SARS-CoV-2 Genomic Analysis to FHIR

Overview

This project develops a platform-agnostic pipeline for SARS-CoV-2 sequencing data from Illumina, Oxford Nanopore to identify variants, assign Pango lineage and Nextstrain clade. Adapted from nf-core/viralrecon, the workflow converts its results into HL7 FHIR Genomics resources so that both the genomic findings and the clinical metadata attached to them can be shared in a structured, interoperable format.

Workflow

The pipeline automatically detects whether the input is Illumina or Nanopore and routes samples to the correct sub-workflow.
Performs quality control, trimming, and human read depletion before alignment.
Handles amplicon data with per-sample primer scheme detection and clipping.
Calls variants and builds consensus genomes with platform-specific tools then annotates them against the reference for gene, HGVS, and Sequence Ontology.
Assigns Pango lineage, Nextstrain clade, WHO variant label, and QC.
Converts annotated results into HL7 FHIR R4 resources including variant observations, a SARS-CoV-2 panel observation, lineage and genome quality observations, and a diagnostic report.
Merges the genomic bundle with patient, organization, and practitioner metadata.

Why This Matters Clinically

SARS-CoV-2 genomic surveillance is limited by how fast a genome travels from swab to a shareable, interpretable record. This pipeline targets that gap.

Timeliness is the binding constraint, not sequencing volume alone. Analysis of 189 countries found that sequencing around 0.5% of confirmed cases with a turnaround time below 21 days is a workable benchmark for surveillance, yet only 25% of genomes from high-income countries and 5% from low- and middle-income countries were submitted within that window (Brito et al. 2022). Turnaround matters because it changes what can be detected in time to act.

Platform heterogeneity mirrors capacity disparity. High-income countries submitted roughly ten times more sequences per COVID-19 case than low- and middle-income countries, and low-income countries sequencing a mean of about 10 genomes per week may miss a lineage circulating at up to 21.7% prevalence (Brito et al. 2022). That capacity gap is also a platform gap, with Illumina dominating well-resourced centres and Nanopore deployed at decentralized and resource-limited sites.

Missing metadata is what makes shared genomes hard to use. Across GISAID submissions, about 63% of sequences lacked demographic information, 84% lacked a sampling strategy, and more than 95% lacked patient-level clinical information, with a global average metadata completeness of 5.6 out of 10 (Chen et al. 2022). The same analysis found that more than one-third of countries with official variant counts had shared fewer than half of their VOC sequences publicly. A sequence without collection context cannot support severity, vaccine breakthrough, or transmission analyses.

FHIR interoperability connects the genome to the health system. Encoding variants, lineage, WHO variant designation, and consensus quality as HL7 FHIR Genomics resources makes them machine-readable by electronic health records, clinical decision support, and national surveillance registries without format translation.

{
  "conclusion": "SARS-CoV-2 lineage B.1.258 detected. Nextstrain clade 20A. Not designated: Lineage B.1.258 carries no WHO variant designation. Spike changes: S:T22I, S:N439K, S:D614G. Lineage assigned by nextclade 3.18.1 (database 2026-06-16--14-30-45Z). Reference genome: NC_045512.2",
  "conclusionCode": [
    {
      "text": "SARS-CoV-2 identified by whole-genome sequencing",
      "coding": [
        {
          "system": "http://snomed.info/sct",
          "code": "840533007",
          "display": "Severe acute respiratory syndrome coronavirus 2"
        }
      ]
    },
    {
      "text": "Pango lineage B.1.258"
    },
    {
      "text": "WHO variant designation: Not designated"
    }
  ]
}

{
  "code": {
    "coding": [
      {
        "system": "http://loinc.org",
        "code": "96895-8",
        "display": "SARS-CoV-2 (COVID-19) lineage [Identifier] in Specimen by Molecular genetics method"
      }
    ]
  },
  "valueCodeableConcept": {
    "coding": [
      {
        "system": "https://cov-lineages.org/lineage_list.html",
        "code": "B.1.258",
        "display": "Pango lineage B.1.258"
      }
    ],
    "text": "B.1.258"
  },
  "method": {
    "text": "nextclade 3.18.1 (database 2026-06-16--14-30-45Z)"
  },
  "component": [
    {
      "code": {
        "text": "WHO variant classification"
      },
      "valueCodeableConcept": {
        "coding": [
          {
            "system": "https://www.who.int/activities/tracking-SARS-CoV-2-variants",
            "code": "not_designated",
            "display": "Not a WHO-designated variant"
          }
        ],
        "text": "not_designated"
      }
    }
  ]
}

{
  "component": [
    {
      "code": {
        "coding": [
          {
            "system": "http://loinc.org",
            "code": "81290-9",
            "display": "Genomic DNA change (gHGVS)"
          }
        ]
      },
      "valueCodeableConcept": {
        "coding": [
          {
            "system": "http://varnomen.hgvs.org",
            "code": "NC_045512.2:g.22879C>A",
            "display": "NC_045512.2:g.22879C>A"
          }
        ]
      }
    },
    {
      "code": {
        "coding": [
          {
            "system": "http://loinc.org",
            "code": "48018-6",
            "display": "Gene studied [ID]"
          }
        ]
      },
      "valueCodeableConcept": {
        "coding": [
          {
            "system": "https://www.ncbi.nlm.nih.gov/gene",
            "code": "43740568",
            "display": "Surface glycoprotein (spike)"
          }
        ],
        "text": "S"
      }
    },
    {
      "code": {
        "coding": [
          {
            "system": "http://loinc.org",
            "code": "48005-3",
            "display": "Amino acid change (pHGVS)"
          }
        ]
      },
      "valueCodeableConcept": {
        "coding": [
          {
            "system": "http://varnomen.hgvs.org",
            "code": "QHD43416.1:p.Asn439Lys",
            "display": "QHD43416.1:p.Asn439Lys"
          }
        ],
        "text": "QHD43416.1:p.Asn439Lys"
      }
    }
  ]
}

Overview

Workflow

Why This Matters Clinically

Links