*3.2. Vaccine Breakthrough*

Vaccination with a minimum of two doses of a COVID-19 mRNA vaccine (BNT162b2 or Pfizer-BioNTech, and mRNA-1273 or Moderna) were recommended for all our LTRs. Fifty patients in this cohort completed a two-shot vaccination series (Pfizer: 33 patients; Moderna: 17 patients), and nine patients were unvaccinated at the time of the data censoring. COVID-19 occurred in 30 patients who received at least a two-doses series of an mRNA vaccine at a median of 123 days (IQR 98–164 days) after vaccination. Twelve of the thirty patients (40%) were hospitalized and four of these patients died (overall mortality: 13.3%; inpatient mortality: 33%). The three patients that required invasive mechanical ventilation died. Of

the 50 vaccinated patients, 31 received a third dose. Of the 31 patients that received a third dose, 19 had breakthrough infections (61.2%), and two patients died.

#### *3.3. Outcomes*

The patients were followed for a median of 150 days (IQR 68–369). The result of the multivariable analysis showed that patients with a higher baseline forced expiratory volume (FEV1) were 9% less likely to be hospitalized (OR = 0.91 and 95% CI 0.87–0.98, *p =* 0.02). The overall mortality was 13% (8/59), with an inpatient mortality of 23.5% (8/34), and 75% of those mechanically ventilated died (6/8). The mortality rate was 8% (28/34) in patients hospitalized without treatment with mechanical ventilation (OR = 36.0 and 95% CI 4.2–310.4, *p <* 0.01). Of the eight patients that died during the study period, four were patients with vaccine-breakthrough COVID-19. The cause of death in seven patients was septic shock and multiorgan failure. One patient died from antibody-mediated rejection 2 months following a COVID-19 infection. Common critical COVID-19 complications were sepsis, invasive mechanical ventilation, and acute kidney injury (Acute Kidney Injury Network stage 3). Bacterial and mold infections were commonly identified.

The characteristics of patients that died and those who survived are shown in Table 2. The patient demographics; underlying comorbidities; time from LT, FEV1, and CLAD; and presumed type of variant were comparable in both groups. Most deaths (four patients) occurred during the period of Delta variant activity. Although there was a trend of lower mortality observed during the Alpha wave (9%), and a higher mortality rate during the Delta wave (36%), no significant risk was detected after adjusting for the other covariates.


**Table 2.** Factors associated with mortality among hospitalized patients.

*Variable Response Hospitalized N = 34 Dead N=8 Alive N = 26 p-Value* Comorbidities 0.33 HTN 3 (9%) 1 (33%) 2 (67%) DM 2 (6%) 0 (0%) 2 (100%) BMI > 30 3 (9%) 2 (67%) 1 (33%) CKD 3 or higher 24 (71%) 5 (21%) 19 (79%) Medical ward 20 (59%) 0 (0%) 20 (100%) <0.01 ICU 14 (41%) 8 (57%) 6 (43%) <0.01 IMV 8 (24%) 6 (75%) 2 (25%) <0.01 SARS-CoV-2 wave First\_wave 10 (29%) 2 (20%) 8 (80%) 0.75 Alpha\_wave 11 (32%) 1 (9%) 10 (91%) 0.17 Delta\_wave 11 (32%) 4 (36%) 7 (64%) 0.22 Omicron\_wave 4 (12%) 1 (25%) 3 (75%) 0.94 Breakthrough N = 30 12 (40%) 4 (33%) 9 (75%) 0.43

**Table 2.** *Cont.*

BMI, body mass index; IIP, idiopathic interstitial pneumonia; PAH, pulmonary arterial hypertension; BOS, bronchiolitis obliterans syndrome; CKD, chronic kidney disease; CLAD, chronic allograft dysfunction following the International Society for Heart and Lung Transplantation 2002 classification; FEV1, forced expiratory volume in 1 s; IMV, invasive mechanical ventilation; RAS, restrictive allograft syndrome; SD, standard deviation.
