Broad Decline in Viral Infections During COVID-19 Lockdown: Association with Lung Function in Lung Transplant Recipients

PURPOSE: In April 2020 COVID-19 lockdown measures were instigated leading to a dramatic drop in non-COVID respiratory virus infections (RVI). This provided a unique situation to assess the impact of RVI on annual FEV1 decline, episodes of temporary drop in lung function suggestive of infection (TDLF) and CLAD in lung transplant recipients (LTR). METHODS: All lung function tests (LFT) of LTR transplanted between 2009-April 2020 were used from post-transplant baseline onward. LFT were censored after COVID-19 infection. Weekly RVI counts from the virology department defined RVI pressure over time. TDLF was defined as sudden, reversible FEV1 drop compared to previous 4 values (any TDLF ≥10% and ≥200ml, severe TDLF ≥20% and ≥500ml). Annual FEV1 decline was estimated using linear mixed effects models with separate estimates for 2009/20 and 2020/21. Effect modification by TDLF frequency of individual LTR (two subgroups, split at median) and RVI pressure was tested. Rates of CLAD and TDLF were analyzed over time. RESULTS: 479 LTR (12,775 LFT) were included. Annual FEV1 change in 2009/20 was -114ml [95%CI -133; -94], while in 2020/21 this was significantly less: 5ml [-38; 48] (p<0.001). RVI pressure significantly affected FEV1 level (an increase in weekly RVI-count of 10 leading to a 7ml [-10; -5] lower FEV1 (p<0.001). FEV1 decline in 2009/20 was faster in frequent TDLF LTR vs. infrequent (-150ml [-181; -120] vs. -90ml [-115; -65] p=0.003 Fig A). 2020/21 showed significant decreases in number of any TDLF (OR 0.53 [0.33; 0.85], p=0.008) and severe TDLF (OR 0.34 [0.16; 0.71] p=0.005) and numerically lower CLAD (OR 0.53 [0.27; 1.02] p=0.060). Effect modification by RVI pressure (Figures B-D) indicated an association between the events and RVI. CONCLUSION: During the lockdown year 2020/21 the broad decline in RVI coincided with substantially less FEV1 decline, TDLFs and possibly CLAD. All these outcomes were moderated by RVI pressure suggesting an important role for RVI in lung function decline in LTR.