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The life cycle of SARS-CoV-2 in host cells; begins its life cycle when S protein binds to the cellular receptor ACE2. After receptor binding, the conformation change in the S protein facilitates viral envelope fusion with the cell membrane through the endosomal pathway. Then SARS-CoV-2 releases RNA into the host cell. Genome RNA is translated into viral replicase polyproteins pp1a and 1ab, which are then cleaved into small products by viral proteinases. The polymerase produces a series of subgenomic mRNAs by discontinuous transcription and finally translated into relevant viral proteins. Viral proteins and genome RNA are subsequently assembled into virions in the ER and Golgi and then transported via vesicles and released out of the cell. ACE2, angiotensin-converting enzyme 2; ER, endoplasmic reticulum; ERGIC, ER–Golgi intermediate compartment.
Viral particle- attach to ACE II in epithelial and endothelial cells- replicate and many virions realeases- the infected cells undergo apoptosis and release numerous toxins. Virus vill be presented to T cells with APC. CD4 cells – relase neumerous IL and cytokine storm- B cells get activated and produce antibody. If immunity is well virus is contained and neutralised in initial stages. But in 20 % significant viral load caue cytokine storm.
II a without hyoxia
Chest CT images in 51-year-old male (A) Day 7 after onset of symptoms: CT demonstrates bilateral ground glass opacities (GGOs) and early vascular enlargement. (B) Day 10: Rapid progression of GGOs with vascular thickening and interstitial pulmonary edema
Cooler box with ice packs.
Reasses A and B every 24- 48 hours
Helmet based NIV- CPAP
Reference: Park S, Park J, Song Y, How S, Jung K. Emerging respiratory infections threatening public health in the Asia‐Pacific region: A position paper of the Asian Pacific Society of Respirology. Respirology. 2019;24(6):590-597. doi:10.1111/resp.13558
COVID 19- Diagnosis and Treatment
COVID 19 –Diagnosis & Treatment
Dr Rohit Kallukadavil
MBBS, MD, DNB, MRCP Sce (Resp)
Consultant Pulmonologist and Critical care specialist
HGM Hospital, Kottayam, Kerala.
• 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
Virus particle emerging from cell
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.
Stage II- Moderate Disease /Pulmonary phase:
• Viral multiplications, Infect lung- epithelial injury – DAD –
• Blood- lymphopenia. Transminitis. Procal- Normal
• Need hospitalisation.
Type L patient- Low elastance, Low V/Q, low lung weight, Low
• 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,
• Histopathology- typical DAD
• May need Invasive ventilation
Ref: COVID-19 pneumonia: different respiratory treatments for different phenotypes? Luciano
Gattinoni, Intensive Care Medicine (2020)
• Heart – elevated Trop/BNP- ? Left ventricular dysfunction,
• Kidney- 4.5% pts, ? Due to cardiac failure, sepsis, fluid
dysregulation, rhabdomyolysis etc
• Neurological- ? CVA.
• 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.
• Prophylactic and therapeutic
anticoagulation showed better
• CT – vessel enlargement near
areas of GGO-in 89% pts
• CTPA – 40% subsegmental
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
• All symptomatic(fever, cough and Dyspnoea) individuals who have undertaken international travel in the
last 14 days
• All symptomatic contacts of laboratory confirmed cases
• All symptomatic healthcare personnel (HCP)
• Hospitalized patients with fever AND cough and/or shortness of breath
• 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:
A person with laboratory confirmation of COVID-19 infection, irrespective of clinical signs and symptoms
Samples for analysis
Nasopharyngeal swab 63%
Oropharyngeal swab 32%
Detection of SARS-CoV-2 in different types of clinical specimens. Wenling Wang, Yanli Xu.
Preferred: Throat &
• RT- PCR(Reverse transcriptase polymerase chain reaction)
• Gold standard for diagnosis(100% specificity)
• Positive result in early phase, later can be –ve due to
• Expensive, time consuming(6-8 Hr), low sensitivity(50-
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.
• 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.
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
• Blood test
• Combined IgG+IgM – better utility
• Negative in early phase
• Specificity is low ?
• Cross sensitivity to other corona viruses.
• 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.
There are no sp antiviral drugs or vaccines available at
• 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
A Mild sore throat/ cough/ rhinitis/ diarrhea
B Fever and /or severe sore throat/ cough / diarrhea
Cat A + Any of the following
Uncontrolled DM, HTN, Cancer, HIV, lung, liver, renal or neurological diseases
On steroids/ immunosuppressants
Age> 60 yrs
C Dyspnoea, chest pain, drowsy, low BP, cyanosis, haemoptysis
Children with ILI
Worsening of underlying chronic conditions
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
• Covid care centre: Confirmed mild cases
• Covid Ward: High risk patients,
Category B pts
• Covid ICU: Category C patients
Moderate – severe ARDS
• A,B,C categories
• Only Paracetamol, avoid other NSAIDs
• All ILI- use oseltamivir till COVID result available
• Broad spectrum antibiotics
• Better avoid steroids
A Symptomatic Rx
Reassess and categorize Q 28-48Hrs
B HCQ 400mcg BDx 1day, 200mg BD x4 days
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
If ARDS /MODS- add Lopinavir/ ritonavir and stop Azithromycin(QTc monitor)
• 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.
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
• 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,
• Cause Increase Ph of endosome and prevents virus entry,
transport and post entry events ?
• invitro action- chloroquine/ hcq against viruses- corona/
• No peer reviewed publications/ well conducted RCT.
• Unpublished study from China and France(HCQ+
Azithromycin) – showed better viral clearance.
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
Int J Antimicrob Agents. 2020 Mar 20 : 105949
Biosci Trends. 2020 Apr 5. doi: 10.5582/bst.2020.03058.
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.
• 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.
• WHO – drug can be tried
• CYP3A4 inhibitor- monitor drug interactions
• QT prolongation, hepatotoxicity.
• IFN-2a, IFN-2b orIFN-1a
• Side effect: Flu like syndrome
• IL-6 inhibitor
• Reduce cytokine storm
• Adverse effects: Hepatitis, can worsen other infections
• 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
• 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
• Volume overload
• Febrile and allergic reactions
• Anaphylaxis(In IgA deficiency)
• 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.
• 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%
• 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
• If supplemental oxygen cannot alleviate
symptoms- use NIV/HFNO.
• NIV – proper interface and PPE reduce chance
• Intubation produce more aerosol and chance
of viral transmission
• Severe resp failure- intubate and ventilate
• Use new tubings and viral filtres
• Low tidal volume, high PEEP strategy
• Prone ventilation/ ECMO
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
• Adjunct to use of NIV- as a rescue therapy
• 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.
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
‘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.
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
Variable Number %
Median Hosp days 8.5
Median ICU days 8
Characteristics and Clinical Outcomes of Adult
Patients Hospitalized with COVID-19 — Georgia,
New york April 14
• 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 –
• Wuhan study Mean duration of viral shedding- 20 days, longest : 37 days
• 50% pts show viral shedding even after symptom resolution