Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study

J S M Peiris, C M Chu, V C C Cheng, K S Chan, I F N Hung, L L M Poon, K I Law, B S F Tang, T Y W Hon, C S Chan, K H Chan, J S C Ng, B J Zheng, W L Ng, R W M Lai, Y Guan, K Y Yuen, HKU/UCH SARS Study Group, J S M Peiris, C M Chu, V C C Cheng, K S Chan, I F N Hung, L L M Poon, K I Law, B S F Tang, T Y W Hon, C S Chan, K H Chan, J S C Ng, B J Zheng, W L Ng, R W M Lai, Y Guan, K Y Yuen, HKU/UCH SARS Study Group

Abstract

Background: We investigated the temporal progression of the clinical, radiological, and virological changes in a community outbreak of severe acute respiratory syndrome (SARS).

Methods: We followed up 75 patients for 3 weeks managed with a standard treatment protocol of ribavirin and corticosteroids, and assessed the pattern of clinical disease, viral load, risk factors for poor clinical outcome, and the usefulness of virological diagnostic methods.

Findings: Fever and pneumonia initially improved but 64 (85%) patients developed recurrent fever after a mean of 8.9 (SD 3.1) days, 55 (73%) had watery diarrhoea after 7.5 (2.3) days, 60 (80%) had radiological worsening after 7.4 (2.2) days, and respiratory symptoms worsened in 34 (45%) after 8.6 (3.0) days. In 34 (45%) patients, improvement of initial pulmonary lesions was associated with appearance of new radiological lesions at other sites. Nine (12%) patients developed spontaneous pneumomediastinum and 15 (20%) developed acute respiratory distress syndrome (ARDS) in week 3. Quantitative reverse-transcriptase (RT) PCR of nasopharyngeal aspirates in 14 patients (four with ARDS) showed peak viral load at day 10, and at day 15 a load lower than at admission. Age and chronic hepatitis B virus infection treated with lamivudine were independent significant risk factors for progression to ARDS (p=0.001). SARS-associated coronavirus in faeces was seen on RT-PCR in 65 (97%) of 67 patients at day 14. The mean time to seroconversion was 20 days.

Interpretation: The consistent clinical progression, shifting radiological infiltrates, and an inverted V viral-load profile suggest that worsening in week 2 is unrelated to uncontrolled viral replication but may be related to immunopathological damage.

Figures

Figure 1
Figure 1
Temporal clinical profiles in 75 patients with SARS Mean (SD) are presented.
Figure 2
Figure 2
Chest radiographs and high-resolution CT scans from two SARS patients A Man aged 34 years admitted for high fever and cough. A: Consolidation seen in left upper and middle zones, which progressed maximally at day 7. B: At day 20, resolution of consolidation in the left upper and middle zones but new widespread air-space opacities noted; those in left lung base were confluent. Man aged 32 years, presented with fever, chills, rigors and myalgia, with clear chest radiograph at admission. C: High-resolution CT of thorax shows peripheral subpleural consolidation in medial basal segment of left lower lobe. D: Resolution of original left lower-lobe consolidation at day 18. E: Disease complicated by spontaneous pneumomediastinum.
Figure 3
Figure 3
Kinetics of IgG seroconversion to SARS-associated coronavirus Cumulative data on earliest time to seroconversion is presented.
Figure 4
Figure 4
Sequential quantitative RT-PCR for SARS-associated coronavirus in nasopharyngeal aspirates of 14 SARS patients

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Source: PubMed

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