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COVID 19- Diagnosis and Treatment

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Approach towards COVID 19

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COVID 19- Diagnosis and Treatment

  1. 1. COVID 19 –Diagnosis & Treatment Dr Rohit Kallukadavil MBBS, MD, DNB, MRCP Sce (Resp) Consultant Pulmonologist and Critical care specialist HGM Hospital, Kottayam, Kerala.
  2. 2. Introduction • COVID 19- caused by SARS CoV-2 • World wide 37L pts infected and 2.6L patients died • Till now there is no specific treatment or vaccinations available.
  3. 3. Pathophysiology Virus particle emerging from cell
  4. 4. Stages of Infection Stage I- Mild (Early Infection): • Local symptoms-throat irritation, dry cough, fever etc. Many asymptomatic. Pt vl be infective. 80% recover in few weeks. • Lymphopenia & neutrophilia.
  5. 5. Stage II- Moderate Disease /Pulmonary phase: • Viral multiplications, Infect lung- epithelial injury – DAD – ARDS- hypoxemia. • Blood- lymphopenia. Transminitis. Procal- Normal • Need hospitalisation.
  6. 6. Stage III- severe (Inflammatory response): • Extrapulmonary systemic hyperinflammation. Decrease T cells. • cytokine storm – IL6,IL2, IL7,TNF alpha , CRP,D dimer, Ferrititn, Trop, BNP: progress to– MODS • myocarditis • Rx: steroids, IL -6 inhibitors
  7. 7. Lung phenotypes Type L patient- Low elastance, Low V/Q, low lung weight, Low recruitability • severely hypoxic without significant dyspnoea(silent hypoxemia). • Better response to O2, may not benefit from high PEEP. Type H patient (30%) – High elastance, R-L shunt, high lung weight, High recruitability- • Histopathology- typical DAD • May need Invasive ventilation Ref: COVID-19 pneumonia: different respiratory treatments for different phenotypes? Luciano Gattinoni, Intensive Care Medicine (2020)
  8. 8. Other organs • Heart – elevated Trop/BNP- ? Left ventricular dysfunction, myocarditis • Kidney- 4.5% pts, ? Due to cardiac failure, sepsis, fluid dysregulation, rhabdomyolysis etc • Neurological- ? CVA.
  9. 9. Vascular Injury • SARS CoV2 bind to ACE receptors in Endothelial cells of blood vessels-injury and cytokine- thrombosis • Resp failure not explained with ARDS alone- microvascular thrombotic process also • Strong association between D Dimer, disease progression and CT features of venous thrombosis • Autopsies showed thrombosis in multiple organs • IL 6 elevation after 13 days of disease onset, but D –Dimer level 10 fold raised before that.
  10. 10. • Prophylactic and therapeutic anticoagulation showed better out comes • CT – vessel enlargement near areas of GGO-in 89% pts • CTPA – 40% subsegmental embolism
  11. 11. Recommendations- Dutch health care
  12. 12. Children safe from Covid ? • Less viral load • ACE 2 expression is lower • Poorly developed humoral and cellular immune system • Recurrent antigenic stimuli from viruses cause more inflammatory immune response in adults
  13. 13. Diagnosis
  14. 14. Covid suspect: • All symptomatic(fever, cough and Dyspnoea) individuals who have undertaken international travel in the last 14 days • or • All symptomatic contacts of laboratory confirmed cases • or • All symptomatic healthcare personnel (HCP) • or • Hospitalized patients with fever AND cough and/or shortness of breath • or • Asymptomatic direct and high risk contacts of a confirmed case (should be tested once between day 5 and day 14 after contact) • Symptomatic pts in Hotspots/cluster (as per MoHFW) and in large migration gatherings/evacuees centres: Confirmed case: A person with laboratory confirmation of COVID-19 infection, irrespective of clinical signs and symptoms
  15. 15. Samples for analysis Specimen Positivity BAL 93% Sputum 72% Nasopharyngeal swab 63% Oropharyngeal swab 32% Faeces 29% Blood 1% Urine 0% Detection of SARS-CoV-2 in different types of clinical specimens. Wenling Wang, Yanli Xu. JAMA.2020. Mar11 Preferred: Throat & nasal swab
  16. 16. Diagnostic Test • RT- PCR(Reverse transcriptase polymerase chain reaction) • Gold standard for diagnosis(100% specificity) • Positive result in early phase, later can be –ve due to immunity devlopment. • Expensive, time consuming(6-8 Hr), low sensitivity(50- 70%)
  17. 17. Sample – treated with chemicals- Extract RNA – Reverse transcribed to DNA – Add a complimentary DNA fragment to detect Corona virus- If virus is present, it will attach to the fragment- fluorescent material also added for labelling— RT PCR machine- each cycle double the DNAA- 35 cycles minimum- machine detect florescence- in real time manor.
  18. 18. • If RT PCR is negative and suspicion is high – test should be repeated- if possibly from lower resp tract • Positivity rates >90% on Day 1-3 of ilnness, <80= at Day6, <50% after day 14.
  19. 19. Rapid antibody tests • ELIZA test- IgM(active infection) and IgG(Past infection) • Can be used as a screen test • Point of care test, rapid results • cheaper • Blood test • Combined IgG+IgM – better utility
  20. 20. Disadvantages: • Negative in early phase • Specificity is low ? • Cross sensitivity to other corona viruses.
  21. 21. • Biosecurity precautions- collection of samples • Only RT PCR(No conventional PCR or Antibody test) • Positive samples- to be transported to ICMR- NIV • Truenat machine – can also be used.
  22. 22. Treatment There are no sp antiviral drugs or vaccines available at present
  23. 23. • All health care providers should take extra precautions – Mask, gloves, PPEs etc • Social distancing • Avoiding unnecessary crowds in hospitals(amplifyng centre for a pandemic) • Isolate suspects and +ve pts in Covid care centres • Only <20% require admission/ ICU care • Ideal to have Neg pressure Isolation room
  24. 24. Categories A Mild sore throat/ cough/ rhinitis/ diarrhea B Fever and /or severe sore throat/ cough / diarrhea or Cat A + Any of the following Cardiovascular disease Uncontrolled DM, HTN, Cancer, HIV, lung, liver, renal or neurological diseases On steroids/ immunosuppressants Pregnancy Age> 60 yrs C Dyspnoea, chest pain, drowsy, low BP, cyanosis, haemoptysis Children with ILI Worsening of underlying chronic conditions
  25. 25. High risk patients • age>60, With comorbidities • spo2<93%, HR>125, RR>30, BP<90/60 • Altered sensorium • CRP>100, CPK> two time upper limit • Ferritin >300, LDH>245, D- dimer>1000, Trop T +ve • MODS
  26. 26. Admission • Covid care centre: Confirmed mild cases • Covid Ward: High risk patients, Category B pts RR>24 Spo2<94% • Covid ICU: Category C patients Moderate – severe ARDS MODS Shock
  27. 27. Treatment • A,B,C categories • Only Paracetamol, avoid other NSAIDs • All ILI- use oseltamivir till COVID result available • Broad spectrum antibiotics • Better avoid steroids
  28. 28. Treatment A Symptomatic Rx Reassess and categorize Q 28-48Hrs B HCQ 400mcg BDx 1day, 200mg BD x4 days Or Chloroquine600mg then 300mg BD x 5 days + Tab Azithromycin 500mg OD x 5 days. Oseltamivir 75mg BD x 5 days in all ILI until PCR reports C All ILI- Oseltamivir HCQ/Chloroquine + Inj Azithromycin Tab Lopinavir/Ritonavir(400/100) x 14 days (If HCQ contraindicated/ on compassionate use with consent, has to be started within 10 days of symptom onset) If ARDS /MODS- add Lopinavir/ ritonavir and stop Azithromycin(QTc monitor)
  29. 29. Cytokine release syndrome • Grade1: Mild fever • Grade 2: High fever, mild O2 requirement, Raised creat/ LFT • Grade 3: B/L lung infiltrates, SPo2<93%, Raised LFT,INR>1.5, encephalopathy, AKI, hypotension, coagulopathy • Grade 4: Life threatening MODS, hypoxia requiring ventilation, hypotension requiring high vasopressors.
  30. 30. • Serum IL-6 is the marker, ferritin • CRP- surrogate marker • Grade 3& 4- use Tocilizumab 8mg/kg IV (max 800mg) over 60min, if no effect repeat x 2 more doses Q8H. • If no response corticosteroids.
  31. 31. Steroids in COVID • Better to avoid • Delays viral clearance • Use in • Refractory shock, Macrophage activation syndrome, cytokine release syndrome Grade 3/ 4 • 1-2mg/kg /day methylprednisolone equivalent x 3-5 days
  32. 32. Chloroquine/HCQ • Change Ph of endosome and viral entry • No renal or hepatic dose adjustement • 400mg BDx 1, then 200mg BD x 4 days. • HCQ is more potent antiviral than chloroquire • Side effect: QT prolongation, ventricular arrhythmias • Contraindications: QTc>500msec, Porphyria, Myasthenia, Retinopathy, Epilepsy
  33. 33. Evidence • Cause Increase Ph of endosome and prevents virus entry, transport and post entry events ? • invitro action- chloroquine/ hcq against viruses- corona/ influenzea • No peer reviewed publications/ well conducted RCT. • Unpublished study from China and France(HCQ+ Azithromycin) – showed better viral clearance.
  34. 34. Conclusion – This study therefore recommends that COVID-19 patients be treated with hydroxychloroquine and azithromycin to cure their infection and to limit the transmission of the virus to other people, Figure - Percentage of patients with PCR-positive nasopharyngeal samples from inclusion to day6 post-inclusion in COVID-19 patients treated with hydroxychloroquine only, in COVID-19 patients treated with hydroxychloroquine and azithomycin combination, and in COVID-19 control patients Ref – Int J Antimicrob Agents. 2020 Mar 20 : 105949 Biosci Trends. 2020 Apr 5. doi: 10.5582/bst.2020.03058.
  35. 35. Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: an observational study • In 80 in-patients receiving a combination of hydroxychloroquine and azithromycin • A rapid fall of nasopharyngeal viral load tested by qPCR was noted, with 83% negative at Day 7, and 93% at Day 8. • Virus cultures from patient respiratory samples were negative in 97.5% patients at Day 5. • This allowed patients to rapidly discharge from highly contagious wards with a mean length of stay of five days.
  36. 36. Remdesivir • In vitro activity against SARS Cov2 • Premature termination of RNA transcription • Only for compassionate use • Interim analysis of RCT in US- faster recovery • Chinese study- No significant recovery or mortality benefits • 200mg IV then 100mg IV OD x 9 days • Side effects: GI intolerance/ hepatotoxicity.
  37. 37. 2nd SIMPLE Trial
  38. 38. Lopinavir/Ritonavir • WHO – drug can be tried • CYP3A4 inhibitor- monitor drug interactions • QT prolongation, hepatotoxicity. Interferons • IFN-2a, IFN-2b orIFN-1a • Side effect: Flu like syndrome
  39. 39. Tocilizumab • IL-6 inhibitor • Reduce cytokine storm • Adverse effects: Hepatitis, can worsen other infections
  40. 40. Solidarity trial COVID Remdesivir Chloroquine/HCQ Lopinavir+Ritonavir Lop/Ritonavir + Interferon B-1a Standard Rx • WHO supported Phase III-IV trial • From 18/3/2020 – started • >100 countries • COVID pt >18 year age. Similar RCT, resp failure pts in Europe- DISCOVERY trial, March 2020 to March 2023
  41. 41. Convalescent plasma • Plasma from recovered pts • Efficiency not known • One study- improved viral clearance and oxygenation by 12 days after transfusion • Another- 5/6 pt died within 3 days despite viral clearance • Dose: 10-15mL/kg • Need high titre of neutralizing antibody • Lack of infectious particles • ABO and Rh compatible
  42. 42. Side effects: • Infections • Volume overload • Febrile and allergic reactions • Anaphylaxis(In IgA deficiency) • TRALI
  43. 43. Ivermectin • Antiparasite drug • Inhibit entry of viral protein into nucleus of cell • In vitro studies-Australia showed : single treatment able to effect 5000 fold reduction in virus at 48 hour in cell culture.
  44. 44. ? Traditional Chinese Medicines • TCM- used for long time • Effective component- unknown or vague • Chinese studies- WM+TCM Vs WM: symptomatic worsening= 7.4% Vs 46.2%, Mortality 8.8%Vs39%
  45. 45. Supportive therapy • Supplemental oxygen- in hypoxia or shock • Target SpO2 ≥90% , pregnant ≥92-95 % • Conservative fluid- in SARI without shock, aggressive fluid Mx can worsen oxygenation • Antimicrobial within 1 hr of identification of sepsis
  46. 46. Hypoxia • If supplemental oxygen cannot alleviate symptoms- use NIV/HFNO. • NIV – proper interface and PPE reduce chance of transmission • Intubation produce more aerosol and chance of viral transmission
  47. 47. Mechanical ventilation • Severe resp failure- intubate and ventilate • Use new tubings and viral filtres • Low tidal volume, high PEEP strategy • Prone ventilation/ ECMO
  48. 48. Septic shock Mx • Use crystalloids (NS/RL) with caution • If no response to fluid vasopressor • Central line or peripheral line • Target MAP >65, urine out put > 0.5ml/kg/hr
  49. 49. Prone positioning Awake proning: • Adjunct to use of NIV- as a rescue therapy before intubation • Based of perfusion redistribution • Benefits are short lived • Consider- if pt can communicate & co operate if pt able to rotate and adjust position • Pt should switch positons every 30min to 2 hours Proning after intubation- follow standard protocols.
  50. 50. Prevention of the transmission of infection • droplet precaution (e.g. wearing mask & PPE), contact precaution (e.g. hand washing or wearing gloves and gown) and airborne precaution (e.g. isolation room with negative pressure) • The use of clinical triage for the early identification of patients with ARI • Isolation or cohorting of patients to prevent the transmission • Use of PPE and adequately ventilated single rooms when performing aerosol generating procedures ‘One Health’ approach communication and collaboration between countries to build trust and academics IPC, infection prevention and control; ARI - acute respiratory Infection; PPE, Personal Protective Equipment Park S, Park J, Song Y, How S, Jung K. Respirology. 2019;24(6):590-7.
  51. 51. Prevention of complications- critically ill pts • Use weaning protocols – daily • Daily interruption of continuous sedation • Semi recumbent position • Closed suctioning • New ventilator circuit for each pt • DVT prophylaxis • Turn pt Q2Hr to reduce bed sores • Early enteral nutrition • Ulcer prophylaxis • Mobilize of limb physiotherapy
  52. 52. Outcomes Variable Number % Total 305 Median Hosp days 8.5 O2 76% NIV 3.6% HFNO 22% ICU 39% Median ICU days 8 MV 30% RRT 7.5% Inotrope 27.5% Death 17% Characteristics and Clinical Outcomes of Adult Patients Hospitalized with COVID-19 — Georgia, March 2020 New york April 14
  53. 53. Viral clearance • Repeat RT PCR should be done every 2 to 4 days- until 2 consecutive results are negative (URT samples) – 24 Hr apart. • Symptomatic pts- after the resolution of symptoms, samples should be collected at least seven days after the onset or after > 3 days without fever. • Asymptomatic infected persons, the tests should be done at a minimum of 14 days after the initial positive test. • Virus can persist 7-12 days in moderate & 2 wks in severe cases • Prolonged viral shedding in some, > 2 wks to months in PCR, but cultures – negative • Wuhan study Mean duration of viral shedding- 20 days, longest : 37 days • 50% pts show viral shedding even after symptom resolution
  54. 54. Thank you

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