Kade Flowers Clare Hunt Emmeline Pinion Background Background Started in Wuhan China in December 2019 Zoonotic from bats andor pangolins A type of Coronavirus Similar to severe acute respiratory syndrome SARS from 2002 ID: 907987
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Slide1
Laboratory Results inCOVID-19
Kade FlowersClare HuntEmmeline Pinion
Slide2Background
Slide3Background
Started in Wuhan, China in December 2019Zoonotic from bats and/or pangolins
A type of Coronavirus
Similar to severe acute respiratory syndrome (SARS) from 2002
SARS-CoV-2 is the
virus
CO
rona
VI
rus
D
isease 20
19
(COVID-19) is the
disease
Slide4Cases and Mortality
As of today
(30/03/20
), there are
741,030
number of confirmed cases,
35,114
number of deaths and 156,838 number of recoveriesMortality rate of 4.7%, but this is likely an overestimation
Source
:
https://coronavirus.jhu.edu/map.html
Slide5Symptoms
Slide6The Vulnerable
Slide7The Vulnerable
CONTEXT
Slide8Spread
Smaller particles remain airborne
Large droplets travel ballistically
Slide9Spread
Source:
Doremalen
,
2020
.
Slide10Laboratory Investigations
Slide11Common Abnormalities (% of Cases)
↑
C-Reactive Protein (CRP) (75-93%)
↑
Lactate Dehydrogenase (LDH) (27-92%)
↑
Erythrocyte Sedimentation Rate (ESR) (85%)
↑
D-Dimer (36-43%)↓ Lymphocytes (35-75%) ↓ Albumin (50-98%)↓ Hb (41-50%)
Source: Lippi, 2020
.
Slide12Other Abnormalities
↑
Cardiac troponin
↑
BNP
↑
AST
↑
ALT↑ Total Bilirubin↑ Creatinine
Source: Lippi, 2020
.
Slide13Determining Severity
In a study with 140 COVID-19 patients, 58 with severe disease had:
D-Dimer x2
CRP x1.7
Procalcitonin x2
Other studies suggest
↑
neutrophils,
↓ Lymphocytes and ↓ albumin are also useful in predicting severe cases
Source: Lippi, 2020
.
Slide14Lymphocyte Count
Lymphocyte count
is often
↓
in COVID-19 patients, regardless of outcome
↓
in non-survivors compared to survivorsRemains ↓ in non-survivors
↑
after day 7 in
survivors
Source: Zhou, 2020
.
Days from illness onset
Reference Limit
Survivors
Non-survivors
Days from illness onset
Slide15LDH
LDH
often
serially
↑
during early
infection, regardless of outcome
↓
after day 13 in survivors
Source: Zhou, 2020.
Lippi, 2020.
Continues to
↑
in
non-survivors
LDH
> 500 U/L is associated with ITU admission
Reference Limit
Survivors
Non-survivors
Slide16Coagulation
In a study with 183 confirmed COVID-19 cases, the 21 who
died
had:
D-Dimer
↑
x3.5
Fibrinogen Degradation Products
↑ x1.9PT ↑ x1.1471.4% of deaths met the criteria for disseminated intravascular coagulation (DIC), compared to only 0.6% of survivors
Source: Lippi, 2020
.
Slide17DIC
DIC is a spontaneous depletion of clotting factors, leading to
bleeding
A
DIC score can be calculated
Early report shows that decreasing platelets = worse disease (Lippi, 2020) – linked to DIC
Slide18DIC score (ISTH)
Source:
Toh
, 2007
Slide19D-Dimer
↑ after 7 days from symptom onset in
non-survivors
Remains stable in people who
survive
Source: Zhou, 2020
.
↑
risk of
death
if > 1000 ng/mL (1
μ
g/mL)
Days from illness onset
Reference Limit = < 300 ng/mL (0.3
μ
g/mL)
Slide20Procalcitonin (PCT)
Production is ↑ in response to IL-6, TNF-
α
and IL-1
β
(bacterial)
Production is
↓
in response to IFN-γ (viral)More specific for sepsis and bacterial infection than CRPPCT ↓ within 15 minutes of dialysis, so samples need to be taken before
Source: Samsudin, 2017
.
Slide21Procalcitonin and COVID-19
A serial increase in procalcitonin suggests poor outcome
Helps to differentiate between viral only pneumonia and mixed viral and bacterial pneumonia (worse outcome)
↑
in serial PCT = almost a 5x risk of progression to more severe disease
Elevated
admission
procalcitonin also suggests severe disease, but a low one does
not exclude it – serial PCT more importantSource: Lippi, 2020.
Slide22Hyperinflammation
Some COVID-19 patients enter hyperinflammation
Triggers a cytokine storm which can cause multi-organ failure and death
These patients
could
benefit from
immunosuppression
Inappropriate immunosuppresion is dangerous
Source: Mehta, 2020
.
Slide23Hyperinflammation
Tocilizumab (IL-6 receptor blockade) has been approved for use in patients with COVID-19 who have pneumonia and ↑ IL-6
All patients should be screened for hyperinflammation using lab trends (Hscore)
Source: Mehta, 2020
.
Slide24Hyperinflammation Hscore
Source: Mehta, 2020
.
Slide25Hyperinflammation
This is reflected in the increasing serial measurements of ferritin and IL-6 in non-survivors
compared to
survivors
Source: Zhou, 2020
.
Days from illness onset
Reference Limit
Survivors
Non-
survivors
Slide26Cardiac Troponin
Rapid increases in troponin I after day 16 have been observed in non-survivors
compared to
survivors
?Troponin T
Source: Zhou, 2020
.
Survivors
Non-survivors
Slide27Possible Test Panel
FBC
UEs
LFTs
Coagulation Profile
D-Dimer
CRP (Chinese papers mention IL-6, ?similar)
LDH
FerritinTroponin?Procalcitonin - ?more useful than CRP
Slide28Sample Handling Guidelines
Risk of routine analysis on blood is low, so normal automated analysis can continue at containment level 2 (CL2)Uncapping and aliquoting of whole blood, serum and plasma is not considered a high-risk aerosol generating procedure
Source: gov.co.uk
Slide29Sample Handling Guidelines
Urine, faecal and respiratory tract fluid should be aliquoted under a fume hood, but can still be in CL2
Centrifugation of samples with “infectious potential” should be done under a fume hood
Source: gov.co.uk
Slide30The Evidence of Risk to the Laboratory
SARS-CoV-2 was not detected in urine (n = 72)
Detected in 1% (n = 307) of blood samples, so is
theoretically
infectious
Detected in 29% (n = 153) of faecal samples and 72% (n = 104) of sputum samples, so these are more risky
Still no known cases of transmission through samples
Source: Wang, 2020.
Slide31The SARS-CoV-2 Test
Reverse transcriptase polymerase chain reaction (RT-PCR)
Converts SARS-CoV-2 RNA into DNA, then amplifies it using PCR
Slide32The SARS-CoV-2 Test
Source: https://bit.ly/33CHl3B
Slide33Note
This research is very new and has not been scrutinised
Slide34R
eferences
Doremalen
NV, et al. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1.
N
Engl
J Med
. 2020.
doi: 10.1056/NEJMc2004973Lippi G, et al. Laboratory abnormalities in patients with COVID-2019 infection. Clin Chem Lab Med. 2020. doi: 10.1515/cclm-2020-0198 – Very good summary
Lippi G, et al. Procalcitonin in patients with severe coronavirus disease 2019 (COVID-19): A meta-analysis.
Clin
Chim
Acta
. 2020.
doi
: 10.1016/j.cca.2020.03.004
Lippi G, et al. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis. 2020.
doi
: 10.1016/j.cca.2020.03.022
Mehta P, et al. COVID-19: consider cytokine storm syndromes and immunosuppression.
Lancet
. 2020.
doi
: 10.1016/S0140-6736(20)30628-0
Samsudin I, et al. Clinical Utility and Measurement of Procalcitonin.
Clin
Biochem
Rev
. 2017;38(2):59-68
Toh
CH, et al. The scoring system of the Scientific and Standardisation Committee on Disseminated Intravascular Coagulation of the International Society on Thrombosis and Haemostasis: a 5‐year overview.
J
Thromb
Haemost
. 2007;5:604-606.
Wang W, et al. Detection of SARS-CoV-2 in Different Types of Clinical Specimens.
JAMA
. 2020. doi:10.1001/jama.2020.3786
Zhou Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.
Lancet
. 2020.
doi
: 10.1016/S0140-6736(20)30566-3