Rhinovirus genetic diversity among immunosuppressed and immunocompetent patients presenting with a severe respiratory infection

To the Editor,

Three species of HRV are currently known: A, B and C. HRV C has been detected primarily in children and immunosuppressed patients in association with severe disease.1, 2, 3, 4, 5, 6, 7 HRV species and their associated clinical outcomes in different patient groups are not well defined.8, 9, 10

We evaluated the occurrence and clinical outcomes of HRV species infections in two distinct populations, immunocompetent and immunosuppressed patients.

A total of 400 swab/nasal wash samples were collected from two populations of hospitalized patients at Hospital São Paulo. Adults patients in a Hematopoietic Stem Cell Transplantation program (HSCT, n  = 202) and patients (children and adults) hospitalized due to severe acute respiratory syndrome who were suspected of having an influenza A (H1N1)pdm09 infection (SII – suspect of influenza virus infection, n  = 198).

The inclusion criteria for HSCT was the presence of acute respiratory illness of probable viral etiology. For the SII population was suspicion of severe influenza A (H1N1)pdm09 virus infection with a negative test for this virus.

Criteria for a severe clinical outcome were admission to the intensive care unit (ICU), length of hospitalization and mortality.

Viral RNA was extracted using the QIAamp Viral RNA Extraction Kit (Qiagen, Germany). RT-PCR was accomplished as described previously.¹¹ DNA sequencing was performed with the BigDye Terminator Cycle Sequencing Ready Reaction Kit (Applied Biosystems, USA). The phylogenetic relationships were assessed by maximum likelihood (Topali software v2.5.). All data were analyzed with SPSS version 11.0 (SPSS Inc., USA).

HRV was detected in 11% (22/202) of HSCT patients and in 31.3% (62/198) of SII patients (p  < 0.001). The hospitalization length was longer for the HRV positive cases from the HSCT group than for those of the SII group (p  < 0.001) but no significant differences were identified for ICU admission or mortality.

A phylogenetic analysis was performed for 92% (77/84) of the samples and 54.6% (42/77) were HRV A, 11.7% (9/77) were HRV B, and 33.8% (26/77) were HRV C. HRV C was predominant among children but for adult patients’ species distribution was similar. Indeed the clinical outcomes were similar (p  > 0.05) for both patient groups regardless of the species (Table 1 ) and when each species was compared between the two groups.

Table 1.

HRV species distribution, ICU admission, hospitalization time and mortality among the HSCT and SII patients.

	HSCT
	HRV A (%)	HRV B (%)	HRV C (%)	p	Total (%)
ICU admission
Yes	2 (50.0)	0 (0.0)	2 (50.0)	0.49	4 (23.5)
No	8 (61.5)	2 (15.4)	3 (23.1)		13 (76.5)
Total	10 (58.8)	2 (11.8)	5 (29.4)		17 (100.0)
Time of hospitalization
Mean	11.1	21.5	30.2	0.23
Median	0.5	21.5	24.0
Range	0–45	12–31	1–51
n	8	2	5
SD	17.2	13.4	21.2
Death
Yes	3 (100.0)	0 (0.0)	0 (0.0)	0.32	3 (16.7)
No	8 (53.3)	2 (13.3)	5 (33.3)		15 (83.3)
Total	11 (61.1)	2 (11.1)	5 (27.8)		18 (100.0)

	SII
	HRV A	HRV B	HRV C	p	Total
ICU admission
Yes	9 (47.4)	3 (15.8)	7 (36.8)	0.74	19 (37.3)
No	18 (56.3)	3 (9.4)	11 (34.4)		32 (62.7)
Total	27 (53.9)	6 (11.8)	18 (35.3)		51 (100.0)
Time of hospitalization
Mean	10.2	9	11.3	0.94
Median	7	9	6
Range	1–68	5–12	1–73
n	25	6	17
SD	13.3	2.8	17.7
Death
Yes	2 (66.7)	0 (0.0)	1 (33.3)	0.78	3 (5.9)
No	25 (52.1)	6 (12.5)	17 (35.4)		48 (94.1)
Total	27 (52.9)	6 (11.8)	18 (35.3)		51 (100.0)

SD, standard deviation; HSCT, patients in the Hematopoietic Stem Cell Transplantation program; SII, patients suspected of having an influenza virus infection.

Some authors12, 13 did not observe any difference in the infection outcomes of HRV and influenza A (H1N1)pdm09 infections, as defined by intensive care unit admission and mortality, but species were not considered in their study. In the present study we attempted to identify differences in clinical outcomes in more detail using an HRV genotyping analysis.

The severe outcomes previously linked to HRV C infection1, 8, 9 and not the other two species should be reevaluated. Parameters such as age, immune status, and enrollment of community or hospitalized patients, may have differed between the studies. In this context, we reported elsewhere that younger ages may have a greater association with HRV C occurrence in both community and hospital settings.¹⁰

In conclusion, HRV can play a role in severe respiratory infections, but the outcomes are not dependent on the viral agent or host factors, such as species diversity or immune status.

Contributions

Ellen Ricci Monteiro da Silva and Aripuana Watanabe authors contributed in study design, laboratory tests, data analysis, manuscript writing and revision. Emerson Carraro, Celso Granato and Nancy Bellei authors involved in study design, data analysis, manuscript writing and revision.

Funding

Financial support of Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP Project number: 2010/09978-5) and Coordenação de aperfeiçoamento de pessoal de nível superior (CAPES).

Competing interests

None of the authors has declared competing interests.

Ethical approval

The present study was approved by the Ethics Committee of Sao Paulo Hospital and the Federal University of Sao Paulo (number: 0710/10).