covid 19 diagnosis updates

1
Current updates on COVID-19 Diagnosis

• Dr. Gurbilas P. Singh, FRCP (London)
• Convener, GI Rendezvous
• Director Education Training, GI, Liver
  specialist and Interventional Endoscopist,
  Sarvhit Gastrocity, Amritsar, India

2
(No Transcript)
3
Our experts Special thanks

• Ms. Harvinder Kaur L.S.
• Malaysian Institute of Medical Laboratory
  Sciences,
• Malaysia
• Dr. Kanwardeep Singh, Professor of Microbiology,
• Pl, Viral Research and Diagnostic Lab.
• Government Medical College, Amritsar,
• India

4
COVID 19, A pandemic (Greek - pan "all" and
demos - "people)

• A pandemic is the worldwide spread of a new
  disease as per WHO
• The US Centers for Disease Control and Prevention
  defines a pandemic as an epidemic that has
  spread over several countries or continents,
  usually affecting a large number of people.
• A widespread endemic disease with a stable number
  of infected people is not a pandemic.

5
(No Transcript)
6
COVID 19 Diagnosis what to expect ?

• How to suspect and diagnose in clinical practice
• Clinical manifestations and variations
• Comorbidities and their impact on outcome
• Current methods of surveillance

7
Background COVID-19

• Newly emergent coronavirus, SARS-CoV-2 
• Respiratory infection, including severe
  pneumonia 
• Respiratory droplets - sneezing, coughing, or
  talking
• Spreads through touching a surface or object that
  has the virus on it and then touching own mouth,
  nose, or possibly eyes
• Some individuals with coronavirus may be
• asymptomatic

8
HOW TO SUSPECT AND DIAGNOSE COVID IN DAILY
PRACTICE

• Common symptoms include cough, fever, chills,
  shortness of breath, muscle aches, sore throat,
  unexplained loss of taste or smell, diarrhea, and
  headache.
• Symptoms can be mild and may aggravate over 5 to
  7 days, sometimes worsening with pneumonia.
• Approximately, 1 out of 5 infected individuals
  becomes seriously ill with difficulty in
  breathing, especially in the elderly with
  underlying health conditions
• REFRENCE
• https//www.cdc.gov/coronavirus/2019-ncov/symptoms
  -testing/symptoms.html
• https//apps.who.int/iris/bitstream/handle/10665/3
  31506/WHO-2019-nCoV-SurveillanceGuidance-2020.6-en
  g.pdf

9
Mr. B, 35 years male Teleconsult

• Symptoms of bloating
• Heartburn
• Nausea, especially on taking Paracetamol
• Sore throat with occasional coughing
• Dysphagia? although only when he had to take
  medicines!
• Background of low grade fever since 9 days !
• But doctor it is not COVID. We got it checked
  and it is negative.

10
TAKING History No assumptions!

• When did the fever start precisely? Saturday
  night
• When was COVID 19 test performed and what test
  was it? Tuesday AM and it was RT PCR test
• Any cough or breathlessness ? Not really, but
  I cough off and on during this season anyway, and
  oxygen levels are between 93 and 95
• Family history Both parents hypertensive and
  mom a diabetic.
• Medical and personal history Fit and well with
  no regular medication and no allergies. Non
  smoker and occasionally takes alcohol.

11
Management of Mr. B COVID status

• A) Happy with the test done and we do not believe
  it is COVID 19.
• B) It could be COVID 19 because the saturations
  seem low!
• C) It is definitely COVID 19 because of the
  symptoms of cough and fever!
• D) It could be COVID 19 and the test may have
  been done too early!

12
Management of Mr. B Next step?

• A) Repeat RT PCR for COVID 19
• B) Do some routine bloods including CRP and D
  -Dimers to clinch the diagnosis.
• C) Do a chest X Ray as there are some respiratory
  symptoms and this would clinch the diagnosis.
• D) Do a CT Chest to assess the lung fields for
  any changes related to COVID 19.

13
Management of Mr. B if Mr. B turns out to be
COVID 19 positive,

1. Immaterial of what the clinical status is he
   should be admitted to a hospital as he is COVID
   positive.
2. Since there is strong family history of diabetes
   and hypertension and hence best to watch him in
   the hospital.
3. For his symptoms of dyspepsia, to keep a close
   watch on him he should be admitted to a hospital.
4. He should be given an emergency (helpline) number
   and advised to closely watch his oxygen levels,
   reporting any changes in his symptoms of cough
   and shortness of breath.

14
(No Transcript)
15
Suspecting diagnosis in routine practice
16
Clinical classifications

• Asymptomatic infection (silent infection)
• Testing positive for SARS-CoV-2, but without
  clinical symptoms or abnormal chest imaging
  findings.
• Acute upper respiratory tract infection
• With only fever, cough, pharyngeal pain, nasal
  congestion, fatigue, headache, myalgia or
  discomfort, etc., and without signs of pneumonia
  (on chest imaging) or sepsis.
• Mild pneumonia
• With or without fever, with respiratory symptoms
  such as cough and chest imaging indicating
  changes of viral pneumonia, but not reaching the
  criteria of severe pneumonia.

17
Clinical classifications

• Severe pneumonia
• Polypnea 60 times/min (lt 2 months), 50
  times/min (212 months), 40 times/min (15
  years), 30 times/min (gt 5 years) (after ruling
  out the effects of fever and crying).
• Oxygen saturation lt 92 under a resting state.
• Dyspnoea assisted breathing (moans, nasal
  flaring, etc), cyanosis, intermittent apnoea.
• Disturbance of consciousness somnolence, coma,
  or convulsion.
• Reduced appetite or feeding difficulty, with
  signs of dehydration.
• Pulmonary high-resolution CT (HRCT) examination
  showing bilateral or multi-lobe infiltrates,
  rapid progression of disease in a short period or
  with pleural effusion

18
(No Transcript)
19
(No Transcript)
20
Comorbidities
21
COMORBIDITIES

• Meta-analysis showed most common comorbidities
  were hypertension , obesity and diabetes.
• Electronic literature review and data collected
  from peer-reviewed articles published from
  January to April 20, 2020, showed comorbidities,
  such as hypertension or diabetes mellitus, are
  more likely to develop a more severe course and
  progression of the disease.
• Furthermore, older patients, especially those 65
  years old and above who have comorbidities and
  are infected, have an increased admission rate
  into the intensive care unit (ICU) and mortality
  from the COVID-19 disease.
• Patients with comorbidities usually have the
  worse prognosis
• https//doi.org/10.1007/s42399-020-00363-4
  Published online 25 June 2020 SN Comprehensive
  Clinical Medicine

22
High mortality in elderly

• Changes in lung anatomy
• Muscle atrophy
• Changes in physiological function due to
  reduction in lung reserve and airway clearance.
• Low immunity

23
Comorbidities

• People with chronic obstructive pulmonary disease
  (COPD) or any respiratory illnesses are also at
  higher risk for severe illness from COVID-19.
• The risk of contracting COVID-19 in patients
  with COPD is found to be 4-fold higher than
  patients without COPD
• Zhao Q, Meng M, Kumar R, Wu Y, Huang J, et al.
  The impact of COPD and smoking history on the
  severity of COVID-19 a systemic review and
  meta-analysis. J Med Virol. 2020.
  https//doi.org/ 10.1002/jmv.25889

24
COMORBIDITIES

• Huang et al. firstly reported the clinical
  features of 41 confirmed patients, and indicated
  13 (32) of them had underlying diseases (Huang
  et al., 2020), including cardiovascular disease,
  diabetes, hypertension, and chronic obstructive
  pulmonary disease.
• Subsequently, Wang et al. reported findings from
  138 cases of COVID-19 the results suggested that
  64 (46.4) of them had comorbidities.
  Importantly, the patients who were admitted to
  the intensive care unit (ICU) had a higher number
  of comorbidities (72.2) than those not admitted
  to the ICU (37.3). This suggested that
  comorbidities maybe risk factors for adverse
  outcomes (Wang et al., 2020).

25
COMORBIDITIES

• The most prevalent comorbidity reported across
  publications are hypertension followed by
  diabetes.
• Many patients reported having two or more
  comorbidities.
• The hazard ratio among patients with at least
  one comorbidity was lower compared to patients
  with two or more comorbidities.
• European Respiratory Journal 2020 55 2000547
  DOI 10.1183/13993003.00547-2020

26
(No Transcript)
27
(No Transcript)
28
Laboratory findings

• Pathogen analysis
• SARS-CoV-2 nuclear acid test
• SARS-CoV-2 can be detected in blood, faeces, anal
  swabs and other specimens

29
Laboratory findings

• The most evident laboratory findings in the first
  large cohort study from China (Guan 2020) are
  shown in table below.

Laboratory findings  All  Severe Disease  Non- Severe
WBC lt4,000 per mm3, 33.7 61.1 28.1
Lymphocytes lt1,500 per mm3, 83.2 96.1 80.4
Platelets lt150,000 per mm3, 36.2 57.7 31.6
C-reactive protein 10 mg/L, 60.7 81.5 56.4
Lactate dehydrogenase 250 U/L, 41.0 58.1 37.1
AST gt40 U/L, 22.2 39.4 18.2
D-dimer 0.5 mg/L, 46.6 59.6 43.2
Lymphocytopenia, thrombocytopenia and
leukopenia. In most patients, C-reactive protein
was elevated to moderate levels Most patients
have normal procalcitonin.
30
Infect Drug Resist. 2020 13 26572665.Published
online 2020 Aug 3. doi 10.2147/IDR.S264020
31
Studies confirmed COVID-19 cases with
identifiable exposure and symptom onset windows
estimated the median incubation period to be 5.1
days .
32
(No Transcript)
33
Blood SARS-CoV-2 antibody detection

• Serum SARS-CoV-2 specific antibodies IgM and IgG
  test positive for two consecutive times is
  helpful for diagnosis.
• However, negative antibody tests cannot exclude
  infection at the early stage of disease onset
• (Non-specific reactions must be ruled out for
  positive IgM antibody detection. The diagnostic
  value of IgM and IgG detection needs further
  evaluation, because it takes a certain period for
  the body to produce serum-specific antibodies and
  reach the detection threshold after virus
  infection and the kinetic features of
  serum-specific antibody production after the
  virus infection are still unclear.)
• Antibody test can be used for retrospective
  auxiliary diagnosis and sero-epidemiological
  surveys.

34
(No Transcript)
35
Characteristics of Different Direct Tests for
SARS-CoV-2
SARS-CoV-2 Test Identification Specimen Optimal Timing for Testing (Days) TAT (minutes) Se () Sp ()
rt-PCR RNA nasopharyngeal /oropharyngeal swabs / lower respiratory specimen At least 2 days after infection until negativization 190 ?89 99
RT-LAMP RNA nasopharyngeal /oropharyngeal swabs/ lower respiratory specimen At least 2 days after infection until negativization 4560 comparable to rt-PCR comparable to rt-PCR
NP antigen detection test Antigen (Ag) of SARS-CoV-2 nasopharyngeal /oropharyngeal swabs/ lower respiratory specimen At least 2 days after infection until negativization 240 7086 9597
36
Advantages, Disadvantages, and Possible
Indications of Different Direct Tests for
SARS-CoV-2
TEST Advantages Disadvantages Indications
rt-PCR Widely used High sensitivity and specificity Need for infrastructure, expensive Medium turnaround time Qualified personnel Restrictions on sample transportation Currently the gold standard in symptomatic and asymptomatic patients
RT-LAMP Lowest turnaround time considering direct methods High sensitivity Less bias in the analytical phase Need for infrastructure Expensive Qualified personnel ,incorrect sampling, restrictions on sample transportation Substitute for rt-PCR where possible in order to reduce the turnaround time
NP antigen detection test Easier analytical procedures Possible even in less equipped labs No real-life studies Qualified personnel, incorrect sampling, restrictions on sample transportation It could be used in facilities with no equipment for rt-PCR, waiting for the rt-PCR test
37
Advantages, Disadvantages, and Possible
Indications of Different Indirect Tests for
SARS-CoV-2
SARS-CoV-2 Test Advantages Disadvantages Indications
ELISA Not very expensive Medium turnaround time Data confirmed by meta-analysis and cohort data Easy collection sampling Needs infrastructure Qualified personnel Population screening and/or second level test in order to confirm Rapid detection test results
CLIA High throughput and sensitivity method Early detection of suspicious cases with nucleic acid false negative High production capacity with advanced automatic production line Needs infrastructure Qualified personnel Data from small cohort Population screening and/or second level test in order to confirm Rapid detection test results
Rapid detection test Does not need infrastructure Easy collection sampling Low specificity and sensitivity Data from small cohort data Weekly screening in high risk population, eg, healthcare personnel
38
Algorithm for COVID-19 test interpretation using
rapid antigen point-of-care
Rapid Antigen Test
Positive (Irrespective of symptom status)
Negative
To be reported as positive
Symptomatic Fever, cough, sore throat
Asymptomatic
Definitely send sample for retesting by RT-PCR
If individual turns symptomatic Repeat test by
RAT or RT-PCR

• All positive and negative result should be
  entered into ICMR portal on a real time basis
  after
• performing the antigen test.
• Result of samples subjected to RT-PCR should be
  entered after the RT-PCR results are available.

39
Chest imaging examination

• Digital X-ray
• X-ray chest is not recommended as the first
  choice, because it is easy to miss diagnosis.
  Infected pediatric patients commonly have normal
  X-ray imaging results at the early stage of
  disease onset. Only those severe cases or those
  at the progression stage show white-lung
  pattern. X-ray can be used for reviewing and
  comparison.
• CT scanning
• To enhance the imaging features of CT examination
  in each stage, to observe pulmonary imaging
  changes in children more clearly, it is
  recommended using a spiral CT volume scan of 16
  rows or more to reconstruct a thin layer of
  1.01.5 mm, with standard algorithms and bone
  algorithms being the best.

40
Radiological findings

• Abnormalities on X-ray,

• Abnormalities on CT,

• 59.1
• 76.7
• 54.2

• 86.2
• 94.6
• 84.4

41
CURRENT SITUATION TESTING OTHER BIOMARKERS

• Tremendous advances made for in-vitro diagnostic
  (IVD) assays for coronavirus disease 2019
  (COVID-19) caused by SARS-CoV-2 using different
  biomarkers.
• SALIVA
• Studies regarding the possible role of oral
  fluids and saliva in the detection of SARS-CoV-2
  has shown
• Saliva is a reliable tool to detect SARS-Cov-2 by
  RT-rPCR analysis.
• Saliva may provide information about the clinical
  evolution of the disease.
• Saliva could represent a valid instrument in
  COVID-19 diagnosis

42
CURRENT SITUATION TESTING OTHERBIOMARKERS -
STOOL

• In one study, PCR positivity in stool was
  observed in 55 of 96 (57) infected patients and
  remained positive in stool beyond nasopharyngeal
  swab by a median of 4 to 11 days.
• Persistence of PCR in sputum and stool was found
  to be similar as assessed by Wölfel et al.
• Wölfel R?, Corman VM?, Guggemos W?, et al.
  Virological assessment of hospitalized patients
  with COVID-2019. ? Nature. 2020. Published online
  April 1, 2020. doi10.1038/s41586-020-2196-x

43
CURRENT SITUATION TESTING OTHER BIOMARKERS -
TEARS/OCULAR FLUID

• It is hypothesized that the nasolacrimal system
  can act as a conduit for viruses to travel from
  the upper respiratory tract to the eye.
• Hence, ocular tissue and fluid may represent a
  potential source of SARS-CoV-2.
• Ocular tropism of respiratory viruses is a known
  fact.

44
CURRENT SITUATION TESTING OTHER BIOMARKERS -
PROTEINS

• In order to improve surveillance efforts,
  serological tests using proteins are needed in
  addition to nucleic acid tests.
• Protein Testing. Viral protein antigens and
  antibodies that are created in response to a
  SARS-CoV-2 infection can be used for diagnosing
  COVID-19

45
CURRENT SITUATION TESTING OTHER BIOMARKERS -
OTHER PROTEINS AND CELLUAR MARKERS

• Guan et al. and 6 other studies showed that
  infected patients had elevated levels of C
  reactive protein and D-dimer as well as low
  levels of lymphocytes, leukocytes, and blood
  platelets.
• Also significant increases in WBC count, total
  bilirubin, creatine kinase, serum ferritin, and
  interleukin 6 (IL-6) were noted in a meta
  analysis study done by Henry et al.
• However, the challenge of using these biomarkers
  are that they are non specific.

46
(No Transcript)
47
Surveillance -objectives

• Monitor trends in COVID-19 disease at national
  and global levels.
• Rapidly detect new cases in countries where the
  virus is not circulating, and monitor cases in
  countries where the virus has started to
  circulate.
• Provide epidemiological information to conduct
  risk assessments at the national, regional and
  global level.
• Provide epidemiological information to guide
  preparedness and response measures.

48
Suspect

1. A patient with acute respiratory illness (fever
   and at least one sign/symptom of respiratory
   disease, e.g., cough, shortness of breath), AND a
   history of travel to or residence in a location
   reporting community transmission of COVID-19
   disease during the 14 days prior to symptom
   onset OR
2. A patient with any acute respiratory illness AND
   having been in contact with a confirmed or
   probable COVID-19 case in the last 14 days prior
   to symptom onset OR
3. A patient with severe acute respiratory illness
   (fever and at least one sign/symptom of
   respiratory disease, e.g., cough, shortness of
   breath AND requiring hospitalization) AND in the
   absence of an alternative diagnosis that fully
   explains the clinical presentation.

49
Contact

• 1. Face-to-face contact with a probable or
  confirmed case within 1 meter and for more than
  15 minutes
• 2. Direct physical contact with a probable or
  confirmed case
• 3. Direct care for a patient with probable or
  confirmed COVID-19 disease without using proper
  personal protective equipment 2OR
• 4. Other situations as indicated by local risk
  assessments.
• (Note for confirmed asymptomatic cases, the
  period of contact is measured as the 2 days
  before through the 14 days after the date on
  which the sample was taken which led to
  confirmation.)

50
Health Care Workers (HCW) passive case finding
strategies

• Suspected cases are identified by the healthcare
  worker who sees the case in their normal work
  activities and who then reports suspect cases.
• Examples
• Inpatients Healthcare workers providing clinical
  care evaluate their patients for signs and
  symptoms of COVID-19 during routine care and
  report suspect cases to appropriate authorities
• Healthcare workers Healthcare workers
  self-monitor their symptoms and act to
  self-exclude from work based on their own
  evaluation of their condition

51
HCW - General Best Practices for Case Finding
Activities 

• Train and educate healthcare workers
• Example Training on detection among inpatients
  and self-recognition of symptoms
• Monitor and manage ill and exposed healthcare
  workers
• Example Implement sick leave policies that are
  flexible and without penalties for missing work
• Establish reporting within and between healthcare
  facilities and to public health authorities
• Example Communicate and collaborate with public
  health authorities

52
HCW - Enhanced Passive Case Finding Strategies

• Suspect cases are identified by the healthcare
  worker who sees the case in their normal work
  activities supplemented by a system that reminds
  the healthcare worker to check for suspect case
  and to report to appropriate authorities
• Examples
• Systems are used to remind healthcare workers of
  their responsibility to check for the presence of
  COVID-19 symptoms and report every day and/or
  before each shift
• Systems are used to remind healthcare workers to
  have a high index of suspicion for COVID-19

53
Routine surveillance - containment zones and
screening at points of entry

• All symptomatic cases including health care
  workers and frontline workers.
• All asymptomatic direct and high-risk contacts
  (in family and workplace, elderly 65 years of
  age, immunocompromised, those with co-morbidities
  etc.) of a laboratory confirmed case to be tested
  once between day 5 and day 10 of coming into
  contact.
• All asymptomatic high-risk individuals (elderly
  65 years of age, those with co-morbidities etc.)
  in containment zones.
• (Ideally,100 people living in containment zones
  should be tested by RAT)

54
Routine surveillance in non-containment areas

• 4. All symptomatic individuals with history of
  international travel in the last 14 days.
• 5. All symptomatic contacts of a laboratory
  confirmed case.
• 6. All symptomatic health care workers /
  frontline workers involved in containment and
  mitigation activities.
• 7. All symptomatic ILI cases among returnees and
  migrants within 7 days of illness.
• 8. All asymptomatic high-risk contacts(contacts
  in family and workplace, elderly 65 years of
  age, those with co-morbidities etc.

55
In hospital settings

• 9. All patients of Severe Acute Respiratory
  Infection (SARI).
• 10. All symptomatic (ILI symptoms) patients
  presenting in a healthcare setting.
• 11. Asymptomatic high-risk patients who are
  hospitalized or seeking immediate hospitalization
  such as immunocompromised individuals, patients
  diagnosed with malignant disease, transplant
  patients, patients with chronic co-morbidities,
  elderly 65 years.
• 12. Asymptomatic patients undergoing surgical /
  non-surgical invasive procedures (not to be
  tested more than once a week during hospital
  stay).
• 13. All pregnant women in/near labour who are
  hospitalized for delivery.

56
References
1. Huang C, Wang Y, Li X, Ren L, Zhao J, et al.
Clinical features of patients infected with 2019
novel coronavirus in Wuhan, China. Lancet.
2020395(10223)497506. https//doi.org/10.1016/S
0140- 6736(20)30183-5 2. Yang J, Zheng Y, Gou
X, Pu K, Chen Z, Guo Q, et al. Prevalence
of comorbidities in the novel Wuhan coronavirus
(COVID-19) infection a systematic review and
meta-analysis. Int J Infect Dis.
2020S12019712(20)301363. https//doi.org/10.10
16/j.ijid. 2020.03.017 3 Chang D, Mo G, Yuan X,
Tao Y, Peng X, Wang FS, et al. Time kinetics of
viral clearance and resolution of symptoms in
novel coronavirus infection. AJRCCM.
202020111502. https//doi.org/10.
1164/rccm.202003-0524LE. 4. https//apps.who.int
/iris/bitstream/handle/10665/331506/WHO-2019-nCoV-
SurveillanceGuidance-2020.6-eng.pdf
57
(No Transcript)
58
Sincere advice

• A clinician should never make assumptions and
  always take a proper history.
• Always keep abreast with the latest medical
  technology as it is always changing. 
• Just like clinical guidelines change with new
  findings the same applies for laboratory testing
  algorithms.
• Understand the rationale of testing and the
  treatment to get an ideal outcome. 
• In all situations, always think about safe
  practices and preventive measures.

59
(No Transcript)
60
Many thanks!
61
Management of Mr. B COVID status

• D) It could be COVID 19 and the test may have
  been done early!

62
Management of Mr. B What would be your next
step?

• A) Repeat RT PCR for COVID 19

63
Management of Mr. B if Mr. B was COVID 19
positive, he should be admitted to a hospital

• D) He should be given an emergency (helpline)
  number and advised to closely watch his oxygen
  levels, reporting any changes in his symptoms of
  cough and shortness of breath.