COVID-19: labs

Table of general laboratory findings described in several studies.

WBC count tends to be normal.
Lymphopenia is common, seen in ~80% of patients (Guan et al 2/28, Yang et al 2/21).
Mild thrombocytopenia is common (but platelets are rarely <100). Lower platelet count is a poor prognostic sign (Ruan et al 3/3).

Coagulation labs are generally fairly normal upon admission, although elevated D-dimer is commonly seen (table above).
Disseminated intravascular coagulation may evolve over time, correlating with poor prognosis (figure below)(Tang et al. 2020).
- Image of DIC labs in survivors versus non-survivors over time here.

Procalcitonin
- COVID-19 does not appear to increase the procalcitonin. For example, the largest series found that procalcitonin levels were <0.5 in 95% of patients (Guan et al 2/28).
- Elevated procalcitonin may suggest an alternative diagnosis (e.g. pure bacterial pneumonia). For patients who have been admitted with COVID-19, procalcitonin elevation may suggest a superimposed bacterial infection.
C-reactive protein (CRP)
- COVID-19 increases CRP. This seems to track with disease severity and prognosis. In a patient with severe respiratory failure and a normal CRP, consider non-COVID etiologies (such as heart failure).
- Young et al. 3/3 found low CRP levels in patients not requiring oxygen (mean 11 mg/L, interquartile range 1-20 mg/L) compared to patients who became hypoxemic (mean 66 mg/L, interquartile range 48-98 mg/L).
- Ruan et al 3/3 found CRP levels to track with mortality risk (surviving patients had a median CRP of ~40 mg/L with an interquartile range of ~10-60 mg/L, whereas patients who died had a median of 125 mg/L with an interquartile range of ~60-160 mg/L)(figure below in the section on prognosis).

PCR for influenza and other respiratory viruses (e.g. RSV) may be helpful. Detection of other respiratory viruses doesn't prove that the patient isn't co-infected with COVID-19 (~5% of patients may be co-infected with both COVID-19 and another virus)(Wang et al.). However, an alternative explanation for the patient's symptoms will reduce the index of suspicion for COVID-19 substantially.
Conventional viral panels available in some hospitals will test for “coronavirus.”
- This test does not work for COVID-19!
- This PCR test for “coronavirus” is designed to evaluate for four coronaviruses which usually cause mild illness.
- Ironically, a positive conventional test for “coronavirus” actually makes it less likely that the patient has COVID-19.
Blood cultures should be performed as per usual indications.

(1) Nasopharyngeal swab should be sent.
(2) If intubated, tracheal aspirate should be performed.
(3) Bronchoalveolar lavage or induced sputum are other options for a patient who isn't intubated. However, obtaining these specimens may pose substantial risk of transmission.
- It's dubious whether these tests are beneficial if done for the sole purpose of evaluating for coronavirus (see the section below on bronchoscopy).

There are several major limitations, which make it hard to precisely quantify how RT-PCR performs.
(1) RT-PCR performed on nasal swabs depends on obtaining a sufficiently deep specimen. Poor technique will cause the PCR assay to under-perform.
(2) COVID-19 isn't a binary disease, but rather there is a spectrum of illness. Sicker patients with higher viral burden may be more likely to have a positive assay. Likewise, sampling early in the disease course may reveal a lower sensitivity than sampling later on.
(3) Most current studies lack a “gold standard” for COVID-19 diagnosis. For example, in patients with positive CT scan and negative RT-PCR, it's murky whether these patients truly have COVID-19 (is this a false-positive CT scan, or a false-negative RT-PCR?).
- (Convalescent serologies might eventually solve this problem, but this data isn't available currently.)

Specificity seems to be high (although contamination can cause false-positive results).

Sensitivity compared to CT scans
- In a case series diagnosed on the basis of clinical criteria and CT scans, the sensitivity of RT-PCR was only ~70% (Kanne 2/28).
- Sensitivity varies depending on assumptions made about patients with conflicting data (e.g. between 66-80%)(Ai et al.).
- Image of analysis of Ai et al to determine sensitivity & specificity of PCR here.
Among patients with suspected COVID-19 and a negative initial PCR, repeat PCR was positive in 15/64 patients (23%). This suggests a PCR sensitivity of <80%. Conversion from negative to positive PCR seemed to take a period of days, with CT scan often showing evidence of disease well before PCR positivity (Ai et al.).
Bottom line?
- PCR seems to have a sensitivity somewhere on the order of ~75%.
- A single negative RT-PCR doesn't exclude COVID-19 (especially if obtained from a nasopharyngeal source or if taken relatively early in the disease course).
- If the RT-PCR is negative but suspicion for COVID-19 remains, then ongoing isolation and re-sampling several days later should be considered.

Anesthesiology and Intensive Care