H1N1-09 Infections In Patients with Hematologic or Oncologic Malignancies: A Single-Centre Experience
Authors: Shayegi Nona , Sockel Katja , Pöhlmann Christoph , Laniado Michael , Bornhaeuser Martin , Ehninger Gerhard , Schetelig Johannes 
Published: October 2019

Abstract
Abstract 4866

Introduction
The first pandemic of the 21st century was caused by the novel influenza A (H1N1) virus, now known as pandemic H1N1-09 virus. Its first wave reached Germany in autumn 2009. Though for the German public health sector this pandemic was a challenge, a state of national emergency could not be recognized. A popular current believe is that the threat by this pandemic had been overestimated by national and international health care experts. Here, we report our experience with the pandemic H1N1-09 virus in hematologic patients when the first wave hit Germany between December 2009 and February 2010.

Methods
Viral diagnostic for all patients was performed in a central virologic laboratory. All patients with at least one sample tested positive by PCR for H1N1-09 between October 2009 and March 2010 were included into the analysis. Samples were obtained by nasal wash, nasopharyngeal swab or broncho-alveolary lavage. The medical charts of all patients with H1N1-09 infection were reviewed systematically.

Results
15 patients with underlying hematologic diseases (10 male and 5 female) with a median age of 52 years (range 18–70 years) were tested positive for H1N1-09 virus by PCR in our department. Notably, in 12 Patients H1N1-09 was nosocomially acquired after a median of 16 days hospitalization (range 6 – 42 days). 13 patients (87%) got infected between December 2 and December 29. At the time of infection all patients were immunocompromised with 11 patients being cytopenic after chemotherapy and four patients after allogeneic hematopoietic cell transplantation (HCT) among the latter two patients were in aplasia after allogeneic HCT (day +5 and day +11 after HCT). CT scan was performed in 8 patients at the time of diagnosis. Seven patients presented with signs of atypical pneumonia on CT scan. Ground glass opacity, consolidation, airway wall thickening, airway dilatation, pleural effusion and lymphadenopathy were common findings.
In 10 patients viral clearance was monitored by RT-PCR. The median duration of viral shedding was 10 days (range 4 – 41 days). Prolonged viral persistence was associated with severe lung injury. All patients received Oseltamivir as first-line therapy, except three patients, who died prior to the confirmation of the diagnosis by RT-PCR. Simultaneously broad spectrum antibiotics and antimycotics were administered.
5 patients (33%) with respiratory failure needed invasive mechanical ventilation (MV) at the time of the H1N1-09 infection. Three out of these patients died.
Within a follow up of 6 months eight patients have died. Six patients (40%) have died from the infection. Among these three patients died from fulminant pulmonary failure whereas three patients died several weeks after H1N1-09 infection from subsequent respiratory or multiorgan failure. The impact on indirect mortality cannot yet be fully assessed, since in some patients the infection caused significant delay of anti-leukemic therapy and acquired comorbidities resulted in dose-reductions of chemotherapy.

Conclusions
In contrast to largely mild infections in the healthy German population pandemic H1N1-09 pneumonia represented a life-threatening infection for hematologic patients associated with a high mortality due to acute respiratory failure, late pulmonary complications and delay of antitumor treatment.
One alarming finding was the frequency of nosocomial infections. This observation points to the possibility of transmission of the virus from patient to patient, visitors to patient or even from medical staff to patient. With this observation in our institution patients admitted to hospital were put under quarantine before they were allowed to be accommodated in a double room in the hematologic unit. Transmission of the virus from asymptomatic staff or visitors to patient is another major concern. The suspected vaccination rate of medical staff in Germany was less than 20%. Especially, when asymptomatic or mild H1N1 infections occur - as it was the case in Germany – the medical staff and visitors could become important vectors of infection. The most effective measure against this threat is active immunization of visitors prior to patient contact and medical staff in hematologic units.

Disclosures:
No relevant conflicts of interest to declare.