Clinical Presentation and Phenotypes in COVID-19

Since the beginning of the COVID-19 pandemic, researchers have focused on the different clinical presentations of the disease. The existence of a broad spectrum of respiratory compromise has been initially interpreted as the manifestation of different clinical phenotypes, with peculiar pathophysiological aspects translating into different requirements of respiratory support. Extensive research now converges on interpreting these phenotypes as different stages rather than distinct manifestations of the same pathology. While not all patients will evolve from an early COVID-19 pneumonia to an established COVID-19 related acute respiratory distress syndrome (ARDS), the correct identification of the disease phase will translate into different therapeutic approaches. This chapter discusses the classification of COVID-19 phenotypes based on imaging and respiratory mechanics parameters, also in relation with the differences and similarities with the ARDS from causes other than COVID-19. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Invasive Mechanical Ventilation in COVID-19

Patients with severe COVID-19 pneumonia present with severe hypoxemic respiratory failure, typically meet the clinical criteria for acute respiratory distress syndrome (ARDS) and often require invasive mechanical ventilation. While peculiar pathophysiological aspects deserve discussion to better tailor the mechanical ventilation settings in these patients, most recommendations on the ventilatory management of these patients are derived from studies in patients with ARDS from causes other than COVID-19. Protective ventilation is recommended in most COVID-19 patients, tidal volume should be kept around 6 mL per kg of predicted body weight, positive end-expiratory pressure (PEEP) should be titrated individually considering that in many patients with COVID-19 improvement of oxygenation at higher PEEP is often accompanied by worsening of respiratory system compliance. Therefore, attention should be paid in limiting plateau and driving pressures to avoid excessive strain potentially resulting in ventilator-induced lung injury. Prone positioning has been used extensively in COVID-19 patients, but its impact on mortality is uncertain. Inhaled nitric oxide, extracorporeal CO2 removal (ECCO2R), and extracorporeal membrane oxygenation (ECMO) should be considered in selected patients as rescue measures. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Role of Point-of-Care Ultrasound in the Management of Mechanical Ventilation

Ultrasound (US) became an essential tool in the hands of the intensivist and is now recommended both for procedural guidance and diagnostic purposes. Point-of-care ultrasound (POCUS) is an immediately available and repeatable, non-irradiating bedside tool integrating the clinical examination. Recent years were characterized by a growing interest in the fields of lung ultrasound (LUS) and diaphragm ultrasound (DUS). The combination of these two ultrasound techniques with critical care echocardiography (CCE) may integrate the classical approach to mechanically ventilated patients, both for monitoring and diagnostic purposes, finally contributing to the titration of mechanical ventilation and to the management of respiratory disease. Lung, diaphragm, and cardiac US provide significant information to improve the management of the critical patient under mechanical ventilation, from the initial assessment, through the ventilation setting (like PEEP) and its complication diagnosis (like pneumothorax, atelectasis), until the weaning process. LUS is of particular help in COVID-19 patients. It is potentially able to distinguish between the two phenotypes (type H and type L) of COVID-19, based on the different signs and patterns and also the assessment of prone positioning effects and lung recruitment maneuvers in these patients. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Olokizumab reduces the risks of death in hospitalized patients with moderate and severe COVID-19

Aim - to evaluate the efficacy and safety of olokizumab in hospitalized patients with moderate to severe coronavirus disease COVID-19. Material and methods. A multicenter non-interventional retrospective study of olokizumab treatment in hospitalized patients with COVID-19 was conducted. The initial population in this study included 2926 patients with COVID-19. Patients with moderate or severe disease who were taking corticosteroids as part of standard therapy were selected for this analysis. The final population was 1738 patients. A test group (standard therapy: corticosteroids, antiviral, pathogenetic or symptomatic therapy in combination with olokizumab) and a comparison group (standard therapy only) were formed. Each group included 869 patients. The primary end point was all-cause mortality from the start of anti-inflammatory therapy to the end of follow-up. We also analyzed the incidence of transfer and the length of stay of patients in the intensive care unit, the duration of hospitalization, as well as the change in C-reactive protein level. Results and discussion. It was found that olokizumab significantly reduces the all-cause mortality compared with standard therapy: 54 (6.21%) cases compared with 111 (12.77%) in the control arm, p<0.001, odds ratio (OR) 2.21 [1.57;3.1]. The results of factor analysis confirmed that olokizumab increases the odds of recovery, OR 2.41 (95% CI 1.64-3.54, p<0.001). In addition, patients in olokizumab group showed significantly lower plasma CRP levels compared with control group. Already on the 2nd day after the start of therapy the CRP level was almost 2 times lower in the olokizumab group than in the control group (the median was 13 [5.6;28.55] mg/l and 25 [15.3;79.25] mg/L in the olokizumab and comparison groups, respectively). Conclusion. The results of the study confirm the clinical data on the efficacy of olokizumab as therapy for COVID-19 patients.Copyright © 2022 Tomsk Polytechnic University, Publishing House. All rights reserved.

Emergency lower segment caesarean section (LSCS) in a patient of corona virus 2019 (COVID19) with Acute Respiratory Distress syndrome (ARDS) under spinal anesthesia -- a case report

Introduction: COVID19 has exposed vulnerable populations, including pregnant women, to an unprecedented public health crisis, leading to increased risk of infection and adverse maternal and perinatal outcomes. Case report: A 31 year old morbidly obese female presented to Nair Hospital with complaints of breathlessness, fever, dry cough, and loss of taste and smell. Her RTPCR of 04/09/2020 was positive for COVID19. Discussion: The decision to use a particular anesthetic technique for cesarean delivery is based on a variety of factors, including risks to the parturient or fetus and the skill set of the provider. Spinal anesthesia was preferred to general anesthesia due to the benefits outweigh the risk. Regional anesthesia aids in the reduction of pain scores and opioid consumption, postoperative nausea and vomiting, and the risk of aspiration and difficult airway associated with general anesthesia. During tracheal intubation, the risk of transmission of upper respiratory tract infection to healthcare providers is known to be 6.6 times greater than those not exposed to intubation. Additionally, the maintenance of pulmonary function may reduce postoperative complications in a patient with COVID-19 and associated pneumonia or acute respiratory distress syndrome. Conclusion: The number of COVID-19 cases has exceeded 92.3 million worldwide, and there is still limited data on the care and management of parturients with COVID-19. It is important to share experiences and practices to ensure the best care for these women. [ FROM AUTHOR] Copyright of Journal of Cardiovascular Disease Research (Journal of Cardiovascular Disease Research) is the property of Journal of Cardiovascular Disease Research and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

COVID-19 ARDS MANAGEMENT IN AN INTENSIVE CARE WARD USING ANTI-CD6 MONOCLONAL ANTIBODY: A CASE SERIES

Background: Covid-19 ARDS is a common presentation in the emergency ward and needs quick assessment and treatment. Material and Methods: This case series was aggregated from patients admitted to the emergency ward, with a diagnosis of mild to moderate ARDS with impending cytokine release syndrome (CRS). Results: These 10 patients were treated with antiCD6 monoclonal antibody, Itolizumab as it had been given emergency use approval for critically ill patients on CRS. Of the 10 patients, 8 received Itolizumab on day 2 while 2 received it on day 1. Nine out of ten patients recovered and were discharged, while one patient died. Patients' progress was monitored by daily evaluation of patients' CRP and cytokine (IL-6) levels, LDH, and clinical and radiological assessment. All 10 patients were observed for oxygen delivery parameters including days of ventilation support, and total oxygen delivery. Conclusion: The administration of antiCD6 monoclonal antibody, itolizumab early has shown to reduce the duration of ventilation support to 5.4 days, total oxygen requirements to 12 days, and hospital stay to 13.3 days. [ FROM AUTHOR] Copyright of Journal of Cardiovascular Disease Research (Journal of Cardiovascular Disease Research) is the property of Journal of Cardiovascular Disease Research and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Pathology of COVID-19 Infection

COVID-19 pandemic which started in 2019 in Wuhan, China, later spread to other parts of the world as a major disaster. Two years back, it was considered predominantly a pulmonary disease, however, it is now thought to be a multisystem disorder. With the emergence of new mutants, the spectrum of disease has changed and widened. The interplay of cytokines and vasculopathy with the development of vascular thrombosis is chiefly responsible for diverse manifestations. The secondary infections in many patients, during as well as in the post-COVID period have resulted in higher morbidity and morbidity. A brief description of pathology in various organs is given below. © The Author(s), under exclusive licence to Springer Nature Singapore Pte Ltd. 2021.

Pathogenesis of COVID-19 Infection

Coronavirus disease 2019 (Covid-19) has produced a grave global pandemic and resulted in a serious public health crisis accompanied by loss of life and economy. The causative virus is known, but the exact pathogenesis and cascade of events that ensue are still poorly understood. It is now known that the virus enters through the respiratory route by attaching to ACE-2 receptors in the ciliated nasal mucosa. Infection of the lower respiratory system causes a surge in the release of a variety of cytokines that trigger a "cytokine storm” resulting in collateral damage to lungs and vascular endothelium. The damage to vascular endothelium results in multisystem involvement. © The Author(s), under exclusive licence to Springer Nature Singapore Pte Ltd. 2021.

Mechanical Ventilation in COVID

From the start of the pandemic, amid the frequency of cases with COVID-19 associated respiratory failure, mechanical ventilation has been the object of controversy. Reports associating its use with higher mortality, likely reflecting the severity of an unknown illness devastating the entire world, as well as the turmoil caused by the lack of sufficient equipment to supply the increasing demands in our hospitals, both were points of attention for media and public in general. However, from the clinical perspective, the need to apply different methods or to deviate from stablished guidelines to be able to adequately support these patients, was soon noticed. Multiple publications were guiding clinicians in the obscured territory of the unknown disease and to its variable impact on the respiratory system. This chapter aims to summarize the knowledge acquired throughout the pandemic, describing some of the elements of COVID-19 respiratory failure as well as its management with mechanical ventilation. The chapter recovers some of the increasing information appearing almost daily in the literature. We recognize that given the changing nature of the disease and the progressive knowledge of the same, some of the concepts covered in this chapter might be subject of some review or modification at the moment of the publication. We, the authors, have attempted to summarize the existing evidence and to maintain a basic conceptual approach to the management of COVID-19 respiratory failure. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Current status and prospect of global development of lung transplantation

During the novel coronavirus pneumonia (COVID-19) pandemic from 2020 to 2021, lung transplantation entered a new stage of development worldwide. Globally, more than 70 000 cases of lung transplantation have been reported to the International Society for Heart and Lung Transplantation (ISHLT). With the development of medical techniques over time, the characteristics of lung transplant donors and recipients and the indications of pediatric lung transplantation recipients have undergone significant changes. Application of lung transplantation in the treatment of COVID-19-related acute respiratory distress syndrome (ARDS) has also captivated worldwide attention. Along with persistent development of lung transplantation, it will be integrated with more novel techniques to make breakthroughs in the fields of artificial lung and xenotransplantation. In this article, research progresses on the characteristics of lung transplant donors and recipients around the world were reviewed and the development trend was predicted, enabling patients with end-stage lung disease to obtain more benefits from the development of lung transplantation technique.Copyright © 2022 Organ Transplantation. All rights reserved.

Mechanical Ventilation in ARDS

Acute respiratory distress syndrome (ARDS) is a form of hypoxemic respiratory failure, which requires supplemental oxygen delivered by mechanical ventilation, either noninvasively or more commonly by invasive mechanical ventilation. Although not currently meeting the definition for ARDS, these patients may also use heated high-flow nasal cannula and can sometimes avoid invasive mechanical ventilation as a result. The avoidance of worsening acute lung injury using lung-protective ventilation is the first principle of invasive mechanical ventilation in these patients. Conventionally, this involves keeping the plateau pressure below 30 cm H2O by using low tidal volume ventilation, based on ideal body weight. Multiple observational series suggest that targeting a low driving pressure concurrently is also important. The determination of the optimal setting for positive end-expiratory pressure (PEEP) remains controversial. The mode of ventilation utilized may be either volume or pressure limited. It has been suggested that vigorous respiratory efforts can worsen lung injury and are best avoided whenever possible. Modes of ventilation such as airway pressure release ventilation lack evidence to support use and should not be used. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Diffuse Alveolar Damage in COVID-19 Infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was the cause of the recent pandemic, with deaths worldwide. Diffuse alveolar damage (DAD) was a universal finding in these COVID-19-related deaths. We present here a case of a COVID-19 infected pregnant woman dying from DAD, confirmed on histopathologic examination of the lungs on autopsy. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022.

Development and prospect of clinical research on lung transplantation in post-COVID-19 era

Lung transplantation has been advanced for nearly half a century around the globe, and it has been developed rapidly for over 20 years in China. The field of lung transplantation in China has been gradually integrated into the international community. The outbreak of novel coronavirus pneumonia (COVID-19) in 2020 brought big challenges, as well as diverted the worldwide attention to the development of lung transplantation in China, accelerating international communication and cooperation. With the steadily deepening of clinical and basic research on lung transplantation for severe cases of COVID-19, organ transplant physicians have deepened the understanding and thinking of the maintenance of donors, selection of elderly and pediatric candidates, and perioperative management of recipients, as the future perspective of lung transplantation in China. For interdisciplinary research related to lung transplantation, it is necessary to carry out multi-center clinical trials with qualified study design and constantly promote the theoretic and practical innovation.Copyright © 2021 The authors.

Prone position in spontaneous ventilation? An induction problem: A scoping review

Intoduction: Prone position in spontaneous ventilation is not a recent strategy, and despite the many years it has been trying to consolidate, it has not been able to prove to be of real utility. During the recent pandemic, prone spontaneous ventilation re-emerged as a practical and simple alternative, although it was highly questioned due to its weak level of evidence. With time and experience, it was gradually relegated to become only an attractive hypothesis. Objective: This study aims to analyze the potential benefits of prone position in spontaneous ventilation in patients with hypoxemia caused by SARS-CoV-2. Methods: A panoramic review of the most relevant studies published in the MEDLINE, Embase and Scopus databases up to December 20, 2021 was performed. Results: After screening, 4 observational studies, 1 randomized clinical trial, and 3 systematic reviews were selected for analysis. Conclusions: By statistical analysis we concluded that prone position in spontaneous ventilation, although it could delay intubation, did not improve survival in hypoxemic subjects with viral pneumonia caused by coronavirus type 2. © 2023 Asociación Colombiana de Medicina Crítica y Cuidado lntensivo

C reactive protein utilisation, a biomarker for early COVID-19 treatment, improves lenzilumab efficacy: results from the randomised phase 3 'LIVE-AIR' trial.

OBJECTIVE: COVID-19 severity is correlated with granulocyte macrophage colony-stimulating factor (GM-CSF) and C reactive protein (CRP) levels. In the phase three LIVE-AIR trial, lenzilumab an anti-GM-CSF monoclonal antibody, improved the likelihood of survival without ventilation (SWOV) in COVID-19, with the greatest effect in participants having baseline CRP below a median of 79 mg/L. Herein, the utility of baseline CRP to guide lenzilumab treatment was assessed. DESIGN: A subanalysis of the randomised, blinded, controlled, LIVE-AIR trial in which lenzilumab or placebo was administered on day 0 and participants were followed through Day 28. PARTICIPANTS: Hospitalised COVID-19 participants (N=520) with SpO2 ≤94% on room air or requiring supplemental oxygen but not invasive mechanical ventilation. INTERVENTIONS: Lenzilumab (1800 mg; three divided doses, q8h, within 24 hours) or placebo infusion alongside corticosteroid and remdesivir treatments. MAIN OUTCOME MEASURES: The primary endpoint was the time-to-event analysis difference in SWOV through day 28 between lenzilumab and placebo treatments, stratified by baseline CRP. RESULTS: SWOV was achieved in 152 (90%; 95% CI 85 to 94) lenzilumab and 144 (79%; 72 to 84) placebo-treated participants with baseline CRP <150 mg/L (HR: 2.54; 95% CI 1.46 to 4.41; p=0.0009) but not with CRP ≥150 mg/L (HR: 1.04; 95% CI 0.51 to 2.14; p=0.9058). A statistically significant interaction between CRP and lenzilumab treatment was observed (p=0.044). Grade ≥3 adverse events with lenzilumab were comparable to placebo in both CRP strata. No treatment-emergent serious adverse events were attributed to lenzilumab. CONCLUSION: Hospitalised hypoxemic patients with COVID-19 with baseline CRP <150 mg/L derived the greatest clinical benefit from treatment with lenzilumab. TRIAL REGISTRATION NUMBER: NCT04351152; ClinicalTrials.gov.

Impact of the MCP-1-2518A>G polymorphism on COVID-19 severity in the Iranian population: A case-control study.

As a result of SARS-CoV-2 infection, the host's immune system is disrupted, and chemokines and cytokines are intensified to eliminate the virus, resulting in cytokine storm syndrome and acute respiratory distress syndrome (ARDS). Patients with COVID-19 have been observed to have elevated levels of MCP-1, a chemokine associated with the severity of the disease. In some diseases, polymorphisms in the regulatory region of the MCP-1 gene correspond to serum levels and disease severity. An attempt was made in this study to assess the relationship between MCP-1 G-2518A and serum MCP-1 levels in Iranian COVID-19 patients and the severity of the disease. In this study, patients were randomly sampled from outpatients on the first day of diagnosis and from inpatients on the first day of their hospitalization. Patients were classified into the outpatient (without symptoms or with mild symptoms) and inpatient (with moderate, severe, and critical symptoms) groups. The serum level of MCP-1 was measured by ELISA and the frequency of MCP-1 G-2518A gene polymorphism genotypes in COVID-19 patients was checked by the RFLP-PCR method. Participants with COVID-19 infection had a higher rate of underlying diseases, such as diabetes, high blood pressure, kidney disease, and cardiovascular disease than the control group (P-value < 0.001). Also, the frequency of these factors in inpatients was significantly higher compared to outpatients (P-value < 0.001). Additionally, the level of MCP-1 in serum was significantly different with an average of 11.90 in comparison to 2.98 in the control group (P-value, 0.05), which is attributed to elevated serum levels among patients in hospitals with an average of 11.72 in comparison to 2.98 in the control group. Compared with outpatients, inpatients had a higher frequency of the G allele of the MCP-1-2518 polymorphism (P-value < 0.05), while a notable difference was observed in the serum level of MCP-1 in COVID-19 patients with the MCP-1-2518 AA genotype in the whole group in comparison to the control group (P-value: 0.024). Totally, the results showed that a high frequency of the G allele is related to hospitalization and poor outcome in COVID-19 cases.

Remdesivir treatment and clinical outcome in non-severe hospitalized COVID-19 patients: a propensity score matching multicenter Italian hospital experience.

INTRODUCTION: Remdesivir exerts positive effects on clinical improvement, even though it seems not to affect mortality among COVID-19 patients; moreover, it was associated with the occurence of marked bradycardia. METHODS: We retrospectively evaluated 989 consecutive patients with non-severe COVID-19 (SpO2 ≥ 94% on room air) admitted from October 2020 to July 2021 at five Italian hospitals. Propensity score matching allowed to obtain a comparable control group. Primary endpoints were bradycardia onset (heart rate < 50 bpm), acute respiratory distress syndrome (ARDS) in need of intubation and mortality. RESULTS: A total of 200 patients (20.2%) received remdesivir, while 789 standard of care (79.8%). In the matched cohorts, severe ARDS in need of intubation was experienced by 70 patients (17.5%), significantly higher in the control group (68% vs. 31%; p < 0.0001). Conversely, bradycardia, experienced by 53 patients (12%), was significantly higher in the remdesivir subgroup (20% vs. 1.1%; p < 0.0001). During follow-up, all-cause mortality was 15% (N = 62), significantly higher in the control group (76% vs. 24%; log-rank p < 0.0001), as shown at the Kaplan-Meier (KM) analysis. KM furthermore showed a significantly higher risk of severe ARDS in need of intubation among controls (log-rank p < 0.001), while an increased risk of bradycardia onset in the remdesivir group (log-rank p < 0.001). Multivariable logistic regression showed a protective role of remdesivir for both ARDS in need of intubation (OR 0.50, 95%CI 0.29-0.85; p = 0.01) and mortality (OR 0.18, 95%CI 0.09-0.39; p < 0.0001). CONCLUSIONS: Remdesivir treatment emerged as associated with reduced risk of severe acute respiratory distress syndrome in need of intubation and mortality. Remdesivir-induced bradycardia was not associated with worse outcome.

A primer on proning in the emergency department.

Historically, the prone position was used almost exclusively in the ICU for patients suffering from refractory hypoxemia due to acute respiratory distress syndrome (ARDS). Amidst the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, however, this technique has been increasingly utilized in settings outside of the ICU, particularly in the emergency department. With emerging evidence that patients diagnosed with COVID-19 who are not intubated and mechanically ventilated may benefit from the prone position, this strategy should not be isolated to only those with critical illness. This is a review of the pertinent physiology and evidence supporting prone positioning along with a step-by-step guide meant to familiarize those who are not already comfortable with the maneuver. Placing a patient in the prone position helps to improve ventilation-perfusion matching, dorsal lung recruitment, and ultimately gas exchange. Evidence also suggests there is improved oxygenation in both mechanically ventilated patients and those who are awake and spontaneously breathing, further reinforcing the utility of the prone position in non-ICU settings. Given present concerns about resource limitations because of the pandemic, prone positioning has especially demonstrable value as a technique to delay or even prevent intubation. Patients who are able to self-prone should be directed into the ''swimmer's position'' and then placed in reverse Trendelenburg position if further oxygenation is needed. If a mechanically ventilated patient is to be placed in the prone position, specific precautions should be taken to ensure the patient's safety and to prevent any unwanted sequelae of prone positioning.