The document provides an in-depth overview of COVID-19 diagnosis, emphasizing clinical manifestations, comorbidities, and variations in symptom severity. It outlines current diagnostic methods, including RT-PCR and other tests, as well as the importance of recognizing comorbidities that exacerbate COVID-19 outcomes. The document also discusses clinical classifications, laboratory findings, and the need for effective surveillance to monitor trends and new cases globally.

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

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. Pandemic
Small Pox,
Tuberculosis
HIV
and
COVID-
19
Spanish
flu and
H1N1

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/10665/331506/WHO-2019-nCoV-SurveillanceGuidance-2020.6-eng.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,
A) Immaterial of what the clinical status is he should be admitted to
a hospital as he is COVID positive.
B) Since there is strong family history of diabetes and hypertension
and hence best to watch him in the hospital.
C) For his symptoms of dyspepsia, to keep a close watch on him 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.

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 (< 2 months), ≥50 times/min (2–12 months), ≥40
times/min (1–5 years), ≥30 times/min (> 5 years) (after ruling out the effects of
fever and crying).
• Oxygen saturation < 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

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

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 <4,000 per mm3,% 33.7 61.1 28.1
Lymphocytes <1,500 per mm3,% 83.2 96.1 80.4
Platelets <150,000 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 >40 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: 2657–2665.
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 .

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.

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
45–60 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 70–86** 95–97**

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
Weekly screening in high risk
population, eg, healthcare
personnel

38. Algorithm for COVID-19 test interpretation using rapid antigen point-of-care
•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.
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

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 1.0–1.5 mm, with standard algorithms and
bone algorithms being the best.

40. Radiological findings
Abnormalities on X-ray,%
• 59.1
• 76.7
• 54.2
Abnormalities on CT,%
• 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. doi:10.1038/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.

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
A. 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
B. 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
C. 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
1. All symptomatic cases including health care workers and frontline
workers.
2. 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.
3. 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. 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. 2020;395(10223):497–506. https://doi.org/10.1016/S0140-
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. 2020;S1201–9712(20):30136–3. https://doi.org/10.1016/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.
2020;201:1150–2. 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
References

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.

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.