Covid Pathophysiology and clinical features

pathophysiology of COVID
Clinical features

1. PATHOPHYSIOLOGY OF COVID 2019 Dr A P Naveen Kumar Chief Specialist – Gen. Med. Visakha Steel General Hospital

2. INTRODUCTION Coronaviruses are enveloped, positive-sense, single-stranded RNA viruses of ~30 kb They are largely divided into four genera; α, β, γ, and δ based on their genomic structure. α and β coronaviruses infect only mammals Human coronaviruses such as 229E and NL63 are responsible for common cold and croup and belong to α coronavirus In contrast, SARS- CoV , Middle East respiratory syndrome coronavirus (MERS- CoV ) and SARS-CoV-2 are classified to β coronaviruses .

3. Route of entry Transmission is believed to occur via respiratory droplets from coughing and sneezing, as with other respiratory pathogens Virus released in respiratory secretions can infect other individuals via direct contact with mucous membranes Droplets usually cannot travel more than 6 feet

4. TRANSMISSION detectable for up to 72 hours on some surfaces despite decreasing infectivity over time. very susceptible to high heat (70°C) At room temperature and moderate (65%) humidity, no infectious virus could be recovered from printing and tissue papers after a 3-hour incubation period or from wood and cloth by day two On treated smooth surfaces, infectious virus became undetectable from glass by day 4 and from stainless steel and plastic by day 7 detectable level of infectious virus could still be present on the outer layer of a surgical mask on day 7

5. incubation period The median incubation period is 5.1 days (range 2–14 days) The precise interval is uncertain. The period of infectivity starts 2 days prior to onset of symptoms and lasts up to 8 days

6. The life cycle of the virus with the host consists of the following 5 steps: Attachment Penetration Biosynthesis Maturation Release Once viruses bind to host receptors (attachment), they enter host cells through endocytosis or membrane fusion (penetration).

7. Coronaviruses consist of four structural proteins Spike (S) Membrane (M) Envelope (E) Nucleocapsid (N) Spike comprises two functional subunits; S 1 subunit is responsible for binding to the host cell receptor and S 2 subunit is for the fusion of the viral and cellular membranes

8. ACE2 Receptor The RBD of the S protein of SARS-CoV-2 specifically recognizes the host angiotensin -converting enzyme 2 (ACE2) receptor ACE2 receptor -type 2 alveolar epithelial cells in the lungs, heart, kidney, and gastrointestinal tract Lungs seem to be particularly vulnerable Large surface area Reservoir for virus replication Direct injury to lung

9. RAAS- ACE -COVID ACE2 is a key counterregulatory enzyme that degrades angiotensin II to angiotensin -(1–7), thereby attenuating its effects on vasoconstriction, sodium retention, and fibrosis Despite substantial structural homology between ACE and ACE2, their enzyme active sites are distinct ACE inhibitors in clinical use do not directly affect ACE2 activity SARS-CoV-2 appears to subsequently downregulate ACE2 expression Unabated angiotensin II activity may be in part responsible for organ injury in Covid-19

10. Cytokine storm Syndrome -CSS CSS is an accentuated immune response to triggers such as viral infections It results from an excess - proinflammatory and inadequate anti-inflammatory stimuli Proinflammatory stimuli - interleukin (IL)–1β, IL-2, IL-6, IL-7, IL-12, IL-18, tumor necrosis factor (TNF)–α, interferon (IFN)–γ, and granulocyte colony-stimulating factor (GCSF) Anti-inflammatory stimuli include regulatory T cells, cytokines such as IL-10, transforming growth factor (TGF)–β, and IL-1ra

11. CSS Increased production of IFNγ by hematopoietic stem cells in response to viral infections is thought to trigger CSS CSS - unremitting fever and MODS including ARDS and acute cardiac and renal injury Laboratory abnormalities include cytopenias , increased ferritin , D- dimer , and increased serum levels of proinflammatory cytokines Significant increased mortality in patients with elevated ferritin (>1200 ng / mL ) and elevated IL-6 levels.

12. COVID 2019- Children Pediatric COVID-19 patients have relatively milder symptoms in general compared to elder patients the expression level of ACE2 may differ between adults and children- expressed on well-differentiated ciliated epithelial cells 2. children have a qualitatively different response to the SARS-CoV-2 virus to adults 3. presence of other viruses in the mucosa lungs and airways, common in young children, can let SARS-CoV-2 virus compete with them and limit its growth

13. COVID -Heart A large Chinese study analyzed 72 314 patient records which consisted of 44 672 (61.8%) confirmed cases, 16 186 (22.4%) suspected cases, and 889 (1.2%) asymptomatic cases. 4 Among confirmed cases in this study, 12.8% had hypertension, 5.3% diabetes and 4.2% CVD infection-induced myocarditis and ischaemia .

14. COVID -Heart CVD - secondary to acute lung injury, which leads to increased cardiac workload, potentially problematic in patients with pre existing HF CSS - result in plaque instability infiltration of the myocardium by interstitial mononuclear inflammatory cells Aside from arterial and venous thrombotic complications presenting as acute coronary syndromes (ACS) and venous thromboembolism (VTE), myocarditis plays an important role in patients with acute heart failure (HF) Wide range of arrhythmias

15. Bonnie Ky , and Douglas L. Mann J Am Coll Cardiol Basic Trans Science 2020;5:501-517 2020 The Authors

16. CLINICAL FEATURES – COVID 2019

17. People with COVID-19 have had a wide range of symptoms reported – ranging from mild symptoms to severe illness. Symptoms - appear 2-14 days after exposure Fever or chills Cough Shortness of breath or difficulty breathing Fatigue Muscle or body aches Headache New loss of taste or smell Sore throat Congestion or runny nose Nausea or vomiting Diarrhea

18. Emergency warning signs* for COVID-19 Trouble breathing Persistent pain or pressure in the chest New confusion Inability to wake or stay awake Bluish lips or face

19. HIGH RISK GROUP Adults 60 years and older Children younger than 2 years old Pregnant women and women up to 2 weeks after the end of pregnancy People who live in nursing homes and other long-term care facilities

20. Health and age factors - risk of getting serious complications COPD ,Moderate to severe Asthma CHF ,CAD , Cardiomyopathies T2DM CKD CLD Obese and BMI > 30 Sickle cell disease Cancer Immunocompromised Pregnancy CVA

21. SUSPECT CASE A. A patient with acute respiratory illness (fever and at least one sign/symptom of respiratory disease, e.g., cough, shortness of breath), AND a history of travel to or residence in a location reporting community transmission of COVID-19 disease during the 14 days prior to symptom onset; OR B. A patient with any acute respiratory illness AND having been in contact with a confirmed or probable COVID-19 case in the last 14 days prior to symptom onset; OR C. A patient with severe acute respiratory illness (fever and at least one sign/symptom of respiratory disease, e.g., cough, shortness of breath; AND requiring hospitalization) AND in the absence of an alternative diagnosis that fully explains the clinical presentation

22. PROBABLE CASE A. A suspect case for whom testing for the COVID-19 virus is inconclusive. OR B. A suspect case for whom testing could not be performed for any reason.

23. CONFIRMED CASE A person with laboratory confirmation of COVID-19 infection, irrespective of clinical signs and symptoms

24. As per data from Integrated Health Information Platform (IHIP)/ Integrated Disease Surveillance Programme (IDSP) portal case investigation forms for COVID 19 (n=15,366) 11-6-20 fever (27%) cough (21%) sore throat (10%) breathlessness (8%) Weakness (7%) running nose (3%) and others 24%.

25. Reported symptoms were as follows -USA Fever (43.1%) Cough (50.3%) Shortness of breath (28.5%) Myalgia (36.1%) Runny nose (6.1%) Sore throat (20%) Headache (34.4%) Nausea/vomiting (11.5%) Abdominal pain (7.6%) Diarrhea (19.3%) Loss of smell or taste (8.3%)

26. Clinical Severity -MILD Clinical presentation Patients with uncomplicated upper respiratory tract infection, may have mild symptoms such as fever, cough, sore throat, nasal congestion, malaise, headache Clinical parameters Without evidence of breathlessness or Hypoxia (normal saturation). Remarks Managed at Covid Care Centre

27. Clinical Severity -MODERATE Clinical presentation Pneumonia with no signs of severe disease Clinical parameters Adolescent or adult - of dyspnea and or hypoxia, fever, cough, including SpO2 <94% (range 90-94%) on room air, Respiratory Rate more or equal to 24 per minute. Child with respiratory distress Fast breathing (in breaths/min): < 2 months: ≥ 60 2–11 months: ≥ 50; 1–5 years: ≥ 40 Remarks Managed in Dedicated Covid Health Centre (DCHC)

28. Clinical Severity -SEVERE Clinical presentation Severe Pneumonia Clinical parameters Adolescent or adult: with clinical signs of Pneumonia plus one of the following; respiratory rate >30 breaths/min, severe respiratory distress, SpO2 <90% on room air. The diagnosis is clinical; chest imaging can exclude complications Remarks Managed in Dedicated Covid Hospital

29. CHILD Child with cough or difficulty in breathing, plus at least one of the following: central cyanosis or SpO2 <90%; severe respiratory distress (e.g. grunting, chest in- drawing); signs of pneumonia with any of the following danger signs: inability to breastfeed or drink, lethargy or unconsciousness, or convulsions. Other signs of pneumonia may be present: chest in drawing, fast breathing (in breaths/min): <2 months ≥60 2–11 months ≥50 1–5 years ≥40

30. ARDS Onset: new or worsening respiratory symptoms within one week of known clinical insult. Chest imaging (Chest X ray and portable bed side lung ultrasound): bilateral opacities, not fully explained by effusions , lobar or lung collapse, or nodules. Origin of Pulmonary infiltrates: respiratory failure not fully explained by cardiac failure or fluid overload. Need objective assessment (e.g. echocardiography) to exclude hydrostatic cause of infiltrates/ oedema if no risk factor present. Oxygenation impairment in adults: Mild ARDS: 200 mmHg < PaO2/FiO2 ≤ 300 mmHg (with PEEP or CPAP ≥5 cm H2O) Moderate ARDS: 100 mmHg < PaO2/FiO2 ≤200 mmHg with PEEP ≥5 cm H2O) Severe ARDS: PaO2/FiO2 ≤ 100 mmHg with PEEP ≥5 cm H2O) When PaO2 is not available, SpO2/FiO2 ≤315 suggests ARDS (including in non- ventilated patients) Oxygenation impairment in Children Note Oxygenation Index (OI) and OSI (Oxygen Saturation Index) Use OI when available. If PaO2 not available, wean FiO2 to maintain SpO2 <_97% to calculate OSI or SpO2/FiO2 ratio:

31. SEPSIS Acute life-threatening organ dysfunction caused by a dys -regulated host response to suspected or proven infection. Signs of organ dysfunction include: altered mental status, difficult or fast breathing, low oxygen saturation, reduced urine output, fast heart rate, weak pulse, cold extremities or low blood pressure, skin mottling, or laboratory evidence of coagulopathy , thrombocytopenia, acidosis, high lactate or hyperbilirubinemia

32. SEPTIC SHOCK Persisting hypotension despite volume resuscitation, requiring vasopressors to maintain MAP ≥65 mmHg and serum lactate level > 2 mmol /L

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