Airway remodeling in COVID-19 lungs

Besides parenchymal changes that have been described extensively in COVID-19, bronchiectasis is also reported but detailed characterization of airway changes is lacking. Hence, we aimed to quantify the number of visible airways and their diameters in end-stage COVID-19 lungs. Explanted right lungs, obtained after lung transplantation (n=2) or autopsy (n=1) (65.3+/-26.7 days after symptom onset), were inflated to total lung capacity, frozen and scanned with whole lung microCT (155 mum). Airways were segmented using Mimics Innovation Suite (Materialise, Belgium) and airway count and diameter were assessed using Neuronstudio. Three discarded donor lungs were used as controls. Number of visible airways increased in COVID-19 lungs compared to controls (fig.1a) potentially caused by airway remodeling and bronchiectasis (fig.1b, red arrows) due to fibrotic rearrangement (fig. 1b). Small airway count (diameter 0-2 mm) in generation (G) 1-11 was lower in COVID-19 patients compared to controls, with a shift of small airways from lower generations (G1-11) to higher generations (G12-27) in COVID-19 patients. Simultaneously, airways with a diameter > 2 mm were increased in all generations in COVID-19 (present until G21 compared to G13 in controls). This study shows that COVID-19 causes a remodeling of the (small) airways, leading to an increase of visible airways and diameter of large and small airways, similar to that seen in idiopathic pulmonary fibrosis due to traction bronchiectasis. (Figure Presented).

Improved peak exercise performance after 12 weeks of pulmonary rehabilitation in patients post COVID-19

Background: Pulmonary Rehabilitation (PR) is recommended for patients that suffered from severe COVID19. The exercise and training response as well as predictors of response are not yet well studied. Aim(s): To study the response to an incremental exercise test performed before and after 12 weeks of outpatient PR. Method(s): An exercise test was conducted in 37 of 70 patients that completed PR after COVID19, (age 52+/-9, BMI 29+/-6, 20 male, FEV1 89+/-21%pre, 31 hospitalized). Result(s): Before starting PR, exercise tolerance was reduced. A cardiac, ventilatory, gas exchange and muscular limitation was observed in 24%, 22%, 37% and 45% of patients respectively. Physiologic limitations were inconclusive in 19% of patients. After completing PR, significant desaturation was still seen in 30% of patients. Rehabilitation increased Wmax by 58+/-55% and VO2max by 40+/-38% of baseline values with significant improvements in O2pulse (see table1). Multiple regression revealed that improvement in VO2peak was associated with gender (+386ml/min in male p=0.01 Partial R2=0.14), and Hospital anxiety and depression scale -21ml/min per baseline point in total score (partial R2 0.18 p=0.03). Quadriceps force did not significantly enter the model (p=0.1). Conclusion(s): Peak exercise tolerance increased rapidly upon initiation of PR in patients after COVID19. In patients with psychologic morbidity at baseline, this response seems somewhat blunted.

The short-term economic effects of COVID-19 on low-income households in rural Kenya: an analysis using weekly financial household data. (Special Section: Pandemics and sustainability.)

This research assesses how low-income households in rural Kenya coped with the immediate economic consequences of the COVID-19 pandemic. It uses granular financial data from weekly household interviews covering six weeks before the first case was detected in Kenya to five weeks after during which various containment measures were implemented. Based on household-level fixed-effects regressions, our results suggest that income from work decreased with almost one-third and income from gifts and remittances reduced by more than one-third after the start of the pandemic. Nevertheless, household expenditures on food remained at pre-COVID levels. We do not find evidence that households coped with reduced income through increased borrowing, selling assets or withdrawing savings. Instead, they gave out less gifts and remittances themselves, lent less money to others and postponed loan repayments. Moreover, they significantly reduced expenditures on schooling and transportation, in line with the school closures and travel restrictions. Thus, despite their affected livelihoods, households managed to keep food expenditures at par, but this came at the cost of reduced informal risk-sharing and social support between households.

Direct antivirals working against the novel coronavirus: azithromycin (DAWn-AZITHRO), a randomized, multicenter, open-label, adaptive, proof-of-concept clinical trial of new antivirals working against SARS-CoV-2-azithromycin trial.

BACKGROUND: The rapid emergence and the high disease burden of the novel coronavirus SARS-CoV-2 have created a medical need for readily available drugs that can decrease viral replication or blunt the hyperinflammatory state leading to severe COVID-19 disease. Azithromycin is a macrolide antibiotic, known for its immunomodulatory properties. It has shown antiviral effect specifically against SARS-CoV-2 in vitro and acts on cytokine signaling pathways that have been implicated in COVID-19. METHODS: DAWn-AZITHRO is a randomized, open-label, phase 2 proof-of-concept, multicenter clinical trial, evaluating the safety and efficacy of azithromycin for treating hospitalized patients with COVID-19. It is part of a series of trials testing promising interventions for COVID-19, running in parallel and grouped under the name DAWn-studies. Patients hospitalized on dedicated COVID wards are eligible for study inclusion when they are symptomatic (i.e., clinical or radiological signs) and have been diagnosed with COVID-19 within the last 72 h through PCR (nasopharyngeal swab or bronchoalveolar lavage) or chest CT scan showing typical features of COVID-19 and without alternate diagnosis. Patients are block-randomized (9 patients) with a 2:1 allocation to receive azithromycin plus standard of care versus standard of care alone. Standard of care is mostly supportive, but may comprise hydroxychloroquine, up to the treating physician's discretion and depending on local policy and national health regulations. The treatment group receives azithromycin qd 500 mg during the first 5 consecutive days after inclusion. The trial will include 284 patients and recruits from 15 centers across Belgium. The primary outcome is time from admission (day 0) to life discharge or to sustained clinical improvement, defined as an improvement of two points on the WHO 7-category ordinal scale sustained for at least 3 days. DISCUSSION: The trial investigates the urgent and still unmet global need for drugs that may impact the disease course of COVID-19. It will either provide support or else justify the discouragement of the current widespread, uncontrolled use of azithromycin in patients with COVID-19. The analogous design of other parallel trials of the DAWN consortium will amplify the chance of identifying successful treatment strategies and allow comparison of treatment effects within an identical clinical context. TRIAL REGISTRATION: EU Clinical trials register EudraCT Nb 2020-001614-38 . Registered on 22 April 2020.

Late Breaking Abstract - Physical activity in lung transplant recipients during Belgian COVID-19 lockdown

Introduction: SARS-CoV-2 caused a pandemic in 2020 with a 'lockdown' resulting in reduced mobility. Activity tracker companies noticed reduced physical activity (PA) in the general population. If observed in patients, this may add to the devastating consequences of physical inactivity. Aim: To investigate PA levels of lung transplant (LTX) recipients before and during the Belgian soft lockdown measures of COVID-19. A decline in daily step count during lockdown measures was hypothesized. Methods: 16 LTX recipients (56% male, mean±SD age 61±6.7 years, 30.2±12.7 months post LTX) involved in an RCT (NCT04122768) were included in the present sub-analysis. Daily step counts were collected by activity trackers, >4 weeks prior to (phase 1) and 4 weeks during the Belgian lockdown (phase 2). The differences in PA between both phases were compared with paired t-tests. Results: Daily number of steps was low in phase 1 (mean±SD 6910±4225 steps/day) but did not change during phase 2 (7016±5665 steps/day), p=0.89, see figure 1. Conclusions: The Belgian COVID-19 lockdown measures did not significantly affect the PA levels of LTX recipients compared to the preceding period.