A review of literature covering current knowledge areas about pathophysiology and progression of CoVid-19 in humans. I gave a day to day disease account along with serum markers and clinical condition of patients. My objectives are: Appreciate the background knowledge about CoVid-19 in most recent literature. Explain the progression of CoVid-19 disease in a human body based on current literature. Correlate the known risk factors for adverse outcomes with pathogenesis of CoVid-19. Describe the pharmacologic mechanisms being used to halt disease progression and prevent adverse outcomes.

1. Afshan Hussain Khattak
Consultant-A, Pediatrics
Internship Supervisor
Ministry of Health & Prevention, UAE
COVID-19
DISEASE PROGRESSION

2. OBJECTIVES;
AT THE END OF THIS SESSION, YOU WILL BE ABLE TO:
1. Appreciate the background knowledge about CoVid-19 in most recent literature.
2. Explain the progression of CoVid-19 disease in a human body based on current
literature.
3. Correlate the known risk factors for adverse outcomes with pathogenesis of CoVid-
19.
4. Describe the pharmacologic mechanisms being used to halt disease progression and
prevent adverse outcomes.

3. OBJECTIVE 1:
AVAILABLE BACKGROUND IN LITERATURE
• Huang et al. 41 cases. Most patients exposed to Huanan Seafood Market, [1]
• Chen et al and Wang et al. 99 and 138 cases in Wuhan. Elderly with comorbidities
were prone to develop acute respiratory distress syndrome (ARDS). [2,3]
• Initial presentation of 13 confirmed patients outside Wuhan, China, [4]
• Guan et al. delineated the clinical characteristics of the largest case series of
COVID-19 in China, confirming epidemic spread by human-to-human transmission
and that the disease severity predict poor clinical outcomes, [5]

4. WHAT IS NOVEL ABOUT THE COVID-19?

5. OBJECTIVE 2: PATIENT PROFILES
PROGRESSION OF COVID-19 IN HUMAN BODY,[6]
• The median age was 51 years old (IQR, 36–64 years). 126 (50.6%) were males.
• Duration from onset of symptoms to hospital admission was 4(2–7) days.
• Ninety patients (36.1%) had one or more coexisting chronic medical conditions.
• Cardiovascular and cerebrovascular diseases were the most common comorbidities
(55[21.7%]) followed by endocrine system diseases (25[10.0%]).

6. OBJECTIVE 2: PATIENT PROFILES
PROGRESSION OF COVID-19 IN HUMAN BODY,[6]
• Most common symptoms at onset of illness were fever 217[87.1%], cough
(91[36.5%]) and fatigue (39[15.7%]).
• Less common symptoms included dizziness and headache, shortness of breath,
rhinorrhea, sore throat, diarrhea and inappetence.
• Seven patients (2.8%) who were close contacts of confirmed COVID-19 cases were
asymptomatic while RT-PCR results were positive in their throat-swab samples.

7. Pictorial Representation
The Hindustan Times
Chen N., Zhou M., Dong X., Qu
J., Gong F., Han Y.
Epidemiological and clinical
characteristics of 99 cases of
2019 novel coronavirus
pneumonia in Wuhan, China: a
descriptive study. Lancet. 2020

8. • Median incubation
period is 5.1 days with
outliers from 14 – 27
days.
• Most index cases.
• Easily transmit disease.
• Case report, [8]
ASYMPTOMATIC STAGE, [7,8]

9. DAYS 1 – 3; [7,8,9]
80% OF PATIENTS RECOVER AFTER THIS STAGE
• Fever appears on day – 1 of this stage.
• Upper respiratory symptoms with cough and sore throat appear by day – 3
• If protective immune response is impaired, virus will propagate and massive
destruction of the affected tissues with high ACE2 expression, such as intestine and
kidney, [8]
• Genetic differences are well-known to contribute to individual variations in the
immune response to pathogens, [8]
• Those recovered from the non-severe stage should be monitored for the virus
together with T/B cell responses, [8]

10. SCHEMATIC REPRESENTATION OF THE PROGRESSION OF COVID-19
INFECTION AND POTENTIAL ADJUVANT INTERVENTIONS. [9]

11. DAYS 4 – 9; [7,9,10,11,12]
14% OF INFECTED EXPERIENCE THIS STAGE
• Labored breathing may start by day 5 – 9.. Alveolar injury sets in between days 8 – 15.
• Cytokine storm, the deadly uncontrolled systemic inflammatory response resulting from
the release of large amounts of pro-inflammatory cytokines and chemokines by immune
effector cells.
• Individuals with severe SARS-CoV and MERS-CoV show elevated levels of IL-6, IFN-α,
and CCL5, CXCL8, CXCL-10 in serum compared to those with the mild-moderate disease.
• The cytokine storm will trigger a violent attack by the immune system to the body, cause
ARDS and multiple organ failure, and finally lead to death in severe cases of SARS-CoV-2
infection, just like what occurs in SARS-CoV and MERS-CoV infection.

12. MOLECULAR IMMUNE PATHOGENESIS OF
COVID-19; [10]

13. OBJECTIVE 3: DAYS 8 – 15; [7,11,13]
5% OF INFECTED WILL REACH THIS STAGE
• From the lungs, the infection may move to the blood and lead to a sepsis like cascade
resulting in the cytokine storm.
• Cardiac complications, including new or worsening heart failure, new or worsening
arrhythmia, or myocardial infarction are common in patients with pneumonia. Cardiac
arrest occurs in about 3% of inpatients with pneumonia.
• Risk factors of cardiac events after pneumonia include older age, pre-existing
cardiovascular diseases, and greater severity of pneumonia at presentation.
• Increased high-sensitivity cardiac troponin I during hospitalization was found in more than
half of those who died.

14. TEMPORAL CHANGES IN D-DIMER / LYMPHOCYTE COUNTS
FROM ILLNESS ONSET IN PATIENTS HOSPITALIZED WITH
COVID-19, [7]

15. TEMPORAL CHANGES IN SERUM LEVELS OF IL-6 AND
FERRITIN FROM ILLNESS ONSET IN PATIENTS
HOSPITALIZED WITH COVID-19, [7]

16. TEMPORAL CHANGES IN SERUM LEVELS OF TROP-I AND
LDH FROM ILLNESS ONSET IN PATIENTS HOSPITALIZED
WITH COVID-19, [7]

17. MAJOR SYMPTOMS AND OUTCOMES AND DURATION OF
VIRAL SHEDDING FROM ILLNESS ONSET IN PATIENTS
HOSPITALIZED WITH COVID-19, [7]

18. REFERENCES
1. Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y. Clinical features of patients infected
with 2019 novel coronavirus in Wuhan, China. Lancet. 2020
2. Chen N., Zhou M., Dong X., Qu J., Gong F., Han Y. Epidemiological and clinical
characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a
descriptive study. Lancet. 2020
3. Wang D., Hu B., Hu C., Zhu F., Liu X., Zhang J. Clinical characteristics of 138
hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan,
China. JAMA. 2020
4. Chang Lin M, Wei L., Xie L., Zhu G., Dela Cruz C.S. Epidemiologic and clinical
characteristics of novel coronavirus infections involving 13 patients outside Wuhan,
China. JAMA. 2020

19. REFERENCES
5. Guan W.J., Ni Z.Y., Hu Y., Liang W.H., Ou C.Q., He J.X. Clinical characteristics of coronavirus
disease 2019 in China. New Engl J Med. 2020
6. Chen J, Qi T, Liu L, et al. Clinical progression of patients with COVID-19 in Shanghai, China
[published online ahead of print, 2020 Mar 19]. J Infect. 2020;S0163-4453(20)30119-5.
doi:10.1016/j.jinf.2020.03.004
7. Fei Zhou, MD, Ting Yu, MD, Ronghui Du, MD. Clinical course and risk factors for mortality of
adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet .
Volume 395 Issue 10229 Pages 1054-1062 (March 2020). DOI: 10.1016/S0140-6736(20)30566-3
8. Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany. N Engl J Med
2020; 382:970-971
9. Shi, Y., Wang, Y., Shao, C. et al. COVID-19 infection: the perspectives on immune
responses. Cell Death Differ (2020). https://doi.org/10.1038/s41418-020-0530-3

20. REFERENCES
10. X. Li et al., Molecular immune pathogenesis and diagnosis of COVID-19, Journal of
Pharmaceutical Analysis, https://doi.org/10.1016/j.jpha.2020.03.001
11. Z. Xu, L. Shi, Y. Wang, et al.Pathological findings of COVID-19 associated with acute
respiratory distress syndrome. Lancet Resp. Med. (2020)
12. C.K. Min, S. Cheon, N.Y. Ha, et al. Comparative and kinetic analysis of viral
shedding and immunological responses in MERS patients representing a broad
spectrum of disease severity. Sci. Rep.
13. Corrales-Medina VF, Musher DM, Shachkina S, Chirinos JA. Acute pneumonia and
the cardiovascular system. Lancet. 2013; 381: 496-505