Another case of “European hantavirus pulmonary syndrome” with severe lung, prior to kidney, involvement, and diagnosed by viral inclusions in lung macrophages

Abstract

Puumala virus (PUUV) is considered a classic Old World etiologic agent of nephropathia epidemica (NE), or hemorrhagic fever with renal syndrome (HFRS). HFRS is considered to be distinct from hantavirus (cardio-)pulmonary syndrome (HPS or HCPS), described in the New World. Here, we report a severe case, which fulfilled most, if not all, Centers for Disease Control and Prevention (CDC) criteria for HPS, needing non-invasive ventilation and subsequent acute hemodialysis. However, the etiological agent was PUUV, as proved by serological testing, real-time polymerase chain reaction (PCR), and sequencing. Viral antigen was detected by specific anti-PUUV immunostaining, showing, for the first time, greenish intracytoplasmic inclusions in bronchoalveolar lavage (BAL) macrophages. This case definitely confirms that HPS can be encountered during PUUV infections. Interestingly, special findings could render the diagnosis easier, such as greenish homogeneous cytoplasmic inclusions, surrounded by a fine clear halo in BAL macrophages. Therefore, although the diagnosis remains difficult before the onset of renal involvement, the occurrence of severe respiratory failure mimicking community-acquired pneumonia must alert the clinician for possible HPS, especially in endemic areas.

Clinical characterization of two severe cases of hemorrhagic fever with renal syndrome (HFRS) caused by hantaviruses Puumala and Dobrava-Belgrade genotype Sochi

“…In contrast, PUUV disease exhibits a low CFR of less than 1% [31]. However, diseases caused by DOBV-Sochi and PUUV infection may also differ individually and cases of severe hantavirus disease due to PUUV infection were reported [14, 32, 33]. We compared two severe hantavirus infections caused by these two different virus species, PUUV and DOBV-Sochi.…”

“…Interestingly, the pathogenicity of related viruses of DOBV genotypes differs enormously with case fatality rates (CFRs) between 0.3%-0.9% for DOBV genotype Kurkino and 14.5% for DOBV genotype Sochi [13]. In addition to severe courses that are linked to specific virus species or genotypes, several serious cases were reported for infection with PUUV that usually causes a milder form of hantavirus disease [14, 15]. These infections often involve extrarenal manifestations [16, 17].…”

Spatio‐temporal analysis of Nova virus, a divergent hantavirus circulating in the European mole in Belgium

“…Although the organ tropism can differ in both clinical presentations, an apparent overlap of symptoms is occasionally noted (Peters & Khan ; Gizzi et al . ). Hantavirus disease, a more suitable name for all clinical manifestations associated with hantavirus infection, can be contracted upon inhalation of aerosols of saliva, urine or faeces of infected reservoirs (Clement et al .…”

Innate and adaptive immune responses against human Puumala virus infection: immunopathogenesis and suggestions for novel treatment strategies for severe hantavirus‐associated syndromes

“…). In infected humans, hantaviruses mainly target vascular endothelial cells, but they also infect epithelial cells, mononuclear phagocytes (MNP), follicular dendritic cells (DC) and likely also other types of cells . Although hantaviruses affect several cellular functions, infection with hantaviruses is not cytopathic per se .…”