Comparison of two antifibrotic treatments for lung fibrosis in post-COVID-19 syndrome: A randomized, prospective study.

BACKGROUND: Although pulmonary fibrosis secondary to COVID-19 infection is uncommon, it can lead to problems if not treated effectively in the early period. This study aimed to compare the effects of treatment with nintedanib and pirfenidone in patients with COVID-19-related fibrosis. METHODS: Thirty patients who presented to the post-COVID outpatient clinic between May 2021 and April 2022 with a history of COVID-19 pneumonia and exhibited persistent cough, dyspnea, exertional dyspnea, and low oxygen saturation at least 12 weeks after diagnosis were included. The patients were randomized to receive off-label treatment with nintedanib or pirfenidone and were followed up for 12 weeks. RESULTS: After 12 weeks of treatment, all pulmonary function test (PFT) parameters, 6MWT distance, and oxygen saturation were increased compared to baseline in both the pirfenidone group and nintedanib groups, while heart rate and radiological score levels were decreased (p<0.05 for all). The changes in 6MWT distance and oxygen saturation were significantly greater in the nintedanib group than in the pirfenidone group (p=0.02 and 0.005, respectively). Adverse drug effects were more frequent with nintedanib than pirfenidone, with the most common being diarrhea, nausea, and vomiting. CONCLUSION: In patients with interstitial fibrosis after COVID-19 pneumonia, both nintedanib and pirfenidone were observed to be effective in improving radiological score and PFT parameters. Nintedanib was more effective than pirfenidone in increasing exercise capacity and saturation values but caused more adverse drug effects.

Comparación de dos tratamientos antifibróticos para la fibrosis pulmonar en el síndrome post-COVID-19: un estudio prospectivo aleatorizado Comparison of two antifibrotic treatments for lung fibrosis in post-COVID-19 syndrome: A randomized, prospective study

Introducción: Aunque la fibrosis pulmonar secundaria a la infección por COVID-19 es poco común, puede generar problemas si no se trata de manera efectiva en el período inicial. Este estudio tuvo como objetivo comparar los efectos del tratamiento con nintedanib y pirfenidona en pacientes con fibrosis relacionada con COVID-19. Métodos: Se incluyeron 30 pacientes que acudieron a la consulta externa post-COVID entre mayo de 2021 y abril de 2022 con antecedentes de neumonía por COVID-19 y presentaron tos persistente, disnea, disnea de esfuerzo y baja saturación de oxígeno al menos 12 semanas después del diagnóstico. Los pacientes fueron aleatorizados para recibir un tratamiento no aprobado con nintedanib o pirfenidona y fueron seguidos durante 12 semanas. Resultados: Después de 12 semanas de tratamiento, todos los parámetros de la prueba de función pulmonar (PFT), la distancia de la PM6M y la saturación de oxígeno aumentaron en comparación con los valores basales tanto en el grupo de pirfenidona como en el de nintedanib, mientras que la frecuencia cardíaca y los niveles de puntuación radiológica disminuyeron (p<0,05). para todos). Los cambios en la distancia de la PM6M y la saturación de oxígeno fueron significativamente mayores en el grupo de nintedanib que en el grupo de pirfenidona (p=0,02 y 0,005, respectivamente). Los efectos adversos del fármaco fueron más frecuentes con nintedanib que con pirfenidona, siendo los más frecuentes diarrea, náuseas y vómitos. Conclusión: En pacientes con fibrosis intersticial después de neumonía por COVID-19, se observó que tanto nintedanib como pirfenidona son efectivos para mejorar la puntuación radiológica y los parámetros de PFT. Nintedanib fue más eficaz que la pirfenidona para aumentar la capacidad de ejercicio y los valores de saturación, pero provocó más efectos adversos del fármaco.

When and how important is anti-fibrotic therapy in the post-COVID-19 period?

PURPOSE: In addition to the highly variable clinical presentation of acute COVID-19 infection, it can also cause various post-acute signs and symptoms. In our study, we aimed to examine the efficacy of anti-fibrotic therapy in patients who developed pulmonary fibrosis after COVID-19. METHODS: In total, 15 patients who applied to the Post-Covid Outpatient Clinic between May 2021 and August 2021 and were diagnosed with COVID-19 pneumonia, and whose cough, dyspnea, exertional dyspnea and low saturation continued to be present at least 12 weeks after the diagnosis, were included in the study. Off-label pirfenidone treatment was started according to the radiological findings, pulmonary function test parameters (PFT) and 6-minute walking test (6MWT) results. The patients were followed up for 12 weeks. RESULTS: While all of the FVC, FVC%, FEV1, FEV1%, DLCO%, DLCO/VA%, 6MWT, and room air saturation levels were observed to increase statistically significantly in the patients at the 12th week, it was determined that there was a statistically significant decrease in the pulse level in room air (p = 0.01, 0.01, 0.01, 0.01, 0.004, 0.001, 0.002, 0.001, and 0.002, respectively). In regression analysis based on radiological scoring, it was observed that the DLCO and room air saturation levels at the 12th week of the treatment were statistically significantly higher in patients with lower scores at the beginning (p = 0.04, 0.03). In addition, it was observed that anti-fibrotic treatment, which was started in the earliest period, i.e., 12 weeks after the diagnosis, resulted in an improvement in radiological, PFT and 6MWT parameters. CONCLUSION: Patients who still had dyspnea and low saturation 12 weeks after the diagnosis, defined as chronic COVID-19, should be evaluated for anti-fibrotic therapy after the necessary radiological and PFT evaluation. Early treatment commencement brings about, besides radiological improvement, a better response obtained in PFT and 6MWT (Tab. 2, Fig. 2, Ref. 21).

The role of exhaled nitric oxide (FeNO) in the evaluation of lung parenchymal involvement in COVID-19 patients.

The inflammatory balance is an important factor in the clinical course of COVID-19 (SARS-CoV-2) infection, which has affected over 300 million people globally since its appearance in December 2019. This study aimed to evaluate the correlation between exhaled nitric oxide (FeNO) level and parenchymal involvement in COVID-19. The study included 106 patients with the delta variant of COVID-19 identified by real-time PCR as well as 40 healthy control groups between October 2021 and March 2022. The patients were analyzed in three groups: moderate COVID-19 (group 1), severe COVID-19 without macrophage activation syndrome (MAS) (group 2), and severe COVID-19 with MAS (group 3). FeNO and CT scores were significantly higher in groups 2 and 3 at admission and discharge compared to group 1 (p = 0.001 for all). In addition, CT score at admission and CT score and FeNO level at discharge were higher in group 3 than in group 2 (p = 0.001 for all). It was found that the FeNO levels were higher in Groups 2 and 3 than in the control group (p = 0.001) during the admission. FeNO and CT scores showed strong positive correlation at admission and discharge (r = 0.917, p = 0.001; r = 0.790, p = 0.001). In receiver operating characteristic curve analysis for prediction of MAS, FeNO at a cut-off of 10.5 ppb had 66% sensitivity and 71% specificity. COVID-19 causes more severe lung involvement than other viral lower respiratory tract infections, leading to the frequent use of chest CT in these patients. FeNO assessment is a practical and noninvasive method that may be useful in evaluating for parenchymal infiltration in the diagnosis and follow-up of COVID-19 patients.

Evaluation of 3-month follow-up of patients with postacute COVID-19 syndrome.

In addition to the highly variable clinical presentation of acute COVID-19 infection, it can also cause various postacute signs and symptoms. This study aimed to evaluate patients with postacute COVID-19 over 12 weeks of follow-up. The study included 151 patients who were diagnosed with COVID-19 by real-time polymerase chain reaction of a nasopharyngeal swab 1 month earlier, had radiologic findings consistent with COVID-19 pneumonia, and presented to the post-COVID-19 outpatient clinic between May and August 2021. The patients were divided into three groups based on COVID-19 severity: nonsevere pneumonia (Group 1), severe pneumonia (Group 2), and severe pneumonia requiring intensive care (Group 3). Evaluation of laboratory parameters at 4 and 12 weeks showed that Group 3 had a higher lactose dehydrogenase (LDH) level and a lower mean platelet volume than the other groups at both time points (p = 0.001 for all). Group 3 also had lower percent predicted forced vital capacity (FVC%), percent predicted forced expiration volume in 1 s (FEV1%), and percent predicted diffusion capacity of the lungs for carbon monoxide divided by alveolar volume (DLCO/VA%) compared to Groups 1 and 2 at Week 4 (p = 0.001, 0.004, 0.001, respectively) and compared to Group 1 at 12 weeks (p = 0.002, 0.03, 0.001, respectively). Patients with persistent dyspnea at 12 weeks had significantly lower FEV1%, FVC%, DLCO/VA%, and saturation levels in room air and significantly higher LDH, pro-BNP, D-dimer, and heart rate compared to those without dyspnea (p = 0.001 for all). Although the lungs are most commonly affected after COVID-19 infection, vascular and endothelial damage also causes multisystem involvement. Our study indicates that laboratory values, radiological signs, and pulmonary functional capacity improved in most patients after 12 weeks of follow-up.

Evaluation of the relationship between pentraxin 3 (PTX3) rs2305619 (281A/G) and rs1840680 (1449A/G) polymorphisms and the clinical course of COVID-19.

Macrophage activation syndrome (MAS) is one of the main causes of morbidity and mortality in patients with coronavirus disease 2019 (COVID-19). This study aimed to investigate the relationship between the pentraxin 3 (PTX3) gene polymorphisms rs2305619 (281A/G) and rs1840680 (1449A/G) and the development of MAS in patients with COVID-19. The study included a total of 94 patients aged 18-45 who were diagnosed as having COVID-19 between June and December 2020. PTX3 281A/G and 1449A/G polymorphism frequencies were evaluated. PTX3 281A/G allele and genotype frequencies did not deviate from Hardy-Weinberg (HW) equilibrium in the MAS or non-MAS group (χ2 : 0.049, df: 2, p = 0.976, χ2 : 0.430, df: 2, p = 0.806). PTX3 1449A/G allele and genotype frequencies deviated significantly from HW equilibrium in the non-MAS group (χ2 : 6.794, df: 2, p = 0.033) but not in the MAS group (χ2 : 2.256, df: 2, p = 0.324). The AG genotype was significantly more frequent in the non-MAS group, while the AA genotype was significantly more frequent in the MAS group (χ2 : 11.099, df: 2, p= 0.004). Analysis of the PTX3 1449A/G polymorphism showed that individuals with the GG genotype had higher serum PTX3 levels than those with the AA and AG genotypes (p = 0.001 for both). Analysis of the PTX3 1449A/G polymorphism in patients with COVID-19 showed that those with the AG genotype were relatively more protected from MAS compared with individuals with the AA genotype. In addition, lower serum PTX3 levels are observed in patients carrying the A allele.

Is endogenous carboxyhaemoglobin level a useful biomarker of clinical course and prognosis in COVID-19 patients?

OBJECTIVE: SARS-CoV-2 has caused nearly 4 million confirmed cases of COVID-19 worldwide in the approximately 4 months since it emerged in Wuhan, China in December 2019. Comorbidities increase morbidity and mortality in COVID-19, and many laboratory parameters have been associated with mortality. The aim of the present study was to identify the relationship between endogenous carboxyhaemoglobin (COHb) level and the clinical course and prognosis of COVID-19. METHODS: The study included 48 non-smokers or ex-smokers aged 18 years or older who presented to the emergency department, were diagnosed with COVID-19 by real-time PCR analysis of nasopharyngeal swab sample and were treated in the pulmonary diseases ward of the Atatürk University hospital after 24 March 2020 and 15 April 2020. The patients' laboratory parameters and demographic data were analysed retrospectively. RESULTS: Prothrombin time and C-reactive protein (CRP), troponin-I, and D-dimer levels decreased in COVID-19 patients during follow-up (P = .024, P = .001, P = .001, P = .001), while PaO2 /FiO2 ratio and COHb increased (P = .002, P = .001). COHb level at admission was significantly lower in patients who developed macrophage activation syndrome (MAS), acute respiratory distress syndrome (ARDS), and those who died compared with the other patients (P = .002, P = .001). COHb level on day 5 of treatment was significantly higher in patients with ARDS and patients who died (P = .001, P = .001). Significant correlations were detected between COHb level and CRP (r=-0.425, P = .001), ferritin (r = -.395, P = .001) and PaO2 /FiO2 ratio (r = .431, P = .001). CONCLUSIONS: COHb level may be an easily accessible biomarker that guides early follow-up and treatment planning to avoid ARDS, MAS and mortality in COVID-19.

Evaluation of the relationship of serum vitamin D levels in COVID-19 patients with clinical course and prognosis.

INTRODUCTION: SARS-CoV-2 (COVID-19), which emerged in Wuhan, China in December 2019, infected more than six million people in a short time. In COVID-19, the relationship of many laboratory parameters to morbidity and mortality has been defined. In our study, we aimed to determine the relationship of serum vitamin D level to clinical course and prognosis. MATERIALS AND METHODS: This study included 108 patients; 88 patients who stayed in Ataturk University and Erzurum City Hospital between March 24, 2020 and May 15, 2020, who were identified as COVID-19 by real-time PCR method from the nasopharyngeal swab and 20 asymptomatic voluntary medical personnel who tested negative for real-time PCR after routine check-up in our hospital. RESULT: In statistical analysis conducted between healthy control group and vitamin D levels of patients admitted due to COVID-19, it was observed that patients infected with COVID-19 had a lower level (p= 0.004). In 20 patients developing MAS, a lower level of vitamin D was observed (p= 0.004) compared to 68 patients who did not develop. In the comparison of vitamin D levels of the patients (n= 8) who developed exitus in their follow up due to COVID-19, it was observed that vitamin D levels were statistically significantly lower compared to the living (p= 0.009). CONCLUSIONS: Due to COVID-19, pandemic, long-running quarantines caused insufficient use of sunlight and worsening of vitamin D deficiency. We wanted to draw attention again with our study to vitamin D which can be responsible for the heavy clinical course of COVID-19 and whose replacement is easy to apply.

Are Serum Interleukin 6 and Surfactant Protein D Levels Associated with the Clinical Course of COVID-19?

PURPOSE: SARS-CoV-2 (COVID-19) has infected more than 7 million people worldwide in the short time since it emerged in Wuhan, China in December 2019. The aim of this study was to investigate the relationship between serum interleukin 6 (IL-6) and surfactant protein D (SP-D) levels and the clinical course and prognosis of COVID-19. MATERIALS AND METHODS: The study included a total of 108 individuals: 88 patients who were diagnosed with COVID-19 by real-time PCR of nasopharyngeal swab samples and admitted to the Atatürk University Pulmonary Diseases and the Erzurum City Hospital Infectious Diseases department between March 24 and April 15, and 20 asymptomatic healthcare workers who had negative real-time PCR results during routine COVID-19 screening in our hospital. RESULTS: Patients who developed macrophage activation syndrome had significantly higher IL-6 and SP-D levels at the time of admission and on day 5 of treatment compared to the other patients (IL-6: p = 0.001 for both; SP-D: p = 0.02, p = 0.04). Patients who developed acute respiratory distress syndrome had significantly higher IL-6 and SP-D levels at both time points compared to those who did not (p = 0.001 for all). Both parameters at the time of admission were also significantly higher among nonsurvivors compared to survivors (IL-6: p = 0.001, SP-D: p = 0.03). CONCLUSION: In addition to IL-6, which has an important role in predicting course and planning treatment in COVID-19, SP-D may be a novel pneumoprotein that can be used in the clinical course, follow-up, and possibly in future treatments.