The clinical picture itself helps explain why progress has been so slow. Long COVID is strikingly heterogeneous, with manifestations that include debilitating fatigue, cognitive dysfunction often described as brain fog, and persistent respiratory compromise, all affecting multiple organ systems. Despite intensive research efforts, the underlying pathophysiological mechanisms remain elusive, and that gap in understanding has directly impeded the development of effective therapies. It is precisely this fragmentation that the special issue set out to address, assembling studies that approach the syndrome from complementary angles rather than competing hypotheses.

The first strand of evidence concerns the lungs, where structural damage from acute infection can linger long after the virus itself has cleared. A team led by Garg and colleagues examined survivors of severe COVID-19 acute respiratory distress syndrome and demonstrated that specific imaging patterns on computed tomography correlate with ongoing symptoms. In particular, reticulations and septal thickening, the fine net-like changes that appear when lung architecture is disrupted, were positively associated with symptomatic dyspnoea, the distressing breathlessness that many survivors report. The researchers also found that parenchymal and atelectatic bands, linear scars within the lung tissue, were associated with reduced forced vital capacity, a standard measure of how much air the lungs can hold.

What makes that study significant, the editors note, is that it moves beyond simply documenting that abnormalities persist. By linking individual CT imaging patterns to both symptomatic and functional measures, the work establishes concrete associations between what radiologists see on a scan and what patients actually feel and how well their lungs perform. That kind of correlation is a prerequisite for using imaging as a meaningful clinical tool in follow-up care, rather than as a descriptive curiosity. It also provides a framework for stratifying patients, since different patterns of lung injury may reflect different underlying processes and may therefore respond differently to future treatments.

A companion study in the same issue addresses a practical barrier to long-term lung surveillance: radiation dose. Devkota and colleagues evaluated ultra-low-dose CT, a technique that dramatically reduces radiation exposure compared with standard protocols, in patients recovering from moderate to severe acute COVID-19 pneumonia. Their results showed that ultra-low-dose CT is comparable to standard-dose CT in accurately detecting persistent lung abnormalities. The authors reported a diagnostic accuracy of 95.0 percent overall, rising to 98 percent among non-obese subjects. Those figures matter because repeated surveillance imaging is only feasible, and ethically justifiable, if the cumulative radiation burden can be kept low. A technique that preserves diagnostic performance while cutting exposure makes serial monitoring of recovering patients a far more realistic proposition for clinics and hospitals.

The special issue then widens the anatomical scope, because the abnormalities associated with Long COVID are not confined to the lungs. In a retrospective CT angiography study, Goksu and colleagues identified significantly enlarged carotid bodies in patients previously hospitalized with COVID-19 pneumonia. The carotid bodies are small paired organs at the bifurcation of the carotid arteries that sense hypoxaemia, low oxygen levels in the blood, and modulate sympathetic nervous system activity in response. Enlargement of these structures in post-COVID patients could reflect prolonged chemoreceptor stimulation resulting from the pathophysiological changes of Long COVID, suggesting that the syndrome’s reach extends well past the respiratory system into the machinery that regulates breathing and cardiovascular tone.

The carotid body finding also raises pointed mechanistic questions. These organs are rich in ACE2 receptors, the same molecular doorway that SARS-CoV-2 uses to enter cells, and they are central to chemoreception. That combination leaves open two possibilities that are not mutually exclusive: the enlargement may be the result of direct viral injury to the tissue, or of chronic hypoxic stimulation as the body adapts to persistently disturbed oxygen dynamics, or of both acting in concert. Disentangling those mechanisms will be important, because a viral injury model and a maladaptive stimulation model would point toward very different therapeutic strategies.

Moving from structure to immunology, Kawaguchi and colleagues investigated serological profiles in an effort to identify clinically useful biomarkers for Long COVID’s heterogeneous manifestations. Their study covered 275 patients with Omicron-related Long COVID, a cohort of particular interest because most of the world’s current infections involve Omicron-lineage viruses. The team found that nucleocapsid N-antibody titers were positively associated with acute disease severity and with antiviral immune responses. Conversely, lower titers of antibodies against the spike protein’s S-antigen correlated significantly with memory impairment, the brain fog that is among the most disabling of Long COVID’s neurocognitive symptoms, and with reduced quality of life.

Those results expand understanding of the immunological underpinnings of neurocognitive symptoms and suggest that a blood test capable of flagging patients at risk of cognitive sequelae may one day be feasible. The authors are careful, however, to flag the interpretive pitfalls. Vaccination status and the time elapsed since infection both shape antibody profiles, and any biomarker built on serology must account for those variables before it can be trusted in the clinic. The caution is a reminder that in a post-vaccine, repeatedly exposed population, the immune signature of Long COVID is layered over a complex history of immunological events.

Finally, the issue turns from diagnosis to treatment, and to an organ system that has become a focal point of Long COVID research: the gut. Amoroso and colleagues conducted a randomized, double-blind, placebo-controlled trial in which patients with Long COVID received four weeks of probiotic supplementation or placebo. The probiotic arm achieved a significantly greater reduction in clinically relevant fatigue scores than placebo, with 24.24 percent of treated patients reaching that threshold compared with 6.06 percent on placebo. Crucially, the clinical improvement was accompanied by concurrent changes in gut microbial taxa, in microbiota-associated metabolites and in immune-related pathways, offering a plausible biological mechanism rather than an unexplained statistical signal. The editors caution that the modest sample size warrants restraint, but they describe the result as an exciting indication that gut-directed therapies deserve serious consideration in the Long COVID treatment landscape.

Read as a whole, the five studies converge on a single conclusion that the editors of the issue emphasize: Long COVID is a syndrome of genuine complexity, and no single measurement, organ or discipline will capture it alone. Continued research using diverse and integrated methodologies, spanning imaging, immunological, physiological and microbiome-related measures, will be essential for improving the characterization, monitoring and treatment of the condition. Much remains unresolved in elucidating the underlying causes of Long COVID, let alone alleviating the burden it places on patients and health systems. But the trajectory on display in this collection, from structural imaging that predicts symptoms, to immune markers that track cognitive decline, to microbial interventions that measurably reduce fatigue, illustrates how multidisciplinary work can turn a bewildering syndrome into a set of tractable, testable questions. The British Journal of Biomedical Science has signalled its commitment to serving as a forum for exactly that kind of rigorous, cross-cutting research, and the field will need more of it if the legacy of the pandemic is to be met with answers rather than open questions.

Subject of Research: Multidisciplinary biomedical research on the pathophysiology, biomarkers and treatment of Long COVID

Article Title: Editorial: Long COVID in the biomedical sciences

Article References: Kunnath, A. P., Kavanagh, O., & Tan, S. C. (2026). Editorial: Long COVID in the biomedical sciences. British Journal of Biomedical Science, 83, Article 17822. https://doi.org/10.3389/bjbs.2026.17822

Image Credits: AI Generated

DOI: 10.3389/bjbs.2026.17822

Keywords: Long COVID, PASC, SARS-CoV-2, computed tomography, carotid body, serological biomarkers, brain fog, probiotics, gut microbiome, fatigue, ARDS, British Journal of Biomedical Science

The cat arrived at the Colorado State University Veterinary Teaching Hospital after its owner noticed a growing mass in the neck. Two weeks earlier, the family veterinarian had measured it at 3.7 by 2.1 centimeters, but by the time of the referral examination it had expanded to roughly 5 centimeters long and 4 centimeters wide, filling the ventral part of the neck. The owner also described six months of gradually worsening snoring noises, lethargy, and a mildly reduced appetite. On physical examination, the cat was bright and alert but showed intermittent stertor and stridor, the harsh breathing sounds produced when the upper airway is partially obstructed. A large, fixed, painless mass dominated the left side of the throat.

Advanced imaging revealed the true scale of the problem. A triple-phase computed tomography scan showed a lobular, strongly and heterogeneously enhancing soft tissue mass measuring 5.2 by 4.1 by 3.9 centimeters that completely enveloped the common carotid artery, the main vessel supplying the head. The mass compressed and displaced the thyroid glands, pushed the pharynx, larynx, and hyoid apparatus markedly to the right, and extended toward the skull base near the tympanic bulla. Multiple branching vessels penetrated deep into the tumor interior, a hallmark of the rich blood supply characteristic of chemoreceptor tissue. A board-certified radiologist judged the growth pattern inconsistent with thyroid carcinoma, and the differential diagnosis narrowed to a carotid body tumor, a metastatic lymph node mass, or a primary soft tissue sarcoma.

Fine-needle aspiration cytology of the mass showed an epithelial neoplasm with endocrine and neuroendocrine morphology: densely cohesive clusters of round to polygonal cells with scant basophilic cytoplasm, ropey chromatin, and absent nucleoli. Critically, immunocytochemical staining for Thyroid Transcription Factor-1, a marker of thyroid origin, came back negative, making a thyroid tumor far less likely. The absence of any secretory phenotype, no hyperthyroidism and no hypercalcemia on bloodwork, further separated this tumor from the functional thyroid and parathyroid carcinomas that typically arise in the feline neck. Taken together with the tumor’s location hugging the carotid bifurcation, the team concluded the mass was most consistent with a paraganglioma of the carotid body, a tumor type never before documented in a cat.

That diagnosis matters because carotid body paragangliomas, also called chemodectomas, arise from the chemoreceptor organs that sense oxygen and carbon dioxide in blood. They are well described in dogs and humans, in whom they are notoriously invasive, enveloping major vessels at the base of the skull and causing retropharyngeal masses, difficulty swallowing, respiratory distress, stridor, gagging, and laryngeal paralysis. This cat’s presentation, including left-sided laryngeal paralysis and bilateral tonsillar protrusion noted on a sedated oral exam, matched that pattern almost exactly. Yet in cats, paragangliomas had only ever been reported in the abdomen, around the kidneys and retroperitoneum, at the aortic body, in the heart, and in the orbit, never at the carotid body, despite the fact that cats possess these normal anatomic structures.

Surgery was off the table. After reviewing the imaging, a board-certified surgical oncologist judged the mass unresectable because of its extensive involvement of the carotid artery, larynx, and hyoid apparatus, and warned that any biopsy attempt risked catastrophic hemorrhage and airway-compromising swelling. The oncology team instead offered definitive-intent stereotactic body radiotherapy, a technique that delivers ablative radiation doses in a handful of fractions with submillimeter targeting. The rationale was technical as much as biological: compared with a conventional 16 to 20 fraction course, a three-fraction protocol meant only three anesthesia episodes for a cat that was already difficult to intubate, with far less cumulative acute toxicity to the pharynx and trachea.

The treatment plan was built on the treatment planning system using pre- and post-contrast CT sequences. The gross target volume encompassed all abnormal contrast-enhancing tissue and abnormal vasculature, including the left tonsil. A 2-millimeter planning target volume expansion accounted for setup uncertainty, but was cropped away from organs at risk, the skin, pharynx, trachea, esophagus, brain, spinal cord, and eyes, to prioritize normal tissue sparing. Two coplanar arcs of 6-megavolt photons delivered 10 Gy per day for three consecutive days, for a total of 30 Gy, using volumetric modulated arc therapy. Dosimetry was calculated with the Acuros algorithm, and quality assurance with an electronic portal imaging device achieved a gamma passing rate above 95 percent at 3 millimeters and 3 percent, confirming the planned dose distribution matched delivery.

The response was fast and durable. Two weeks after the final fraction, the tumor had shrunk roughly 30 percent in length and 37.5 percent in width on caliper measurement, the cat’s breathing signs had resolved, and its appetite had normalized. By three months, the mass was no longer palpable at all. Ultrasound at 15 months showed a residual soft tissue structure surrounding the left carotid artery, and a 24-month scan by a second radiologist documented a highly vascular mass measuring 3.2 by 2.2 centimeters, a persistent partial response under RECIST 1.0 criteria with no local or systemic progression for 755 days. Thyroid hormone values, which had been suppressed by euthyroid sick syndrome at presentation, returned to and remained within normal ranges through repeated monitoring.

Tolerability was equally striking. The only radiation-related adverse event was leukotrichia, whitening of the fur in the treatment field, graded as a mild VRTOG grade 1 late skin toxicity. A transient episode of hiding, drooling, and poor appetite after the first fraction resolved when gabapentin was stopped and an anti-nausea drug given. Later weight loss at 20 to 24 months was traced to newly diagnosed chronic kidney disease and a progressively enlarging hepatic cystadenoma, both judged unrelated to the cervical tumor or its radiation. At the time of manuscript submission, the cat was alive with no evidence of disease progression, more than two years after treatment.

The authors caution that without surgical histopathology, which was deliberately avoided given the hemorrhage risk, the diagnosis remains presumptive; cytology alone cannot fully exclude ectopic thyroid or parathyroid tumors, and the definitive classification would have required immunohistochemistry on tissue. Even so, the convergence of imaging, cytomorphology, TTF-1 negativity, and the non-secretory clinical picture makes carotid body origin the leading explanation. The team recommends that carotid body paraganglioma be added to the differential list for feline cervical neuroendocrine masses, and that endocrine function screening be built into both initial work-up and long-term follow-up, since radiation can induce endocrine changes, as seen in dogs. For veterinary oncologists facing cats with otherwise untreatable advanced neck tumors, the report suggests external beam radiotherapy, and stereotactic body radiotherapy in particular, can now be offered as a definitive local option rather than a palliative afterthought.

Beyond this single patient, the case fills a genuine gap in comparative oncology. In human medicine, carotid body paragangliomas are the most common head and neck paragangliomas, and while surgery remains the mainstay, definitive radiotherapy and stereotactic techniques are established alternatives for tumors encasing the carotid artery, where resection carries stroke risk. In dogs, these tumors are typically encountered as incidental, slowly growing masses at the heart base, and complete surgical excision is rarely achieved. The feline report suggests that the radiotherapy experience accumulated in those species may translate across species lines.

The diagnostic work-up also illustrates a subtlety of feline endocrinology. The cat’s low total thyroxine with inappropriately low thyroid-stimulating hormone was interpreted as euthyroid sick syndrome, a reversible suppression of thyroid hormone values caused by non-thyroidal illness, rather than true hypothyroidism. Recognizing this pattern prevented a misdiagnosis that could have steered the work-up toward thyroid disease, and the later normalization of thyroid values on follow-up confirmed the interpretation.

Finally, the durability of response matters for fractionation debates in veterinary radiation oncology. Ablative hypofractionated schedules trade convenience and reduced anesthesia exposure against uncertainty about late toxicity, and this report, with more than two years of follow-up and only grade 1 leukotrichia, provides early evidence that such schedules can be both effective and well tolerated in cats with deeply seated cervical disease.

Subject of Research: First reported use of stereotactic body radiotherapy to treat a suspected feline carotid body paraganglioma

Article Title: Locally advanced cervical neuroendocrine tumor of presumptive carotid body origin in a cat treated with stereotactic body radiotherapy (SBRT): a case report

Article References: Gualtieri, P., Benedict, W. M., Tremolada, G., & Boss, M.-K. (2026). Locally advanced cervical neuroendocrine tumor of presumptive carotid body origin in a cat treated with stereotactic body radiotherapy (SBRT): a case report. Veterinary Oncology, 3(1), Article 18. https://doi.org/10.1186/s44356-026-00071-6

Image Credits: AI Generated

DOI: 10.1186/s44356-026-00071-6

Keywords: cat, carotid body, paraganglioma, chemodectoma, neuroendocrine tumor, SBRT, stereotactic body radiotherapy, veterinary oncology, VMAT, cervical mass, TTF-1, radiation therapy