Effects of SARS-CoV-2 on Pulmonary Function and Muscle Strength Testing in Military Subjects According to the Period of Infection: Cross-Sectional Study.

BACKGROUND: Pulmonary function can be impaired as a long-term consequence of SARS-CoV-2 infection. The aim of this study was to evaluate the effect of SARS-CoV-2 infection on pulmonary function, exercise tolerance, and muscle strength in healthy middle-aged military outpatients according during the period of infection. METHODS: A cross-sectional study was carried out from March 2020 to November 2022 at the Military Hospital "Celio" (Rome, Italy). If someone had a diagnosis of SARS-CoV-2 infection certified by molecular nasal swab and if they performed pulmonary function tests, diffusion of carbon monoxide (DL'co), a six Minute Walk Test (6MWT), a Handgrip (HG) Test, and a One Minute Sit to Stand Test (1'STST). The included subjects were divided into two groups, A and B, according to the period of infection: A) from March 2020 to August 2021 and B) from September 2021 to October 2022. RESULTS: One hundred fifty-three subjects were included in the study: 79 in Group A and 74 in Group B. Although the values were within the normal range, Group A had smaller FVC, FEV1, and DL'co compared to Group B. Group A also walked a shorter distance at the 6MWT and performed fewer repetitions in the 1'STS test compared to Group B. In both groups, the DL'co (%predicted) correlated with the 6MWT distance (R2 = 0.107, p < 0.001), the number of repetitions of the 1'STST (R2 = 0.086, p = 0.001), and the strength at the HG test (R2 = 0.08, p < 0.001). CONCLUSIONS: This study shows that the SARS-CoV-2 infection in healthy middle-aged military outpatients was more severe in the first waves than in the later ones and that, in healthy and physically fit individuals, even a marginal reduction in resting respiratory test values can have a major impact on exercise tolerance and muscles strength. Moreover, it shows that those infected more recently had symptoms related to the upper respiratory tract infection compared to those of the first waves.

The BNT162b2 mRNA COVID-19 Vaccine Increases the Contractile Sensitivity to Histamine and Parasympathetic Activation in a Human Ex Vivo Model of Severe Eosinophilic Asthma.

The BNT162b2 COVID-19 vaccine is composed of lipid-nanoparticles (LNP) containing the mRNA that encodes for SARS-CoV-2 spike glycoprotein. Bronchospasm has been reported as an early reaction after COVID-19 mRNA vaccines in asthmatic patients. The aim of this study was to investigate the acute impact of BNT162b2 in a human ex vivo model of severe eosinophilic asthma. Passively sensitized human isolated bronchi were challenged with the platelet-activating factor to reproduce ex vivo the hyperresponsiveness of airways of patients suffering from severe eosinophilic asthma. BNT162b2 was tested on the contractile sensitivity to histamine and parasympathetic activation via electrical field stimulation (EFS); some experiments were performed after mRNA denaturation. BNT162b2 increased the resting tone (+11.82 ± 2.27%) and response to histamine in partially contracted tissue (+42.97 ± 9.64%) vs. the control (p < 0.001); it also shifted the concentration-response curve to histamine leftward (0.76 ± 0.09 logarithm) and enhanced the response to EFS (+28.46 ± 4.40%) vs. the control. Denaturation did not significantly modify (p > 0.05) the effect of BNT162b2. BNT162b2 increases the contractile sensitivity to histamine and parasympathetic activation in hyperresponsive airways, a detrimental effect not related to the active component but to some excipient. A possible candidate for the bronchospasm elicited by BNT162b2 could be the polyethylene glycol/macrogol used to produce LNP.

Expert guidance on the management and challenges of long-COVID syndrome: a systematic review.

INTRODUCTION: Long-COVID is a condition characterized by the permanence of symptoms beyond 4 weeks after an initial infection. It affects 1 out of 5 people and is loosely related to the severity of acute infection and pathological mechanisms, which are yet to be understood. AREAS COVERED: This article looks at currently available and under-studied therapies for long-COVID syndrome. It particularly gives focus to ongoing trials and reviews the underlying mechanisms. A comprehensive literature search was performed on PubMed and clincaltrial.gov of clinical trials concerning the management of long-COVID syndrome. EXPERT OPINION: 'Long-COVID' syndrome is a new emergency characterized by several symptoms such as fatigue, dyspnea, cognitive and attention disorders, sleep disorders, post-traumatic stress disorder, muscle pain, and concentration problems. Despite the many guidelines available to date, there are no established treatments of long-COVID. Pharmacological research is studying known drugs that act on the reduction or modulation of systemic inflammation, or innovative drugs used in similar pathologies. Rehabilitation now seems to be the safest treatment to offer, whereas we will have to wait for the pharmacological research trials in progress as well as plan new trials based on a better understanding of the pathogenic mechanisms.

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

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to cause long-term pulmonary sequelae. OBJECTS: The aim of this study was to evaluate the consequences of the SARS-CoV-2 infection on pulmonary function and on the 6-min walk test related to the severity of the disease. METHODS: A cross-sectional study was conducted at the "Policlinico Tor Vergata" Academic Hospital (Rome, Italy), including 75 patients evaluated in post-COVID clinics at the Respiratory Units between November 2020 and September 2021. Complete pulmonary function tests, 6-min walk tests and persistence of symptoms were performed. RESULTS: Of the 75 subjects, 23 had mild, 16 moderate, 26 severe and 10 very severe COVID-19, classified according to WHO. Very severe patients had a lower FVC (100 ± 10%pr) compared to the other 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). DLco and DLco/VA were similar among groups. At the 6MWT, distance, rest and nadir SpO2 were similar among groups, but all groups presented a significant decrease in SpO2 from rest to nadir (Rest 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 (rest-nadir) (R: 0.29, p < 0.05) and the Distance Desaturation Product (R: 0.39, p < 0.01). CONCLUSIONS: These results showed that, although the PFTs are within the normal range, there is still a mild restrictive spirometric pattern after six months in very severe subjects. Moreover, the only persistent pathological sequalae of SARS-CoV-2 infection were a mild desaturation at 6MWT, despite the severity of the infection.

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.

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.

Happy hypoxemia, or blunted ventilation?

Happy hypoxemia is an unspecified definition that is used in COVID-19 patients to define hypoxemia without dyspnoea. Dyspnoea is a very complex symptom, and although hypoxemia can cause breathlessness, dyspnoea is not related to hypoxemia, but is more closely related to inspiratory drive and mechanical alterations. The lack of dyspnoea in the early stages of the disease is likely related to the absence of increased inspiratory drive due to compensatory mechanisms of hypoxemia, while in the advanced stages there is no evidence of a lack of dyspnoea in COVID-19 patients.

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.

Dyspnea perception and neurological symptoms in non-severe COVID-19 patients.

INTRODUCTION: The relationship between dyspnea and COVID-19 is unknown. In COVID-19 patients, the higher prevalence of neurological symptoms and the lack of dyspnea may suggest common underlying pathogenetic mechanisms. The aim of this preliminary study is to address whether there is a lack of dyspnea in COVID-19 patients and if there is a relationship between neurological symptoms and the perception of dyspnea. METHODS: A structured interview regarding the occurrence of subjective neurological symptoms was performed and coupled with a questionnaire about the intensity and qualities of dyspnea. Respiratory rate (RR) and an arterial blood gas on room air were concurrently evaluated. RESULTS: Twenty-two patients (age 68.4 ± 13.9 years, 13 males and 9 females) were included and divided into two groups according to the Borg dyspnea scale: dyspneic patients BU ≥ 1(DYSP) and non-dyspneic patients BU < 1 (NDYSP). The prevalence of dyspnea overall was 31.8%. The prevalence of neurological symptoms, dyspnea descriptors, RR, pH, PaCO2, PaO2, or lactate was similar between groups. CONCLUSION: This study confirms that the prevalence of dyspnea is low in non-severe COVID-19 patients, but contrary to our hypothesis of a relationship between shortness of breath and neurological symptoms, we have not been able to find any evidence of an impairment in dyspnea perception, either in the DYSP or NDYSP group.

Subjective neurological symptoms frequently occur in patients with SARS-CoV2 infection

OBJECTIVE: Coronavirus disease 2019 (COVID-19) represents a novel pneumonia leading to severe acute respiratory syndrome (SARS). Recent studies documented that SARS-Coronavirus2 (SARS-CoV2), responsible for COVID-19, can affect the nervous system. The aim of the present observational study was to prospectively assess subjective neurological symptoms (sNS) in patients with SARS-CoV2 infection. METHODS: We included patients hospitalized at the University Hospital of Rome Tor Vergata, medical center dedicated to the treatment of patients with COVID-19 diagnosis, who underwent an anamnestic interview about sNS consisting of 13 items, each related to a specific symptom, requiring a dichotomized answer. RESULTS: We included 103 patients with SARS-CoV2 infection. Ninety-four patients (91.3%) reported at least one sNS. Sleep impairment was the most frequent symptom, followed by dysgeusia, headache, hyposmia, and depression. Women more frequently complained hyposmia, dysgeusia, dizziness, numbeness/paresthesias, daytime sleepiness, and muscle ache. Moreover, muscle ache and daytime sleepiness were more frequent in the first 2 days after admission. Conversely, sleep impairment was more frequent in patients with more than 7 days of hospitalization. In these patients we also documented higher white blood cells and lower C-reactive protein levels. These laboratory findings correlated with the occurrence of hyposmia, dysgeusia, headache, daytime sleepiness, and depression. CONCLUSIONS: Patients with SARS-CoV2 infection frequently present with sNS. These symptoms were present from the early phases of the disease. The possibly intrinsic neurotropic properties of SARS-CoV2 may justify the very high frequency of sNS. Further studies targeted at investigating the consequences of SARS-CoV2 infection on the CNS should be planned.