Approach towards COVID 19

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. 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.

4. Pathophysiology
Virus particle emerging from cell

6. 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.

7. Stage II- Moderate Disease /Pulmonary phase:
• Viral multiplications, Infect lung- epithelial injury – DAD –
ARDS- hypoxemia.
• Blood- lymphopenia. Transminitis. Procal- Normal
• Need hospitalisation.

8. 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

10. 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)

11. 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.

12. 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.

13. • Prophylactic and therapeutic
anticoagulation showed better
out comes
• CT – vessel enlargement near
areas of GGO-in 89% pts
• CTPA – 40% subsegmental
embolism

14. Recommendations-
Dutch health care

15. 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

16. Diagnosis

17. 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

18. 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

20. 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%)

21. 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.

22. • 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.

23. 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

24. Disadvantages:
• Negative in early phase
• Specificity is low ?
• Cross sensitivity to other corona viruses.

26. • 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.

27. Treatment
There are no sp antiviral drugs or vaccines available at
present

30. • 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

31. 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

32. 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

33. 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

34. Treatment
• A,B,C categories
• Only Paracetamol, avoid other NSAIDs
• All ILI- use oseltamivir till COVID result available
• Broad spectrum antibiotics
• Better avoid steroids

35. 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)

36. 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.

37. • 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.

38. 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

39. 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

40. 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.

41. 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.

42. 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.

43. 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.

44. 2nd SIMPLE Trial

45. 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

46. Tocilizumab
• IL-6 inhibitor
• Reduce cytokine storm
• Adverse effects: Hepatitis, can worsen other infections

47. 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

48. 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

49. Side effects:
• Infections
• Volume overload
• Febrile and allergic reactions
• Anaphylaxis(In IgA deficiency)
• TRALI

50. 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.

51. ? 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%

52. 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

53. 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

54. Mechanical ventilation
• Severe resp failure- intubate and ventilate
• Use new tubings and viral filtres
• Low tidal volume, high PEEP strategy
• Prone ventilation/ ECMO

55. 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

56. 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.

57. 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.

58. 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

59. 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

61. 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

62. Thank you