Acute exacerbation of rheumatoid arthritis-associated interstitial lung disease triggered by COVID-19: What is the best practice for treatment?

We present a case of 79-year-old female with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) developed an acute exacerbation (AE) triggered by coronavirus disease 2019 (COVID-19). The patient was unresponsive to a combination therapy of remdesivir, dexamethasone, and tocilizumab. Given that a recent multicenter cohort study reported ILD as a poor prognostic contributor in patients with RA and COVID-19, there may be potentially a certain number of patients with AE of RA-ILD triggered by COVID-19. This case highlights the need for a discussion how to treat these patients in a daily clinical practice.

Risk factors contributing to impaired cough-specific quality of life at the time of admission for coronavirus disease 2019 treatment.

Background: Cough is the most common symptom of coronavirus disease 2019 (COVID-19). However, the factors contributing to impaired cough-specific quality of life (QoL) during the acute phase of COVID-19 infection remain unknown. We sought to identify such factors using the Japanese version of acute cough with the Leicester Cough Questionnaire (LCQ-acute). Methods: Three hundred and two patients with COVID-19 admitted to Aichi Hospital between October 2020 and October 2021 completed the LCQ-acute at the time of admission. Clinical indices at the time of admission, such as presenting symptoms including cough, patient characteristics, disease severity, and biomarkers, were reviewed from the medical records. The impact of cough-specific QoL on clinical indices was assessed using two- or three-group comparisons and Pearson's correlation coefficient. Multivariate analysis was performed to determine the factors contributing to impaired cough-specific QoL at the time of admission for COVID-19 treatment. Results: Two hundred and nine patients (69.2%) were coughing at the time of admission. Cough prevalence was highest, but cough-specific QoL was lowest at 8-11 days after onset. Multivariate analysis revealed that female sex, young age, gastrointestinal (GI) symptoms, and dysgeusia and/or dysosmia contributed to impaired cough-specific QoL at the time of admission for COVID-19 treatment, along with systemic and respiratory symptoms such as fever, higher C-reactive protein (CRP) levels, sputum, and dyspnea. Conclusions: Female sex, young age, asthma, GI symptoms, dysgeusia, and/or dysosmia, along with systemic and respiratory symptoms, indicated impaired cough-specific QoL at the time of admission for COVID-19 treatment.

Human Lung Fibroblasts Exhibit Induced Inflammation Memory via Increased IL6 Gene Expression and Release.

Fibroblasts of different origins are known to possess stromal memory after inflammatory episodes. However, there are no studies exploring human lung fibroblast memory which may predict a subsequent inflammatory response in chronic respiratory diseases and COVID-19. MRC-5 and HF19 human lung fibroblast cell lines were treated using different primary and secondary stimulus combinations: TNFα-WD-TNFα, Poly (I:C)-WD-TNFα, TNFα-WD-Poly (I:C), or LPS-WD-TNFα with a 24-h rest period (withdrawal period; WD) between the two 24-h stimulations. TLR3 and NF-κB inhibitors were used to determine pathways involved. The effect of SARS-Cov-2 spike protein to inflammatory response of lung fibroblasts was also investigated. mRNA expressions of genes and IL6 release were measured using qRT-PCR and ELISA, respectively. Statistical significance was determined by using one- or two-way ANOVA, followed by Bonferroni's post hoc analysis for comparison of multiple groups. Preexposure with Poly (I:C) significantly increased TNFα-induced IL6 gene expression and IL6 release in both cell lines, while it affected neither gene expressions of IL1B, IL2, IL8, and MMP8 nor fibrosis-related genes: ACTA2, COL1A1, POSTN, and TGFB1. Inhibition of TLR3 or NF-κB during primary stimulation significantly downregulated IL6 release. Simultaneous treatment of MRC-5 cells with SARS-CoV-2 spike protein further increased TNFα-induced IL6 release; however, preexposure to Poly (I:C) did not affect it. Human lung fibroblasts are capable of retaining inflammatory memory and showed an augmented response upon secondary exposure. These results may contribute to the possibility of training human lung fibroblasts to respond suitably on inflammatory episodes after viral infection.

Successful Treatment with High-dose Steroids for Acute Exacerbation of Idiopathic Pulmonary Fibrosis Triggered by COVID-19.

We herein report a case of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) triggered by COVID-19. An 87-year-old woman tested positive for COVID-19 on a polymerase chain reaction test, and computed tomography revealed ground-glass opacity (GGO) superimposed on a background pattern consistent with usual interstitial pneumonia. Considering these data, we diagnosed her with AE-IPF. She experienced worsening of dyspnea and expansion of the GGO. Therefore, we introduced high-dose steroids (methylprednisolone 250 mg/day for 3 days). After the treatment, the pulmonary infiltrates improved. She was discharged from our hospital without severe disability. High-dose steroids can be a viable treatment option for AE-IPF triggered by COVID-19.