Emergencies preparedness, response

Prospective study of the clinical progression and viral load of SARS associated coronavirus pneumonia in a community outbreak

JSM Peiris, CM Chu, VCC Cheng, KS Chan, IFN Hung, LLM Poon, KI Law, BSF Tang, TYW Hon, CS Chan, KH Chan, JSC Ng, BJ Zheng, WL Ng, RWM Lai, Y Guan, KY Yuen and members of the HKU / UCH SARS Study Group

This paper has been accepted by The Lancet and will be published next week. We are grateful to The Lancet for the permission to publish the summary of this paper in advance.

Summary

Background:
A community outbreak of severe acute respiratory distress syndrome (SARS) with epidemiological linkage was reported. The temporal progression of the clinical, radiological, and virological changes was investigated.

Methods:
A prospective study of the clinical, haematological, radiological, and microbiological findings of 75 patients managed with a standardized treatment protocol of the Hospital Authority, Hong Kong Special Administrative Region using ribavirin and corticosteroid was performed over a 3 week period. The pattern of clinical disease, viral load, the risk factors for a poor clinical outcome and the usefulness of virological diagnostic methods was presented and analyzed.

Findings:
The fever and pneumonia initially responded to treatment. However, patients developed recurrent fever (85.3%) on day 8.9 ± 3.1 (range 4 to 18), watery diarrhoea (73.3%) on day 7.5 ± 2.3 (range 3 to 15), radiological deterioration (80%) on day 7.4 ± 2.2 (range 3 to 13) and respiratory deterioration (45.3%) on day 8.6 ± 3 days (range 5 to 19). In 45.3% of patients, marked improvement of initial pulmonary lesions was closely associated with appearance of new radiological lesions at other sites. Twenty percent progressed to acute respiratory distress syndrome (ARDS) during the third week. Quantitative RT-PCR of nasopharyngeal aspirates in 14 patients (4 had ARDS and 10 without ARDS) consistently demonstrated a peak viral load at day 10 and a decrease to admission level at day 15. Age and chronic HBV infection are independent significant risk factors for progression to ARDS on multivariate analysis. Faecal excretion of coronavirus was present and continued through the period of follow-up. Seroconversion and RT-PCR of nasopharyngeal aspirates and stool are useful for confirmation of SARS.

Interpretation:
The consistent clinical progression, shifting radiological infiltrates and an inverted V viral load profile suggested that deterioration during the second week is not related to uncontrolled viral replication but may rather be related to immunopathological damage. Age and HBV status are risk factors for progression to ARDS.

Subsequent analysis of clinical specimen of 20 patients with initial NPA RT-PCR positive and antibody seroconversion to SARS associated coronavirus

Day after onset of symptoms (day)

10

13

16

19

21

NPA

(positivity rate)

19 / 20 (95%) 18 / 20 (90%) 18 / 20 (90%) 15 / 20 (75%) 9 / 19 (47.4%)
Stool

(positivity rate)

20 / 20 (100%) 20 / 20 (100%) 19 / 20 (95%) 12 / 15 (80%) 10 / 15 (66.7%)
Urine

(positivity rate)

10 / 20 (50%) 9 / 20 (45%) 7 / 20 (35%) 6 / 20 (30%) 4 / 19 (21.1%)