Skip to main content
PMC home page
Wiley - PMC COVID-19 Collection logoLink to Wiley - PMC COVID-19 Collection
. 2009 Nov 30;82(1):1–7. doi: 10.1002/jmv.21664

Viral load in patients infected with pandemic H1N1 2009 influenza A virus

Kelvin KW To 1, Kwok‐Hung Chan 1, Iris WS Li 1, Tak‐Yin Tsang 4, Herman Tse 1, Jasper FW Chan 1, Ivan FN Hung 2, Sik‐To Lai 4, Chi‐Wai Leung 5, Yat‐Wah Kwan 5, Yu‐Lung Lau 3, Tak‐Keung Ng 6, Vincent CC Cheng 1, Joseph SM Peiris 1, Kwok‐Yung Yuen 1,✉
PMCID: PMC7167040  PMID: 19950247

Abstract

Viral shedding profile of infections caused by the pandemic H1N1 2009 influenza A virus has not been reported. The aim of this study was to determine the viral load in different body sites. Viral loads of pandemic H1N1 virus in respiratory specimens, stool, urine, and serum were determined by quantitative reverse transcriptase‐polymerase chain reaction (RT‐PCR). Respiratory specimens from patients with seasonal influenza were used as historical controls. Initial pre‐treatment viral load were compared between these two groups. Serial respiratory specimens from patients with pandemic H1N1 virus infection were obtained for analysis of viral dynamics. Twenty‐two pandemic H1N1 cases and 44 seasonal influenza historical controls were included. The mean initial viral load before oseltamivir therapy was 1.84 × 108 copies/ml for pandemic H1N1 virus compared with 3.28 × 108 copies/ml in seasonal influenza historical controls (P = 0.085). Among patients with pandemic H1N1 virus infection, peak viral load occurred on the day of onset of symptoms, and declined gradually afterwards, with no virus being detectable in respiratory specimens by RT‐PCR 8 days and by culture 5 days after the onset of symptoms respectively, except in one patient. Pandemic H1N1 virus was detected in stool and in urine from 4/9 and 1/14 patients, respectively. Viral culture was also positive from the stool sample with the highest viral load. Younger age was associated with prolonged shedding in the respiratory tract and higher viral load in the stool. Data from this quantitative analysis of viral shedding may have implications for formulating infection control measures. J. Med. Virol. 82:1–7, 2010. © 2009 Wiley‐Liss, Inc.

Keywords: pandemic, urine, stool, serial

REFERENCES

  1. Boivin G, Coulombe Z, Wat C. 2003. Quantification of the influenza virus load by real‐time polymerase chain reaction in nasopharyngeal swabs of patients treated with oseltamivir. J Infect Dis 188: 578–580. [DOI] [PubMed] [Google Scholar]
  2. Buchy P, Mardy S, Vong S, Toyoda T, Aubin JT, Miller M, Touch S, Sovann L, Dufourcq JB, Richner B, Tu PV, Tien NT, Lim W, Peiris JS, Van der Werf S. 2007. Influenza A/H5N1 virus infection in humans in Cambodia. J Clin Virol 39: 164–168. [DOI] [PubMed] [Google Scholar]
  3. Centers for Disease Control and Prevention . 2009. Serum cross‐reactive antibody response to a novel influenza A (H1N1) virus after vaccination with seasonal influenza vaccine. MMWR 58: 521–524. [PubMed] [Google Scholar]
  4. Chan KH, Peiris JSM, Lim W, Nicholls JM, Chiu SS. 2008a. Comparison of nasopharyngeal flocked swabs and aspirates from pediatric patients for rapid diagnosis of respiratory viruses. J Clin Virol 42: 65–69. [DOI] [PubMed] [Google Scholar]
  5. Chan KH, Yam WC, Pang CM, Chan KM, Lam SY, Lo KF, Poon LL, Peiris JS. 2008b. Comparison of the NucliSens easyMAG and Qiagen BioRobot 9604 nucleic acid extraction systems for detection of RNA and DNA respiratory viruses in nasopharyngeal aspirate samples. J Clin Microbiol 46: 2195–2199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cheng VC, Hung IF, Tang BS, Chu CM, Wong MM, Chan KH, Wu AK, Tse DM, Chan KS, Zheng BJ, Peiris JS, Sung JJ, Yuen KY. 2004a. Viral replication in the nasopharynx is associated with diarrhoea in patients with severe acute respiratory syndrome. Clin Infect Dis 38: 467–475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cheng VC, Tang BS, Wu AK, Chu CM, Yuen KY. 2004b. Medical treatment of viral pneumonia including SARS in immunocompetent adult. J Infect 49: 262–273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chowell G, Bertozzi SM, Colchero MA, Lopez‐Gatell H, Alpuche‐Aranda C, Hernandez M, Miller MA. 2009. Severe respiratory disease concurrent with the circulation of H1N1 influenza. N Engl J Med 381: 674–679. [DOI] [PubMed] [Google Scholar]
  9. Chu CM, Poon LL, Cheng VC, Chan KS, Hung IF, Wong MM, Chan KH, Leung WS, Tang BS, Chan VL, Ng WL, Sim TC, Ng PW, Law KI, Tse DM, Peiris JS, Yuen KY. 2004. Initial viral load and the outcomes of SARS. CMAJ 171: 1349–1352. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. de Jong MD, Simmons CP, Thanh TT, Hien VM, Smith GJ, Chau TN, Hoang DM, Chau NV, Khanh TH, Dong VC, Qui PT, Cam BV, Ha do Q, Guan Y, Peiris JS, Chinh NT, Hien TT, Farrar J. 2006. Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia. Nat Med 12: 1203–1207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Frayha H, Castriciano S, Mahony J, Chernesky M. 1989. Nasopharyngeal swabs and nasopharyngeal aspirates equally effective for the diagnosis of viral respiratory disease in hospitalized children. J Clin Microbiol 27: 1387–1389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hall CB, Douglas RG Jr, Geiman JM, Meagher MP. 1979. Viral shedding patterns of children with influenza B infection. J Infect Dis 140: 610–613. [DOI] [PubMed] [Google Scholar]
  13. Hatakeyama N, Suzuki N, Yamamoto M, Kuroiwa Y, Hori T, Mizue N, Tsutsumi H. 2006. Detection of BK virus and adenovirus in the urine from children after allogeneic stem cell transplantation. Pediatr Infect Dis J 25: 84–85. [DOI] [PubMed] [Google Scholar]
  14. Hayden FG, Fritz R, Lobo MC, Alvord W, Strober W, Straus SE. 1998. Local and systemic cytokine responses during experimental human influenza A virus infection. Relation to symptom formation and host defense. J Clin Invest 101: 643–649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hayden FG, Treanor JJ, Fritz RS, Lobo M, Betts RF, Miller M, Kinnersley N, Mills RG, Ward P, Straus SE. 1999. Use of the oral neuraminidase inhibitor oseltamivir in experimental human influenza: Randomized controlled trials for prevention and treatment. JAMA 282: 1240–1246. [DOI] [PubMed] [Google Scholar]
  16. Hung IF, Cheng VC, Wu AK, Tang BS, Chan KH, Chu CM, Wong MM, Hui WT, Poon LL, Tse DM, Chan KS, Woo PC, Lau SK, Peiris JS, Yuen KY. 2004. Viral loads in clinical specimens and SARS manifestations. Emerg Infect Dis 10: 1550–1557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Khakpour M, Nik‐Akhtar B. 1977. Epidemics of haemorrhagic cystitis due to influenza A virus. Postgrad Med J 53: 251–253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lambert SB, Whiley DM, O'Neill NT, Andrews EC, Canavan FM, Bletchly C, Siebert DJ, Sloots TP, Nissen MD. 2008. Comparing nose‐throat swabs and nasopharyngeal aspirates collected from children with symptoms for respiratory virus identification using real‐time polymerase chain reaction. Pediatrics 122: e615–e620. [DOI] [PubMed] [Google Scholar]
  19. Lau SK, Che XY, Woo PC, Wong BH, Cheng VC, Woo GK, Hung IF, Poon RW, Chan KH, Peiris JS, Yuen KY. 2005. SARS coronavirus detection methods. Emerg Infect Dis 11: 1108–1111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lau SK, Yip CC, Que TL, Lee RA, Au‐Yeung RK, Zhou B, So LY, Lau YL, Chan KH, Woo PC, Yuen KY. 2007. Clinical and molecular epidemiology of human bocavirus in respiratory and faecal samples from children in Hong Kong. J Infect Dis 196: 986–993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lau SK, Chan KH, Yip CC, Ng TK, Tsang OT, Woo PC, Yuen KY. 2009. Confirmation of the first Hong Kong case of human infection by novel swine‐origin influenza A (H1N1) virus using ultra‐rapid & real‐time RT‐PCR. J Clin Microbiol 47: 2344–2346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Likos AM, Kelvin DJ, Cameron CM, Rowe T, Kuehnert MJ, Norris PJ. National Heart, Lung, Blood Institute Retrovirus Epidemiology Donor Study‐II (REDS‐II) . 2007. Influenza viremia and the potential for blood‐borne transmission. Transfusion 47: 1080–1088. [DOI] [PubMed] [Google Scholar]
  23. Lowen AC, Steel J, Mubareka S, Carnero E, García‐Sastre A, Palese P. 2009. Blocking interhost transmission of influenza virus by vaccination in the guinea pig model. J Virol 83: 2803–2818. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Novel Swine‐Origin Influenza A (H1N1) Virus Investigation Team . 2009. Emergence of a novel swine‐Origin Influenza A (H1N1) virus in humans. N Engl J Med 360: 2605–2615. [DOI] [PubMed] [Google Scholar]
  25. Pozo F, García‐García ML, Calvo C, Cuesta I, Pérez‐Breña P, Casas I. 2007. High incidence of human bocavirus infection in children in Spain. J Clin Virol 40: 224–228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Uiprasertkul M, Puthavathana P, Sangsiriwut K, Pooruk P, Srisook K, Peiris M, Nicholls JM, Chokephaibulkit K, Vanprapar N, Auewarakul P. 2005. Influenza A H5N1 replication sites in humans. Emerg Infect Dis 11: 1036–1041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. von Linstow ML, Eugen‐Olsen J, Koch A, Winther TN, Westh H, Hogh B. 2006. Excretion patterns of human metapneumovirus and respiratory syncytial virus among young children. Eur J Med Res 11: 329–335. [PubMed] [Google Scholar]
  28. Wang YH, Huang YC, Chang LY, Kao HT, Lin PY, Huang CG, Lin TY. 2003. Clinical characteristics of children with influenza A virus infection requiring hospitalization. J Microbiol Immunol Infect 36: 111–116. [PubMed] [Google Scholar]
  29. Ward CL, Dempsey MH, Ring CJ, Kempson RE, Zhang L, Gor D, Snowden BW, Tisdale M. 2004. Design and performance testing of quantitative real time PCR assays for influenza A and B viral load measurement. J Clin Virol 29: 179–188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Wilhelmi I, Roman E, Sánchez‐Fauquier A. 2003. Viruses causing gastroenteritis. Clin Microbiol Infect 9: 247–262. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Wootton SH, Scheifele DW, Mak A, Petric M, Skowronski DM. 2006. Detection of human influenza virus in the stool of children. Pediatr Infect Dis J 25: 1194–1195. [DOI] [PubMed] [Google Scholar]
  32. World Health Organization Writing Group . 2006. Nonpharmaceutical interventions for pandemic influenza, international measures. Emerg Infect Dis 12: 81–87. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. World Health Organization . 2009. Human infection with new influenza A (H1N1) virus: Clinical observations from Mexico and other affected countries, May2009. Wkly Epidemiol Rec 84: 185–189. [PubMed] [Google Scholar]
  34. Writing Committee of the Second World Health Organization Consultation on Clinical Aspects of Human Infection with Avian Influenza A (H5N1) Virus . 2008. Update on avian influenza A (H5N1) virus infection in humans. N Engl J Med 358: 261–273. [DOI] [PubMed] [Google Scholar]
  35. Yuen KY, Chan PK, Peiris M, Tsang DN, Que TL, Shortridge KF, Cheung PT, To WK, Ho ET, Sung R, Cheng AF. 1998. Clinical features and rapid viral diagnosis of human disease associated with avian influenza A H5N1 virus. Lancet 351: 467–471. [DOI] [PubMed] [Google Scholar]
  36. Zhang Z, Zhang J, Huang K, Li KS, Yuen KY, Guan Y, Chen H, Ng WF. 2009. Systemic infection of avian influenza A virus H5N1 subtype in humans. Hum Pathol 40: 735–739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Zou S. 2006. Potential impact of pandemic influenza on blood safety and availability. Transfus Med Rev 20: 181–189. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Medical Virology are provided here courtesy of Wiley

RESOURCES