Global Perspective on COVID-19 Therapies, Cardiovascular Outcomes, and Implications for Long COVID: A State-of-the-Art Review.

The COVID-19 pandemic has resulted in many therapies, of which many are repurposed and used for other diseases in the last decade such in Influenza and Ebola. We intend to provide a robust foundation for cardiovascular outcomes of the therapies to better understand the rationale for the clinical trials that were conducted during the COVID-19 pandemic, and to gain more clarity on the steps moving forward should the repurposing provide clinical benefit in pandemic situations. With this state-of-the-art review, we aim to improve the understanding of the cardiovascular involvement of the therapies prior to, during, and after the COVID-19 pandemic to provide meaningful findings to the cardiovascular specialists and clinical trials for therapies, moving on from the period of pandemic urgency.

Assessing the knowledge, attitude, and practice measures against tuberculosis in patients in ambulatory department facilities in Pakistan: a cross-sectional analysis.

Tuberculosis (TB), at present, is the leading infectious etiology of death globally. In Pakistan, there are approximately 510,000 new cases annually, with more than 15,000 of them developing into drug-resistant TB, making the nation the fifth-leading country in TB prevalence in the world. Due to the ongoing COVID-19 pandemic, the focus has drifted away from TB screening, diagnostic and health awareness campaigns, and therapeutic measures endangering knowledge, attitude, and practices (KAP) towards TB in our population. We conducted a cross-sectional descriptive study in Pakistan to assess the KAP of Pakistani residents attending the adult outpatient departments of public hospitals for any health-related concerns. Our sample size was 856 participants, with a median age of 22 years. Occupation-wise, those who were employed had better knowledge of TB than those who were unemployed [odds ratio (OR): 1.011; 95% confidence interval (CI): 1.005-1.8005]. No differences were observed in TB knowledge between those adherents to common preventive practices versus those not adherent (OR: 0.875; 95% CI: 0.757-1.403). More than 90% of participants agreed that TB is dangerous for the community, and the majority opted against stigmatizing TB patients (79.1%). People who could read and write were 3.5 times more likely to have a good attitude towards TB compared to those who could not (OR: 3.596; 95% CI: 1.821-70.230; p=0.037). Similarly, employed subjects had better attitudes compared to unemployed ones (OR: 1.125; 95% CI: 0.498-1.852; p=0.024) and those with better knowledge of TB had a better attitude grade (OR: 1.749; 95% CI: 0.832-12.350; p=0.020). Age, occupation, and educational status were statistically significant among the two groups (p=0.038, p=0.023, p=0.000). Literate subjects had three times better practice towards TB than illiterate subjects (OR: 3.081; 95% CI: 1.869-4.164; p=0.000). Future education and awareness programs should target specific groups, such as the unemployed and illiterate, with practice-focused approaches. Our study outcomes can enable the concerned officials and authorities to take appropriate evidence-based steps to direct the efforts efficiently to curtail the burden of TB in Pakistan and to limit its progression, which could potentially lead our nation to become a multi drug-resistant TB endemic territory.

Use of Dupilumab in Glucocorticoid-Dependent Asthma.

Of the patients with asthma, 20% to 25% progress to severe symptoms, resulting in poor quality of life and increased episodes of exacerbation. There is a broad range of drugs used for asthma; the most used medications for severe asthma are inhaled glucocorticoids with or without long-acting ß-agonists. Systemic glucocorticoids and other treatments as add-on therapies are also given as needed. Chronic glucocorticoid use is associated with numerous adverse effects, including diabetes mellitus, osteoporosis, anxiety, depression, and cataracts. The occurrence of these side effects has been reduced because of the emergence of new biological therapies. One such treatment is dupilumab, which helps in the reduction of type 2 inflammation involved in the pathophysiology of asthma. We conducted a literature review to assess the efficacy, adverse effects, and pharmacological benefits of dupilumab in glucocorticoid-dependent asthma. In most randomized controlled trials, dupilumab has shown significant efficacy and safety profile in patients with severe asthma with corticosteroid dependence. Associated adverse effects such as injection site reaction and transient eosinophilia have been reported. Our review of the literature indicates that dupilumab has proven to improve lung function, reduce the rate of asthma exacerbations, and reduce the use of corticosteroids.

Isolated Pneumopericardium: A Rare Complication Secondary to COVID-19 Infection.

Pneumopericardium in the setting of COVID-19 is a rare incident. Typically, COVID-19 manifests with respiratory failure, cytokine storm, and gastrointestinal and cardiac symptoms. Chest X-ray (CXR) shows patchy peripheral opacities in bilateral lung fields and computed tomography (CT) shows multifocal ground-glass opacities in a COVID-19 patient. However, CXR is relatively less specific when compared to CT. In this case report, we present a case of isolated pneumopericardium (without pneumomediastinum) in a young female patient with COVID-19 pneumonia. Not only is the mechanism of development of pneumopericardium in COVID-19 patients poorly understood, but it is also considered a bad prognostic factor that leads to mortality.

Treatment with therapeutic plasma exchange in severe COVID-19 pneumonia: A case report and review of the literature.

The role of various therapeutic approaches on the clinical improvement in patients with severe COVID-19 is being researched. Few published studies show positive outcomes after the use of therapeutic plasma exchange (TPE). However, additional clinical evidence is required to understand better the role of therapeutic plasma exchange in severe COVID-19 patients. Thereby, we report a case of a 57-year-old female with laboratory-confirmed COVID-19 who was included in clinical trial NCT04592705. Prompt treatment with TPE facilitated improved clinical-laboratory parameters and speedy recovery and prevented further deterioration of the condition or complications. Successful therapeutic strategies in our case suggest that TPE as a therapeutic option in critically ill COVID-19 patients could prevent the disease from worsening and reduce the need for mechanical ventilation and intensive supportive care in these patients.

Association of Intestinal Microbial Dysbiosis With Chronic Obstructive Pulmonary Disease.

Normal gut flora plays various beneficial roles for the human body, including the protection against inflammatory states and mucosal viral infections. It also influences the immune system of the body. The metabolites produced by the gut bacteria control local and other systemic organs' immune functions like the lungs and brain, playing a role in their response to acute and chronic illnesses. Probiotics have shown beneficial effects on lung health. On the contrary, dysbiosis is associated with several diseases, including asthma, chronic bronchitis, emphysema, allergies, and other acute viral infections. By altering the diet of patients with respiratory diseases like patients with chronic obstructive pulmonary diseases (COPD), we may be able to mitigate their conditions. This literature review aims to discuss the mechanisms altering the gastrointestinal flora, the pathophysiology of gut and lung axis, the role of diet in gut microbe health, and the association of COPD with gut dysbiosis and peptic ulcer disease (PUD). We have extracted the data from PubMed and Google Scholar, consisting of review articles, case-control studies, and animal studies. The studies showed an association between gut microbes and different lung diseases. It is found that gut dysbiosis not only disrupts intestinal immunity but may also facilitate the development of COPD. Present studies also show an increased seroprevalence of Helicobacter pylori in patients with COPD. The strategies that can improve lung functions, especially in COPD patients, include prebiotics and probiotic supplementation to a diet more balanced than the current average American diet.

Cerebral Venous Sinus Thrombosis in a Patient With Mild Symptoms of COVID-19 Pneumonia.

Although coronavirus disease 2019 (COVID-19) infection is mainly associated with pneumonia, several non-respiratory complications may also occur. Cerebral venous sinus thrombosis (CVST) is a rare but potentially fatal complication of COVID-19 infection. In order to increase awareness about such life-threatening complications to a large population of patients with otherwise mild COVID-19 infection, we present the clinical course of a 29-year-old unvaccinated female who developed CVST, with eight days of mild COVID-19 infection, that proved fatal despite adequate therapeutic measures. Clinicians should carefully consider the risk of thrombosis in patients who present with COVID-19 infection regardless of the intensity of the disease, including prophylaxis (to reduce the risk of hypercoagulable complications) and treatment beyond discharge. More data and research is needed to identify COVID-19 as an independent risk factor for thromboembolism so that future efforts can be aimed at appropriate management e.g. with prophylactic anticoagulants to avoid such complications. In case of unexplained neurological manifestations in patients with an active or recent COVID-19 infection, early investigations for cerebrovascular integrity should be done by using MRI and magnetic resonance angiography (MRA)/magnetic resonance venography (MRV).

Airway Hygiene in COVID-19 Pneumonia: Treatment Responses of 3 Critically Ill Cruise Ship Employees.

BACKGROUND COVID-19, the disease entity caused by the novel severe acute respiratory coronavirus 2 (SARS-CoV-2), continues to pose a major therapeutic challenge for clinicians. At present, an effective treatment regimen and vaccination has not been established. Many patients develop severe symptoms requiring endotracheal intubation and a prolonged stay in the Intensive Care Unit (ICU). In early postmortem examinations of COVID-19 patients, profuse viscous secretions were observed throughout the respiratory tract. Thus, oxygen supplementation without aggressive pulmonary hygiene management may be suboptimal. In the present case series, pulmonary hygiene management encompassed mucolytics, bronchodilators, and tracheal suctioning. We report 3 severe cases of COVID-19 pneumonia in cruise ship employees who were admitted to the ICU and responded to supportive mechanical ventilation and pulmonary hygiene management. CASE REPORT Three cruise ship employees with COVID-19 underwent endotracheal intubation and were admitted to the ICU for acute hypoxemic respiratory failure. Initial chest X-rays suggested multifocal pneumonia with superimposed acute respiratory distress syndrome (ARDS). A regimen of hydroxychloroquine, azithromycin, and dexamethasone was initiated on admission in all cases. Additionally, medications used for pulmonary hygiene were administered through a metered-dose inhaler (MDI) in line with the ventilator circuit. Endotracheal suctioning was performed prior to medication administration. The duration from endotracheal intubation to extubation ranged from 9 to 24 days. All 3 patients reached 30-day survival. CONCLUSIONS The cases reported highlight the importance of the use of airway hygiene with mucolytics, bronchodilators, and tracheal suctioning for patients with COVID-19 pneumonia requiring ventilatory support.

Treatment of Severe COVID-19 with Tocilizumab Mitigates Cytokine Storm and Averts Mechanical Ventilation During Acute Respiratory Distress: A Case Report and Literature Review.

COVID-19, caused by the novel severe acute respiratory coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China, in 2019 and has resulted in the current pandemic. The disease continues to pose a major therapeutic challenge. Patient mortality is ultimately caused by acute respiratory distress syndrome (ARDS). Cytokine release syndrome (or "cytokine storm") is likely to be a contributing factor to ARDS in many patients. Because interleukin 6 (IL-6) is known to play a key role in inflammation, IL-6 receptor inhibitors such as tocilizumab may potentially treat COVID-19 by attenuating cytokine release. We present the case of a 48-year-old male with severe COVID-19, on the verge of meeting intubation requirements, who needed progressive oxygen support for respiratory distress. The patient was treated with a non-weight-based dosage of tocilizumab to prevent the onset of a cytokine storm. We chose to administer an IL-6 inhibitor because of the gradually increasing levels of acute phase reactants identified on serial blood draws, as well as his declining respiratory status. The treatment was well-tolerated in conjunction with standard drug therapies for COVID-19 (hydroxychloroquine, azithromycin, and zinc). The patient subsequently experienced marked improvements in his respiratory symptoms and overall clinical status over the following days. We believe that tocilizumab played a substantial role in his ability to avert clinical decline, particularly the need for mechanical ventilation. Ultimately, the patient was downgraded from the ICU and discharged within days. We highlight the potential of IL-6 inhibitors to prevent the progression of respiratory disease to a point requiring ventilator support. This case underscores the potential importance of early serial measurements of IL-6 and cytokine storm-associated acute phase reactants, such as ferritin, D-dimer, and C-reactive protein, in guiding clinical decision-making in the management of patients with suspected COVID-19. Conclusion: The early, proactive identification of serum acute phase reactants should be implemented in the treatment of COVID-19 in order to screen for a primary contributor to mortality-the cytokine storm. This screening, when followed by aggressive early treatment for cytokine storm, may have optimal therapeutic benefits and obviate the need for mechanical ventilation, thereby decreasing mortality. Additionally, we review current evidence regarding cytokine release syndrome in COVID-19 and the use of IL-6 receptor inhibition as a therapeutic strategy, and examine other reported cases in the literature describing IL-6 antagonist treatment for patients with COVID-19.

A Pathophysiological Perspective on COVID-19's Lethal Complication: From Viremia to Hypersensitivity Pneumonitis-like Immune Dysregulation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the coronavirus responsible for our recent coronavirus disease 2019 pandemic, is driving a lung immunopathology that strongly resembles a severe form of hypersensitivity pneumonitis (HP). A review of recent Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV-2 medical reports, as well as described characteristics of HP, lead us to postulate a theory for SARS-CoV-2 severe disease. We propose that the novel SARS-CoV-2 can act as a trigger and substrate of an HP-like severe immune reaction especially in genetically vulnerable individuals in addition to those with immune senescence and dysregulation. Accordingly, the purpose of our letter is to shift the emphasis of concern surrounding immune activity from viral infection to an HP-like severe immune reaction. We review similarities in disease presentation between infection and allergy, relevant immunopathology, and outline phases of SARS-CoV-2 disease with perspectives on therapy and critical care. Altogether, the favored course is to begin treatments that address the disease at the earliest phase before immune dysregulation leading to uncontrolled pulmonary inflammation.