A total of 46 patients (Fig. 1) with RT-PCR-confirmed COVID-19 were enrolled in the study. Eight of 46 (17%) patients were excluded from the analysis for the following reasons: two received convalescent plasma with no detectable antibody titer; one was transferred to another hospital; five were made comfort care only (CMO) and medical care was withdrawn within 5 days of plasma administration. The remaining patients (n = 38) included in this analysis received convalescent plasma with adequate total anti-SARS-CoV-2 antibody titer of 1:320 (32 received 2 units, 5 were re-dosed with 1 unit, 1 received 1 unit).
Patient demographics, clinical presentation, hospital course, and clinical outcomes are shown in Tables 1, 2, 3, 4, and 5. Mean age was 63 years (95% CI 59–70), 53% were male, 34% black, 32% white, and 34% were Hispanic; 61% of the patients were from Connecticut, 37% from Harford County, 21% New Haven County, and 40% were from Hampden County, Massachusetts (Table 1). More than 68% had been diagnosed with hypertension and nearly half (47.4%) with diabetes mellitus; overall, 31.5% had three or more comorbidities (Table 2). As shown in Table 3, mean days from onset of symptoms to hospitalization was 7.3 days (95% CI 6.4–8.2), with the most common symptoms at admission being fever, cough, and dyspnea. With the exception of one patient who arrived in critical condition, subjects presented initially to the hospital with moderate to severe COVID-19 pneumonia without evidence of ARDS or requiring invasive ventilation support at the time of admission (Table 4). The most common laboratory abnormalities on admission included severe rise in inflammatory markers [C-reactive protein (CRP) ≥ 10 mg/dL] (66%), lymphopenia (absolute lymphocyte count < 1000 per microliter) (50%), and hyponatremia (Na < 135 mEq/L) (47%)—see Table 4.
Severe and Critical Illness Groups
At the time of plasma infusion, 16 patients (42%) met criteria for severe illness. These patients were enrolled in the study and received convalescent plasma earlier in their hospital and disease course on average 4.6 days (95% CI 2.9–6.3) following hospital admission, and 12.6 days (95% CI 10–15.2) following symptoms’ onset while on high-flow oxygen supplementation prior to any evidence of ARDS. The remaining 22 patients (58%) met the criteria for critical illness at the time of convalescent plasma therapy. They enrolled in the study and received convalescent plasma later in their hospital and disease course on average 16.4 days (95% CI 13–19.8) following hospital admission, and 23.1 days (95% CI 19.5–26.7) following symptoms’ onset after developing ARDS and had been on ventilation support for an average of 10.6 days (95% CI 7.3–13.9).
The two cohorts were comparable in demographics; comorbidities and home medications; pre-illness functional status; onset of symptoms to seeking hospital care; initial clinical presentation and findings; initial disease severity; and the care they received during their hospitalization including essential medications (see Tables 1, 2, 3, 4 and 5). Clinically, hyponatremia on initial hospital presentation was more prevalent in the severe illness group (p = 0.047). Vasopressors (p < 0.01), hydroxychloroquine (p < 0.01), and antibiotics (p < 0.01) were more frequently used during hospitalization in the critical illness group. Renal replacement therapy was utilized at higher rate in the critical illness group but did not reach statistical significance (p = 0.05).
One patient in the severe illness group experienced a transient transfusion reaction (fever and hematuria) within 2 h of plasma infusion. No other adverse effects of convalescent plasma infusion were observed. Of the 38 patients included in the analysis, 24 (63%) recovered and were discharged from the hospital, and 14 (37%) died. Patients who died included two in the severe illness group and 12 in the critical illness group. The difference in mortality (13% severe vs 55% critical) was statistically significant (p = 0.02). Overall, patients who survived (n = 24) regardless of disease severity at time of infusion received convalescent plasma earlier in their course of disease (mean 15.3 days, SD 6.9) and hospital stay (8.4 days, SD 6.8) compared to those who died (n = 14) with mean durations of (24.5 days, SD 9.6), (16.6 days, SD 9.5) respectively.
Among patients with severe illness at the time of convalescent plasma therapy, 25% (4/16) progressed to ARDS after receiving convalescent plasma (Table 5). Three of the four required mechanical ventilation and two of the four died. One of those patients received convalescent plasma 18 days following onset of symptoms and died of refractory shock in ICU while on ventilator support. The other patient received convalescent plasma 16 days following symptom onset, developed respiratory failure secondary to ARDS, and was placed on comfort measures at the request of the family. The remainder (14/16, 88%) did not progress to ARDS, recovered with resolution of COVID-19 pneumonia, and were discharged from the hospital.
In the patients with critical illness at the time plasma therapy, 10/22 (45%) recovered with resolution of ARDS and restoration of organ function and left the hospital. Of the 12/22 (55%) who died, six died of refractory shock while on ventilator support with evidence of pneumoperitonium in four of them; three patients died of refractory respiratory failure with terminal extubation; two died of complications of upper airway edema; and one patient died of an acute cardiac complication.
Mean hospital length of stay was 25.6 days (95% CI 20.8–30.4) (Table 5). Length of stay was significantly shorter in the severe illness group (15.4 days, 95% CI 9.3–21.6) compared to patients in the critical illness group (33.0 days, 95% CI 27.3–38.7) (p < 0.01). Statistical analyses showed that patients treated earlier in the course of COVID-19 disease (severe group) had significantly lower hospital mortality (p = 0.02) and shorter hospital length of stay (p < 0.01) after convalescent plasma therapy compared to patients that were treated later in their disease course in presence of ARDS (critical group) (Table 5). Other prognostic factors that were significantly associated with good clinical outcomes included shorter durations between symptoms onset and convalescent plasma administration (p < 0.01), and hospital admission and administration of convalescent plasma (p < 0.01).