COVID-19 PDF

COVID – 19 Dr. Dina Elhammady EPIDEMIOLOGY Novel coronavirus causing a cluster of pneumonia cases was first identified in Wuhan, China, at the end of 2019 → rapidly spread → epidemic throughout China → global pandemic. In February 2020, the WHO named the disease COVID-19 (coronavirus dise...

COVID – 19 Dr. Dina Elhammady EPIDEMIOLOGY Novel coronavirus causing a cluster of pneumonia cases was first identified in Wuhan, China, at the end of 2019 → rapidly spread → epidemic throughout China → global pandemic. In February 2020, the WHO named the disease COVID-19 (coronavirus disease 2019) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Globally, over 500 million confirmed cases of COVID-19 have been reported (this underestimate the overall burden of COVID-19 as only a fraction of acute infections are diagnosed and reported). TRANSMISSION 1.Inhalation of very small droplets and aerosol particles containing infectious virus. 2.Deposition of virus carried in exhaled droplets and particles onto exposed mucous membranes (e.g. being coughed on). 3.Touching mucous membranes with hands soiled by exhaled respiratory fluids containing virus or from touching inanimate surfaces contaminated with virus. VIROLOGY Enveloped positive-stranded RNA virus In the same subgenus as the SARS virus SARS-CoV-2 evolves over time, but most mutations have no impact on viral function. 1. Alpha Was the globally dominant variant until emergence of the Delta variant About 50-75% more transmissible than previously circulating strains 2. Beta Identified in several countries but was not globally dominant variant 3. Gamma Identified in several countries but did not become globally dominant Mutations in this variant associated with increased transmissibility 4. Delta Was the most prevalent variant worldwide until emergence of Omicron variant. Compared with the Alpha variant, the Delta variant was: a. More transmissible b. Associated with a higher risk of severe disease and hospitalization Vaccine may be slightly less effective against symptomatic Delta infection but remain highly effective against severe disease and hospitalization. 5. Omicron May escape humoral immunity Associated with: ⎯ ↑ risk of reinfection in individuals previously infected with a different strain. ⎯ ↓ Risk of severe disease than with other variants. CLINICAL PICTURE 1.Asymptomatic infection Well documented About 33% of people with SARS-CoV-2 infection never develop symptoms. 2.Symptomatic infection Simplified case definition: Mild No pneumonia or hypoxia Moderate Pneumonia without hypoxia Severe Pneumonia + hypoxia responding to O2 therapy Critically Pneumonia + hypoxia not responding to O2 ill therapy and/or organ dysfunction  Risk factors for severe illness - Age ≥65 Demographic - Male sex factors - Black, Hispanic, and Southern Asian ethnicities - Obesity (BMI>40) - Pregnancy Pre-existing - Uncontrolled Co-morbidities conditions - Active Malignancy - On Chemotherapy Immunosuppressive Drug - Unvaccinated or not fully vaccinated - Persistent fever > 38 - Heart Rate ≥ 110 Clinical features - Respiratory Rate ≥ 25/min - Saturated oxygen (Sa02) 1 mcg/mL) -  Prothrombin time -  Troponin -  Creatine phosphokinase Detection of viral RNA in the blood has been associated with severe disease, including organ Viral factors damage (lung, heart, kidney), coagulopathy, and mortality Genetic factors  Clinical manifestations ▪ Incubation period: ⎯ 14 days (most cases occur about 4-5 days after exposure) ⎯ Slightly shorter for Omicron variant (symptoms appear at around 3 days) ▪ Clinical course may progress rapidly in some patients. A. Initial presentation No specific symptoms or signs can reliably distinguish COVID-19 1. Fever, cough, myalgias, headache (most common) 2. Sore throat, and smell/taste abnormalities 3. Dyspnea developing about one week after onset of initial symptoms is highly suggestive of COVID 4. Mild upper respiratory symptoms (nasal congestion, sneezing) more common with Delta and Omicron variants 5. Pneumonia - Most frequent serious manifestation - Characterized by fever, cough, dyspnea, and bilateral infiltrates on chest imaging 6.GIT findings (nausea and diarrhea) may present 7.Dermatologic findings: a.Maculopapular/morbilliform, urticarial, and vesicular eruptions b.Transient livedo reticularis 8. Other findings a.Conjunctivitis b.Delirium, especially in older adults Urticarial and maculopapular/morbilliform rashes Livedo reticularis Complications 1. Respiratory failure due to acute respiratory distress syndrome (ARDS) can manifest shortly after onset of dyspnea 2. Cardiac and cardiovascular complications 3. Thromboembolic complications 4. Neurologic complications, such as encephalopathy 5. Inflammatory complications due to massive inflammatory response (leading to death) manifested by: a. Persistent fevers b. Elevated inflammatory markers (D-dimer, ferritin) c. Elevated proinflammatory cytokines 6. Chronic Fatigue Syndrome DIAGNOSIS 1. History of contact with diagnosed COVID-19 case. 2. Findings suggestive of COVID-19: a. Clinical manifestations b.Laboratory findings i. Lymphopenia ii. aminotransaminase levels iii. lactate dehydrogenase levels iv. inflammatory markers (e.g., ferritin, C-reactive protein, ESR) v.Abnormalities in coagulation test vi. D-dimer levels (denotes critical infection and mortality) c. Radiological findings e.g., consolidation and ground-glass opacities in bilateral, peripheral, and lower lung zones 3.Viral testing a.Nucleic acid amplification tests (NAATs), e.g., PCR Detect viral genetic material for up to 90 days (false positive result if subject had tested positive in last 90 days) Most reliable tests for people with or without symptoms b.Antigen tests Rapid tests (results in 15-30 minutes) Less reliable than NAATs Single, negative antigen test result does not exclude infection (repeat after 48 hours, i.e. serial testing) Follow-up NAAT confirms antigen test result TREATMENT A.GENERAL MANAGEMENT 1.Close monitoring of all patients with: a.Symptomatic COVID-19 b.Risk factors for progression of disease 2. Antiviral drugs Timing of antiviral drug administration is critical a.Before day 12 (stage of viral load) → antiviral drugs are essential b.After day 12 (stage of hyper-immune state): -  role of antiviral drugs -  role of anti-inflammatory immunomodulators  Potential antiviral drugs under evaluation for the treatment of COVID-19: a.Molnupiravir 800 mg (4 x 200mg capsules) twice/day for 5 days (used within 7 days of onset of symptoms) b.Favipiravir 1600mg 2x/day on the first day then 600 mg 2x/day for 4 days c.Remdesivir 200 mg IV on day 1 then 100 mg IV daily for 5 to 10 days in high-risk populations (indicated in failure of response to oral therapy) d.Nirmatrelvir 300mg with ritonavir 100mg (Paxlovid) orally 2x/day for 5 days (if available) 3.Monoclonal antibodies in mild and moderate cases with any risk of progression 4.Antibiotics Indications - Rapid development of consolidation pattern - Development of lobar consolidation - Leucocytosis with absolute neutrophilia - Reappearance of fever after febrile days -  CRP with improved other markers e.g. ferritin (procalcitonin is highly specific)  Drugs a.Low-risk inpatients: i. Combination therapy: Macrolide (azithromycin ß-lactam or clarithromycin) (ceftriaxone or Plus OR cefotaxime) Doxycycline ii.Monotherapy: Fluoroquinolone (levofloxacin or moxifloxacin) b.High-risk inpatients: ß-lactam plus a macrolide or fluoroquinolone 5. Therapeutic anticoagulants or antiplatelet if indicated 6. Pregnancy: Remdesivir (compassionate use approval) Monoclonal antibodies used if there is any other risk factor B. MANAGEMENT ACCORDING TO SEVERITY 1. Mild case (No pneumonia or hypoxia) a. If risk factors are present: i. Antiviral therapy: Molnupiravir 800 mg 2x/day for 5 days Favipiravir 1600mg 2x/day first day then 600 mg 2x/d/4d Nirmatrelvir 300mg with ritonavir 100mg (Paxlovid) orally 2x/day for 5 days (if available) ii. Monoclonal antibodies with any risk factor for progression iii.  Supportive measures when necessary b. Absent risk factors in patients over 65 years: i. Strict home isolation ii. Symptomatic treatment (paracetamol is the preferred antipyretic) iii. Hospitalization if deterioration occurs 2. Moderate case = patient with pneumonia without hypoxia Antiviral i. Molnupiravir 800 mg 2x/day for 5 days (used within 7 days of onset of symptoms) ii. Nirmatrelvir 300mg with ritonavir 100mg (Paxlovid) orally 2x/day for 5 days (if available) iii. Remdesivir 200 mg IV on day 1 then 100 mg IV daily for 5 -10 days in high-risk groups or failure of response to oral Anti-inflammatory, Dexamethasone (6mg) in patient with: e.g. steroids Severe dyspnea Respiratory rate 24 CT scan shows rapid deterioration Monoclonal In moderate cases with any risk factor for progression antibodies to severe disease Anticoagulants i. Prophylactic anticoagulant (parenteral heparin or (only for hospitalized enoxaparin 0.5mg/kg/day) patients) ii. Therapeutic anticoagulant (specific indications) 3. Severe case Characterized by any of the following criteria: ⎯ Respiratory rate  30 ⎯ Saturated oxygen (SaO2)  92 at room air ⎯ PaO2/FiO2 ratio  300 (PaO2/FiO2 = partial pressure of arterial blood oxygen to fractional inspired oxygen) ⎯ Chest X-ray showing: > 50% lesions Progressive lesions within 24-48 hours Requires hospitalization  Requires hospitalization Antiviral Remdesivir 200 mg IV on day 1 then 100 mg IV /d / 5-10 days Anti- i. Steroids (methyl prednisolone 1mg/kg/day) inflammatory ii. Anti-interleukin-6 (anti-IL-6) Drugs (not used together due to risk of immunosuppression) - Tocilizumab 4-8mg/kg/day for 2 doses 12 hours apart - Sarilumab 400mg single dose - Baricitinib (started with remdesivir) 4mg once daily for 14 days or hospital discharge Contraindications - Bacterial infection - Absolute neutrophil count (ANC)  500 cells/mm3 - Platelets  50,000 cells/mm3 - ALT  5x upper limit of normal (ULN) Anticoagulants Therapeutic anticoagulant (parenteral heparin or enoxaparin 1mg/kg/day) 4. Critically ill patients Characterized by any of the following criteria: - Respiratory rate  30 - Saturated oxygen (SaO2)  92 at room air - PaO2/FiO2 ratio  200 despite oxygen therapy - Additional organ dysfunction Requires intensive care unit  Requires intensive care unit Antiviral Same as severe cases Anti-inflammatory i. Prophylactic anticoagulant (parenteral heparin or enoxaparin 0.5mg/kg/day) ii. Therapeutic anticoagulant (specific indications) Anticoagulants Use of therapeutic parenteral anticoagulant in severe cases and prophylactic parenteral anticoagulant in critically ill cases is due to the increased risk of bleeding. i. HFN (high-flow nasal oxygen therapy), NIV (non- invasive ventilation), or CPAP (continuous positive Breathing aids airway pressure) ii. Invasive mechanical ventilation if patient becomes distressed