Effects of SARS-CoV-2 Infection on Pulmonary Function Tests and Exercise Tolerance

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has showed to cause long-term pulmonary sequelae. Objects: The aim of this study was to evaluate the consequences on pulmonary function of the SARS-CoV-2 infection related to the severity of the disease and exercise tolerance. Method(s): a retrospective cohort study was performed at the "Policlinico Tor Vergata" Academic hospital (Rome, Italy) where 75 patients evaluated in the post-COVID outpatient clinics at the Respiratory units were included in the study. Complete pulmonary function tests, 6-minute walk tests and persistence of symptoms were evaluated. Result(s): among the 75 subjects, 23 were mild, 16 moderate, 26 severe and 10 very severe based on the WHO classification. Very severe patients had a lower FVC (100+/-10%pr) compared to the others groups (116+/-16%pr, 116+/-13%pr, 122+/-20%pr from mild to severe;p<0,05) and a lower TLC (94+/-13%pr) compared to the others (102+/-10%pr, 108+/-15%pr, 108+/-12%pr from mild to severe;p<0,05). DL'co and DL'co/VA were similar among groups. At the 6MWT, distance, basal and nadir SpO2 were similar among groups, but all groups presented a significant decrease of SpO2 from basal to the nadir (Basal SpO2: 97,0+/-1,0% vs Nadir SpO2: 93,6+/-2,7%, p.<0,01). A positive correlation was found between desaturation and delta SpO2 (basal-nadir) (R: 0.29, p<0,05) and the Distance Desaturation Product (R: 0.39, p<0,01). Conclusion(s): These results showed that, although the PFTs are within the normal range, there is a restrictive spirometric pattern in very severe subjects. Moreover, the only persistent pathological sequalae of SARS-CoV-2 infection were a mild desaturation at 6MWT, despite the severity.

Brensocatib: Dipeptidyl peptidase 1 (DPP1) inhibitor Treatment of non-cystic fibrosis bronchiectasis

Neutrophils, which are among the first immune cells to respond to both infection and injury, when activated can release pre-stored serine proteases such as neutrophil elastase, cathepsin G and proteinase 3. An abundant release of these proteolytic enzymes in the alveolar compartment as well as the airways can trigger collateral pulmonary tissue damage. Indeed, much of the tissue destruction that characterizes non-cystic fibrosis bronchiectasis appears to be caused by serine proteases. The transitory pharmacological inhibition of bone marrow dipeptidyl peptidase 1 (DPP1), which converts neutrophil proteolytic enzymes into their mature active form, is a therapeutic possibility to decrease the constitutively produced serine protease pool of neutrophils. Brensocatib (also called INS-1007 or AZD-7986) is a potent reversible DPP1 inhibitor that has been successfully evaluated in a phase II trial as a treatment for non-cystic fibrosis bronchiectasis and, consequently, has been granted breakthrough therapy designation by the U.S. Food and Drug Administration and Priority Medicines (PRIME) designation by the European Medicines Agency.

Factors Influencing the Efficacy of COVID-19 Vaccines: A Quantitative Synthesis of Phase III Trials

To date, there is still a paucity of data from Phase III trials concerning the efficacy of vaccines against COVID-19. Furthermore, no studies investigated the variables that may modulate the efficacy of vaccination. The aim of this analysis was to assess whether there are modifying factors that may potentially influence the clinical efficacy of COVID-19 vaccines. A quantitative synthesis of data from Phase III trials was performed via pairwise and network meta-analyses, along with meta-regression analysis. Data from Phase III trials are currently available only for AZD1222, BNT162b2, mRNA-1237, and Sputnik V. Vaccination resulted to be generally effective (90.0%, 95%CI 72.6-96.4;p < 0.001), although the efficacy of AZD1222 (62.1%) introduced a significant level of heterogeneity in the meta-analysis (I² 92.17%, p < 0.001). No significant modifying factors resulted from the meta-regression analysis. However, considering the mRNA-based vaccines, a trend toward significance (p = 0.081) resulted for age. The network meta-analysis provided the following rank of effectiveness: BNT162b2 mRNA-1273 > Sputnik V >> AZD1222. In conclusion, no modifying factors seem to modulate the efficacy of vaccines against COVID-19. This quantitative synthesis will need to be updated as soon as further clinical results on the efficacy profile are available from Phase III trials for further licensed COVID-19 vaccines.