2. Discuss the biomakers being requested/observed in the diagnosis of Covid-19
FERRITIN
Studies investigating ferritin in COVID-19 were collected from PubMed, EMBASE, CNKI, SinoMed, and
WANFANG. A meta-analysis was performed to compare the ferritin level between different patient
groups: non-survivors versus survivors; more severe versus less severe; with comorbidity versus without
comorbidity; ICU versus non-ICU; with mechanical ventilation versus without mechanical ventilation.
The ferritin level was significantly increased in severe patients compared with the level in non-severe
patients [WMD 397.77 (95% CI 306.51-489.02), P < .001]. Non-survivors had a significantly higher ferritin
level compared with the one in survivors [WMD 677.17 (95% CI 391.01-963.33), P < .001]. Patients with
one or more comorbidities including diabetes, thrombotic complication, and cancer had significantly
higher levels of ferritin than those without (P < .01). Severe acute liver injury was significantly associated
with high levels of ferritin, and its level was associated with intensive supportive care, including ICU
transfer and mechanical ventilation.
Ferritin was associated with poor prognosis and could predict the worsening of COVID-19 patients.
D-dimer
D-dimer level is tested using immunoturbidimetric assay with reference range of 0–0.50 mg/L (Sysmex,
CS5100). Doppler ultrasound and CT pulmonary angiography were done for any patients with high
clinical suspicion of pulmonary embolism/deep vein thrombosis (PE/DVT).
D-dimer elevation (≥ 0.50 mg/L) was seen in 74.6% (185/248) of the patients. Pulmonary embolism and
deep vein thrombosis were ruled out in patients with high probability of thrombosis. D-dimer levels
significantly increased with increasing severity of COVID-19. D-dimer is commonly elevated in patients
with COVID-19. D-dimer levels correlate with disease severity and are a reliable prognostic marker for
in-hospital mortality in patients admitted for COVID-19. patients diagnosed with COVID-19, D-dimer
elevation upon admission was common and was associated with both increased disease severity and inhospital mortality. D-dimers are one of the fragments produced when plasmin cleaves fibrin to break
down clots. The assays are routinely used as part of a diagnostic algorithm to exclude the diagnosis of
thrombosis. However, any pathologic or non-pathologic process that increases fibrin production or
breakdown also increases plasma D-dimer levels [13]. Examples include deep vein
thrombosis/pulmonary embolism, arterial thrombosis, disseminated intravascular coagulation, and
conditions such as pregnancy, inflammation, cancer, chronic liver diseases, post trauma and surgery
status, and vasculitis.
CRP
serum C‐reactive protein (CRP) has been found as an important marker that changes significantly in
severe patients with COVID‐19. CRP is a type of protein produced by the liver that serves as an early
marker of infection and inflammation. In blood, the normal concentration of CRP is less than 10 mg/L;
however, it rises rapidly within 6 to 8 hours and gives the highest peak in 48 hours from the disease
onset. Its half‐life is about 19 hours 8 and its concentration decreases when the inflammatory stages
end and the patient is healing. CRP preferably binds to phosphocholine expressed highly on the surface
of damaged cells. This binding makes active the classical complement pathway of the immune system
and modulates the phagocytic activity to clear microbes and damaged cells from the organism. When
the inflammation or tissue damage is resolved, CRP concentration falls, making it a useful marker for
monitoring disease severity. A significant increase of CRP was found with levels on average 20 to 50
mg/L in patients with COVID‐19. 10 , 12 , 21 Elevated levels of CRP were observed up to 86% in severe
COVID‐19 patients .
PCR
The polymerase chain reaction (PCR) test for COVID-19 is a molecular test that analyzes your upper
respiratory specimen, looking for genetic material (ribonucleic acid or RNA) of SARS-CoV-2, the virus that
causes COVID-19. Scientists use the PCR technology to amplify small amounts of RNA from specimens
into deoxyribonucleic acid (DNA), which is replicated until SARS-CoV-2 is detectable if present. The PCR
step then uses special chemicals and enzymes and a PCR machine called a thermal cycler. Each heating
and cooling cycle increases (amplifies) the amount of the targeted genetic material in the test tube.
After many cycles, millions of copies of a small portion of the SARS-CoV-2 virus’s genetic material are
present in the test tube. One of the chemicals in the tube produces a fluorescent light if SARS-CoV-2 is
present in the sample. Once amplified enough, the PCR machine can detect this signal. Scientists use
special software to interpret the signal as a positive test result.
FBS
High fasting blood glucose levels were tied to increased COVID-19 mortality, even for patients without a
previous diabetes diagnosis. Blood sugar testing and control should be recommended to all COVID-19
patients even if they do not have pre-existing diabetes," wrote the authors, led by Sufei Wang, from the
Department of Respiratory and Critical Care Medicine at Union Hospital in Wuhan.
This study shows, for the first time, that elevated [fasting blood glucose] at admission is independently
associated with increased 28-day mortality and percentages of in-hospital complications in COVID-19
patients without previous diagnosis of diabetes," the authors wrote.
During a pandemic of COVID-19, measuring fasting blood glucose can facilitate the assessment of
prognosis and early intervention of hyperglycaemia to help improve the overall outcomes in treatment
of COVID-19," the authors concluded.
12L ECG
A prior history of cardiovascular disease is one of the main risk factors for COVID-19 mortality among
affected patients, and COVID-19 may exacerbate preexisting heart conditions, adding to the burden of
care clinicians must face. Performing an ECG also raises the risk of cross-infection among medical
personnel, so physicians should carefully determine when and if ECG is necessary in the course of caring
for patients. When providers are considering the timing of ECG, it is important to confirm a COVID-19
diagnosis first so that proper resources, such as face masks, may be utilized. While exact guidance
concerning the timing and frequency of ECG is still unclear, physicians should prioritize ECG for patients
in certain scenarios.
According to the FDA, devices like the KardiaMobile 6L should only be used to measure QTc in the
specific case where a patient is diagnosed with COVID-19 and also receiving medications which may
prolong the QT interval.
While personal ECG devices may prove useful in certain situations during the COVID-19 era, 12-lead ECG
monitoring is still standard, as it provides information in three orthogonal directions and generally gives
more detailed insights regarding arrhythmias. With that said, using a 12-lead ECG comes with certain
risks, most notably machine contamination and the risk of COVID-19 exposure for ECG technicians.
PCT
Procalcitonin (PCT) is the 116-amino acid precursor of the hormone calcitonin. Recently, several studies
reported that elevated PCT levels are positively associated with the severity of COVID-19. A metaanalysis also demonstrated that increased PCT values are related to an ~5-fold higher risk of severe
SARS-CoV-2 infection. In order to improve the diagnosis to distinguish between severe/critical patients
and moderate patients with COVID-19 and to better predict the prognosis, the aim of this study was to
investigate the role of changes in PCT values.
Study further classified severe infections into severe patients and critical patients. The results showed
that mean serum PCT levels were approximately four times higher in severe patients than in moderate
patients and approximately eight times higher in critical patients than in moderate patients. PCT levels
appeared to be disease severity-dependent and may be associated with bacterial co-infection, as the coinfection rate was close to the rate of elevated PCT levels in patients with moderate disease severity.
Recent study hypothesised that a progressive increase in PCT levels may predict a worse prognosis. A
total of 38 patients who had serially measured PCT values were included in the current study, of whom
32 were discharged from hospital and 6 died. For the 32 discharged patients, both high-normal and
abnormal PCT levels decreased during recovery. However, for the 6 death cases, serum PCT levels
increased as the disease worsened. These results demonstrate that serial PCT measurements can predict
the prognosis of COVID-19 patients.
PCT may be an indicator of disease severity and may contribute to determining the severity of patients
with COVID-19. In addition, serial PCT measurements may be useful in predicting the prognosis.
Additional investigation is needed to further illustrate the mechanisms by which increased PCT is
synthesised and released in patients infected with SARS-CoV-2.
SGOT
Liver impairment is an emerging concern with COVID-19, as it was observed with the similar coronavirus
SARS. According to previous studies, up to 60% of patients had a liver impairment, with liver biopsy
specimens suggesting viral nucleic acid and damage (3–5). In these studies authors noted that this might
have been the result of drug-induced liver damage, given that the majority of the patients were treated
with high doses of antibiotics, hepatotoxic antiviral drugs and steroids.
Some studies have reported the clinical features and laboratory test results associated with liver
dysfunction in patients with COVID-19 infection (6–13). Although, pre-existing liver conditions have not
been listed in most of these studies and the interaction of pre-existing liver disease with COVID-19 has
not been investigated, which are major limitations in evaluating the underlying causes of liver injury in
the severe disease course. However, the elevated levels of alanine aminotransferase and reduced
platelet counts and reduced levels of albumin showed an association with higher fatality in COVID-19
patients (2). It is still unknown whether these laboratory analyses are an indicator of pre-existing hepatic
diseases in severe patients, whether they rather mirror liver failure caused by the SARS-CoV-2 itself.