Brigham and Women's Hospitals

Diagnostics

Updated May 22, 2020

SARS-CoV-2 Testing

Overview

  1. BWH-specific inpatient COVID-19 testing pathways and infection control guidelines can be found here (Partners login required)
  2. There are numerous possible methods for diagnosing COVID-19. These include:
  1. Reverse transcription-polymerase chain reaction (RT-PCR) is currently the standard of care for diagnosis of active COVID-19
  2. Serologic testing is becoming available and may be useful for certain clinical scenarios, discussed below
  3. Viral culture is impractical due to need for Biosafety Level 3 laboratory
  4. Radiologic findings, in particular CT of the chest, may be more sensitive though less specific for diagnosis of COVID-19
  1. Assessment of the validity of diagnostics is made challenging as there is lack of a “gold standard” for diagnosis
  2. It is important to note that in the setting of high clinical suspicion, no currently available clinical test can adequately rule out a diagnosis of COVID-19

RT-PCR

  1. RT-PCR from a nasopharyngeal swab is the current standard of care for the diagnosis of SARS-CoV-2 infection
  2. Sensitivity of RT-PCR from nasopharyngeal swab is not optimal
  1. One Chinese study of 1014 patients with suspected COVID-19 found that only 59% had positive nasopharyngeal RT-PCR, compared with 88% who had findings on CT chest (Ai et al, Radiology, 2020)
  2. In confirmed cases in Shenzhen, nasal and throat swabs were 60-70% sensitive early in illness. This declines, particularly in mild cases, by the second week of symptoms (Yang et al, preprint)
  1. Multiple studies have demonstrated that viral shedding, and thus sensitivity of RT-PCR from nasopharyngeal swab, declines over time (Yang et al, preprint; Zou et al, N Eng J Med, 2020; To et al, Lancet Infect Dis, 2020)
  2. In the setting of high clinical suspicion, expectorated sputum, tracheal aspirate, or (rarely) bronchoalveolar lavage fluid may be sent for RT-PCR testing
  1. Deeper respiratory samples including sputum or bronchoalveolar lavage have higher sensitivity, with reported values of 70-90% (Yang et al, preprint; Wang et al, JAMA, 2020)
  2. Ongoing suspicion for COVID-19 with negative nasopharyngeal RT-PCR typically warrants an ID consult
  1. Recent reports suggest that salivary samples may potentially be more sensitive for detection of SARS-CoV than nasopharyngeal swab (Wyllie et al, unpublished data)
  1. This testing modality is being validated and may become available at BWH in the future
  1. Viral shedding has been identified from other body sites (Wang et al, JAMA, 2020)
  1. Viral RNA is shed in stool, but may not represent live transmissible virus. Limited viral culture data available indicate little to no live virus is present (Wolfel et al, Nature, 2020)
  2. Rarely, viral RNA can be present in blood, but this is not typical
  3. No viral RNA has been identified in urine

Guidelines for RT-PCR Testing at BWH

  1. Current Partners guidelines for inpatient and outpatient testing can be found here (login required)
  2. For symptomatic patients with suspicion of COVID-19:
  1. Inpatients require two nasopharyngeal tests separated by 12 hours
  2. Outpatients require a single nasopharyngeal swab
  1. For asymptomatic patients being screened for COVID-19, all patients require a single nasopharyngeal swab
  2. All symptomatic testing generates a CoV Risk flag
  1. This flag will expire in 14 days
  2. If a flag needs to be removed for purposes of precautions and bed placement (inpatient) or because of planned admission or procedure (outpatient), please page corresponding Biothreats pager
  1. All positive tests generate a COVID-19 flag
  2. All patients with known or highly suspected COVID-19 require repeat testing for clearance:
  1. Testing can be performed after 10 days from initial positive test
  2. Clearance requires two negative nasopharyngeal swabs separated by 24 hours
  3. Alternatively, clearance can be considered after 30 days from positive test
  1. Questions about appropriateness of testing or interpretation of results should be directed to respective inpatient or outpatient Biothreats pager

Serologic testing

  1. For details on antibody response, please see “Immunity” section.
  2. Serologic testing in clinical practice:
  1. Numerous antibody tests developed by commercial laboratories and manufacturers are currently on the market
  1. Not all marketed tests have been evaluated by the FDA
  2. Currently 7 tests (Mt Sinai Laboratory, Chemobio Diagnostic Systems, Cellex, Ortho-Clinical Diagnostics, Autobio Diagnostics, DiaSorin, and Abbott Laboratories) have been issued an Emergency Use Authorization (EUA) by the FDA
  1. The most up-to-date list of tests issued an EUA can be found on the FDA’s website
  1. Testing Methods
  1. Qualitative Assays: Lateral Flow Assay
  2. Quantitative Assays: Enzyme-linked immunosorbent assay (ELISA)
  1. Test characteristics and performance are variable, and there appears to be substantial variability between assays
  1. Differences in viral antigen targets (i.e., nucleocapsid, spike, RBD)
  2. No standard criteria for defining “positive” and “negative” results
  3. Detection thresholds vary by product
  4. Validation done internally by manufacturer
  5. False positives and negatives depending on disease prevalence
  1. False Positives: Cross-reactivity with other coronaviruses
  2. False Negatives: Lower sensitivity early in disease course
  1. Current Potential Roles for Antibody testing (IDSA, 2020)
  1. Identification of symptomatic patients who are rt-PCR negative
  1. The addition of IgM ELISA to PCR-negative patients detected 98.6% of cases versus 51.9% with a single PCR (Guo et al, Clin Infect Dis, 2020)
  2. Total Antibody may be more sensitive than IgM or IgG alone (Zhao et al, Clin Infect Dis 2020)
  1. Assessing seroprevalence in the community
  2. Identification of convalescent plasma donors

  1. Serologic testing at BWH:
  1. Indications
  1. Indicated for an ED or inpatient with at least 7 days of a clinical syndrome compatible with COVID-19, but 1 or 2 negative PCRs
  2. Testing is not currently indicated in clinically well patients who wish to know if they were previously infected or immune, due to lack of testing capacity and lack of data to confirm the presence of antibodies confers protection from future infection
  3. Testing for outpatients is discouraged and not currently available through BWH
  1. A patient who reports a positive serology obtained at an outside facility and is scheduled for an in-person visit within 10 days must be referred for COVID-19 PCR testing
  1. Assay
  1. ELISA IgM and IgG antibodies using kits from Epitope Diagnostics, Inc.
  2. Results reported as units on semi-quantitative scale:
  1. IgM Antibody
  1. Negative: <0.82 units
  2. Borderline: 0.82-0.999 units
  3. Positive: >0.999 units
  1. IgG Antibody
  1. Negative: <0.82 units
  2. Borderline: 0.82-0.999 units
  3. Positive: >0.999 units

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 this excellent resource from Radiopedia.
  1. Primary features are of atypical pneumonia or organizing pneumonia.
  1. Distribution is typically bilateral, peripheral, and basal
  1. Bilateral findings in about 85% of patients; 33 - 86% predominantly peripheral and 70 - 80% predominantly posterior (Chung, RSNA, 2020; Song, RSNA, 2020)
  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 fibrotic changes
  1. Small bilateral effusions can be seen in <10% of patients; large effusions are not.
  1. Large effusions, cavitations, discrete nodules, lymphadenopathy suggestive of another process (eg superimposed bacterial infection)
  1. Portable CXR: Sufficient in most cases. Avoid routine daily CXR (unlikely to change management, evaluate case-by-case).
  1. May be initially normal in up to ~30% of hospitalized COVID patients, particularly in early disease (Wong, Radiology, 2019).
  1. Sensitivity 59% in one study, as compared to 86% for CT scan (Guan, NEJM, 2020)
  1. CT Chest: Often will not change management and is associated with potentially unnecessary risk (risk to staff of transmission in transit, risk to patient for desaturation in transit)
  1. Avoid unless otherwise indicated: e.g. for abscess or empyema, or other causes of hypoxemia like pulmonary embolism
  1. If chest CT obtained, non-contrast scan (or contrast and non-contrast phases if concerned for PE)
  1. 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. For experienced providers, sensitivity is likely superior to portable chest X-ray (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 are forthcoming

Other Tests

  1. Cardiovascular 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. 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.
  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. Specific considerations:
  1. Stress testing is likely not expected to be commonly indicated in individuals with active COVID. If needed, consider pharmacologic nuclear stress testing or coronary CTA.
  2. TEE
  1. Only for absolute necessity
  2. Consider alternative noninvasive imaging modalities (e.g. cardiac CT to rule out left atrial appendage thrombus, cardiac CT or PET/CT for endocarditis complications).