Among the 339 patients with suspected SARS admitted to the Prince of Wales Hospital between10 March and 20 May 2003, 92 demonstrated clinical deterioration despite treatment with methylprednisolone. Eighty of these patients (43 females and 37 males) were given convalescent plasma around day 14 (range, 7–30 days) following the onset of symptoms. The median age of the patients receiving convalescent plasma was 45 years (range, 21–82 years). The mean volume of plasma infused was 279.3±127.1 ml (range, 160–640 ml). Thirty-three patients had a good clinical outcome; they were given convalescent plasma earlier than the patients with a poor outcome (11.67±2.3 vs 16.04±6.0 days; P<0.001; Table 1). Patients (n=48) given convalescent plasma before day 14 had a better outcome than those given plasma after day 14 (58.3% vs 15.6%; P<0.001). The mortality rates in the two groups were 6.3% and 21.9%, respectively (P=0.08). One major factor affecting the timing of convalescent plasma administration was plasma availability. Overall, the mortality rate was 12.5% among the 80 patients given convalescent plasma. The overall SARS-related mortality rate in Hong Kong was 17% (299/1755) during the SARS epidemic from 6 March to 24 May.

Table 1 Comparison of clinical characteristics of patients with SARS according to outcome Full size table

Sixty-one percent of the patients with a good outcome were PCR positive and seronegative for coronavirus at the time of plasma infusion as compared with 21% in the group with a poor outcome (P<0.001). The 30 patients who were PCR positive and seronegative for coronavirus at the time of convalescent plasma therapy had a better outcome than those who were already seropositive (66.7% vs 20%; P=0.001). Age was a poor prognostic factor (Table 1). In the multivariate analysis, only the time of convalescent plasma therapy and coronavirus PCR positivity were significant factors.

No immediate adverse effects were observed with convalescent plasma infusion. There was no correlation between clinical outcome and either the volume of plasma infused or the coronavirus antibody titers of the donors.

In our experience, patients whose clinical condition deteriorated after receiving ribavirin and methylprednisolone had a higher discharge rate by day 22 when convalescent plasma was administered before day14 of illness onset. Patients receiving convalescent plasma after day 14 had a longer hospital stay and a higher mortality rate.

For most viral illnesses, viremia peaks in the first week of infection. The patient usually develops a primary immune response by day 10–14, which is followed by clearance of the virus. Therefore, convalescent plasma should, theoretically, be more effective when given early in the course of disease. In a study of patients with Lassa fever in Nigeria, all eight patients who received convalescent plasma on or before day 10 of illness recovered and survived, while only three of eight patients who received plasma after day 10 survived [7]. In SARS, the viral load also peaks in the first week of infection [12], and clinical deterioration in the third week is thought to be the result of inflammatory or hyperimmune attacks on lung tissue rather than direct viral-induced tissue damage. This was consistent with our finding of better clinical outcome in patients given convalescent plasma early in the course of the disease (i.e., before day 14, or during the viremic and seronegative stage).

The volumes of convalescent plasma we administered were similar to those given to patients with Ebola hemorrhagic fever [8]. Although we did not observe any correlation between clinical outcome and either the volume of convalescent plasma given or the antibody titers of the donors, this observation could be misleading; since the attending physicians tend to give repeated infusions from multiple donors to patients responding poorly in a desperate attempt to reverse the course.

Our study has several limitations. (i) It was not randomized: whether or not patients received convalescent plasma was at the discretion of the attending physicians and according to plasma availability. Fluctuations in plasma availability also resulted in some patients receiving plasma earlier in the course of illness than others, but this allowed us to make an interesting comparison of the effects of early versus late plasma therapy. (ii) The amount of antibodies given to each patient was not standardized. This might have contributed to the variations in clinical outcome. (iii) Even though we did not observe any immediate adverse reactions, the potential risk of transfusion-transmitted infection was present. Ideally, convalescent plasma should go through a viral inactivation procedure before being infused into recipients. (iv) We did not have a placebo group for comparison. Although there were 12 patients whose condition deteriorated after methylprednisolone treatment and never received plasma therapy, these patients were given further doses of methylprednisolone, penta-globulin or other antiviral drug-like protease inhibitors. Using them for comparison, one may argue that methylprednisolone or another therapy may have a deleterious effect and convalescent plasma had minimal benefits or vice versa.

Despite the many limitations, our data suggest it may be worthwhile to test the effectiveness of therapy with convalescent plasma or SARS-specific hyperimmune globulin in patients in the early phase of SARS during the next outbreak.