When polymerase chain reaction does not help: cytomegalovirus pneumonitis associated with very low or undetectable viral load in both blood and bronchoalveolar lavage samples after lung transplantation

Abstract

Cytomegalovirus (CMV) pneumonitis occurs frequently among solid organ transplant recipients and is classically associated with significant viral replication in both blood and bronchoalveolar lavage (BAL) samples. We present a case of a 64-year-old lung transplant recipient who presented with CMV pneumonitis that was diagnosed based on the association of viral inclusion in the BAL sample, rapid response to ganciclovir, and absence of other infectious etiology. Surprisingly, we observed very low or undetectable viral load both in blood and BAL samples. Diagnosis of CMV pneumonitis should rely on the association of clinical, pathological, radiological, and microbiological signs, while quantitative nucleic acid amplification testing should be interpreted with caution.

Virus-specific memory T cell responses unmasked by immune checkpoint blockade cause hepatitis

“…Reactivation of CMV causes cellular injury through the cytopathic effect of viral replication, but more conspicuously through triggering T cell immunity. Pneumonitis in transplant recipients illustrates how CMV-reactive T cells provoke extensive, life-threatening inflammation despite low-level viral replication 22 . Even in anatomical locations from which T cells are normally excluded, such as the retina, T cell-mediated responses significantly contribute to CMV-related disease.…”

Cytomegalovirus (CMV) DNA Quantitation in Bronchoalveolar Lavage Fluid From Hematopoietic Stem Cell Transplant Recipients With CMV Pneumonia

“…In 1988, CMV detection by rapid culture of bronchoalveolar lavage (BAL) fluid became the mainstay of diagnosis for CMV pneumonia [4]. However, while CMV DNA-specific PCR is widely used as a surveillance method for blood and serum specimens and because many laboratories have largely abandoned traditional virologic techniques, the usefulness of quantitative PCR of BAL as a diagnostic tool for CMV pneumonia is poorly defined [5][6][7][8], and the recently updated international definition guidelines provide only limited definitive evidence for using PCR as an acceptable test for disease diagnosis [9,10]. The key reason for the dilemma is that the presence of CMV DNA may not constitute disease, owing to the well-described phenomenon of pulmonary CMV shedding [11,12].…”

Prediction of immune checkpoint blockade‐related hepatitis in metastatic melanoma patients

“…Reactivation of latent viruses characteristically follows immune compromise and triggers T‐cell immunity [13, 14]. Low‐level and compartmentalized CMV reactivation can provoke extensive and life‐threatening clinical manifestations [15]. However, we were unable to detect replicating virus in blood, saliva, or stool samples from patients with elevated CD4 + T EM at baseline.…”