Introduction:

• COVID-19 stands for Corona Virus Disease 2019
• Causative agent is Severe Acute Respiratory Syndrome  Corona Virus 2 (SARS- CoV-2)
• Route of infection- Exposure to respiratory droplets carrying infectious virus (Generally within space of 6 feet)
• Mean incubation period is 5 days
• Duration of viral spreading is approximately 20 days (8-37 days). Some studies have shown that, even if PCR is positive, person may not harbour infective agent.
• On March 11 of 2020, it was declared as global pandemic

Factors associated with high risk of severe illness

• Age >60 years
• Cancer
• COPD
• Cerebrovascular disease
• Chronic kidney disease
• Chronic liver disease
• Diabetes mellitus
• Hypertension
• Cardiac illness- Heart failure, coronary artery disease, cardiomyopathy
• Immunocompromised status
• Obesity
• Pregnancy
• Smoking
• Sickle cell disease

Clinical features:

• Asymptomatic- 40-45% cases
• Fever or child
• Cough
• Shortness of breath or difficulty in breathing
• Fatigue
• Muscle/ body ache
• Headache
• New loss of taste or smell
• Sore throat
• Nasal congestion/ running nose
• Nausea or vomiting
• Diarrhoea

Complications: (Seen in 5% of patients)

• Pneumonia
• Acute respiratory distress syndrome
• Thrombotic manifestations
• Cardiac injury
• Arrythmia
• Septic shock
• Liver dysfunction
• Acute kidney injury
• Multi organ failure

Investigations:

• Viral DNA detection by RT-PCR
• Viral antigen detection
• Detection of antibodies to virus
• Hemogram- Leukopenia, leukocytosis, lymphopenia
• LDH, Ferritin- Often raised
• D-Dimer- Elevated levels is associated with higher risk of complications
• CT Chest:
  • Ground glass opacification- possibly with consolidation
  • Usually involve lower lobe and have peripheral distribution
  • Rarely- Pleural thickening, pleural effusion and lymphadenopathy

Treatment:

• Mild (Upper respiratory tract symptoms +/- Fever WITHOUT shortness of breath/ hypoxia)- Covid care center/ Home isolation and care
  • Do following tests- CBC, RBS, Chest X ray, CRP
  • Physical distancing, indoor mask use, strict hand hygiene
  • Symptomatic management
    • Hydration
    • Antipyretics
    • Anti-tussive
    • Multivitamins, Vitamin C 500mg BD, Zinc- 50mg- OD
  • Ivermectin- 200mcg/kg (Adults- 12mg)- OD for 3 days or HCQS- 400mg- BD on day 1 followed by OD for 4 days
  • Inhaled Budesonide- 800mics- BD- for 5 days if persistent cough beyond 5 days
  • Monitor SpO2-  6hrly
  • Do 6 minute walk test once a day with self monitoring of symptoms and SpO2 (For >60 years- do this for only 3 min)
  • Seek medical care immediately (these are the indications for shifting to hospital and treating as cases with moderate severity. Have low threshold for high risk patients)
    • Difficulty in breathing
    • High fever/ severe cough (lasting >5 days)
    • SpO2- <94%
    • 6 minute walk test- Drop in saturation below 94% or absolute drop of >4% or feeling unwell (light headedness/ short of breath)
    • Resting pulse- 100/min
    • Neutrophil lymphocyte ratio- >3.5
  • Discharge after 10 days of symptom onset/ date of sampling and no fever for 3 days. No need for repeating RT-PCR. Patient should isolate himself and self-monitor his health for further 7 days.
• Moderate (Respiratory rate >24/min/ Brathlessness/ SpO2- 90-93% in room air)- Admit in ward
  • Investigations-CBC, LFT, RFT, RBS, ECG, Chest X ray/HRCT, CRP, D-Dimer
  • Maintain oxygen saturation- Nasal canula (Up to 6L/min)- Face mask (Up to 12L/min)-Non rebreathing Mask (up to 15L/min)- High flow nasal canula- Non invasive ventilator- Invasive mechanical ventilator
  • Target SpO2- 92-96% (88-92% for COPD patients)
  • Awake proning is encouraged for all patients requiring oxygen support (Sequential position changing every 2 hrs)
  • CovidAwake Repositioning Proning(CARP) protocol: To change Position between the following every 2 hours.Check Saturation after 10 mins of position change, if it has not improved, change to different position.
    • Left Lateral Recumbent
    • Right Lateral Recumbent
    • Sitting upright 60-90 degree
    • Lying Prone in bed
  • Inj. Methyl prednisolone- 0.5-1mg/Kg in 2 divided doses (or dexamethasone- 6mg- OD)- for 5-10 days. Change to oral, once patient is stable
  • Heparin or low molecular weight heparin in prophylactic dose (Enoxaparin- 0.5mg/kg- SC- OD)- If there is no contraindication
  • T. Ivermectin- 12mg- OD- for 3 days
  • Vitamin C- 500mg- 1-0-1, Zinc- 50mg- OD
  • Inj. Remdesivir- 200mg- IV- on day 1 followed by 100mg- OD for next 4 days (Use with caution if hepatic or renal impairment)
  • Antibiotics, if there are clinical signs of bacterial infection
  • Monitor- CBC, CRP, D-Dimer, IL-6 levels, RFT, LFT- every 48 hrs
  • HRCT (Chest)- If worsening symptoms
  • Discharge after 10 days of symptom onset, if there is
    • Absence of fever
    • Resolution of breathlessness
    • No oxygen requirement
  • No need for repeating RT-PCR. Patient should isolate himself and self-monitor his health for further 7 days.
• Severe (Respiratory rate >30/min or SpO2 <90% at room air or ROS index- Ratioof SpO2/FiO2 to respiratory rate- <4.8)- Admit in ICU
  • Investigations-CBC, LFT, RFT, RBS, ECG, HRCT Chest, CRP, D-Dimer, LDH, Ferritin, ABG, triglycerides, Procalcitonin, IL-6, Trop I and CK-MB
  • Consider use of NIV, if work of breathing is low
  • Consider HFNC in patients with increasing oxygen requirement
  • Intubation if
    • NIV is not tolerated
    • Patients have high work of breathing
  • Inj. Methyl prednisolone- 0.5-1mg/Kg in 2 divided doses (or equivalent dexamethasone)- for 5-10 days. Change to oral, once patient is stable
  • Heparin or low molecular weight heparin in prophylactic dose (Enoxaparin- 0.5mg/kg- SC- OD)- If there is no contraindication
  • IV Antibiotics for prevention/ treatment of sepsis
  • Inj. Remdesivir- 200mg- IV- on day 1 followed by 100mg- OD for next 4 days (Use with caution if hepatic or renal impairment)
  • Inj. Tocilizumab- 8mg/Kg- IV- in 100ml NS over 1hr- Single dose- IF paient continues to be hypoxic despite higher respiratory support
  • Monitor- CBC, CRP, D-Dimer, IL-6 levels, RFT, LFT- every 24 hrs if baseline values are anormal/ clinically indicated
  • HRCT (Chest)- If worsening symptoms
  • If there is no improvement + CRP/IL-6 are rising + No active bacterial/fungal/tubercular infection- Inj. Tocilizumab- 4-6mg/kg (400mg in adults)- in 100ml NS over 1hr
  • Discharge after 10 days of symptom onset, if there is
    • Absence of fever
    • Resolution of breathlessness
    • No oxygen requirement
    • Repeat RT-PCR should be negative

Other treatment options:

• Convalescent plasma
  • Useful if patient has
    • Moderate disease
    • 3-7 days from onset of symptoms
    • No IgG antibodies against COVID-19
  • Donor criteria
    • Age- 18-60 years
    • Weight >60Kg
    • After 14 days of symptom resolution
    • Negative for transfusion transmitted diseases
    • IgG titres
      • > 1:640 by ELISA
      • >13AU/mL- by CLIA
      • >1:80 by PRNT/MNT

Vaccine induced Immune Thrombotic Thrombocytopenia (VIITT)

• Seen mainly with Astra Zeneca vaccine
• Usually seen 4-28 days after vaccination
• Clinical features
  • Severe headache +/- seizure like activity
  • Severe abdominal pain
  • Pedal edema
  • Chest pain/ dyspnea
• Investigations
  • VTE on imaging studies- Commonly CVST
  • Thrombocytopenia
  • Markedly elevated D-Dimer supports diagnosis
  • PF4 antibodies
• Treatment
  • IVIg- 0.5-1gm/Kg for 2 days
  • Prednisolone- 1-2mg/kg
  • Avoid platelet transfusions and heparin
  • Fondaparinux/ Rivaroxaban- Once platelet count is >50,000/cmm
  • Consider plasma exchange if there is persistent thrombocytopenia (<30,000/cmm) after 2 days of IVIg

Vaccination for hematology patients

• Hemato-oncology patients- Everyone must receive vaccine as soon as it is available.
• Hemophilia- If severe, they can receive intramuscular vaccination after factor replacement
• Patients of warfarin- Can receive IM vaccine , if INR is <3
• Patients on DOACs- delay the dose on the day of vaccination. They must receive IM injection and then take their daily dose of tablet
• Patients on aspirin can receive vaccine, without any drug modifications
• Vaccine can be given 3-6 months after HSCT

Recent advances:

Histone methyltransferase MLL1/KMT2A in monocytes drives coronavirus-associated coagulopathy and inflammation 

Coronavirus-associated coagulopathy occurs in conjunction with exaggerated activation of monocytes/macrophages. Present study used experimental models that use the murine betacoronavirus MHVA59, which is a well-established model of SARS-CoV-2 infection. The study identified that the histone methyltransferase mixed lineage leukemia 1 (MLL1/KMT2A) is an important regulator of monocytes/macrophages expression of procoagulant and profibrinolytic factors such as tissue factor, urokinase, and urokinase receptor. 

https://doi.org/10.1182/blood.2022015917