Bronchiectasis and COVID-19 infection: a two-way street.

ABSTRACT: Bronchiectasis (BE) has been linked to past viral infections such as influenza, measles, or adenovirus. Two years ago, a new pandemic viral infection severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) broke out and it still persists today, and a significant proportion of surviving patients have radiological and clinical sequelae, including BE. Our aim was to thoroughly review the information available in the literature on the bidirectional relationship between SARS-CoV-2 infection and the development of BE, as well as the impact of this infection on patients already suffering from BE. Available information indicates that only a small percentage of patients in the acute phase of coronavirus disease 2019 (COVID-19) pneumonia develop BE, although the latter is recognized as one of the radiological sequelae of COVID-19 pneumonia, especially when it is caused by traction. The severity of the initial pneumonia is the main risk factor for the development of future BE, but during the COVID-19 pandemic, exacerbations in BE patients were reduced by approximately 50%. Finally, the impact of BE on the prognosis of patients with COVID-19 pneumonia is not yet known.

Mucolytic and Antioxidant Properties of Carbocysteine as a Strategy in COVID-19 Therapy.

SARS-CoV-2 infection leads to a heterogenous spectrum of clinical conditions ranging from self-limiting upper airway infection to severe respiratory failure. Carbocysteine is a thioether mucolytic with antioxidant and anti-inflammatory activities. Carbocysteine has been shown to have anti-viral effects on human rhinovirus, RSV and the influenza virus as well as interfering with upper airway ciliary motility, the first site of SARS-CoV-2 infection, leading to more effective mucus clearance and potential containment of viral spread towards the lower airway. Positive effects, in terms of limiting superimposed bacterial infection and reducing oxidative stress, have also been documented in COPD patients. Accordingly, Carbocysteine should also be considered in both post-exposure prophylaxis and early-phase treatment of COVID-19 in combination with other agents (monoclonal antibodies, antivirals, non-steroidal anti-inflammatory agents, and inhaled corticosteroids). In this review, we explored the pharmacokinetic and pharmacodynamic aspects of Carbocysteine to delineate its potential therapeutic impact in patients with COVID-19.

Can FeNO be a biomarker in the post-COVID-19 patients monitoring?

The nature of the inflammatory and fibrotic processes found in patients with post-COVID-19 syndrome makes it possible to speculate that in such patients fractional exhaled nitric oxide (FeNO) may be a useful biomarker. Consequently, we set out to verify the consistency of this hypothesis. We consecutively enrolled 68 post-COVID patients after being hospitalized for persistent clinical manifestations within 2 months from disease onset and 29 healthy volunteers as control group. None of post-COVID patients had bronchial asthma or were being treated with a corticosteroid. Only 19 out of 68 post-COVID-19 patients reported a FeNO value > 25 ppb. The mean FeNO value in post-COVID-19 patients was 18.55 ppb (95% CI: 15.50 to 21.58), while in healthy subjects it was 17.46 ppb (95% CI: 15.75 to 19.17). The mean difference was not statistically significant (P = 0.053). However, the mean FeNO value of post-COVID-19 patients was higher in men than in women (20.97 ppb; 95% CI: 16.61 to 25.33 vs 14.36 ppb; 95% CI: 11.11 to 17.61) with a difference between the two sexes that was statistically significant (P = 0.016). Mean FeNO was 14.89 ppb (95% CI: 10.90 to 18.89) in patients who had been treated with systemic corticosteroids because of their COVID-19, and 20.80 ppb (95% CI: 16.56 to 25.04) in those who had not taken them, with a difference that was statistically significant (P = 0.043). The data generated in this study suggest that measurement of FeNO is not useful as a biomarker in post-COVID-19 patient. However, this hypothesis needs solid validation with additional specifically designed studies.

Advances in the Pharmacological Management of Pediatric Acute Respiratory Distress Syndrome.

INTRODUCTION: Noninvasive mechanical ventilation is the main supportive measure used in patients with pediatric ARDS (PARDS), but adjunctive pharmacological therapies (corticosteroids, inhaled nitric oxide [iNO], surfactant replacement therapy and neuromuscular blocking drugs) are also used, although limited data exists to inform of this practice. AREAS COVERED: The authors review the current challenges in the pharmacological management of PARDS and highlight the few certainties currently available. EXPERT OPINION: Children with PARDS must not be treated as young adults with ARDS, essentially because children's lungs differ substantially from those of adults and PARDS occurs in children differently than ARDS in adults. Pharmacological treatments available for PARDS are relatively few and, since there is great uncertainty about their effectiveness also because of the extreme heterogeneity of this syndrome, it is necessary to conduct large clinical trials using currently available definitions and considering recent pathobiological knowledge. The aim is to identify homogeneous subgroups or phenotypes of children with PARDS that may benefit from the specific pharmaceutical approach examined. It will be then necessary to link endotypes and outcomes to appropriately target therapies in future trials, but this will be possible only after it will be possible to identify the different PARDS endotypes.

Use of Thiols in the Treatment of COVID-19: Current Evidence.

There is a possible role for oxidative stress, a state characterized by an altered balance between the production of free radicals or reactive oxygen species (ROS) and antioxidant defences, in coronavirus disease 2019 (COVID-19), the genesis of which is quite complex. Excessive oxidative stress could be responsible for the alveolar damage, thrombosis, and red blood cell dysregulation observed in COVID-19. Apparently, deficiency of glutathione (GSH), a low-molecular-weight thiol that is the most important non-enzymatic antioxidant molecule and has the potential to keep the cytokine storm in check, is a plausible explanation for the severe manifestations and death in COVID-19 patients. Thiol drugs, which are considered mucolytic, also possess potent antioxidant and anti-inflammatory properties. They exhibit antibacterial activity against a variety of medically important bacteria and may be an effective strategy against influenza virus infection. The importance of oxidative stress during COVID-19 and the various pharmacological characteristics of thiol-based drugs suggest a possible role of thiols in the treatment of COVID-19. Oral and intravenous GSH, as well as GSH precursors such as N-acetylcysteine (NAC), or drugs containing the thiol moiety (erdosteine) may represent a novel therapeutic approach to block NF-kB and address the cytokine storm syndrome and respiratory distress observed in COVID-19 pneumonia patients.

Controversy surrounding the Sputnik V vaccine.

The Sputnik V COVID-19 vaccine is a member of the so-called vector vaccines and uses two different vectors (Ad26 priming and Ad5 boost) to reduce the risk of a reduction in the effectiveness of the vaccination. Real life data indicate an efficacy of the vaccine above 97%. Low cost and no need for ultra-cold storage temperature temperatures are other pluses of the Sputnik V vaccine. However, there are also several important shortcomings that must be considered such as the possible reduction of its immunogenicity in the presence of very high Ad5 neutralizing antibody titres and the decrease with age of the antibody titres neutralizing the virus. Furthermore, there is emerging documentation that Sputnik V has a reduced neutralizing capacity against the Beta variant and all variants with the spike protein carrying the E484K substitution. Nevertheless, due to its characteristics, Sputnik V could be another useful means of satisfying the need for mass vaccination. However, it is imperative to document the efficacy and safety of the Sputnik V vaccine in individuals with high pre-existing anti-Ad26 and Ad5-neutralizing antibody titres and in those under the age of 18 or older than 60 years and be certain that Sputnik V does not cause the rare development of immune thrombotic thrombocytopenia. It is hoped that the now widespread use of this vaccine will generate a large pragmatic real-world study with data accessible to anyone interested in verifying them.

Preexisting cardiorespiratory comorbidity does not preclude the success of multidisciplinary rehabilitation in post-COVID-19 patients.

Patients recovering from coronavirus disease 2019 (COVID-19) may not return to a pre-COVID functional status and baseline levels of healthcare needs after discharge from acute care hospitals. Since the long-term outcomes of COVID-19 can be more severe in patients with underlying cardiorespiratory diseases, we aimed at verifying the impact of a preexisting cardiorespiratory comorbidity on multidisciplinary rehabilitation in post-COVID-19 patients. We enrolled 95 consecutive patients referring to the Pulmonary Rehabilitation Unit of Istituti Clinici Scientifici Maugeri Spa SB, IRCCS of Telese Terme, Benevento, Italy after being discharged from the COVID-19 acute care ward and after recovering from acute COVID-19 pneumonia. Forty-nine of them were not suffering from underlying comorbidities, while 46 had a preexisting cardiorespiratory disease. Rehabilitation induced statistically significant improvements in respiratory function, blood gases and the ability to exercise both in patients without any preexisting comorbidities and in those with an underlying cardiorespiratory disease. Response to the rehabilitation cycle tended to be greater in those without preexisting comorbidities, but DLco%-predicted was the only parameter that showed a significant greater improvement when compared to the response in the group of patients with underlying cardiorespiratory comorbidity. This study suggests that multidisciplinary rehabilitation may be useful in post-COVID-19 patients regardless of the presence of preexisting cardiorespiratory comorbidities.

Management of COPD patients during COVID: difficulties and experiences.

Introduction: The role of COPD in COVID-19 is not yet well understood. However, there is increasing evidence showing that COPD patients with COVID-19 have a higher risk of presenting a serious infection, a greater likelihood of requiring ICU support, and a higher mortality than other groups.Areas covered: In this article, we address some critical questions on COVID-19 as they pertain to COPD. In particular, we discuss whether the usual algorithms of pharmacological and non-pharmacological management in COPD still apply.Expert opinion: Patients with COPD must continue their regular therapy, regardless of whether they are affected by COVID-19. Corticosteroids reduce mortality in COVID-19 patients in need of supportive oxygen therapy or invasive mechanical ventilation. It is essential that a COPD patient who has tested positive for SARS-CoV-2 is closely followed over time because any delay in diagnosis and initiation of appropriate therapy could negatively affect his/her prognosis. However, we still do not know if COVID-19 infection occurs and evolves differently in each of the recognized COPD phenotypes and, therefore, whether it needs a different management. There are other open questions concerning COVID-19 and COPD that need to be considered. Future studies are absolutely necessary to answer these questions.

Bronchodilator reversibility testing in post-COVID-19 patients undergoing pulmonary rehabilitation.

BACKGROUND: The usefulness of bronchodilators in coronavirus diseases 2019 (COVID-19) survivors is still uncertain, especially for patients with a concomitant obstructive lung disease. We aimed at verifying the level of bronchodilator reversibility in COVID-19 patients undergoing multidisciplinary pulmonary rehabilitation after the acute phase. METHODS: We enrolled 105 consecutive patients referring to the Pulmonary Rehabilitation Unit of Istituti Clinici Scientifici Maugeri Spa SB, IRCCS of Telese Terme, Benevento, Italy after being discharged from the COVID-19 acute care ward and after recovering from acute COVID-19 pneumonia. All subjects performed a spirometry before and after inhalation of salbutamol 400 µg to determine the bronchodilation response within 48 h of admission to the unit. RESULTS: All patients had suffered from a moderate to severe COVID-19, classified 3 or 4 according to the WHO classification, Seventeen patients had concomitant obstructive lung disease (14 suffering from COPD and 3 from asthma). FEV1 after salbutamol improved on average by 41.7 mL in the entire examined sample, by 29.4 mL in subjects without concomitant obstructive lung diseases, by 59.3 mL in COPD patients and by 320.0 mL in asthma patients. Mean FVC after salbutamol improved by 65.7 mL in the entire examined sample, by 52.5 mL in subjects without concomitant obstructive lung diseases, by 120.0 mL in COPD patients, and by 200.0 mL in asthma patients. CONCLUSIONS: This study suggests that a treatment with bronchodilators must always be taken into consideration in post-COVID-19 patients because it can induce a functional improvement that, even if small, can facilitate the breathing of these patients.

Disputes over the production and dissemination of misinformation in the time of COVID-19.

Ultimate coronavirus disease 2019 (COVID-19) mitigation and crisis resolution is dependent on trustworthy data and actionable information. At present time, there is still no cure for COVID-19, although some treatments are being used in severe illness. Regrettably, as the SARS-CoV-2 virus spreads, the lack of cure has been accompanied by an increasing amount of medical misinformation. In particular, there is a lot of misinformation about how to treat patients who have tested positive for SARS-CoV-2 and who are asymptomatic or have mild symptoms and for whom management at home is deemed appropriate. In this editorial, we highlight the risks deriving from this misinformation, which often arises from the publication of studies that are not conceptually and methodologically accurate.

Guidance on nebulization during the current COVID-19 pandemic.

Awareness of the risk of airborne transmission of SARS-CoV-2 makes patients hesitant about using inhaled medications that are considered as a potential source of viral transmission and immunosuppression. However, patients with asthma or COPD should continue all prescribed inhaled medications. Apparently, inhalers, including pMDIs, DPIs, or SMIs, have a low risk of contamination although characteristics of drug formulation can precipitate cough, whereas some researchers do not rule out the probability that nebulizer treatments may increase the risk of infection transmission via droplet nuclei and aerosols. Considering that aerosol therapy generates fugitive emissions that are not inhaled by the patient and are released from the device during expiration, several international professional bodies have provided recommendations for drug delivery via inhalers and in particular, nebulizers. Unfortunately, these recommendations are often in conflict with each other and do not clarify whether it is appropriate to use nebulizers during this COVID-19 pandemic. Considering what is available in literature, there are no known infection-related hazards to an uninfected patient and also a patient with COVID-19 that preclude the use of a nebulizer at home, but it fundamental that all patients, regardless of whether or not suffering from COVID-19, always follow some practical advices.

ACE2: The Major Cell Entry Receptor for SARS-CoV-2.

Despite the unprecedented effort of the scientific community, the novel SARS-CoV-2 virus has infected more than 46 million people worldwide, killing over one million two hundred thousand. Understanding the mechanisms by which some individuals are more susceptible to SARS-CoV-2 infection and why a subgroup of them are prone to experience severe pneumonia, and death should lead to a better approach and more effective treatments for COVID-19. Here, we focus our attention on ACE2, a primary receptor of SARS-CoV-2. We will discuss its biology, tissue expression, and post-translational regulation that determine its potential to be employed by SARS-CoV-2 for cell entry. Particular attention will be given to how the ACE2 soluble form can have a great impact on disease progression and thus be used in a potential therapeutic strategy. Furthermore, we will discuss repercussions that SARS-CoV-2/ACE2 binding has on the renin-angiotensin system and beyond. Indeed, although mostly neglected, ACE2 can also act on [des-Arg 937]-bradykinin of the kinin-kallikrein system regulating coagulation and inflammation. Thorough comprehension of the role that ACE2 plays in different pathways will be the key to assess the impact that SARS-CoV-2/ACE2 binding has on organismal physiology and will help us to find better therapies and diagnostic tools.

Pharmacological management of COVID-19 patients with ARDS (CARDS): A narrative review.

Coronavirus disease 2019 (COVID-19) is highly infectious. It has been highlighted that if not expertly and individually managed with consideration of the vasocentric features, a COVID-19 patient with an acute respiratory distress syndrome (CARDS) may eventually develop multiorgan failure. Unfortunately, there is still no definite drug for CARDS that is capable of reducing either short-term or long-term mortality and no specific treatments for COVID-19 exist right now. In this narrative review, based on a selective literature search in EMBASE, MEDLINE, Scopus, The Cochrane Library, Web of Science, and Google Scholar and ClinicalTrials.gov, we have examined the emerging evidence on the possible treatment of CARDS. Although numerous pharmacologic therapies to improve clinical outcomes in CARDS have been studied also in clinical trials, none have shown efficacy and there is great uncertainty about their effectiveness. There is still no recommendation for the therapeutic use of any specific agent to treat CARDS because no drugs are validated to have significant efficacy in clinical treatment of COVID-19 patients in large-scale trials. However, there exist a number of drugs that may be useful at least in some patients. The real challenge now is to link the right patient to the right treatment.

Severe respiratory SARS-CoV2 infection: Does ACE2 receptor matter?

SARS-CoV-2 is a novel virus of the Coronaviridiae family that represents a major global health issue. Mechanisms implicated in virus/host cells interaction are central for cell infection and replication that in turn lead to disease onset and local damage. To enter airway and lung epithelia, SARS-CoV-2 attaches to ACE2 receptors by spike (S) glycoproteins. Molecular mechanisms that promote interaction between SARS-CoV-2 virus and host with particular focus on virus cell entry receptor ACE2 are described. We further explore the impact of underlying medical conditions and therapies including renin-angiotensin inhibitors on modulating ACE 2, which is the major SARS-CoV-2 cell entry receptor.