We report a case series of 31 patients with either serious or life-threatening COVID-19 infection treated with COVID-19 convalescent plasma who demonstrated favorable clinical outcomes when compared to those reported in the literature to date. For both severe and life-threatened patients, respiratory support requirements began to decrease at about day 7. Once the ventilatory requirements began to decrease, they did so rapidly. Most patients were able to be discharged home on room air. The overall mortality was 13% (4/31). Among patients who were admitted with infection that met the criteria for severe disease and were transfused convalescent plasma prior to the development of respiratory failure the mortality to date is zero, and only one patient (6%) has had subsequent escalation of respiratory failure requiring mechanical ventilation. Among our patients with life-threatening disease we report an extubation rate of 67%. Overall, compared to outcomes reported in the literature to date, patients transfused convalescent plasma appear to have better outcomes in the face of both severe and life-threatening disease. (12,13) Our results would have been more significant with a larger sample size, however our hospital did not experience a large COVID-19 patient surge prior to this manuscript. Also, as the large majority of our COVID-19 patients were transfused with convalescent plasma in this time period, a matched control group was not possible.
Our results are consistent with other early reports of outcomes in COVID-19 patients transfused with convalescent plasma. A recent cohort study by Liu and colleagues of 39 cases and 156 matched controls from Mount Sinai hospital in New York City reported a 12.8% mortality rate among patients with severe or worse disease who received convalescent plasma, and significantly better outcomes among patients transfused prior to mechanical ventilation. (14) Transfused patients were very similar to ours with respect to inflammatory markers and distribution of respiratory support requirements. Although we have no basis for internal comparison because our transfused rate was high and overall case numbers prevented us from matching a control group, our experience reinforces the suggestion that early administration is of greater clinical benefit than delaying transfusion under the development of severe disease. This is in line with one of the first published randomized clinical trials of convalescent plasma, in which Li and colleagues found clinical improvement was limited to those with without life-threatening disease, with 91% improvement in the plasma group compared to 68% in the control arm. (15)
We observed a high rate clinical improvement among mechanically ventilated patients who received COVID-19 convalescent plasma. Although 4 (29%) of our patients with life-threatening disease died, 9 (64%) has improve respiratory by 14 days after transfusion. Improvement with convalescent plasma in patients already requiring mechanical ventilation is in line with one of the early reports of convalescent plasma treatment by Shen et al., who reported on improvement in multiple clinical parameters in five of five (100%) patients transfused convalescent plasma. (5) Li and colleagues, by contrast, saw only a 10% rate of improvement among intubated patients receiving convalescent plasma 14 days after transfusion.
One potential confounding factor in the improved outcomes we have seen could be the regional/geographical differences in outcomes as have been reported in the literature. Unlike the large patient surges experienced in Seattle and then in New York City, the healthcare system in Dane County/Madison, including at University Hospital, has not experienced a large or overwhelming surge of patients. In the initial reports from the Seattle area, a substantial number of patients (81%) were initially admitted to the intensive care unit, requiring intubation and mechanical ventilation, and by mid-March, 2020, they reported a mortality of 67% and the continued critical care needs of an additional 24% of patients. (10) Similarly, from March and April, 2020, New York City area hospitals experienced mortality rates as high as 70 to 90% in patients requiring mechanical ventilation. (11) Among 257 critical care admissions in the New York Presbyterian/Columbia hospital system 39% have died with the death rate being much higher at 79% for the 203 patients requiring mechanical ventilation. By contrast the overall death rate in our transfused cases was only 13% and to date, at worst 29% in those requiring mechanical ventilation. (12)
Ji and colleagues described how infection prevalence compared to resource availability and healthcare burden are directly related to differences in mortality as seen in various areas of China. For instance, in the Wuhan province, the epicenter of the pandemic, mortality rates were reported to be greater than 3-4% where in other, even more populous areas, of China mortality was less than 1%. They go on to describe that mortality appears to be related to the incidence of disease per capita and the resources available in the local healthcare system to absorb and care for the number of cases in need. (16) This may well be part of the phenomenon of less aggressive appearing disease seen in the Dane County and Madison area. Dane County, with a population of approximately 550,000, has an infection rate of 143/100,000 population and a mortality rate of only 5/100,000. Other more populated and dense areas such as New York City have incidence rates 20 times greater than ours and mortality rates 50 times higher. (12)
Our report has significant limitations. Because our institution did not see a large COVID-19 patient surge like those experienced elsewhere, we were unable to develop a well-matched control group for the purposes of comparison. Our patient population is also relatively homogenous and with good access to medical care. In addition, because most of our convalescent plasma came from donors in the earliest phases of collection, we did not have donor antibody titers available for analysis.