Brigham and Women's Hospitals

Diagnostics

Updated November 20, 2020

SARS-CoV-2 Testing

Whom to test

  1. BWH-specific inpatient COVID-19 testing pathways and infection control guidelines can be found here (Partners login required)
  2. The latest Mass. Dept of Public Health guidance is here.

General Comments

  1. Assessment of the validity of diagnostics is difficult given the lack of a ‘gold standard.’
  2. In the setting of high clinical suspicion, no currently available test can adequately rule out a diagnosis of COVID-19.
  1. Ongoing clinical concern for active COVID-19 infection with negative PCR testing may warrant ID consult.
  1. The correlation between positive test results and active, infectious virus remains incompletely understood.
  1. Persistently positive PCR testing in a patient with minimal or no residual symptoms may warrant ID consult.

Test Characteristics and Options

  1. RT-PCR: This is the current standard of care for the diagnosis of active COVID-19
  1. Test characteristics
  1. Sensitivity is suboptimal and is estimated to range from 60-70% (Ai et al, Radiology, 2020, Yang et al, preprint)
  2. Sensitivity declines with time from symptom onset (Yang et al, preprint; Zou et al, N Eng J Med, 2020; To et al, Lancet Infect Dis, 2020)
  1. Test options
  1. NP Swab: This is the primary site of PCR testing.
  2. OP Swab: In rare patients who cannot tolerate NP swabs (e.g. due to recent surgery or epistaxis), OP swabs can be performed although with reduced sensitivity.
  3. Sputum/NT aspirate: Deeper respiratory samples may have improved sensitivity over NP swabs, particularly later in the disease course. (Yang et al, preprint; Wang et al, JAMA, 2020).
  1. In intubated patients, NT aspirates are preferred. In non-intubated patients with a productive cough, sputum may be sent for PCR testing. The sensitivity is dependent upon the quality of the sample. High quality sputum samples are characterized by gram stains with many polys and few or no epithelial cells.
  1. Saliva: Saliva may have similar or improved sensitivity compared to NP swabs (Wyllie et al, unpublished data). This is not currently available at BWH, but may be in the near future.
  2. Other sites: Viral RNA has been identified from other body sites including stool and rarely blood, but it is not clear if this represents transmissible virus (Wang et al, JAMA, 2020). We do not routinely test other body sites. If there is a clinical indication for testing other sites, please discuss with ID.

  1. Serologies
  1. For details on antibody response, please see Immunity” section.
  2. Test characteristics: Numerous antibody tests have been developed by commercial laboratories and manufacturers. There is no standard criteria for defining “positive” and “negative” results and detection thresholds vary by product. Test performance is variable between assays. Not all have been evaluated by the FDA.
  1. Positive
  1. True Positive: Patient has been exposed to COVID-19
  2. False Positives: Can occur with cross-reactivity with other coronaviruses.
  1. Negative
  1. True Negative:
  1. Patient was not exposed to COVID-19
  2. Patient was exposed, but no longer has circulating antibodies (we do not yet know what this means about immunity if re-introduced to the virus)
  1. False Negatives: More common early in disease course before an antibody response has had time to develop. Also an issue in patients with impaired humoral immunity.
  1. Test options:
  1. Multiple serologic techniques are available such as qualitative lateral flow assay (LFA) and quantitative enzyme linked immunosorbent assay (ELISA).
  2. Tests evaluate for antibodies to various viral antigen targets (ie nucelocapsid, spike, RBD)
  3. The most up-to-date list of tests issued an EUA can be found on the FDA’s website

  1. Viral Cultures: This is not currently being performed due to the need for a Biosafety Level 3 laboratory

Test ordering practices

  1. PCR
  1. Inpatient
  1. Symptomatic patients require two tests separated by 12 hours.
  2. Asymptomatic inpatients require 1-2 tests depending upon their risk based upon epidemiology.
  3. Testing can be ordered through the symptomatic and asymptomatic testing pathways in Epic. (Partners login required)
  1. Outpatient
  1. Symptomatic outpatients require only a single NP swab to evaluate for active infection.
  2. Asymptomatic outpatients require a single NP swab 48-72 hours prior to planned aerosol-generating procedures to evaluate for asymptomatic carriage.
  3. PCR: Testing is ordered in Epic through a telephone visit using the COVID-19 triage tool. When testing is ordered, it automatically prompts schedulers at the designated testing site to arrange outpatient testing. For guidance, see the Ambulatory Epic Test Ordering Tip Sheet (Partners login required)
  1. Serologies
  1. Indications for testing:
  1. Improve the sensitivity in diagnosis of COVID-19 in a patient with at least 7 days of symptoms, but 1 or 2 negative PCRs (Guo et al, Clin Infect Dis, 2020)
  2. Test currently asymptomatic patients for evidence of prior infection.
  3. Current test is estimated to have >90% sensitivity and >99% specificity, but false positives and negatives are present.
  4. Note that it remains unclear whether the presence of antibodies indicates an individual is no longer infectious or no longer susceptible to re-infection.
  1. Inpatient and outpatient SARS-CoV-2 serology can be ordered through Epic.
  2. Further guidance about sending and interpreting SARS-CoV-2 serology can be found on here. (Partners login required)

Inpatient Laboratory Workup for COVID Patients

On admission

If not obtained in ED, draw following morning

CBC with differential

BMP, Magnesium

LFTs, Troponin & CPK, NT-proBNP

LDH, CRP, D-dimer, Procalcitonin

PTT/INR, Ferritin

Baseline EKG

Extended Respiratory Viral Panel - only if would change management (high risk patients such as transplant, onc, ICU)

Daily

Can change to every other day in stable floor patients

CBC with differential

BMP, Magnesium

If ICU: Troponin & CPK, NT-proBNP, SCV02, PTT, PT, Fibrinogen

Every other day

LFTs, Troponin & CPK, NT-proBNP

LDH, CRP, D-dimer, Ferritin, PTT, PT, Fibrinogen

If on propofol: Triglycerides, lipase

Twice Weekly

sIL-2R

Weekly - only in heme malignancy / stem cell transplant patients

Glucan, Galactomannan

+/- additional per primary oncologist

If clinical worsening

CBC with differential

BMP, Magnesium, LFTs

Troponin & CPK, NT-pro-BNP

LDH, CRP, D-dimer, Procalcitonin

PTT/INR, Fibrinogen, Ferritin

ABG preferred over VBG

Repeat EKG

Radiology

  1. Findings: Please see CEBI COVID Protocols, the HMS Library of Evidence and Radiopedia.
  1. Typical Appearance: Mimics organizing pneumonia.
  1. Distribution is typically bilateral, peripheral, and basal predominant. Ground-glass opacities with or without consolidation
  2. Reverse-halo sign is present in a large minority (Simpson, RSNA, 2020)
  3. Bilateral findings in about 85% of patients; 33 - 86% predominantly peripheral and 70 - 80% predominantly posterior (Chung, RSNA, 2020; Song, RSNA, 2020)
  4. “Crazy paving” often develops later in the course of disease
  1. Indeterminate Appearance: Nonspecific
  1. Multifocal, perihilar or unilateral GGO with or without consolidation, lacking specific distribution, non-rounded or non-peripheral
  2. Few, very small GGO, non-rounded and non-peripheral
  1. Atypical Appearance
  1. Isolated lobar or segmental consolidation without GGO
  2. Discrete small nodules (centrilobular, “tree-in-bud”)
  3. Cavitation
  4. Smooth interlobular septal thickening with pleural effusions
  1. Parenchymal imaging findings are variable and depend on timecourse (Wang, RSNA, 2020):
  1. Days 0-5: ~65% pure GGOs, 24% GGOs with intralobular lines
  2. Days 6-11: ~40% pure GGOs, 22% pure GGO with intralobular lines, 28% GGO with irregular lines and interfaces
  3. Days 12 - 17: more consolidations (38% show “mixed” pattern of consolidation, GGOs, and reticular opacities with architectural distortion)
  4. Late findings may include architectural distortion
  1. Small bilateral effusions can be seen in <10% of patients; large effusions are not typical.
  2. Large effusions, cavitations, discrete nodules, lymphadenopathy suggestive of another process (eg superimposed bacterial infection)
  1. Portable CXR: Sufficient in most cases.
  1. Avoid routine daily CXR (unlikely to change management, evaluate case-by-case).
  2. May be initially normal in up to ~30% of hospitalized COVID patients, particularly in early disease (Wong, Radiology, 2019). Sensitivity 59% in one study, as compared to 86% for CT scan (Guan, NEJM, 2020)
  1. CT Chest: Routine Screening CT for diagnosis or exclusion is not currently recommended. (Simpson, RSNA, 2020).
  1. CT will often not change management and is associated with potentially unnecessary risk (risk to staff of transmission in transit, risk to patient for desaturation in transit).
  2. Avoid unless otherwise indicated: e.g. for abscess or empyema, or other causes of hypoxemia like pulmonary embolism
  3. Approximately 50% of CT scans are normal up to 2 days after symptom onset
  1. Point of Care Ultrasound: Can be used by experienced providers, but is operator-dependent. (Mayo, Intensive Care Med, 2019).
  1. Findings: Focal or diffuse B lines with sparing of uninvolved areas, irregular thickened pleural line with “scattered discontinuities”, subpleural consolidations (relatively avascular on Doppler), alveolar consolidations with air bronchograms
  1. May help distinguish cardiogenic pulmonary edema from ARDS. (Mayo, Intensive Care Med, 2019).

For Radiologists

  1. Guidelines for Radiologists reading and reporting COVID lung imaging
  2. Guidelines for precautions for radiology studies (in radiology suite as well as bedside ultrasound and portable chest X-Ray)

Cardiac Testing

  1. Telemetry:
  1. Telemetry should be used for all critically-ill patients
  2. At BWH, COVID-19 intermediate-care patients also have telemetry.
  3. For hospitals, with resource-limitations, telemetry is most important for patients who meet AHA criteria (Sandau et al, Circulation, 2017).
  1. ECGs:
  1. Daily ECGs are reasonable for individuals with severe COVID-19.
  1. When possible, print ECGs from the in-room monitor to minimize contamination of equipment
  1. Bedside TTE:
  1. Do not order routine TTEs on COVID-19 patients.
  2. Indications for POCUS:
  1. Marked elevation in troponin or NTproBNP or decline in ScvO2/MvO2
  2. Shock
  3. New heart failure (not pre-existing heart failure)
  4. New persistent arrhythmia
  5. Significant ECG changes
  1. If abnormalities are identified on POCUS (e.g. new reduction in LVEF < 50%), a formal TTE should be obtained and cardiology consulted. Where possible order limited TTEs instead of full TTEs to conserve resources.
  2. Findings: Evaluate for both left and right ventricular function.
  1. The differential diagnosis of abnormal right ventricular dysfunction includes myocardial injury / myocarditis, hypoxic vasoconstriction, pulmonary embolus, and cytokine mediated dysfunction.
  2. The differential diagnosis of abnormal left ventricular dysfunction include myocardial injury / myocarditis, acute coronary syndrome, and stress induced cardiomyopathy. In the setting of elevated cardiac troponin, the presence of regional wall motion abnormalities suggests the presence of an acute coronary syndrome; however, myocardial injury may also result in focal wall motion abnormalities.
  1. Advanced CV Imaging (Stress Testing, TEE, CT, CTA, MRI, Invasive Coronary Angiography)
  1. All testing should be limited to cases where the information is thought to be critical to patient care. Consideration of all advanced imaging should be discussed with cardiology consultation or individual imaging teams.
  2. Exercise stress testing:
  1. Likely not expected to be commonly indicated in individuals with active COVID. If needed, consider pharmacologic nuclear stress testing or coronary CTA.
  1. Transesophageal Echocardiogram (TEE)
  1. Only order if absolutely necessary
  2. Consider alternative noninvasive imaging modalities (e.g. cardiac CT to rule out left atrial appendage thrombus, cardiac CT and/or PET/CT for endocarditis complications).
  1. Cardiac CT
  1. Consider for selected patients with elevated cardiac biomarkers with possible myocardial injury versus acute coronary syndrome. The decision to pursue this vs conventional angiography must be done in conjunction with cardiology.
  2. Consider in selected patients as a substitute for TEE to rule out left atrial appendage clot or to evaluate for endocarditis.
  3. Concurrent multiphase data acquisition may also be used to evaluate left and right ventricular function, and can be performed concurrently with chest CT (to evaluate lungs) or pulmonary angiogram (to rule out PE, though this requires a wider field of view and a higher contrast dose).
  1. Cardiac MRI
  1. Consider for selected patients with elevated cardiac biomarkers with possible myocarditis, if this information will impact patient management.
  1. In the acute and sub-acute periods, T1 and T2 mapping as well as assessment of extracellular volume fraction (ECV) may improve the sensitivity of detecting myocarditis. However, the prognostic significance of such abnormalities (especially in the presence of normal ventricular function or when LGE abnormalities are absent) is uncertain.
  1. In selected patients who have recovered from COVID, Cardiac MRI using Late gadolinium enhancement (LGE) may be useful for evaluating residual scar from myocarditis.
  1. Nuclear imaging
  1. In COVID patients who require stress testing, vasodilator stress testing is preferred over exercise testing.
  2. In selected patients who have recovered from COVID, PET MPI using a quantitative assessment of myocardial blood flow may be useful for evaluating microvascular dysfunction.