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  1. COVID 19
  2.  Home isolation and symptomatic treatment  Hospitalization for patients with uncontrolled comorbidities# (Age> 60 years, DM, HTN, immunocompromised, chronic liver and kidney disease  Monitor vitals: PR, RR, SpO2 (at rest and after walking for 6 minutes)  Complete blood count and inflammatory markers to be checked, if clinically indicated (on 5th to 7th day of clinical illness)  May consider Favipiravir 1800 BD on day 1 followed by 800 mg BD from day 2 (7-14 days)$  Remdesivir may be used in special circumstances$ Mild disease Fever and/or respiratory illness without dyspnea or hypoxemia* COVID-19 treatment according to disease severity
  3.  Oxygen support with nasal prongs or face mask. Target SpO2 92-96%  Steroids: Dexamethasone 0.1-0.2 mg/kg or Methylprednisolone 0.5 to 1 mg/kg  Anticoagulation: Inj Enoxaparin 1 mg/kg OD (if there is no contraindication)  Antivirals: Inj Remdesivir 200 mg single dose on day 1 and 100 mg once a day from day 2 to 5 (if there is no con- traindication)  Investigational therapies^  Monitor CBC, LFT, KFT, serum electrolytes and check inflammatory at baseline and on 5th day (early if clinically indicated)&  Monitor blood sugars. Start insulin for high blood sugars  High Resolution CT of thorax should be done in all patients. Moderate disease Pneumonia with RR≥24/min, SpO2≤94% and absence of signs of severe disease
  4.  Oxygen support with HFNC/NIV  Consider awake proning  Consider intubation for those who are not tolerating HFNC/NIV and or worsening breathlessness  For intubated patients use lung protective ventilation strategy using ARDS net protocol  Prone ventilation for refractory hypoxemia  Steroids: Methylprednisolone 1-2mg/kg or Dexamethasone 0.2-0.4 mg/kg. Consider methylprednisolone 250 to 500 mg for initial 1 to 3 days for very severe disease (SpO2/FiO2 <100 or PaO2/FiO2 <100)$  Anticoagulation: : Inj Enoxaparin 1 mg/kg BD (if there is no contraindication)  Antivirals: inj Remdesivir 200 mg single dose on day 1 and 100 mg once a day from day 2 to 5 (if there is no con- traindication)  Investigational therapies^  Monitor CBC, LFT, KFT, serum electrolytes and check inflammatory markers (every third day or when indicated)&  Monitor blood sugars. Start insulin for high blood sugars Severe disease RR≥30/min or SpO2<90% on room air
  5.  Convalescent plasma therapy: 200 mg single dose, may be repeated after 24 hours. May be considered in moderate to se- vere disease not improving on steroids (with persistent or worsening symptoms and raising inflammatory markers). Not to be used after tenth day of illness. Antibody titres in the recpient should be negative before using CPT.  Tocilizumab: 8 mg/kg, maximum dose of 800 mg, as a single dose may be considered in moderate to severe disease with progression of disease despite of steroid treatment and raising inflammatory markers. Dose may be repeated after 12 to 24 hours if there is no symptomatic improvement with first dose. Exclude secondary infections clincally. Investigational therapies
  6. Myocarditis  Myocarditis is one of the most dreaded complications of COVID19  Myocarditis should be suspected in cases of new onset arrhythmia, Tachycardia (>110 beath/minute) or severe unexplained bradycardia (<50 beats per minute)  Investigations: ECG, CKBM, TropI/T, echocardiography  Monitoring: Inflammatory markers, ECG at regular intervals  Management: Dexamethasone 0.1-0.2 mg/kg or Methylprednisolone 0.5 to 1 mg/kg  Anticoagulation: : Inj Enoxaparin 1 mg/kg BD (if there is no contraindication) along with Aspirin
  7. Footnote  Hypoxemia is to be checked using a pulse oximeter, in right hand middle finger for a duration of one minute (till the waveform stabilizes). Normal value of saturation is 95% or above. Repeat assessment of hypoxemia has to be done after walking for 6 minutes (in case of inability to walk, hand grip exercises for 6 minutes can be done). A fall of greater than 3% is considered clinically significant. well controlled co-morbidities like diabetes mellitus, heart failure, hypertension, can be managed at home. Low quality of evidence. Clinical efficacy in COVID19 is not known. CBC must be done to document neutrophil to lymphocyte ratio (<3 is suggestive of severe disease), Renal function test should be done to rule out COVID19 related kidney injury and eligibility for remdesivir. LFT should be done to rule out hepatic injury due to COVID19 as well as eligibility for remdesivir. Inflammatory markers must include CRP and ferritin.
  8. Assessment of Dyspnea/respiratory Distress  Complaint of breathlessness or cough is suggestive of pulmonary involvement in COVID19  Respirator rate should be measured in all subjects. Patients with RR >22/minute should be admitted and monitored.  Saturation should be measured in all patients by the method mentioned above  Breath holding time is beneficial tool to pick cases of pulmonary involvement early (BHT < 30 seconds in a afebrile patient should be an indication for HRCT thorax scan for assessment of lung involvement).  Similarly single breath count should also be measured in triage areas where saturation of chest radiography are not easily available. SBC of <30 is suggestive of lung involvement.  Inability to complete sentences is also suggestive of worsening severity of COVID19.
  9. Home Isolation Practices  Home isolation can be recommended for stable MILD cases with no other indication for admission  Facility of home isolation must be assessed prior to sending patient for home isolation. Facility includes, separate room, attached washroom, presence of care giver and 24 x 7 availability of emergency care.  Use of experimental drugs like Ivermectin, alternative medicines should not be used outside clinical trials.  Hospitals should follow the cases who are sent on home isolation, daily and regularly.  Utilization of remote monitoring applications like CARESHARE™should be encouraged  Post recovery from COVID19 illness, all patient should be screened for signs of depression or anxiety
  11. Incubation period Exposure Symptomatic phase Onset of symptoms Early pulmonary phase ICU admission Hyperinflammatory phase Cytokine storm/macrophage activation syndrome/MODS Death Time line of COVID-19 disease
  12. Timeline of autopsy studies Virchows Archiv (2020) 477:359–372
  13. Autopsy in COVID-19 • Presence of thrombosis and microangiopathy in the small vessels and capillaries of the lungs, with associated haemorrhage. • Features of diffuse alveolar damage, including hyaline membranes • Cardiac findings included individual cell necrosis without lymphocytic myocarditis. • There was no evidence of secondary pulmonary infection by microorganisms Lancet Respir Med 2020; 8: 681–86
  14. Electron microscopy in COVID 19 Numerous viral particles are enclosed in single membrane vacuoles
  15. CASE VIGNETTE • A 42-year-old businessman presented with • Fever-5 days • Cough -5 days • Diabetic (Metformin 500 mg BD • Hypertensive (Telmisartan + Amlodipine - 40mg+5mg OD) • Non smoker, non alcoholic
  16. COVID-19 RT-PCR positive (Civil hospital on7/7/20) referred to PGIMS for further management • On examination: • Conscious, oriented • No pallor, icterus, cyanosis, clubbing, lymphadenopathy, edema • Temp- 101 F • PR -102/ min • B.P- 132/78 mm Hg • RR-18 breaths/min • SpO2 – 98 % on room air • Chest- B/L vesicular breath sounds • CVS – S1,S2+ • P/A – Soft, non-tender, no organomegaly • CNS – No neck rigidity, plantar-flexor, no focal neurological deficits • Routine investigations: • CH,LFT,KFT : WNL • D-Dimer- 200 ng/ml (0- 500 ng/ml) • CRP- 2 mg/L (0-5 mg/L) • Chest radiograph-normal • ECG-normal
  17. What is Mild Covid-19? Treatment guidelines, MOHFW, Govt of India, 3/7/20
  18. Risk factors for Severe disease in patients with COVID-19 •Age ≥65 years •Residence in a nursing home or long-term care facility •Immunocompromised state, including solid organ transplant, HIV infection, other immune deficiency, immunosuppressant medication including systemic corticosteroids •Chronic lung disease, including COPD, moderate to severe asthma, cystic fibrosis, pulmonary fibrosis •Cardiovascular disease •Cancer •Hypertension •Overweight/ Obesity (BMI ≥30 kg/m2) •Diabetes mellitus-uncontrolled •Chronic kidney disease •Chronic liver disease •Cerebrovascular disease •Neurologic disorders, including dementia •Tobacco use disorder •Hematologic disorders, including sickle cell disease and thalassemia •Pregnancy????
  19. Management • Isolated (Home/Hospital) • Source control is most important strategy to prevent chain of transmission • Symptomatic treatment such as antipyretic (Paracetamol) for fever and pain, antitussives for cough • Adequate nutrition and appropriate hydration to ensured *MOHFW, Govt of India, Treatment guidelines for Covid-19, version 5,last updated on 3/7/20
  20. Home Isolation • Increasingly practiced • Readily accepted • ‘Supervised’ • Emphasis on picking complications early – 1. Breathlessness – pulse oximetry 2. Fever – indicator of cytokine excess 3. Cough When to seek medical attention? • Difficulty in breathing • Unremitting fever • Dip in oxygen saturation (SpO2 < 95%), • Persistent pain/pressure in the chest, • Mental confusion or inability to arouse, • Slurred speech/seizures, • Weakness or numbness in any limb or face, • Developing bluish discolorations of lips/face. Separate room ✔️ Care giver. ✔️ Separate toilet ✔️
  22. Role of Ivermectin.... • Broad-spectrum antiviral activity – in Vitro • Inhibition of importin α/β-mediated nuclear transport of viral proteins. • The clinical efficacy and utility of ivermectin in SARS-CoV-2 unpredictable at this stage
  23. Role of Favipiravir.. Evidence… AVIFAVIR for Treatment of Patients with Moderate COVID-19: Interim Results of a Phase II/III Multicenter Randomized Clinical Trial Clinc dis 2020 Aug 9;ciaa1176. doi: 10.1093/cid/ciaa1176 The rate of viral RNA clearance from upper respiratory tract specimens at day 5 was higher with Favipiravir compared with standard of care, which included hydroxychloroquine (clearance rates of 62 versus 36 percent) Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study Cai Q, Yang M, Liu D, et al Engineering. 2020 FPV showed better therapeutic responses on COVID-19 in terms of disease progression and viral clearance. These preliminary clinical results provide useful information of treatments for SARS-CoV-2 infection. Favipiravir versus Arbidol for COVID-19: A Randomized Clinical Trial medRxiv. 2020 doi: 10.1101/2020.03.17.20037432 In ordinary COVID-19 patients untreated with antiviral previously, favipiravir has higher 7 day’s clinical recovery rate and more effectively reduced incidence of fever, cough except some antiviral-associated adverse effects. DATA EVOLVING
  24. * Clinical signs of worsening Unremitting fever/2nd peak Cough Breathlessness Increase in Respiratory rate(>20) Decreasing saturation (≤94%) Altered sensorium Decreased urinary output COVID 19 Minimal symptomatic/Asymptomatic Without Risk Factors With Risk Factors (Age > 60 years/Obesity/Diabetes/Hypertension/ Hypothyroidism) Observation (Monitor symptoms BD) Symptomatic treatment Close monitoring for clinical worsening* Tab HCQS 400mg BD (D1) followed by 200mg BD for 4 days (or) Tab Favipiravir 1800mg BD(D1) followed by 800mg BD for 7-14 days DAY 5-7 CBC, CRP, D-dimer, Ferritin, LDH Warning signs Clinical signs of worsening* and/or Leucocytosis N/L ratio >3.5 Eosinopenia ↑CRP, d – dimer, ferritin, HRCT THORAX ?? Ivermectin12 mg OD x 3 days with or without Doxycycline (100 mg BD x 5 days- Data insufficient. Should be given only under clinical trials
  25. CASE CONTINUED… • Admitted in Isolation ward (8-7-20) • Treatment given • Inj. Ceftriaxone 1 gm/IV/BD • Tab. Hydroxychloroquine 400 mg BD on day-1 followed by 200 mg BD from day-2 to day-5 • Other supportive treatment • 2 Days later (10-7-20) • Complained of breathlessness • RR-24 breaths/min • SpO2-92 % on room air and 97% with 4 lit of oxygen- on nasal prongs • Shifted to ICU • Started on venturi mask (FiO2 requirement was 60%) • Blood sugars-346 mg/dl- insulin was started (basal bolus regimen- regular insulin and glargine)
  26. MODERATE DISEASE Treatment guidelines, MOHFW, Govt of India, 3/7/20 HDU/ICU
  27. SpO2 On room air < 94% Nasal cannula @1-6 L/min NRBM@ 10-15 L/min HFNC/NIV IMV • Oxygenation not improving • Use of accessory muscles of breathing • Oxygenation not improving • Use of accessory muscles of breathing • Rising PaCO2 or Obtundation Oxygen Therapy ECMO
  28. Nasal canula/NRBM /venturi mask •1 -6 L/min (NC) •6-15 L/min (NRBM) HFNC/CPAP/ NIV •HFNC - Preferred modality (with triple ply mask) •Flow rate 60-80 L/min •FiO2 to target SpO2 > 84% •Consider “Awake Proning” •If HFNC not available – consider NIV (preferably Helmet mask/FFM) •Use HME filter between mask and tube and tube and machine •Look for signs of increased work of breathing (RR, accessory muscle usage) IMV • RSI by most experienced doctor •Preoxygenation with HME filter attached between mask and reservoir bag •CMV (VCV/PCV) with Low tidal volume strategy ( Vt 6-8 ml/PBW)* •Initial PEEP 5-10 cm H20, titrate according PEEP – FiO2 table or to keep driving pressure < 15 cm H20 •Adjust RR (< 35/min) •Adequate sedation and analgesia (NMBs if necessary) Proning •Consider early Proning ( Within 36 hours of IMV) •Mild to moderate ARDS (P/F < 150, FiO2 > 0.6) •14- 16 hours/day until improvement in oxygenation ECMO •Refractory hypoxemia in spite of Proning and neuromuscular paralysis •PaO2/FiO2 < 60 mmHg for > 6h •PaO2/FiO2 < 50 mmHg for > 3h •Ph < 7.2 + PaCO2 > 80 mmHg > 6h *Dead Space Calculation D E T E R I O R A T I O N I M P R O V E M E N T ACCEPT PERMISSIVE HYPOXIA – SpO2 > 84%
  29. Those who received remdesivir had a median recovery time of 10 days as compared with 15 days among those who received placebo. The Kaplan–Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 Better clinical status at day 11 in remdesivir group compared to standard care Patients hospitalized for severe Covid-19 who were treated with compassionate-use Remdesivir, clinical improvement was observed in 36 of 53 patients (68%) Patients receiving Remdesivir had a faster time to clinical recovery than placebo REMDESIVIR
  30. Remdesivir NIH recommendations ( 01/9/20) Patients With Mild or Moderate COVID-19 There are insufficient data to recommend either for or against the use of Remdesivir Patients With COVID-19 Who Require Supplemental Oxygen Remdesivir for 5 days or until hospital discharge, whichever comes first Patients Who Require Oxygen Delivery Through HFNC,NIV,IMV, or ECMO The Panel cannot make a recommendation either for or against starting remdesivir. Duration of Therapy for Patients Who Have Not Shown Clinical Improvement After 5 Days of Therapy There are insufficient data on the optimal duration of remdesivir therapy for patients who have not shown clinical improvement after 5 days of therapy. In this group, some experts extend the total remdesivir treatment duration to up to 10 days.
  31. Convalescent plasma therapy • Passive antibody therapy • Mechanism of action • Neutralising antibodies, • Antibody-dependent cellular cytotoxicity(ADCC) and • Antibody-mediated phagocytosis. • ICMR trial finished allowed for compassionate use in early Pulmonary phase PROVEN COVID < 10 days duration Evidence of respiratory failure No clinical response Treatment with steroids and antivirals for 24-48 hours Consider for convalescent plasma therapy ELIGIBILITY CRITERIA FOR CPT: Age > 18 years Has any of the two PaO2/ FiO2: 200-300 RR > 24/min and SaO2 < 93% on room air Availability of matched donor plasma at the point of enrolment Antibody negative
  32. Corticosteroid...
  33. Recovery trial Inclusion: Patients hospitalized with suspected or laboratory confirmed COVID 19 Intervention: (1:2) SOC + dexamethasone 10 mg up to 10 days or hospital discharge Vs. SOC Outcome 28 days mortality Results : • Dexamethasone decreased overall mortality. • Most beneficial group was ventilated patients. • Increased mortality in patients not receiving oxygen(not statistically significant) • Decrease risk of progression to mechanical ventilation (RR-0.76) • More benefits after 7 days than before DOI: 10.1056/NEJMoa2021436
  34. Final word -Corticosteroids… • Hypoxemic COVID-19 patients should receive dexamethasone(or equivalent) based on current evidence, given the reduced risk of death and increased likelihood of hospital discharge. • Reduced length of oxygen therapy and risk of progression to invasive mechanical ventilation among those on supplemental oxygen. • No benefit among patients who do not require supplemental oxygen
  35. Moderate illness Persistent fever > 7days Reappearance of fever Unremitting high grade fever Breathlessness ↑ Inflammatory parameters Normal oxygen saturation CT severity score >10/25 ↑ Inflammatory parameters SPO2< 94% (or) RR > 24 Steroid* (Methylprednisolone 1-2 mg/kg body weight/day) for 3-5 days Inj. Enoxaprin (1mg/kg BW) S/C OD/BD Remdesivir# Steroid* (Methylprednisolone 1-2 mg/kg body weight/day) x 5-10 days Gradual tapering over 3 weeks Remdesivir# Inj. Enoxaprin (1mg/kg BW) S/C OD/BD Awake proning • Steroid 1-2 mg/kg of methyl prednisolone or equivalent dose • Gradual tapering to prevent fibrosis #Remdesivir (200mg on Day 1, 100mg from Day 2-5) • Enoxaprin OD/BD as per d-Dimer values ** Convalescent plasma (200 ml in single dose, can be repeated after 24 hours from a different donor may be considered in moderate to severe patients with persistent or increasing oxygen requirement). Both donor and recipient must be screened for antibodies *Strict control of blood sugars with insulin (Basal-bolus) ACTIVE PRINCIPLE EQUIVALENT DOSE Hydrocortisone 20 mg Prednisolone 5 mg Methyl prednisolone 4 mg Dexamethasone 0.75 mg
  36. Case continued… 1 Day later (11-7-20) • Complained increasing breathlessness • RR-28 breaths/min • SpO2-84% on room air and 88% with 10 lit of oxygen- on NRBM • Started on HFNC On 60% FiO2 Arterial Blood Gas pH 7.49 PCO2 32 PO2 53.7 SaO2 90.8 HCO3 - 24 BE 3.3 Na+ 134 K+ 3.6 COVID-19 ARDS
  37. Severe COVID -19: classification CDC Severe Illness 1. RR >30 /minute 2. SpO2 <94% on room air at sea level 3. PaO2/FiO2 <300 mmHg 4. Lung infiltrates >50%. Critical Illness 1. Respiratory failure 2. Septic shock, and/or 3. Multiple organ dysfunction. MoHFW-GOI Severe illness clinical signs of Pneumonia plus one of the following : 1. Respiratory rate >30 breaths/min 2. Severe respiratory distress 3. SpO2 <90% on room air ARDS : Berlin definition /Kiagli modification Sepsis: Organ failure due to infection (SOFA increased by ≥ 2) Septic shock : MAP <65 mm of hg or lactate ≥ 2 mmol/L after adequate fluid resuscitation
  38. Risk Factors &Laboratory markers of severity ✓ Severity of illness ✓ Mortality ▪ D-dimer >1000ng/ml ▪ CRP>100mg/L ▪ Ferritin >500 mcg/L ▪ LDH>245 U/L ▪ High sensitivity Troponin > 2 times of ULN ▪ CPK> 2times ULN ▪ Lymphocyte count <800/ ▪ NLR≥9 ▪ NT Pro BNP ▪ Increasing SOFA ▪ SAA ▪ Urea, creatinine ▪ Older age ▪ Smoking ▪ Comorbidity: DM, HTN, CHD, CLD, CKD, chronic pulmonary diseases malignancy etc. ▪ Immunosuppressive conditions ▪ Obesity /Overweight
  39. Tocilizumab NIH (1/9/20) • The Panel recommends against the use of anti-IL-6 receptor monoclonal antibodies (e.g.,sarilumab, tocilizumab) or anti-IL-6 monoclonal antibody (siltuximab) for the treatment of COVID-19, except in a clinical trial MoHFW version 5. 3/7/20 • Tocilizumab (Off Label) may be considered in patients with moderate disease with progressively increasing oxygen requirements and in mechanically ventilated patients not improving despite use of steroids. • Special considerations before its use include: • Presence of raised inflammatory markers (e.g., CRP, Ferritin, IL-6) • Patients should be carefully monitored post Tocilizumab for secondary infections and neutropenia • The drug is contraindicated in PLHIV, those with active infections(systemic bacterial/fungal), Tuberculosis, active hepatitis, ANC < 2000/mm3 and Platelet count < 1,00,000/mm3
  40. High dose/ Pulse corticosteroid • Few case series and case reports • High dose methylprednisolone 500-1000 mg for 3 days followed by rapid tapering • Improvement in P/F ratio and early extubation • Limitation : study design, small sample • A case series from japan including 7 patients with COVID pneumonia and P/F <150 requiring mechanical ventilation showed benefit of pulse steroid (1000 or 500 mg/day for three days of methylprednisolone intravenously, followed by 1 mg/kg and tapered off, median duration 13 days.) in terms extubation of the patients within seven days and hospital discharge [Respirology Case Reports, 8 (6), 2020, e00596] • A RCT is under going comparing standard ICU care (± 6 mg dexa) Vs. standard ICU care + 24mg dexa ( NCT04395105)
  41. COVID 19 and Coagulopathy • 3000 individuals hospitalized with COVID-19 • Most patients received prophylactic-dose anticoagulation. • Venous thromboembolism was seen in 16 percent (13.6 percent of individuals in the intensive care unit and 3.6 percent on the medical ward). • Arterial thrombosis (mostly myocardial infarction) was seen in 11.1 percent. • Factors associated with increased thrombosis risk included older age, male sex, Hispanic ethnicity, coronary artery disease, prior myocardial infarction, and high D-dimer on presentation. JAMA.
  42. Echocardiography in fatal COVID19 Pulmonary Embolism
  43. Dose & duration of anticoagulation • Patients hospitalized for acute medical illness are at increased risk for VTE for up to 90 days after discharge. • A symptomatic VTE incidence between 0-0.6% at 30-42 days post discharge has been reported in patients with COVID-19. • Routine post-discharge thromboprophylaxis – Not advised. • Patients who warrant extended thromboprophylaxis following discharge from the hospital: • Patients with major prothrombotic risk factors such as a history of VTE or recent major surgery or trauma BUT at the cost of increase in bleeding events • Options for post-discharge prophylaxis include those used in clinical trials, such as Rivaroxaban 10 mg daily for 31 to 39 days anticoagulation
  44. **INDICADTIONS FOR TOCILIZUMAB/Pulse methyl prednisolone: • Rapid deterioration • RR > 30 bpm, • SaO2 < 93% on room air • PaO2/FiO2 < 300 mm Hg in room air, and • Lung infiltrates > 50% within 24–48 h CONTRAINDICATIONS: • Coexistent infection other than COVID-19; • PaO2/FiO2 > 300 mm Hg; chronic or current glucocorticoid use • H/O severe allergic reactions to monoclonal antibodies • ANC < 500 per µL; platelets < 50×10⁹ • Active diverticulitis, IBD , or another symptomatic gastrointestinal tract condition that might predispose patients to bowel perforation; • Severe haematological, renal, or liver function impairment. # Evidence for pulse methyl prednisolone is evolving Remdesivir (day 1-200 mg, day 2 to 5-100 mg once a day)* Steroids - Methylprednisolone 1-2 mg/kg BW or equivalent Inj. Enoxaparin 1 mg/kg SC q 12 hourly Tab Aspirin 75 mg OD + OXYGEN Severe illness Respiratory distress RR > 30bpm or SpO2 < 90% IMPROVED Continue same treatment Taper steroid gradually NO IMPROVEMENT Increasing( Double) the steroid dose #Pulse methyl prednisolone 500 mg – 3 days Anti IL-6 (Tocilizumab)** NO IMPROVEMENT Salvage therapies: Low dose thrombolysis Cytosorb IVIG Plasma exchange Evolving immunomodulators IMPROVEMENT Taper steroids gradually *REMDESIVIR NOT RECOMMENDED: • AST/ALT > 5 times elevated • Creatinine clearance < 30 ml/min • Pregnant and breast feeding women • Known hypersensitivity to study drug
  45. Pathophysiology based management of COVID-19
  46. Steroids COVID positive patient with hypoxia SpO2 <96% RR > 24 Antivirals Moderate to severe disease ? Early use?? Tocilizumab/ Convalescent plasma therapy • No clinical response after 24-48hrs of steroid and antiviral therapy • Increasing CRP, ferritin, IL-6 levels Anticoagulation Moderate to severe disease with D-dimer > 500 ng/ml Learning points
  47. Covid suspect but RT PCR -ve Exclusion of other diagnosis: • Negative influenza PCR test • Negative respiratory viral panel • Negative testing for clinically indicated respiratory infections (urine antigen for legionella and streptococcus pneumoniae, blood cultures, sputum cultures or BAL) HRCT THORAX REPEAT RT-PCR ALTERNATIVE DIAGNOSIS CORADS 4/5 POSITIVE NEGATIVE CLINICAL SUSPICION HIGH MANAGE AS COVID LOW LOOK FOR ALTERNATIVE DIAGNOSIS
  48. Courtesy: EVMS Critical Care COVID-19 Management Protocol TIMING OF INITIATION OF ANTI INFLAMMATORY THERAPY Remdesivir days
  49. COVID 19 is a steroid responsive disease, however timing is important or Equivalent Dose of Dexamethasone/Hydrocortisone *Tab Apixaban 2.5mg BD Adapted from EVMS Critical Care COVID-19 Management Protocol 5-17 days *Use with caution with Tocilizumab – increased risk of bleeding
  50. Blood Markers in Covid 1. C Reactive Protein C-reactive protein (CRP) is a blood test marker for inflammation in the body. CRP is produced in the liver. •Normal Levels - 0-5 mg/L •In general, the main causes of increased CRP and other markers of inflammation are a variety of conditions, including burns, trauma, infections, such as pneumonia or tuberculosis, heart attack, chronic inflammatory diseases such as lupus, vasculitis, or rheumatoid arthritis. 2. D-dimer D-dimer (or D dimer) is a fibrin degradation product (or FDP), a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis. •Normal Levels - mg/L or µg/mL < 0.5 3. S Ferritin The ferritin test measures the level of ferritin, stored protein in the body. •Normal Levels 12 to 300 ng/mL for males and 12 to 150 ng/mL for females.
  51. BLOOD MARKERS IN COVID 4. Lactate dehydrogenase (LDH) • LDH is expressed extensively in body tissues, such as blood cells and heart muscle. Because it is released during tissue damage, it is a marker of common injuries and disease such as heart failure. • Normal Levels - 50 -150 U/L 5. Interlukin 6 • Interleukin 6 is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the IL6 gene. In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation • Normal Levels - 0– 16.4 pg/mL
  52. 6. Troponin I • Troponin I is a cardiac and skeletal muscle protein family. It is a part of the troponin protein complex, where it binds to actin in thin myofilaments to hold the actin-tropomyosin complex in place. Troponin I prevents myosin from binding to actin in relaxed muscle. When calcium binds to the troponin C, it causes conformational changes which lead to dislocation of troponin I. Afterwards, tropomyosin leaves the binding site for myosin on actin leading to contraction of muscle. The letter I is given due to its inhibitory character. It is a useful marker in the laboratory diagnosis of heart attack.[1] It occurs in different plasma concentration but the same circumstances as troponin T - either test can be performed for confirmation of cardiac muscle damage and laboratories usually offer one test or the other.[2] • Normal Levels - 0 and 0.4 ng/mL 7. Pro Calcitonin • Measurement of procalcitonin can be used as a marker of severe sepsis caused by bacteria and generally grades well with the degree of sepsis,[50] although levels of procalcitonin in the blood are very low. PCT has the greatest sensitivity (90%) and specificity (91%) for differentiating patients with systemic inflammatory response syndrome (SIRS) from those with sepsis, when compared with IL-2, IL-6, IL-8, CRP and TNF-alpha.[51] Evidence is emerging that procalcitonin levels can reduce unnecessary antibiotic prescribing to people with lower respiratory tract infections. • Normal Levels - 0.10 – 0.49 ng/mL
  53. REMDESIVIR • As an adenosine nucleoside triphosphate analog (GS-443902),[80] the active metabolite of remdesivir interferes with the action of viral RNA-dependent RNA polymerase and evades proofreading by viral exoribonuclease (ExoN), causing a decrease in viral RNA production.[10][81] In some viruses such as the respiratory syncytial virus it causes the RNA- dependent RNA polymerases to pause, but its predominant effect (as in Ebola) is to induce an irreversible chain termination. Unlike with many other chain terminators, this is not mediated by preventing addition of the immediately subsequent nucleotide, but is instead delayed, occurring after five additional bases have been added to the growing RNA chain. For the RNA- Dependent RNA Polymerase of MERS-CoV, SARS-CoV-1, and SARS-CoV-2 arrest of RNA synthesis occurs after incorporation of three additional nucleotides. Hence, remdesivir is classified as a direct-acting antiviral agent that works as a delayed chain terminator. • Dosage - 200 mg IV on day 1 followed by 100 mg IV daily for 4 days (5 days in total). • Note It is a heptatoxic and renal toxic drug so LFT and RFT should be monitored regularly.
  54. PRECAUTIONS AND CHALLENGES The medical operatories should gear themselves Preparatory Phase(I), Implementation Phase(II) and Follow up (III) Phase I: Preparatory phase for a medical clinic • Doctor and health care prophylaxis against COVID 19. • asymptomatic Health care workers not exposed to corona virus infection are not required to undergo a test before resuming to work. • asymptomatic healthcare workers involved in care of suspected or confirmed cases of COVID-19 are advised to take HCQ prophylaxis after medical consultation.
  55. Ventilation air quality management in stand-alone clinics I. Maintain air circulation with natural air through a frequent opening of windows and exhaust. II. Avoid the use of a ceiling fan while performing procedure. III. Table fan behind the operator and let the airflow towards the patient. IV. window air condition system/ split AC should be frequently serviced, and filters cleaned. V. Use of indoor portable air cleaning system equipped with HEPA filter and UV light may be used. Allow fresh air into rooms by opening of windows or doors slightly.
  56. Clinic entrance, reception and waiting : • Display visual alerts at entrance (e.g., waiting areas or elevators) about respiratory hygiene, cough etiquette, social distancing and disposal of contaminated items in trash cans. • Install glass or plastic barrier at the reception desk. • Ensure availability of sufficient three-layer masks, sanitisers ,paper tissue at the registration desk. • Distant waiting chairs, preferably a meter apart. • All areas to be free of all fomite such as magazines, toys, TV remotes or similar articles. Contactless payment methods. • A bin with lid should be available at triage.
  57. Changing Room Dedicated area for donning and doffing of PPE, sterilisation. • A dedicated and trained person should be available to undertake Transport, Cleaning, Drying, Packing, Sterilisation, Storage and Testing the quality of sterilisation as per the standard guidelines and manufacturer’s instructions. space for storage of additional items of PPE, sterilisation, disinfection instruments and chemicals must be ensured. Washrooms: Sensor taps. No towels.
  58. Instrumentation I. Fumigation systems II. High volume extra oral suction III. The indoor air cleaning system IV. Used hand pieces with anti-retraction valves only V. Chemicals required for disinfection VI. Appropriate PPE and ensure it is accessible to HCW. VII. Maintain a supply of all consumables related to PPE, Sterilisation and Disinfection
  59. Training of Healthcare Workers (HCWs) I. Train administrative personnel working in the reception of patients on hand hygiene, social distancing, use of facemask, for them and incoming patients. II. Educate all HCW on proper selection and use of PPE. They may require psychological support and morale-boosting to maintain their level of confidence and strict adherence of guidelines. III. Staff should rotate more frequently, preferably, should avoid long working hours, should ensure proper nutrition and sleep. IV. All staff and doctors must use surgical attire in the office, and all personal clothing should be avoided. Hand hygiene: As per the WHO guidelines Standard .
  60. Donning and doffing: Use of n95 masks: Disinfection of Clinic : • COVID-19 virus can potentially survive in the environment for several hours/days. • potentially contaminated areas to be cleaned before their re-use. • Remove the majority of bioburden, and disinfect equipment and environmental surfaces.
  61. Environment and Surface Disinfection: • Floors: 2 Step Cleaning Procedure (Detergent and freshly prepared 1% sodium hypochlorite with a contact time of 10 minutes. Mop the floor starting at the far corner of the room and work towards the door. Frequency: after any patient/ major splash or two hourly. • Rest of the surfaces: Freshly prepared 1% sodium hypochlorite (Contact Time: 10 minutes). Damp dusting should be done in straight lines that overlap one another. Frequency: before starting daily work, after every procedure and after finishing daily work Delicate Electronic equipment: Should be wiped with alcohol-based rub/spirit (60-90% alcohol) swab before each patient contact.
  62. Phase II Implementation : Tele-consult Tele-screening: I. Encouraged as the first point of contact between the patient and the dentist or reception office. II. Current medical history and past history particularly pertaining to symptoms of Severe Acute Respiratory Illness (fever AND cough and/or shortness of breath) or All symptomatic ILI (fever, cough, sore throat, runny nose) must be analysed. III. Any positive responses to either of the questions should raise concern, and care should be postponed for 3 weeks except in emergencies. IV. Encourage all to download the Arogya Setu App.
  63. Protocols of patient handling in the clinic area : • For appointments (no aerosols) - only wear a triple layer surgical mask with protective eyewear/face shield and gloves. • Wear N95 face masks, protective eyewear/face shields and gloves along with coverall for High Risk and very high-risk procedures. • Increase shelf life of N95 masks( cover with surgical mask and discard only the surgical mask). • Moderate risks patient examination require all PPE as high risk except coveralls can be substituted with surgical gowns. • Practice non-aerosol generating procedures. Use of rubber dam is encouraged. The 4-handed technique is beneficial for controlling the infection.
  64. Patient discharge protocol : I. The patient drape will be removed by the assistant, the patient is asked to perform hand wash and guided out of the clinic towards reception and handed back his foot wears and belongings. II. The procedures and prescription is recorded only after doffing the PPE. III. Patient to perform hand hygiene and to be provided with follow up instructions.
  65. Patient turn around and disinfection protocol I. After patient leaves, Assistant will collect all hand instruments immediately, rinse them in running water to remove organic matter and as per standard sterilisation protocol. II. All 3 in 1 syringe, water outlets, hand piece water pipelines, etc. should be flushed with the disinfectant solution for 30-40 seconds. III. Remove water containers and wash them thoroughly and disinfect with 1% sodium hypochlorite using clean cotton/ gauge piece and then fill with fresh 0.01% sodium hypochlorite solution
  66. Protocol for clinic closure Fogging: • It is used as 'No-touch surface disinfection' and not for disinfection of air after a large area has been contaminated. The commercially available hydrogen peroxide is 11% (w/v) solution which is stabilized by 0.01% of silver nitrate. • A 20% working solution should be prepared. The volume of working solution required for fogging is approximately 1000ml per 1000 cubic feet. After the procedure has been completed in the operatory (in case of no negative pressure), exit the room and close the operatory for half hour for the aerosols/droplets to settle down. • Perform the 2 Step surface cleaning followed by fogging. The fogging time is usually 45min followed by contact time/dwell time of one hour. • After that the room can be opened, fans can be switched on for aeration. Wet surfaces can be dried/cleaned by using a sterile cloth or clean cloth (other surfaces).
  67. Protocol for health care workers on reaching home : Follow all precautions and on return, follow the removal of shoes, change of clothes, having a wash and disinfect your mobile wristwatch etc.
  68. BMW GUIDLINES 1. COVID ISOLATION WARDS: • separate colour coded bag and segregation as per BMWM rules. DOUBLE layered bags for collection from covid 19 isolation wards(ensure adequate strength and no leaks). • Mandatory labelling- easy identification. “COVID-19 WASTE”. Separate record from covid-19 isolation wards. Use dedicated trolleys and collection bins. • Both surfaces of container to be disinfected with 1%hypochlorite solution daily. • Report opening of covid-19 ward to SPCBs and respective CBWTF located in area. 2. SAMPLE COLLECTION CENTRE AND LAB FOR COVID-19: • Report to concerned SPCB.
  69. 3. RESPONSIBILTY OF PERSONS OPERATING QUARANTINE CAMPS/HOMES: • General waste hand over to waste collector as per prevailing local method. • Biomedical waste separately in yellow color bags by ULBs. • Persons operating should call CBWTF operator. Any difficulty should be reported to ULBs. 4. CBWTF-COMMON BIOMEDICAL WASTE TREATMENT FACILITY: • Report receiving of waste. Ensure REGULAR sanitation of workers involved. • Provide adequate PPEs. Dedicated vehicles sanitized by 1%sodium hypochlorite.
  70. 5. DUTIES OF SPCBs/PCCs: • Maintain record in respective sates. • ENSURE collection and disposal asper bmw rules. • Allow CBWTFs to operate for extra hpurs as per requirement. • Coordinate with CBWTFs and ULBs in adequate collection and disposal of covid 19 waste. • In case large volume of yellowcolor waste HW incinerators at existingTSDFs by ensuring separate arrangement.
  71. Proposed Plan for Early Intervention in Home Isolation Cases in Haryana There has been an increase in average daily new positive cases . It was due to the combined effect of Festival seasons gathering, opening of all commercial establishments and non-compliance of Covid Appropriate Behaviour by the public. This also resulted in increase in the death cases due to Covid during this period (Aug -5, Sept- 49, Oct-71 and Nov 92). As per Covid death audit 65% of total deaths were among age group >60 yrs and 20% in 50 - 60 yrs, 9% in 40-50 yrs age group and 6% were less than 40 yrs of age. Similarly, 45% cases were suffering from Diabetes Mellitus, 20% from Heart problems & Hypertension, 7% from Respiratory Diseases, 6% from Renal Diseases, 2% carcinoma, 7% from other diseases and 14% had no co-morbid conditions. Out of total 227, 10% were either brought dead or at home and 90% were institutional death. In majority of cases, patient is reporting late for investigation and admission when Health condition of patient has already become very much compromised. This inappropriate behaviour (not testing timely) is due to the fear of getting positive and thus their family will be under house arrest for 14 days with social stigma, not full faith in public hospitals & high treatment cost in private hospitals. They are also worried about consequential loss of their earning. It has also been found that many of these patients took self medication (as prescribed in social media) and lost the precious time. When these patients report to health centre, their condition is already compromised and results in increase in fatality rate. Presently 87% of active cases are in Home Isolation and 13% are in institutional isolation. Hence, there is need for early detection of complications and intervention in the Covid positive cases under Home isolation.
  72. Following steps are proposed for the same: 1. Ward wise Screening: Urban Haryana is having 80% of total case load. It is divided in 20 MC Wards. Ward wise House to House survey by Health Workers will be done and screening of all high-risk groups will be done. Intensive efforts will be done in the areas where more cases are detected. Nigam Parshad (Counsellor) of the area to be taken into confidence and with their help, people will be encouraged to come forward to get tested early. All contacts to be encouraged to test well in time. Involvement of personnel from Urban local bodies/Corporation and local Police authorities will also be solicited. It will help in proper contact tracing, increase sampling rate and enforce administrative action if required. 2. First Contact: Once a patient is detected Covid positive, an early Telephonic/ Video consultation to be given to the patients by a Doctor to allay their fears and detect cases with co-morbidities early. Services of IMA Haryana doctors also to be taken for this purpose. Day of symptom onset to be recorded properly. If assessment in elderly and patients with co- morbid conditions is made to keep them at home only, various precautions and monitoring to be explained to the attendants. For this purpose, there will be a need to setup a Unified Call Centre, which besides taking patients’ calls, will also connect them to their treating doctor.
  73. 3. Follow up: Home isolation teams to follow up all cases diligently. Medicines and SpO2 monitors (Home Isolation Kit) to be provided to cases in Home Isolation. Regular supply of required medicines to be ensured to home isolated patients. Priority to be given to elderly and patients with co-morbidities. Patients and attendants to be taught SpO2 monitoring, both in resting and after a 6 minutes’ walk. Other symptoms to be asked for the purpose of assessing complications, with special mention of: a. Persistence/ recurrence of fever after three days b. Cough and/or Breathlessness c. Severe Fatigue/ weakness d. Nausea e. SpO2 <95% Modified version of NEWS protocol to be used for assessment. 4. Physical Examination: If no other indication earlier, every patient to have a physical examination by a paramedical staff or a doctor attached to home isolation team around 5th day of symptoms. Team should personally record SpO2, both in resting and after a 6 minutes’ walk.
  74. 5. Lab Investigations: If not indicated earlier, following lab investigations of all cases to be carried out on 5th to 7th day of symptoms: a. CBC (Complete Blood Count) with NLR (Neutrophil-Lymphocytic Ratio) b. RBS (Random Blood Sugar) c. CRP (C-Reactive Protein) Quantitative If reports are within normal limits, treatment to be continued as such, else treating doctor to make a call for need of hospitalization of the patient.  If CRP is raised up to four times the normal and other parameters are normal, it is to be repeated in two days, with other investigations indicated.  If CRP raised more than four times the normal, other investigations to be done immediately to detect complications early. This may include other blood and Radiological investigations. 6. Managing Complications: In case of anticipated complications, on the basis of lab investigations or docors’ assessment, patient to be hospitalised as per entitlement in Private or Public setup. 7. Day Care: If treating doctor feels that patient doesn’t require Oxygen support but requires some other therapy (e.g. Steroids, Heparin, Remdesivir etc) under supervision, same maybe allowed on Day-care basis. Ayushman charges maybe allowed for the same. 8. Repeat Physical Examination: It will be carried out around 10th day of home isolation. Final assessment to be made in consultation with the treating doctor about continuing care. 9. Discharge: If patient is not having any complications, patient to be discharged from Home Isolation as per guidance.
  75. SOPs to be established Blood Investigation Process: MOU to be done with multiple local labs for home sample collection of above samples (CBC, RBS and CRP Quantitative). A fixed rate to be arrived at by the Civil Surgeon, including Lab investigations and Sample collection. Cost of lab investigations to be borne by the affording patients and to be borne by the government in case of poor patients. Advanced investigations (like D-Dimer, Ferritin, LDH, IL-6, Procalcitonin etc) to be done as per MOU of GH Haryana. Radiological Investigations: As per indication and advice of the treating physician, HRCT Scan to be advised in cases having deranged investigations or other high-risk factors. Same process of payment by the affording cases and subsidy by the government for the poor patients may be worked out.
  76. Role of IMA Doctors: Many of IMA Doctors have volunteered for telephonic consultations. As patients are comfortable talking to their own doctors, those on Home Isolation will be linked up with IMA doctors, preferably one of their own choice. These doctors will be connected to the patients through Haryana helpline control room. If attending doctor feels the need, patient will be shifted to institutional care. A detailed transcript for consultation to be made. Request will be made to Covid Care Hospitals to keep a bed reserved for the patients transferred from Home isolation. Request will be made to these hospitals to make additional space available for the Day care patients as per requirement.
  77. Home Isolation Practice:  Recommended to Asymptomatic and MILD symptomatic cases with NO OTHER INDICATION (Uncontrolled Co-morbidities) for admission.  Home must have facility for Separate Room with Separate Bathroom for the patient. A Caretaker must be available.  Patient and Caretaker must be given 24x7 contact number for any emergency.  Patient and Caretaker must be trained in use of Pulse Oximeter and Six minutes’ walk test (6 minutes’ hand grip exercise, if patient is unable to walk).  Kit containing medicines including Zinc tablets (50 mg OD), Vitamin C (500 mg BD) and Vitamin D (1000 units OD) must be provided to the patient.  Favipiravir to be provided to the patient on paid basis ONLY on demand. Dosage should be 1800 mg BD for first day and then 800 mg BD from day 2 for next 7-14 days.
  78. Home Isolation Practice:  Every patient to have a physical examination by a paramedical staff or a doctor attached to home isolation team around 5th day of symptoms. Team should personally record SpO2, both in resting and after a 6 minutes’ walk. Scoring on Modified NEWS protocol to be done.  Lab Investigations also to be done on 5th day of symptoms. Radiological investigations to be done only if indicated.  If abnormalities on investigations or on examination, patient to be shifted to Institutional or Day-care as advised by the treating physician.  If patient remains asymptomatic throughout, then may be considered for discharge from supervised care on 10th day of symptoms/ test being positive.
  79. Modified Protocol For Home Monitoring Parameter Finding Score Scoring 0 1 2 3 Age (in Years) <65 ≥65 Respiratory Rate (per minute) 12-20 9-11 21-24 ≥25 ≤8 Sp02 (%) <95 94-95 92-93 ≤91 Systolic BP (mmHg) 111-219 101-110 91-100 ≥220 ≤90 Pulse rate (per minute) 51-90 91-110 41-50 111- 130 ≥131 ≤40 Consciousness Alert Drowsy Lethargy Temperature (oC) 36.1- 38.0 38.1-39.0 OR 35.1-36.0 ≥39.1 ≤35.0 Temperature (oF) 97- 100.4 100.6- 102.2 OR 95.2-96.8 ≥102.4 ≤95 Total Score Score Recommendation 0 Routine Monitoring to continue 1-4 Advise Lab Testing and Increased Monitoring 5-6 Immediately talk to Treating Physician and Transfer per advice ≥7 Immediately transfer to Casualty
  80. RTPCR/ RAT Positive Home Isolation Telephonic Consultation Institutional Care Lab Investigations/ HRCT Normal Deranged (CRP >4 times) HRCT Abormal Borderline (CRP Up to 4 times) After 5 Days of Symptoms Discharge Process Flow For Home Isolation Physical Examination Re-Assess in 2 Days After 10 Days of Symptoms Daycare SpO2 >95% SpO2 <95%
  82. A wave of chronically ill and slow-healing survivors is an inevitability we can and must prepare ourselves for.
  83. CASE VIGNETTE -1 • 43 yr old male doctor with no comorbidities presented with complaints of fever and myalgias for 5 days • Covid RT PCR was positive on 12/8/2020 • Spo2 – 95% on room air • Started on antipyretics, antivirals (daclatasvir and sofosbuvir) and other supportive management
  84. INVESTIGATIONS- 12/8 HEMOGRAM Hemoglobin 14.9 gm% TLC 4,000 cells/cu mm DLC P55%, L36%, M 7%, Platelets 1.5Lakhs/mm3 ESR 38 mm/hr CRP 11 mg/L KIDNEY FUNCTION TESTS Blood urea 23 mg% Serum creatinine 0.8 mg% LIVER FUNCTION TESTS AST 30 U/L ALT 40 U/L Alkaline phosphatase 94 U/L Serum bilirubin 0.4 mg% Direct/indirect bilirubin 0.1/0.3 mg% Serum proteins 7gm% Serum albumin 4.3 gm% LDH 204U/L Ferritin – 748mcg/l D-dimer – 0.24 mcg/ml
  85. CT THORAX-17/8
  86. • Was on home quarantine • Repeat PCR was negative on 19/8/2020 • On follow-up: Patient complaining persisting fever and myalgias
  87. INVESTIGATIONS- 30/08 HEMOGRAM Hemoglobin 13.9 gm% TLC 11,000cells/cumm DLC P80%, L16%, M 2%, Platelets 2.0Lakhs/mm3 ESR 38 mm/hr CRP 10 mg/L KIDNEY FUNCTION TESTS Blood urea 26 mg% Serum creatinine 1.0 mg% LIVER FUNCTION TESTS AST 77 U/L ALT 148 U/L Alkaline phosphatase 88 U/L Serum bilirubin 0.6 mg% Direct/indirect bilirubin 0.2/0.4 mg% Serum proteins 6.4gm% Serum albumin 3.9gm% LDH 204U/L Ferritin – 857mcg/l D-dimer – 0.41 mcg/ml Procalcitonin –ve IL-6 – 39.2pg/ml
  88. CT THORAX- 01/9
  89. • Started on corticosteroids (methyl prednisolone 32mg) on 02/09/2020 • Fever subsided 2 days after steroid initiation, Inflammatory markers normalised.. • Steroids gradually tapered (now on 8mg methyl prednisolone) • Present issue : Persistent fatigue….
  90. Defining post-acute covid-19 Symptom extension beyond 3 weeks from the onset of first symptoms & Chronic covid-19 as extending beyond 12 weeks BMJ 2020;370:m3026
  92. 10% “LONG COVID”
  93. • Post-acute covid-19 - “long covid” seems to be a “multisystem disease” • Management of post covid-19 is currently based on limited evidence • Approximately 10% of people experience prolonged illness after covid-19 • Many such patients recover spontaneously with holistic support, rest, symptomatic treatment, and gradual increase in activity
  95. JAMA. 2020;324(6):603- 605 Persistent symptoms in patients after acute COVID-19
  96. J Med Virol. 2020;1–10
  97. Important distinction between…. Persistent inflammation Sequelae of organ damage Non specific effects of hospitalisation & social isolation
  98. Myalgic encephalomyelitis / chronic fatigue syndrome 'My fatigue was like nothing I've experienced before' 'I don’t have a life, I currently have an existence'
  100. The Five Mutually Reinforcing Drivers Of CFS/ME BMSystems 2020 CONFIDENTIAL
  101. Pathogenesis – Superposition of Humoral and cellular Responses??? BMSystems 2020 CONFIDENTIAL
  102. Management BMSystems 2020 CONFIDENTIAL
  103. "Covid Recovery Plan" “The Four Ps" Post COVID-19 Patient information pack – NHS Foundation Trust
  104. • 55 Covid survivors included in the study • Patients were followed up after 3 months • The presenting symptoms during follow up included gastrointestinal (GI) symptoms (30.91%), headache (18.18%), fatigue (16.36%), exertional dyspnea (14.55%), as well as cough and sputum (1.81%). Yu-miao Zhao et al, EClinicalMedicine,2020
  105. CASE VIGNETTE -2 • A 42-year-old diabetic and hypertensive presented with • Fever-5 days • Cough -5 days • Shortness of breath- 2 days • On examination: RR-18 breaths/min, SPO2-96% on room air • Covid-19 RT-PCR positive • Initially received symptomatic treatment • 2 days later- developed breathlessness and hypoxemia • Dexamethasone 8 mg OD and Remdesivir started
  106. • Symptoms persisted-Received HFNC support and 2 doses of convalescent plasma therapy • Given tocilizumab in view of worsening hypoxemia • Patient improved clinically and weaned off from HFNC support 21/7/20
  107. • Hypoxemia persisted requiring 3 lit of oxygen support with nasal prongs • Blood investigations • CRP-0.93 mg/L (0-5 mg/L) • Ferritin-94.6 ng/ml (30-400 ng/ml) • Pirfenidone (200 mg TDS) started in view of persistent opacities (secondary to pulmonary fibrosis) but was stopped due to drug intolerance (diarrhoea) • Advised home oxygen therapy at the time of discharge 31/7/20
  108. Serial Chest Radiographs 10/7/20 31/7/20 21/7/20
  109. • He now presented to OPD with complaints of • Persistent breathlessness • Fatigue and • Dry cough • On examination: • PR -82/ min • B.P- 124/78 mm Hg • RR-20 breaths/min • SpO2 – 97 % on room air at rest and 94-95% on exertion
  111. Respiratory Issues Post Covid
  112. • Fifty-seven patients completed the serial assessments. • There were 40 non-severe cases and 17 severe cases. • Compared with non-severe cases, severe patients showed higher incidence of DLCO impairment (75.6% vs4 2.5%) and significantly lower %age of predicted TLC and 6MWD. ABNORMAL CT FINDINGS 54.3% ABNORMAL PFTs 75.4% DECREASE IN DLCO 52.6% DECREASE IN TLC 12.3% Huang et al. Respiratory Research (2020) 21:163 Pulmonary recovery in COVID-19 lags behind virological clearance.
  113. Respiratory symptoms Cough • Best managed with simple breathing control exercises • Medication where indicated (such as proton pump inhibitors if reflux is suspected) • Adequate hydration • Steam inhalation
  114. Breathlessness • One of the more serious symptoms of COVID19—the infection • A degree of breathlessness is common after acute covid-19. • Etiology: • Residual pulmonary fibrosis • Residual pulmonary thrombi
  115. Pulmonary fibrosis Acute or chronic inflammation Alveolar epithelium damage Overexpression of proinflammatory cytokines Fibroblasts and myofibroblasts activation Excessive deposition of collagen in ECM J. Clin. Med. 2020, 9, 1917; doi:10.3390/jcm9061917
  116. PULMONARY FIBROSIS TREATMENT ANTIVIRALS DRUGS FOR IPF (NINTEDANIB, PIRFENIDONE) PLASINOGEN ACTIVATION (tPA, STK, Urokinase) Hyperbaric oxygen Mesenchymal Stem cells Spironolactone J. Clin. Med. 2020, 9, 1917; doi:10.3390/jcm9061917
  117. Role of antifibrotics • They do not address the immune dysregulation of SARS-CoV-2 infection, nor can they be expected to attenuate the prothrombotic aspects of this complex pathogenic process. • If antifibrotic therapy is to have a role, it is likely to take the form of inclusion in combination regimens, once effective anti-inflammatory treatments have been identified.
  118. Pirfenidone: A novel hypothetical treatment for COVID-19 Inhibit apoptosis Downregulate ACE receptors expression Decrease inflammation Ameliorate oxidative stress Medical Hypotheses 144 (2020) 110005
  119. Novel antifibrotics Lancet Respir Med 2020; 8: 807–15
  120. Lancet Respir Med 2020; 8: 807–15 Antiviral effects??? Can be preventive??
  121. Uncertainties… Choice of drug Duration of treatment Identification of biomarkers (predictive & prognostic)
  123. Patients at highest risk of COVID-19 pneumonia complications • All patients managed on ICU/HDU • All patients discharged with a new oxygen prescription. • All patients with protracted dependency on high inspired fractions of oxygen, continued positive pressure ventilation and bi-level non- invasive ventilation.
  124. George PM, et al. Thorax 2020;0:1–8
  125. George PM, et al. Thorax 2020;0:1–8
  126. Covid 19 and Heart
  127. Circulation. 2020;142:342–353
  128. Patients recently recovered from COVID-19 infection, CMR revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), independent of pre-existing conditions, severity and overall course of the acute illness, and time from the original diagnosis. These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19. JAMA Cardiol. doi:10.1001/jamacardio.2020.3557
  130. CRITERIA 1) Severe illness requiring hospitalization in a person aged ≥21 years 2) Positive test result for current or previous SARS-CoV-2 infection during admission or in the previous 12 weeks 3) Severe dysfunction of one or more extrapulmonary organ systems 4) Laboratory evidence of severe inflammation 5) Absence of severe respiratory illness
  131. Pathogenesis Nat Rev Immunol. 2020 Aug;20(8):453- 454. ? Unknown
  132. INTERVAL • Interval between infection and development of MIS is unclear • In patients who reported typical COVID-19 symptoms before MIS onset, MIS was experienced approximately 2–5 weeks later
  133. MANAGEMENT • Aspirin • Anticoagulation • IvIg • Corticosteriods • Vasopressors • Ventilatory management
  134. Covid 19 & Psychiatric illness The Hindu- August 2020
  135. Covid 19 & Psychiatric illness • Anxiety - 12 to 20% • Depression - 15 to 25% • Insomnia - 8% • Traumatic distress - 35 to 49% HCW • Insomnia – 42 % • Impaired attention or concentration – 38 % • Anxiety – 36 % • Memory impairment – 34 % • Depressed mood – 33 % • Confusion – 28% Patients JAMA Psychiatry.
  136. PTSD • Seen in upto 32% • Epidemiological data indicate that the median time for PTSD to remit is ✓ 36 months for individuals who sought help ✓ 64 months for individuals who never sought help for a mental health problem. Fear of infection, social isolation, stigmatisation Witnessing of patients who suffer from, struggle against and die Direct experiencing and suffering from symptoms Xiao et al. Global Health Research and Policy (2020) 5:29
  138. Rehabilitation for Severe COVID-19 • The illness may be complicated by respiratory failure and other forms of multi organ failure, resulting in ICU admission with likely invasive mechanical ventilation. • Rehabilitation needs are typically related to the consequences of ventilatory support, and prolonged immobilization
  139. Rehabilitation for Severe COVID-19 • Impairments most likely to encounter: • Physical deconditioning and muscle weakness, fatigue • Impaired lung function • Delirium and other cognitive impairments • Impaired swallow and communication • Mental health disorders and psychosocial support needs. • Multi-disciplinary team approach is key • Still many unknowns related to the pathophysiology of COVID-19 and the long-term complications, many organs can be affected
  140. Acute Objectives - Optimize oxygenation - Manage secretions - Prevent complications Post-acute Objectives - Identify and manage impairments for affected functioning domains - Facilitate safe discharge and onward referral Long-term Objectives - Optimize functioning/ minimize impact of impairments on independence and quality of life Rehabilitation in COVID-19
  141. Comprehensive Post Covid Care
  142. Conclusion… • The long-term effect of COVID-19 is still largely unknown. • Potential areas of research and innovation need could include: • Developing new treatments that prevent the deterioration of lungs in the acute presentation of the virus. • Understanding the mental impact of post COVID damage. • Creating the tools to help people to self-manage their long-term recovery. • Establishment of “Post Covid Care Clinics” with involvement of multidisciplinary teams
  143. BMJ 2020;370:m3565
  144. THANKS