Polymerase Chain Reaction (PCR) Testing: Selected Indications
Customize your policy alerts
Sign up for Aetna Policy 0650 alerts
Get alerted when Policy 0650 changes without checking for updates manually.
Monitor payer policy activity
Clinical policy governing medical necessity, covered indications, and experimental/investigational determinations for qualitative, multiplex, and quantitative PCR tests for Aetna members.
No material clinical or coverage changes in this revision.
Coverage Criteria
Qualitative PCR: selected individual indications (partial list)
Aetna considers the following qualitative PCR tests medically necessary (not an all‑inclusive list):
See full policy list for additional qualitative PCR indications.
Qualitative multiple PCR (multiplex) panels — coverage criteria
Multiplex PCR panels are covered when the documented clinical selection criteria below are met:
Use alongside standard CSF and blood cultures; PCR does not provide susceptibility data.
Applies to panels up to 5 respiratory pathogens when selection criteria met.
Map to CPT codes 87505/87506/87507/0369U as applicable and include ICD-10 linkage (eg, R19.7).
Respiratory panel CPT/HCPCS map to panel size (eg, 87631/87632/87633, 0202U/0223U/0225U).
Use only on positive culture material per policy.
Quantitative PCR testing — covered indications (examples)
Aetna considers the following quantitative PCR tests medically necessary for diagnosis, monitoring disease progression, or to assess response to therapy:
PML/RARA RT‑PCR is diagnostic for APL.
Use per guideline‑based indications to guide therapy/monitoring.
EBV screening: begin day of transplant and at least weekly for first 3 months in high‑risk allogeneic recipients; BK viremia/viruria thresholds referenced in policy.
Experimental and Investigational — qualitative and quantitative PCR tests
Aetna considers the following PCR tests experimental and investigational (not medically necessary) because their clinical role or impact on patient management has not been established:
See policy enumerated lists (chunks 16–19) for full items.
See policy enumerated lists (chunks 18–20) for complete items.
Selected Indications (enumerated list)
Aetna provides an enumerated list of selected indications and agents; coverage depends on whether the indication is listed and applicable selection criteria are met.
Refer to the policy enumerated list items 50–101 and related entries for full detail.
Quantitative PCR tests considered experimental/investigational
Aetna considers the following quantitative PCR tests experimental/investigational (not medically necessary) because their role in clinical management has not been established:
See chunks 19–20 for complete enumerated items.
Coverage conditional on selection criteria
Coverage of many PCR tests is conditional on meeting the clinical selection criteria and submitting appropriate procedure and diagnosis code linkage:
Examples: CPT 87483 (CSF panel), respiratory panel U‑codes/8763x series, GI panel codes 87505/87506/87507/0369U, orthopoxvirus 87593 when selection criteria/ICD‑10 mapping met.
General coverage contingent on selection criteria
The policy states tests are covered when ALL of the following are met:
Providers must map the ordered CPT/HCPCS to the covered indications and ICD‑10 codes per the policy code tables.
Clinical use and investigational contexts
Contextual clinical-use statements and limitations where PCR may be recommended, adjunctive, or investigational:
Use in conjunction with clinical and cytogenetic data.
Culture/antigen remain preferred in many settings; use per AAP guidance.
Interpret results in clinical context; repeat testing may improve specificity.
Follow CDC guidance for use.
Study‑derived G. vaginalis qPCR threshold ≥10^7 copies/mL associated with Nugent‑defined BV in some studies.
BV NAATs — Appropriate Use
Appropriate use of BV NAATs / molecular tests for bacterial vaginosis:
Traditional methods (Amsel, Nugent, wet mount) remain useful initial tests; internal validation required for laboratory‑developed tests.
Clonality and bcl-2 PCR — Appropriate Use
Appropriate use of clonality and bcl-2 PCR testing in suspected lymphoproliferative disease:
Interpret results with morphologic and clinical correlation; results may be non‑diagnostic in polyclonal/reactive processes.
BK/JCV PCR — Appropriate Use
Appropriate use of BK and JC viral PCR testing:
Provide specimen type and clinical context (plasma vs urine); monitoring frequency guided by clinical protocol.
Selected clinical indications and considerations
Selected clinical indications and operational considerations where PCR testing is supported or should be used adjunctively:
Follow NCCN guidance; interpret with clinical and morphologic data.
Document transplant status and suspected graft dysfunction.
Provide supporting neurologic and imaging documentation.
Useful when prior antimicrobials may reduce culture yield; reported sensitivity/specificity high for panel.
Pathogen-specific PCR coverage statements
Pathogen‑specific PCR coverage statements — summaries of when PCR is appropriate, adjunctive, limited, or investigational by organism:
Be aware of cross‑reactivity concerns with some assays; follow CDC specimen recommendations.
Use culture/antigen testing per guidelines.
Refer to CDC containment lab guidance.
Document clinical indication (diagnosis, monitoring, neonatal testing) when ordering.
Follow AAP/CDC guidance for specimen selection.
Chromosomal integration may confound interpretation; testing limited to reference labs.
Pathogen-specific coverage guidance
Additional pathogen‑ and condition‑level coverage guidance and limitations:
Exclude chromosomal integration for HHV‑6 when interpreting results.
Document infant age and clinical indication when ordering.
Coordinate with public health authorities for H5N1 testing.
Follow CDC guidance for specimen choice and timing.
Positive respiratory viral PCR does not exclude Kawasaki disease.
Condition-level coverage assessments (selected indications)
Condition‑level assessments — statements on clinical utility or investigational status for selected conditions:
Use conventional diagnostics per clinical context.
Specimen choice and species identification informs therapy.
Follow guideline‑based serologic testing algorithms.
Use smear/rapid test for acute management; PCR for species confirmation when needed.
Molecular methods are among the most accurate techniques for MRSA identification.
Agent-specific PCR utility and limitations
Agent‑specific utility and limitations — guidance to inform ordering, interpretation, and sample selection:
NCCN referenced; provide clinical context when ordering.
Avoid overreliance on PCR for non‑validated specimen types.
Wright/Giemsa staining of lesion core can demonstrate characteristic inclusions.
Testing available at LRN and select commercial labs; follow CDC/FDA specimen guidance.
Selected pathogen-specific PCR coverage guidance
Selected pathogen‑specific guidance emphasizing sample type, interpretation caveats, and investigational status:
Follow CDC case definitions and FDA guidance regarding specimen types.
PCR positivity may reflect prolonged DNAemia up to 9 months.
Heterogeneous study results; interpret cautiously.
Definitive diagnosis relies on demonstration in respiratory specimens (BAL, induced sputum).
Larger studies are needed to establish clinical utility.
Testing required solely to meet non-medical requirements (for example, clearance for work, school, or recreational activities) is excluded under standard benefit plans. Providers and facilities should verify benefit plan descriptions and not bill such testing as medically necessary clinical care.
Testing with the C. difficile toxin gene PCR (CPT 87493) is not covered when performed in asymptomatic persons or for a routine "test of cure". Repeat or surveillance testing outside stated diagnostic indications may be denied.
The policy lists examples of ICD-10 codes not covered for indications in this CPB (not exhaustive). Examples include certain bacterial intestinal infections, Lyme disease, Creutzfeldt-Jakob disease, selected fungal/mycotic diseases, and other codes shown in the CPB ICD-10 lists. Claims using these ICD-10 codes for CPB-listed PCR indications may not meet coverage criteria.
CPT code 87913 (SARS‑CoV‑2 genotype/mutation identification) is listed as not covered for the indications described in this clinical policy bulletin.
Specific named commercial consumer/self-directed assays (for example, EoGenius, uBiome SmartGut, SmartJane, SmartFlu, Explorer) and similar consumer/genetic-type panels are explicitly listed as not covered. These assays and related organism‑quantification codes are excluded when submitted for CPB-listed indications unless otherwise specified.
Multiple guideline bodies currently do not recommend routine PCR testing for bacterial vaginosis (BV). Molecular assays have been used in research and investigational settings and their clinical utility remains uncertain; PCR/NAATs for BV should be considered only when symptomatic and when results will influence management.
NAATs/quantitative PCRs for BV are appropriate for symptomatic women when results will guide therapy, but are not recommended for routine testing of asymptomatic women because accuracy and clinical-value thresholds are not well defined for screening populations.
PCR assays for candidiasis (Candida spp.) have not been validated for routine clinical use in many settings and are described in guidelines as largely research tools. Real‑time PCR for candidemia remains investigational pending further assay validation and demonstration of clinical benefit compared with standard methods (culture, microscopy, antigen tests).
Current evidence-based guidelines from NCCN and NCI indicate no role for PCR testing to detect metastases from cervical cancer; PCR is not supported for this purpose in the cited guidance.
Per cited NCCN/NCI sources, PCR does not have an established role for detection of metastases from cervical intraepithelial neoplasia or cervical cancer and is not recommended for that indication.
The American Academy of Pediatrics characterizes PCR tests for cryptococcus as investigational. Antigen detection in CSF or serum remains the recommended rapid diagnostic approach for cryptococcal disease.
Molecular diagnostic assays for Cyclospora are described as investigational and are primarily available at CDC and selected reference laboratories; stool microscopy and specialized staining remain standard diagnostic methods.
PCR-based species or genotype identification for Cryptosporidium in immunocompetent patients is unlikely to change clinical management and therefore is of limited clinical utility; such testing is generally not indicated for routine care.
Testing for Cyclospora and Donovanosis (Klebsiella granulomatis) by PCR or serology is described as investigational/research in the CPB and is mainly available through reference or public health laboratories rather than routine clinical labs.
Covered Indications
CSF pathogen panel
Covered CSF multiplex panel indication (example):
CPT 87483 covered if selection criteria met; order alongside standard microbiologic testing.
Gastrointestinal pathogen panel
Covered gastrointestinal panel indications and coding guidance:
CPT 87505 (3–5 targets) and 87506 (6–11 targets) covered if selection criteria met; >11 targets (eg, 0369U/87507) allowed for critically ill or immunocompromised persons; R19.7 required for claims.
Respiratory virus/bacteria panel
Covered respiratory panel indications (including SARS‑CoV‑2‑containing panels):
Different CPT/HCPCS map to panel size (eg, 0240U/0241U for 3–4 targets; 0202U/0223U/0225U/87631/87632/87633 for larger panels); include appropriate ICD‑10 mapping per policy.
Sepsis pathogen panel
Covered sepsis panel use when specific criteria are met:
Examples include BioFire BCID and ePlex BCID panels; use only on culture‑positive material per policy.
Wide range of infectious and some genetic indications enumerated
Broad coverage note — multiple infectious and selected genetic indications are enumerated in the policy; coverage contingent on meeting selection criteria and code mapping:
Refer to policy lists for full enumeration and code mapping.
CSF pathogen panel for meningitis/encephalitis signs and symptoms
CSF pathogen panel coverage for meningitis/encephalitis signs and symptoms (coding examples):
Panel should be ordered with concurrent CSF/blood cultures per guidance.
Multiplex respiratory pathogen panels including SARS-CoV-2 for acute respiratory illness
Multiplex respiratory panels (including SARS‑CoV‑2) covered when criteria met and appropriate ICD‑10 linkage provided:
Panel size determines CPT/HCPCS selection per policy tables.
Gastrointestinal pathogen panel for infectious diarrhea/Clostridium difficile
Gastrointestinal pathogen panel coverage specifics (coding and selection criteria):
Claims must include required diagnosis codes per policy.
Orthopoxvirus testing (eg, monkeypox) when selection criteria met
Orthopoxvirus (including monkeypox) PCR testing indication and coding guidance:
Follow CDC/FDA specimen guidance; avoid non‑lesion samples for routine testing.
Respiratory, gastrointestinal, vaginal, sepsis, and other infection-related indications when specific ICD-10 diagnoses and selection criteria are met
Other infection‑related indications (respiratory, GI, vaginal, sepsis) are covered when specific ICD‑10 diagnoses and selection criteria are met:
See CPT/ICD‑10 code tables in the policy for mapping and R19.7 requirement for GI panels.
Detection and monitoring of AML-associated fusion transcripts (AML1/ETO, CBFß/MYH11, PML/RARA).
Molecular testing for AML‑associated fusion transcripts — diagnostic and monitoring use:
Use RT‑PCR for serial monitoring per hematology protocols.
Quantitative adenovirus PCR to detect viremia and monitor response in hematopoietic stem cell transplant recipients.
Quantitative adenovirus PCR use in transplant recipients:
Serial monitoring frequency as clinically indicated.
Aspergillus PCR as adjunctive test
Aspergillus PCR role as adjunctive testing:
Consider repeat testing and combined assays to improve specificity.
Diagnosis of symptomatic vaginitis/BV using NAAT/PCR when results will influence management
Molecular testing for symptomatic vaginitis/BV when results will influence management:
Investigational tests require validation; some qPCR thresholds (eg, G. vaginalis ≥10^7 copies/mL) have been proposed in studies.
Monitoring or diagnosing BK/JC infection in immunocompromised/transplant patients
BK/JC PCR testing for transplant recipients — monitoring and diagnostic role:
Provide transplant status and clinical context for interpretation; monitoring frequency per clinical protocol.
Adjunctive clonality PCR testing and bcl-2 translocation assays
Clonality and bcl‑2 translocation testing as adjuncts in lymphoproliferative disorders:
Interpret clonality results in the context of morphology and immunophenotyping.
PCR or serology for suspected Bartonella infection when clinically warranted
Bartonella testing considerations:
PCR availability may be limited to reference laboratories; interpret with clinical features.
Monitoring and diagnosis of BK virus infection in transplant recipients (blood and urine PCR)
BK virus monitoring and interpretation guidance for transplant recipients:
Document transplant type, clinical signs of nephropathy, and specimen type with orders/claims.
Rapid detection of multiple CSF pathogens in suspected meningitis/encephalitis
Rapid CSF pathogen detection using multiplex PCR panels — recommended adjunctive use:
FilmArray ME panel has reported high sensitivity/specificity but does not replace culture or susceptibility testing.
B-cell and T-cell clonality testing to support lymphoma diagnosis
Clonality testing to support lymphoma diagnosis per guideline recommendations:
Integrate results with morphology and immunophenotyping.
CSF PCR for bacterial and viral meningitis
CSF PCR for bacterial and viral meningitis — diagnostic role when culture/Gram stain negative or after prior antimicrobials:
Order cultures concurrently; PCR does not provide susceptibility data.
Chlamydia trachomatis NAAT
Chlamydia trachomatis NAAT/ PCR screening and diagnostic guidance:
Follow USPSTF and AAP guidance for screening intervals and specimen types.
Clostridioides difficile molecular testing
Clostridioides difficile molecular testing coverage and frequency considerations:
87493 not covered for asymptomatic persons or test‑of‑cure scenarios.
Chikungunya RT-PCR on serum
Chikungunya RT‑PCR — timing and specimen guidance:
Document travel/epidemiologic history and specimen timing when ordering.
BCR-ABL (bcr/abl) testing by PCR/RT-PCR
BCR‑ABL testing by PCR/RT‑PCR for CML and subset of ALL — diagnostic and monitoring role:
RT‑PCR is the most sensitive technique for low‑level detection.
Diagnosis and monitoring of CMV infection (including quantitative PCR viral load testing)
CMV PCR (quantitative viral load) — diagnostic and monitoring contexts:
DBS PCR for newborn CMV screening has shown low sensitivity in studies and is not established as a primary screening method.
Detection of enterovirus RNA, especially in CSF for suspected viral meningitis.
Enterovirus RNA detection — CSF testing preferred for suspected viral meningitis:
Order CSF PCR when clinical features suggest viral meningitis.
Acute-phase diagnosis of ehrlichiosis/anaplasmosis via PCR
Ehrlichiosis/anaplasmosis — acute‑phase PCR use and ordering considerations:
Document travel/exposure history and timing relative to symptom onset.
Consider EBV PCR in immunocompromised patients or when CNS lymphoma suspected
EBV PCR consideration — limited to immunocompromised contexts or suspected EBV‑related lymphoma:
Order with appropriate clinical documentation when used for monitoring/diagnosis in transplant recipients.
N. gonorrhoeae testing on recommended specimen types
Neisseria gonorrhoeae testing — specimen and screening guidance:
Use approved NAAT platforms and follow specimen guidance to avoid cross‑reactivity and false positives.
HCV RNA testing for early diagnosis, neonatal/perinatal infection detection, and monitoring
HCV RNA testing — indications for early diagnosis, neonatal detection, and monitoring therapy:
Quantitative assays are used for prognosis/therapy decisions; document clinical indication.
HBV DNA and HBeAg testing to select candidates for antiviral therapy and to monitor response
HBV DNA / HBeAg testing — role to select candidates for antiviral therapy and to monitor response:
Use guideline‑based thresholds to guide therapy initiation and monitoring.
HSV PCR (CSF) for suspected CNS infection; PCR preferred for genital herpes diagnosis
HSV PCR (CSF) — preferred diagnostic method for CNS infection and genital herpes:
Order CSF PCR in patients with neurologic features suggestive of HSV encephalitis.
HHV-6 PCR testing indications and chromosomal integration consideration
HHV‑6 PCR — indicated in selected clinical scenarios with integration caveat:
Chromosomal integration may lead to persistently high DNA loads and confound interpretation.
HIV diagnosis in infants up to 18 months
HIV PCR for infant diagnosis — preferred testing approach:
Document infant age and exposure history when ordering.
Suspected H5N1 influenza in hospitalized severe respiratory illness with recent travel to affected country
Criteria for H5N1 influenza PCR testing (per CDC):
Follow CDC guidance and coordinate with state/local health departments.
HPV testing as adjunct to cervical cancer screening
HPV testing — limited adjunctive screening role and restrictions:
Use FDA‑approved assays and follow screening guidelines.
MRSA detection
MRSA molecular detection — role of mecA PCR:
Use validated molecular assays for mecA detection.
Leishmaniasis species identification
Leishmaniasis — species identification utility:
Order species‑level testing when clinical management depends on species identification.
Microsporidia diagnosis by PCR
Microsporidia diagnosis — PCR utility:
Interpret results in clinical context and confirm with microscopy/culture as appropriate.
Detection of t(11;18) translocation in gastric MALT lymphoma
t(11;18) translocation testing in gastric MALT lymphoma — clinical utility:
Document H. pylori status and histologic context when ordering.
PCR testing for orthopoxvirus (including monkeypox) on lesion specimens
Orthopoxvirus/monkeypox PCR testing guidance and specimen recommendations:
Avoid non‑lesion specimens (blood, saliva) for routine clinical diagnosis per FDA guidance.
Coding
| 0017U | Oncology (hematolymphoid neoplasia), JAK2 mutation, DNA, PCR amplification of exons 12-14 and sequence analysis |
| 0040U | BCR/ABL1 (t(9;22)) translocation analysis, major breakpoint, quantitative |
| 0353U | Infectious agent detection by nucleic acid (DNA), Chlamydia trachomatis and Neisseria gonorrhoeae, multiplex amplified probe technique |
| 81206 | BCR/ABL1 (t(9;22)) translocation analysis |
| 81210 | BRAF gene analysis, V600 variant(s) |
| 81220-81224 | CFTR gene analysis |
| 81225 | CYP2C19 gene analysis |
| 81226 | CYP2D6 gene analysis |
| 81227 | CYP2C9 gene analysis |
| 81240 | F2 (prothrombin) gene analysis, 20210G>A variant |
| 81291 | MTHFR gene analysis (listed as CPT code not covered for indications in this CPB) |
| 0301U | Infectious agent detection by nucleic acid (DNA or RNA), Bartonella henselae and B. quintana, ddPCR |
| 0068U | Candida species panel, amplified probe technique (CPT not covered for CPB indications) |
| 0109U | Infectious disease (Aspergillus species), real-time PCR for detection of DNA from 4 species |
| 0140U | Fungal pathogen identification DNA (15 fungal targets), blood culture, amplified probe technique |
| 0141U | Bacterial and fungal gram-positive identification and resistance gene detection, blood culture |
| 0142U | Gram-negative bacterial identification and resistance gene detection, blood culture |
| 0152U | Bacteria, fungi, parasites, and DNA viruses; PCR and NGS, plasma; detection of >1,000 potential organisms |
| 0321U | Genitourinary pathogens identification and antibiotic-resistance genes, multiplex amplified probe technique |
| 0370U-0374U | Multiplex panels for wound and genitourinary pathogens with resistance gene ID (various U-codes) |
| 87468-87471 | Amplified probe techniques for tickborne and Bartonella agents |
| 87476 | Borrelia burgdorferi nucleic acid detection |
| 87500 | Vancomycin resistance detection (e.g., vanA, vanB) |
| 87526 | Hepatitis G virus, amplified probe technique |
| 87541 | Legionella pneumophila, amplified probe technique |
| 87551 | Mycobacteria species, amplified probe technique |
| 87561 | Mycobacterium avium-intracellulare, amplified probe technique |
| 87913 | SARS-CoV-2 genotype analysis, mutation identification |
| U0001 | CDC 2019 Novel Coronavirus Real-Time RT-PCR Diagnostic Panel |
| U0002 | 2019-nCoV Coronavirus, any technique, multiple types or subtypes, non-CDC |
| U0003 | SARS-CoV-2, amplified probe technique, high throughput technologies |
| U0004 | 2019-nCoV, any technique, high throughput technologies, non-CDC |
| U0005 | SARS-CoV-2 amplified probe technique, high throughput, completed within 2 calendar days (add-on) |
| C18.0-C20 | Malignant neoplasm of colon, rectosigmoid junction, and rectum |
| C43.0-C43.9 | Malignant melanoma of skin |
| C81.00-C91.42 | Various lymphoid and leukemic malignancies enumerated for coverage alignment |
| D57.00-D57.819 | Sickle-cell disorders |
| E84.0-E84.9 | Cystic fibrosis |
| B20 | Human immunodeficiency virus [HIV] disease |
| B25.0-B25.9 | Cytomegaloviral disease |
| C94.80-C94.82 | Other specified leukemia [Xenotrophic murine leukemia] — listed as ICD-10 not covered for CPB indications |
| G60.0-G60.9 | Hereditary and idiopathic neuropathy — listed as ICD-10 not covered for CPB indications |
| C61 | Malignant neoplasm of prostate — listed as ICD-10 not covered for CPB indications |
| A75.2 | Typhus fever due to rickettsia typhi. |
| A77.0 - A77.3, A77.9 | Spotted fever [tick-borne rickettsioses]. |
| A77.40 - A77.49 | Ehrlichiosis. |
| A78 | Q Fever. |
| A80.0 - A80.9 | Acute poliomyelitis. |
| A81.2 | Progressive multifocal leukoencephalopathy. |
| A87.0 | Enteroviral meningitis. |
| A90 | Dengue fever [classical dengue]. |
| A91 | Dengue hemorrhagic fever. |
| A92.30 - A92.39 | West Nile virus infection. |
| 87593 | Infectious agent detection by nucleic acid (DNA or RNA); orthopoxvirus, amplified probe technique, each. |
| 87483 | Infectious agent detection by nucleic acid (DNA or RNA); central nervous system pathogen, includes multiplex RT, 12-25 targets. |
| 0202U | Infectious disease pathogen-specific nucleic acid, 22 targets including SARS-CoV-2, qualitative RT-PCR, each pathogen reported. |
| 0223U | Infectious disease pathogen-specific nucleic acid, 22 targets including SARS-CoV-2, qualitative RT-PCR, nasopharyngeal swab. |
| 0225U | Infectious disease pathogen-specific DNA and RNA, 21 targets including SARS-CoV-2, amplified probe technique. |
| 87632 | Respiratory virus nucleic acid detection, multiplex RT, 6-11 targets. |
| 87633 | Respiratory virus nucleic acid detection, multiplex RT, 12-25 targets. |
| 0240U | Infectious disease pathogen-specific RNA, 3 targets (SARS-CoV-2, influenza A/B). |
| 0241U | Infectious disease pathogen-specific RNA, 4 targets (SARS-CoV-2, influenza A/B, RSV). |
| 87631 | Respiratory virus nucleic acid detection, multiplex RT, 3-5 targets. |
| 87913 | Infectious agent genotype analysis by nucleic acid; SARS-CoV-2 mutation identification in targeted region(s). |
| 87505 | Infectious agent detection by nucleic acid (DNA or RNA); gastrointestinal pathogen, 3-5 targets |
| 87506 | Infectious agent detection by nucleic acid (DNA or RNA); gastrointestinal pathogen, 6-11 targets |
| 0369U | Infectious agent detection by nucleic acid (DNA and RNA), gastrointestinal pathogens, 31 organisms and 21 resistance genes |
| 87507 | Infectious agent detection by nucleic acid (DNA or RNA); gastrointestinal pathogen, 12-25 targets |
| 0115U | Respiratory infectious agent detection by nucleic acid (DNA and RNA), 18 viral types/subtypes and 2 bacterial targets |
| 0373U | Infectious agent detection by nucleic acid; respiratory tract infection, multiple bacteria, fungi, viruses, and resistance genes |
| 0330U | Infectious agent detection by nucleic acid; vaginal pathogen panel, 27 organisms |
| 0352U | Multiplex amplified probe technique for bacterial vaginosis and vaginitis organisms |
| 81513 | Infectious disease, bacterial vaginosis, quantitative real-time amplification of RNA markers |
| 81514 | Infectious disease, bacterial vaginosis and vaginitis, quantitative DNA markers, algorithm |
| 87481 | Infectious agent detection by nucleic acid; Candida species, amplified probe |
| 87511 | Gardnerella vaginalis, amplified probe technique |
| 87512 | Gardnerella vaginalis, quantification |
| 87799 | Infectious agent detection by nucleic acid (DNA or RNA), not otherwise specified; quantification, each organism |
| 87040 | Culture, bacterial; blood, aerobic, with isolation and presumptive identification of isolates |
| 87472 | Bartonella quantification |
| 87477 | Borrelia burgdorferi, quantification |
| 87482 | Candida species, quantification |
| 87487 | Chlamydia pneumoniae, quantification |
| 87527 | Hepatitis G, quantification |
| 87530 | Herpes simplex virus, quantification |
| 87533 | Herpes virus-6, quantification |
| 87542 | Legionella pneumophilia, quantification |
| 87562 | Mycobacteria avium-intracellulare, quantification |
| 87582 | Mycoplasma pneumoniae, quantification |
Provider Actions / Documentation
Coverage tied to selection criteria and coding
Criteria-based coverage: Multiplex PCR panels (eg, CSF, respiratory, gastrointestinal, sepsis panels) are covered only when the specific selection criteria in the policy are met (signs/symptoms, immunocompromised/high-risk status, duration, specimen/source and that results will be used to guide therapy). Coding for claims must match the covered indication and required ICD-10 documentation (eg, R19.7 for GI panels when required).
- Multiplex CSF pathogen panel (eg, 87483) — covered when CSF findings are consistent with CNS infection (meningitis/encephalitis), viral etiology suspected or culture inconclusive; culture and Gram stain should still be ordered as appropriate.
- Respiratory panels — covered when member has signs/symptoms of respiratory infection and is immunocompromised/high-risk AND test will guide therapy (COVID-19 panels: up to 5 targets covered with criteria; >5 targets require criteria for broader panels).
- Gastrointestinal pathogen panels — up to 11 targets covered for immune-competent persons meeting diarrhea/travel/severe disease criteria; >11 targets covered for critically ill or immunocompromised when criteria and ICD-10 coding (eg, R19.7) are documented.
- Sepsis pathogen panels (eg, blood culture–based BCID panels) — covered when testing is performed on a positive culture and will guide therapy.
COVID-19 testing: clinical indication required; non-clinical testing not covered
COVID-19 testing: Molecular/genotyping testing related to SARS-CoV-2 has limited coverage pathways and must follow indication-specific rules. Testing performed solely for non-clinical reasons (eg, travel, employment, surveillance) is not supported by clinical-necessity criteria and is not covered under the clinical indications in this policy.
- Multiplex SARS-CoV-2/flu/RSV panels (eg, 87636, 87637) and upper respiratory multiplex assays (0240U/0241U/0202U etc.) — covered only when respiratory signs/symptoms and selection criteria met.
- Genotype/mutation analysis (CPT 87913) — coverage limited; must be ordered for clinical management when mutation identification will change care decisions and meet documented indication.
- Tests for non-clinical purposes (eg, screening for travel or workplace clearance) — not covered; such use may lead to claim denial.
Documentation requirements and ICD-10 coding
Document required clinical context and specimen information: Claims for PCR/NAAT testing must include diagnosis codes that match covered indications and required documentation (clinical signs/symptoms, immunocompromised/high-risk status, specimen type, timing relative to symptoms or therapy, and how results will guide management). Missing or non-supported ICD-10 codes or lack of clinical documentation risks denial.
- ICD-10 codes not covered for CPB indications: listed excluded codes (examples include A07.2 Cryptosporidiosis, A04.6 Yersinia enterocolitica enteritis, A07.1 Giardiasis, etc.).
- Required ICD-10 note: R19.7 (Diarrhea, unspecified) is required for many GI panel claims; transplant/status and immunocompromised codes (eg, Z94.x, T86.x) are referenced where applicable.
- Specimen/timing documentation: For many assays (eg, CSF panel, BK/JC, CMV, measles, monkeypox) the specific specimen type and timing relative to symptom onset or therapy must be documented in the medical record.
Specimen, sample-type and initial testing guidance
Provider actions for specific tests and sample-type cautions: Use recommended specimen types only, avoid non-lesion or non-recommended samples that increase false results, and prefer initial lower-cost or traditional tests when appropriate before reflexing to molecular assays.
- BV NAATs: Use among symptomatic women only (vaginal discharge, odor, itch); PCR/NAAT for BV is not recommended for asymptomatic screening — traditional Amsel/Nugent methods remain useful and lower cost.
- Gonorrhea NAATs: Certain specimen types (eg, blood, urine for extragenital disease) are not recommended for NAAT — follow test-specific specimen guidance to avoid false negatives/positives.
- Monkeypox PCR: Use lesion swab specimens; non-lesion sample types (eg, blood) carry higher risk of false or indeterminate results — document lesion type and timing per CDC guidance.
- Hantavirus RT-PCR: Limited sensitivity; negative RT-PCR does not rule out infection; interpret in clinical context and consider serology for confirmation.
- Highly pathogenic avian influenza and other high-risk pathogens: Follow public health/lab reporting pathways; some assays may be reserved for public health laboratories.
- Avoid shotgun or broad 'shotgun' PCR panels for nonspecific indications without clinical justification — broad panels without matching clinical need may be deemed not medically necessary.
- Mycobacterium tuberculosis PCR assays: Use according to established diagnostic algorithms; molecular assays are adjuncts and specimen selection matters (sputum, BAL, tissue) for sensitivity.
Adjunct testing and repeat-testing risk
Adjunctive use and repeat testing considerations: Multiplex panels and advanced molecular tests are often adjunctive to traditional methods and should be used when results will impact management. Routine repeat testing within short intervals is generally of low yield and may not be necessary.
- CSF multiplex panels: Consider as adjunct when CSF findings are consistent with CNS infection and Gram stain/culture are negative or prior antimicrobials received; culture and directed testing should not be omitted.
- Repeat C. difficile testing: Little value in repeat PCR or EIA within 7 days; repeat testing yields small diagnostic gain and is discouraged unless clinically indicated.
- Repeat PCR testing risk: Many assays (eg, C. difficile, HBV/HCV, BK/JC) can show intermittent detection; repeat testing without new clinical indication may not change management and can risk denial.
- Cryptosporidium species-level PCR: Species-level identification has limited clinical impact in many cases and may not be necessary for routine management.
Transplant and viral load testing — document clinical context
High-risk and transplant-related testing: Viral load and quantitative PCR tests (eg, BK, JC, CMV, EBV, HBV, HCV) are clinically indicated to guide therapy and monitoring in transplant and immunocompromised patients; document transplant status, immunosuppression, and monitoring plan.
- BK/JC testing: Require clinical context (eg, renal allograft dysfunction, neurologic signs for JC/PML) and appropriate specimen (plasma for BK viremia; CSF for JC in suspected PML) with timing and correlation to imaging and clinical findings.
- EBV viral load: Document transplant type and surveillance plan; high-risk allogeneic stem cell transplant recipients may require weekly monitoring for the first 3 months or longer per note in policy.
- CMV: Specify specimen (plasma/whole blood) and clinical reason (diagnosis vs. monitoring); quantitative CMV assays are used to monitor response to therapy.
- HBV/HCV molecular testing: Use quantitative assays to guide antiviral therapy selection and monitor response; document treatment intent and baseline viral load/genotype where relevant.
Limited/Investigational PCR uses
Tests with limited or investigational roles: Some PCR assays are investigational or not routinely recommended (eg, Pneumocystis jirovecii PCR, certain broad microbiome or ‘shotgun’ panels, some quantitation assays) and may be denied when ordered outside defined clinical indications.
- Pneumocystis jirovecii PCR: Considered experimental/investigational for routine diagnosis per some guidelines — use established invasive sampling methods (BAL, tissue) and follow institutional guidance.
- Shotgun cfDNA/NGS panels (eg, plasma microbial cfDNA) — interpret cautiously; results require clinical correlation and may be limited in immunocompromised hosts; use only when results will change management.
- Quantitative/novel arrays and consumer microbiome tests (eg, EoGenius, SmartGut, uBiome, SmartJane) — not covered for routine indications and may be considered investigational.
Measles and monkeypox — specimen and documentation
Measles and orthopoxvirus (monkeypox) testing documentation: For measles, serologic IgM testing or RT‑PCR from appropriate specimens are acceptable diagnostic options; for suspected monkeypox, document clinical case criteria and epidemiologic risk per CDC case definitions when submitting PCR testing.
- Measles: Acceptable diagnostic documentation includes positive measles IgM or RT‑PCR from urine, blood, throat, or nasopharyngeal secretions; single IgM during first encounter often sufficient.
- Monkeypox: Document characteristic lesion description and epidemiologic criteria (contact/exposure/travel or high clinical suspicion). Follow CDC specimen guidance (lesion swabs) and case reporting requirements.
Herpesvirus PCR — limited to specified clinical scenarios
Herpesviruses and related guidance: PCR testing for HHV-6/HHV-7/HHV-8 and other herpesviruses is generally limited to specific clinical scenarios (eg, immunocompromised hosts, encephalitis) — routine testing in immunocompetent persons is not indicated and may be denied.
- HHV-6/HHV-7: Testing reserved for immunocompromised patients or when differential diagnosis requires exclusion (eg, encephalitis, febrile mononucleosis-like illness) — document why testing will affect management.
- HHV-8: Tests largely limited to research settings; diagnosis typically will not alter management and routine screening is not supported.
H. pylori / MALT lymphoma — t(11;18) testing implications
H. pylori–associated MALT lymphoma: Detection of the t(11;18) rearrangement by PCR predicts lack of response to H. pylori eradication; document H. pylori–associated MALT lymphoma when ordering t(11;18) testing and use results to guide alternative therapy.
- Ordering note: Document diagnosis of MALT lymphoma and intent to use t(11;18) result to direct therapy; positive t(11;18) suggests antibiotic therapy for H. pylori is unlikely to be effective.
Ordering Requirements
Document clinical indication and intended impact on management
Clinical indication and documentation that test results will guide therapy are required for covered multiplex panels and quantitative viral load tests; ordering clinicians should record how results will affect management when placing the order.
- State intended clinical use (diagnosis, therapy selection, monitoring) on requisition
- Provide supporting clinical notes or prior test results when applicable
Order tests with appropriate diagnosis codes
Tests must be ordered with appropriate diagnosis codes corresponding to the covered indications; include the CPT/HCPCS code and the supporting ICD‑10 code that meets the CPB selection criteria to avoid claim denials.
- Include both procedure code and matching ICD‑10 on claim
- Ensure ICD‑10 maps to CPB selection criteria
Link orders to ICD‑10 diagnoses that meet CPB criteria
Orders must be linked to ICD‑10 diagnoses that meet the CPB selection criteria for the specific PCR panel or pathogen test being requested; unsupported ICD‑10 diagnoses or missing codes (eg, R19.7 for GI panels) may result in noncoverage.
- Link panel CPT to ICD‑10 that meets selection criteria
- R19.7 required for many GI panel claims
Submit required ICD‑10 codes with claims (eg, R19.7)
Submit the appropriate ICD‑10 diagnosis codes with claims (for example, R19.7 for gastrointestinal pathogen panels) as required by the CPB; failure to include required ICD‑10 codes can lead to denial.
- R19.7 required for GI panel claims
Follow specialty guidelines for molecular testing in oncology/infectious disease
Follow specialty and guideline recommendations (eg, CAP/IASLC/AMP, ASCO, IDSA) for molecular testing in oncology and infectious disease contexts when ordering molecular assays; document adherence to guideline‑based indications when applicable.
Document symptoms (BV) and transplant status (BK/JC)
Document symptomatic status for BV testing (symptoms such as vaginal discharge, odor, itch) and transplant/immunocompromised status for BK/JC testing to justify molecular assays per CPB selection criteria.
- Record vaginal symptoms when ordering BV NAATs
- Document transplant or immunocompromised status for BK/JC PCR orders
Order CSF multiplex panels only with CNS signs/symptoms and concurrent cultures
CSF multiplex panels should be ordered for patients with signs or symptoms of meningitis/encephalitis and when pretest probability supports testing; document CNS signs/symptoms and consider concurrent CSF and blood cultures as recommended.
- Document meningitis/encephalitis clinical signs
- Order CSF/blood cultures alongside multiplex PCR
Document specimen type and timing on orders
Pay attention to specimen type and timing when ordering PCR tests (eg, acute‑phase serum for chikungunya RT‑PCR within first week of illness; upper respiratory tract specimens for SARS‑CoV‑2 NAAT); document specimen source and timing on the requisition.
- Specify specimen and time since symptom onset
- Use acute‑phase serum for arboviral RT‑PCR when within first week
Confirm test availability at reference/CDC labs before ordering
Some PCR tests (eg, Cyclospora, ehrlichiosis) are primarily available at reference or CDC laboratories; confirm test availability and routing before ordering and document if testing will be sent to a reference lab.
- Verify laboratory capability prior to ordering
- Document reference/CDC lab referral on requisition if applicable
Document clinical indication and select appropriate ICD‑10 codes
Document the clinical indication clearly and select ICD‑10 codes that correspond to the CPB-covered indications; incomplete or non‑matching documentation may result in denial.
- Provide concise clinical rationale on requisition
- Ensure ICD‑10 matches CPB selection criteria
Document infant age and indication for HIV PCR
When ordering HIV PCR for infant diagnosis, document the infant’s age and the clinical indication (eg, perinatal exposure) to support use of nucleic acid testing (PCR of PBMC DNA) rather than serology.
- Record infant age and exposure history
- Indicate why PCR is required vs serology
Suspected H5N1 testing — consult public health and document criteria
Testing for suspected highly pathogenic avian influenza (H5N1) should be done in consultation with public health authorities and is indicated only when severe respiratory illness plus recent travel to an affected country are present; document severity and travel history when ordering.
- Consult state/local health departments for H5N1 testing
- Document radiographic pneumonia/ARDS and travel within 10 days
Align ordering with clinical presentation for Kawasaki disease/measles
Order testing for Kawasaki disease and measles in alignment with clinical presentation; document timing for measles serology or PCR and note that positive respiratory viral PCR does not exclude Kawasaki disease.
- Document clinical diagnostic criteria for Kawasaki disease
- Time measles serology/PCR appropriately relative to symptom onset
Order arbovirus/orthopoxvirus testing based on clinical & epidemiologic context
Arbovirus and orthopoxvirus (monkeypox) testing should be guided by clinical and epidemiologic context; consult public health or reference labs as needed and document exposure/travel and characteristic findings when ordering.
- Document epidemiologic risk factors and lesion characteristics for monkeypox
- Use public health/reference labs for specialized arbovirus testing
Order lesion swab PCR for monkeypox; respiratory panels for symptomatic patients
For monkeypox, order lesion swab PCR; multiplex respiratory PCR panels are generally ordered for symptomatic patients, especially those who are immunocompromised or high‑risk — document symptoms and risk status when placing the order.
- Order lesion swab for monkeypox PCR
- Reserve respiratory multiplex panels for symptomatic, high‑risk or immunocompromised patients
Not Covered / Experimental & Investigational
COVID‑19 testing performed solely for non‑clinical reasons (for example, testing required for work, school, or recreational activities) is excluded under standard benefit plans and may be denied if billed as medically necessary clinical testing.
The CPB enumerates numerous qualitative and quantitative PCR assays and multiplex panels that are considered experimental/investigational and not covered because evidence is insufficient to establish clinical utility; consult the policy lists for specific agents and panels when determining coverage.
Reiterating policy exclusions: C. difficile toxin gene PCR (CPT 87493) is not covered when used in asymptomatic persons or as a routine test of cure and such uses may result in claim denial.
MTHFR gene analysis (CPT 81291) is listed among CPT codes not covered for the indications addressed in this CPB.
The policy lists specific CPT/HCPCS codes and routine screening indications that are not covered (for example, certain pharyngitis panel codes or routine trichomonas screening in asymptomatic individuals); providers should map the claim codes to the CPB selection criteria to verify coverage.
Consumer-oriented commercial panels and certain organism‑quantification assays (for example, EoGenius, uBiome SmartGut, SmartJane, SmartFlu, Explorer) are explicitly excluded from routine coverage in the CPB unless otherwise stated.
Routine PCR testing for bacterial vaginosis is considered investigational or of uncertain clinical utility by multiple guideline bodies; use should be limited to symptomatic patients and validated assays with demonstrated clinical value.
The policy does not support use of investigational molecular assays that lack clinical validation or that may over-diagnose colonization rather than infection; laboratory‑developed tests should be internally validated before clinical use and claims should reflect validated, guideline-supported indications.
PCR assays that are not routinely available or validated in clinical laboratories (for example, PCR for Brucella species, Burkholderia, certain caliciviruses, or unvalidated fungal PCRs) are not supported for routine clinical testing and may be considered investigational.
PCR testing for the detection of metastases from cervical cancer is not supported by the cited NCCN/NCI guidelines and therefore is not considered an appropriate use of PCR in that context.
Dried blood spot (DBS) PCR as a standalone newborn screening method for congenital CMV is not supported in this CPB due to low sensitivity reported in studies compared with saliva rapid culture.
EoGenius and other gene expression / microRNA assays (e.g., 96‑gene arrays) are characterized as investigational and require further validation; they are not established as routine diagnostic replacements.
PCR testing for gonorrhea on non‑recommended specimen sites (vaginal, rectal, conjunctival, pharyngeal) is not recommended by CDC guidance and may not be supported; similarly, routine PCR testing for some agents (e.g., HBoV, HHV‑7) is limited to research and does not usually change management.
Routine PCR testing for HHV‑7 and HHV‑8 is limited to research settings and is of limited clinical utility in most cases; diagnosis typically will not change patient management.
Screening for subclinical genital HPV infection using DNA or RNA tests is not recommended; HPV nucleic acid testing is primarily an adjunct to cervical cancer screening in specified clinical contexts (e.g., women >30 years, ASCUS triage).
RT‑PCR testing to detect circulating melanoma cells or micrometastases is considered experimental/investigational and is not supported as routine diagnostic testing.
PCR testing for Lyme disease (Borrelia burgdorferi) is not validated for routine diagnosis or monitoring and is considered investigational/unsupported for routine clinical use per available guidelines.
Broad multiplex or 'shotgun' panels that test for many pathogens in patients with nonspecific symptoms (for example, malaise or chronic fatigue) are not medically necessary and may be denied; testing should be directed by clinical presentation and suspicion for specific pathogens.
PCR testing for Mycoplasma fermentans and for nanobacteria is considered experimental/investigational and therefore not covered for routine clinical use.
The CPB indicates that PCR is not established for routine management of several infections (for example, parainfluenza, Proteus mirabilis, Plesiomonas shigelloides) where standard culture, serology, or other diagnostic methods remain the recommended approaches.
Definitions
Frequency Limits and Monitoring
Background and Clinical Considerations
This policy covers a broad set of infectious, genetic, oncologic, and transplant‑related indications where PCR testing may be clinically relevant. Coverage varies by qualitative/multiplex versus quantitative assays and is contingent on meeting the specific selection criteria and documented ICD‑10 diagnoses required by the CPB.
Selected clinical indications include pathogen‑specific PCR uses (eg, CSF pathogen panels for suspected meningitis/encephalitis, GI panels for prolonged/severe infectious diarrhea, respiratory multiplex panels for high‑risk or immunocompromised patients), quantitative viral load testing for transplant monitoring (eg, CMV, EBV, BK), and molecular tests for hematologic malignancy monitoring (eg, AML translocations, BCR‑ABL). Coverage depends on meeting the CPB selection criteria and submitting appropriate documentation and ICD‑10 coding.
Respiratory, gastrointestinal, vaginal, sepsis, and other infection‑related multiplex panels are covered only when the policy's selection criteria are met and the submitted CPT/HCPCS codes are linked to the required ICD‑10 diagnoses. Providers should ensure ordering documentation demonstrates that results will guide therapy and that the correct panel size/code maps to the clinical indication.
Agent‑specific PCR utility and limitations are described throughout the CPB: some assays (for example, CSF multiplex panels, BK/JC quantification in transplant recipients, and certain oncologic fusion transcript PCRs) have established clinical roles, while many other pathogen‑ or condition‑specific PCR tests remain experimental or of limited clinical usefulness pending further validation.
Additional Definitions
Revision History
Policy last reviewed (document 'last_review' date).
Policy originally became effective on 2002-09-24.
Policy status marked CURRENT with next review scheduled 2024-07-11.
OpenPayer is powered by Trek Health's payer performance platform. Trek continuously ingests, validates, and normalizes Transparency in Coverage data alongside payer policies and other commercial payer data to create a structured payer intelligence foundation. OpenPayer uses this foundation to deliver personalized search results, dynamically generated policy pages, and tailored policy monitoring based on each user's payers, specialties, billing codes, and areas of interest. The same intelligence powers broader payer performance workflows, including reimbursement benchmarking, contract evaluation, payer negotiations, and financial decision-making.