS STANDPOINT
Viral infection trigger Vigorous immune respond
(innate and adaptive immune response)  Viral clearance

COVID-19 is a new emerging disease little is known

about immunological alteration (maladaptive)
INTRODUCTION : MALADAPTIVE
IMMUNE RESPONSE
INTRODUCTION : VIRUS AND
AUTOINFLAMMATORY/IMMUNE RESPONSE
Covid-19 shares a similar inflammatory immune response
as autoimmune disease

Enteric virus Type I Diabetes

Hepatitis C Virus Cryoglobulinemic vasculities,

Sjorgen’s-like syndrome

Influenza Virus Acute disseminated encephalomyelitis

Systemic Lupus Erythemathosus,

Herpes Virus RA, AOSD

SARS-CoV 2 GBS
INTRODUCTION :COVID-19 AS EVOLVING
OVERLAPPING PHASES
COVID-19 : THE GENETICS
PREDISPOSITION TO DISEASE

A small study In a Han population suggested that HLA-C*07:29 and

HLA-B*15:27 alleles may be associated with COVID-19

The first genome-wide association study in a European population,

published as a preliminary report, showed that carriers of ABO A-
positive group were at a 45% Increased for respiratory failure.
Were Blood O group at 35% decreased risk for respiratory failure.

Clusters gene from 3p21 chromosome (SLC6A20)encode

transporter protein ACE2
COVID-19 : THE INNATE IMMUNE
RESPONSE

Reduction in percentage Innate immune cell : Low eosinophil, Low

NK cell (high NKG2A inhibitory receptor) lowering cytolytic
activity
BAL increase activated neutrophil, Monocyte and dendritic cell

Delayed response Type I&III IFN loss viral control at early stage

After 7 day infection Paradoxical increased chemokine (CXCL17,

CXCL16, CXCL9, CXCL8 enhance additional innate cell migration
COVID-19 : THE INNATE IMMUNE
RESPONSE
 COVID-19 : THE ADAPTIVE IMMUNE
RESPONSE

Lymphopenia  homeostatic proliferation response proliferative

capacity depends on avidity of self-antigen

Lymphocyte express ACE2

Direct destroy lymphatic organ

CSS  Apoptosis/blockage
lymphopoiesis
Metabolic alteration  cell depletion

Lymphocyte homing out into cell

COVID-19 : THE START OF MALADAPTIVE
IMMUNE RESPONSE

Reduced CD4 , CD8 T-cell & B cell lymphopenic state

Failure of maintain
peripheral tolerance
The loss off self-tolerance

Induce T cell effector with

autoimmune potential
Autoimmunity

IgM & IgG occur simultaneously or sequentially

Xu et al., “ the IgM as an early marker acute phase might not be on par
with other viral infection diagnostic”
COVID-19 : THE ADAPTIVE IMMUNE
RESPONSE

Fafi-Kremer et al., “13 Days post-disease onset , 99% pts had

antibodies of COVID-19 and 97% pts had neutralizing antibody
(NAbs) after 1 month onset , which correlated with antibody level”

Recovered patient have low level NAbs BUT they do have anti-viral activity
persist up to 40 day after onset

This Support the Using convalescent plasma as artificial immunity

NAbs against Receptor binding domain may interrupt SARS-CoV-2 and ACE2

Study of 5000 pts less than 1% presented TACO, TRALI or Allergic

Reaction on CP therapy
COVID-19 : CYTOKINE STORM SYNDROME
(CSS)

High plasma level of cytokine & chemokine pts COVID-19 : ( IL-1ß, gamma-
IFN, IFN gamma-inducible protein (IP10), monocyte chemotactic protein
(MCP)-1.

GCSF, MCP-1, Macrophage inflammatory proteins (MIP)-1a, IL-2, IL-7 

Higher in hospitalized non-ICU pts.

IL-6 highest in ICU Patients

CSS a group variety of inflammatory etiologies with final common result of

overwhelming systemic inflammation, hemodynamic instability, MODs and
Death
 COVID-19 : CYTOKINE STORM SYNDROME
(CSS)

IL-1B, MAS
Rituximab,
activation 
Secukinumab 
propose Anakinra
worse outcome
& canakinumab
Tx?

IL-6 activate Coagulation pathway, alter vascular endothelial cell, inhibit

myocardial function  The Use of Tocilizumab (Phase II clinical trial)
COVID-19 : CYTOKINE STORM
SYNDROME (CSS)
COVID-19 :THE REINFECTION

Reinfection in human have been suggested, BUT Presence positive PCR

doesn’t mean viral activity and infectious capacity

PCR-based diagnosis does not reveal the presence of live and Replicating
viruses, merely the presence of viral RNA

A longitudinal study 176 pts Previously infected by SARS-CoV, showed level

IgG antibodies were Maintained for 2 years, and after 3years after disease
onset, these Antibodies drastically reduced

Korean CDC analyze 285 positive case called “re-detected PCR’, because
NAbs and negative culture

PCR detect the RNA not Complete virus, some Lack of complete removal
nucleic acid will prolonged positivity.
COVID-19 :THE CONCLUSION

COVID-19 dominant global health issue outpaced human science

Virus trigger several Auto-inflammatory/Autoimmunity

The pathogenic mechanism of covid-19 its not fully understood

4 phase of COVID 19Viral phase mild symptom, but Host-virus interaction

dictate the outcome

So…

“Is Covid-19 just an infectious disease or something else??”

Thank You.