Acute Respiratory Syndrome Disease Research Articles

Active vitamin D supplementation and COVID-19 infections: review.

SARS-CoV-2, causing the lethal disease COVid-19, is a public health emergency in the 2020 global pandemic. The outbreak and fast spreading of SARS-CoV-2 have a high morbidity and mortality specifically in elder patients with chronic diseases such as diabetes mellitus, arterial hypertension, chronic kidney disease, and organ transplanted patients with immunosuppressive therapy. Preliminary results support different treatments such as chloroquine and convalescent plasma infusion in severe cases, with good outcome. On the other hand, the efficacy of supplementation with active vitamin D, an immunomodulator hormone with antiinflammatory and antimicrobial effects, is unproven. A recent study reported that vitamin D attains antiviral effects, via blocking viral replication directly. SARS-CoV-2 primarily uses the immune evasion process during infection via the envelope spike glycoprotein, which is followed by a cytokine storm, causing severe acute respiratory disease syndrome and death. SARS-CoV-2, by using the well-known angiotensin-converting enzyme 2 by the protein spike, as the host receptor to enter into alveolar, myocardial, and renal epithelial cells, can be disrupted by vitamin D. However, the correlation between vitamin D levels and COVID-19 deaths in previous studies was insignificant. Retrospective studies demonstrated a correlation between vitamin D status and COVID-19 severity and mortality, while other studies did not find this correlation. Studies have shown that, vitamin D reduces the risk of acute viral respiratory tract infections and pneumonia via direct inhibition of viral replication, antiinflammatory and immunomodulatory effects. The data available today regarding the beneficial protective effect of vitamin D is unclear and with conflicting results. Large randomized control trials are necessary to test this hypothesis. In this review, we will explain the cross talk between the active vitamin D and the angiotensin-converting enzyme 2, and summarize the data from the literature.

Are numbers deceptive? Is death auditing a solution for death analysis, among the COVID-19 deceased?: A study from a dedicated COVID-19 hospital in Faridabad, Haryana.

Background:COVID-19 pandemic has havocked the entire world and India has not been spared. The focus is not only on the containment but on the reduction in mortality also. The objective of the study was to know the trend of COVID-19 deaths in a 510-bedded dedicated COVID-19 hospital and to determine the cause of death and various factors associated with these deaths.Method:A descriptive study was conducted in a COVID-dedicated hospital setting to analyze deaths occurring during April--July, 2020 using a standard death audit proforma.Results:A total number of 95 COVID-19 patients died in ICU. The mortality rate among ICU patients varied from 24.6% to 52.9%. Most of the cases were referred from other hospitals. About 64% of the deceased was admitted in severe condition and 34% of cases were referred on ventilator support. The week-wise trend revealed a positive association between the number of deaths and the number of referred cases as well as the number of patients received on ventilator support and in severe condition. About one-third of cases were late in seeking treatment at health centers with the same weekly trend. Being unaware of the condition (1%) and the stigma associated with the disease (32%) were the reasons behind it. Common direct causes of death were pneumonia (73%), pneumonia complicated with sepsis (16%), and acute respiratory disease syndrome (ARDS) (7%).Conclusion:High case fatality rate in the ICU of a referral COVID-dedicated hospital is mainly because of the admission of patients in severe conditions.

384. Invasive aspergillosis in COVID-19 patients in an intensive care unit in Mexico City

BackgroundAn elevated incidence of invasive pulmonary aspergillosis (IPA) in patients with COVID-19 without traditional risk factors for IPA has been recently reported around the world. This co-infection has been described in patients requiring treatment in an intensive care unit. The risk factors for its development are still unclear.MethodsWe conducted a nested case-control study using the COVID-19 registry of the ARMII study group, based in the Centro Médico ABC, a private hospital in Mexico City. We included all patients that required admission to the intensive care unit (ICU) from March 12 to June 15, 2020, and excluded patients without serum galactomannan measurements or bronchial secretion cultures. We used the modified definition of IPA proposed by Schauwvlieghe et al for IPA in influenza patients. The control group was formed by patients with ruled-out IPA (negative galactomannan and secretion cultures). We compared both groups to identify risk factors for IPA using the chi-squared test or the Mann-Whitney U test as applicable.ResultsOut of a total 239 patients, 54 met the inclusion criteria. We identified 13 patients with IPA (24.07%) that met the definition of IPA (2 with positive cultures and 11 with positive galactomannan) and 41 without IPA. Only three patients with IPA had important comorbidities (COPD, chronic kidney disease, and HIV). Patients with IPA tended to have a higher median age (64.6 vs 53.59, p=0.075) and a higher serum glucose at their arrival (145 vs 119, p=0.028). All patients with IPA presented to the hospital with ARDS (100% vs 72.5%, p=0.034), but ultimately did not have a higher requirement for mechanical ventilation (100% vs 82.93%, p=0.110). There were no statistical significant differences in use of Tocilizumab, use of glucocorticoids, mortality (23.07% vs 17.50%, p=0.563) or length of stay.ConclusionIt has been previously described that patients with acute respiratory disease syndrome triggered by viral infection, like the influenza virus, are prone to invasive aspergillosis even in the absence of underlying immunodeficiency. The use of antifungals to prevent aspergillosis in COVID-19 patients should be assessed because of the gravity presented in the patients with this co-infection.Disclosures All Authors: No reported disclosures

Validating Measures of Disease Severity in Acute Respiratory Distress Syndrome.

Rationale: Quantifying acute respiratory disease syndrome (ARDS) severity is essential for prognostic enrichment to stratify patients for invasive or higher-risk treatments; however, the comparative performance of many ARDS severity measures is unknown.Objectives: To validate ARDS severity measures for their ability to predict hospital mortality and an ARDS-specific outcome (defined as death from pulmonary dysfunction or the need for extracorporeal membrane oxygenation [ECMO] therapy).Methods: We compared five individual ARDS severity measures including the ratio of arterial oxygen tension/pressure to fraction of inspired oxygen (PaO2/FiO2 ratio), oxygenation index, ventilatory ratio, lung compliance, and radiologic assessment of lung edema (RALE); two ARDS composite severity scores including the Murray Lung Injury Score, and a novel score combining RALE, PaO2/FiO2 ratio, and ventilatory ratio; and the Acute Physiology and Chronic Health Evaluation IV score, using data collected at ARDS onset in patients hospitalized at a single center in 2016 and 2017. Discrimination of hospital mortality and the ARDS-specific outcome was evaluated using the area under the receiver operator characteristic curve (AUROC). Measure calibration was also evaluated.Results: Among 340 patients with ARDS, 125 (37%) died during hospitalization and 36 (10.6%) had the ARDS-specific outcome, including one who received ECMO. Among the five individual ARDS severity measures, the RALE score had the highest discrimination of the ARDS-specific outcome (AUROC = 0.67; 95% confidence interval [CI], 0.58-0.77), although other ARDS severity measures had similar performance. However, their ability to discriminate overall mortality was low. In contrast, the Acute Physiology and Chronic Health Evaluation IV score best discriminated overall mortality (AUROC = 0.73; 95% CI, 0.67-0.79) but was unable to discriminate the ARDS-specific outcome (AUROC = 0.54; 95% CI, 0.44-0.65). Among ARDS composite severity scores, the lung injury score had an AUROC = 0.67 (95% CI, 0.58-0.75) for the ARDS-specific outcome whereas the novel score had an AUROC = 0.70 (95% CI, 0.61-0.79). Patients grouped by quartile of the novel score had a 6%, 2%, 10%, and 24% rate of the ARDS-specific outcome.Conclusions: Although most ARDS severity measures had poor discrimination of hospital mortality, they performed better at predicting death from severe pulmonary dysfunction or ECMO needs. A novel composite score had the highest discrimination of this outcome.

278: Potential Biomarkers for Severe ARDS in the Setting of SARS-CoV-2 ICU Admission

INTRODUCTION: Acute respiratory disease syndrome (ARDS) is due to compromised lung oxygen exchange in the setting of severe alveolar inflammation This can be assessed and diagnosed using the ratio of alveolar oxygen saturation (PaO2) to the fraction of inspired oxygen (FiO2), P-F ratio In hospitalized COVID-19 patients, the role of trending inflammatory markers to categorize levels of ARDS severity in the clinical setting has yet to be established In this study, we describe the correlational relationship of five biomarkers to the PaO2/FiO2 ratio (P-F ratio), a key diagnostic criterion, and a measure of severity in ARDS METHODS: This is a prospective cohort analysis of SARs-CoV-2 patients admitted to the ICU at a single urban academic center from March to June 2020 Levels of Endotoxin activity assay (EAA), CRP, ferritin, LDH, and d-dimer were obtained from intubated patients throughout their ICU stay PaO2 and FiO2 values matching the same days as the biomarkers and demographic information were abstracted from the medical record The inflammatory markers were matched to the P-F ratios of the same day, and Spearman Correlation Coefficients were performed to detect the relationship between them RESULTS: A total of 45 intubated COVID patients were included, with baseline characteristics of: median age 55 years and 33% female, 62% Black, 27% Hispanic, 9% Asian, and 2% White Spearman Correlation Coefficient (ρ) showed statistically significant relationships between P/F ratios and EAA, IL-6, CRP, and ESR, with respective values of: ρ (89)=-0 2366, p=0 02;ρ (13)=-0 7143, p=0 006;ρ (77)=-0 3670, p=0 001;ρ (17)=-0 5569, p=0 02 ρ was also calculated between P/F ratios and Ferritin, D-dimer, WBC, and LDH with respective values of: ρ (77)=0 0819, p=0 47;ρ (78)=-0 2105, p=0 06;ρ (88)=-0 1046, p=0 33;ρ (73)=0 0420, p=0 72, showing no statistically significant relationship between these variables CONCLUSIONS: EAA, IL-6, CRP, and ESR levels had a statistically significant negative correlation with the P-F ratio Elevations in these biomarkers correlated with worsening P-F ratios, suggesting that they could serve as useful biomarkers to predict ARDS severity Additional studies are needed to further understand the trend of these biomarkers and validate their clinical use in prognostication in ARDS

270: Extracorporeal Membrane Oxygenation for COVID-19 Treatment in a Community Hospital

INTRODUCTION: Coronavirus disease 2019 (COVID-19) infection may result in severe acute respiratory disease syndrome (ARDS) and death For COVID-19 patients failing mechanical ventilation, extra corporeal membrane oxygenation (ECMO) has been used with varying efficacy in academic medical centers and quaternary referral centers METHODS: During the three-month study period, 70 patients with COVID-19 were admitted to the ICU at Regional Medical Center of San Jose From this cohort, 57 (81%) developed acute respiratory failure requiring mechanical ventilation Seven (12%) of the mechanically ventilated patients developed progressive ARDS and met criteria for initiation of ECMO All patients receiving VV ECMO were younger than 70 years of age with a median age of 57 years Four of the seven patients were women and three were men The median body mass index (BMI) was 36 kg/ m2 and two of the seven patients met the criteria for morbid obesity with a BMI greater than 40 kg/m2 The median duration of VV ECMO was eleven days with a minimum of six days and a maximum of 37 days The median duration of mechanical ventilation pre-ECMO was five days and post-ECMO eight days Five of the seven (71%) VV ECMO patients survived to discharge Two of the seven patients were discharged home, two to long-term ambulatory care (LTAC) facilities and one transferred to another hospital due to third-party payer request Two patients died, one during ECMO cannulation with perforation of the right ventricle Another patient died after six days of VV ECMO following cardiopulmonary arrest that resulted in severe cerebral anoxia For the mechanically ventilated patients in our ICU who did not receive VV ECMO, 34 of 50 patients (68%) survived to discharge With VV-ECMO rescue treatment the overall mortality rate for all mechanically ventilated COVID-19 patients decreased from 40 3% to 31 5% RESULTS: We report the successful use of veno-venous (VV) ECMO to treat refractory ARDS due to COVID-19 in a community hospital setting with survival to discharge rate of 71% over a three-month period In a community hospital with adequate resources, VV ECMO can be an effective rescue therapy for selected COVID-19 patients who fail all other available treatments

Pathway enrichment analysis of virus-host interactome and prioritization of novel compounds targeting the spike glycoprotein receptor binding domain–human angiotensin-converting enzyme 2 interface to combat SARS-CoV-2

SARS-CoV-2 has become a pandemic causing a serious global health concern. The absence of effective drugs for treatment of the disease has caused its rapid spread on a global scale. Similarly to the SARS-CoV, the SARS-CoV-2 is also involved in a complex interplay with the host cells. This infection is characterized by a diffused alveolar damage consistent with the Acute Respiratory Disease Syndrome (ARDS). To explore the complex mechanisms of the disease at the system level, we used a network medicine tools approach. The protein-protein interactions (PPIs) between the SARS-CoV and the associated human cell proteins are crucial for the viral pathogenesis. Since the cellular entry of SARS-CoV-2 is accomplished by binding of the spike glycoprotein binding domain (RBD) to the human angiotensin-converting enzyme 2 (hACE2), a molecule that can bind to the spike RDB-hACE2 interface could block the virus entry. Here, we performed a virtual screening of 55 compounds to identify potential molecules that can bind to the spike glycoprotein and spike-ACE2 complex interface. It was found that the compound ethyl 1-{3-[(2,4-dichlorobenzyl) carbamoyl]-1-ethyl-6-fluoro-4-oxo-1,4-dihydro-7-quinolinyl}-4-piperidine carboxylate (the S54 ligand) and ethyl 1-{3-[(2,4-dichlorobenzyl) carbamoyl]-1-ethyl-6-fluoro-4-oxo-1,4-dihydro-7-quinolinyl}-4 piperazine carboxylate (the S55 ligand) forms hydrophobic interactions with Tyr41A, Tyr505B and Tyr553B, Leu29A, Phe495B, respectively of the spike glycoprotein, the hotspot residues in the spike glycoprotein RBD-hACE2 binding interface. Furthermore, molecular dynamics simulations and free energy calculations using the MM-GBSA method showed that the S54 ligand is a stronger binder than a known SARS-CoV spike inhibitor SSAA09E3 (N-(9,10-dioxo-9, 10-dihydroanthracen-2-yl) benzamide). Communicated by Ramaswamy H. Sarma

Digestive symptoms and liver injury in patients with coronavirus disease 2019 (COVID-19): A systematic review with meta-analysis.

Although most COVID‐19 patients typically present with respiratory symptoms, many patients could experience digestive symptoms as the major complaint. We performed a systematic review and meta‐analysis to investigate the exact prevalence of digestive symptoms and liver injury in COVID‐19 patients and compare the difference between patients with and without digestive symptoms. PubMed, Embase, Ovid, Wanfang data, and CNKI were searched until 24 April 2020 to identify studies that reported digestive symptoms and liver injury in COVID‐19 patients. A random‐effect model was used to combine the data. Finally, 64 studies with 15 141 patients were included. The pooled rate of digestive symptoms and liver dysfunction was 31.8% (95 CI 21.0–42.5%, I 2 = 97.6%) and 27.4% (95 CI 16.9–37.9%, I 2 = 97.9%), respectively. Patients with digestive symptoms were more likely to present with fatigue (OR 2.28, 95 CI 1.66–3.14, P < 0.00001, I 2 = 31%), myalgia (OR 1.96, 95 CI 1.06–3.65, P = 0.03, I 2 = 69%), and acute respiratory disease syndrome (ARDS) (OR 2.94, 95 CI 1.17–7.40, P = 0.02, I 2 = 0) and had a trend to present as severe/critical type (OR 1.87, 95 CI 0.98–3.57, P = 0.06, I 2 = 58%). Severe/critical patients were more likely to present with diarrhea (OR 2.02, 95 CI 1.16–3.50, P = 0.01, I 2 = 64) and have high alanine aminotransferase (ALT) (OR 2.08, 95 CI 1.55–2.81, P < 0.00001, I 2 = 13%,) and aspartate aminotransferase (AST) (OR 3.53, 95 CI 2.76–4.51, P < 0.00001, I 2 = 0). The pooled rate of patients with digestive symptoms was 28.7% (95 CI 17.6–39.8%) and 42.8% (95 CI 23.4–62.3%) in studies from China and out of China, respectively. COVID‐19 patients had a high rate of digestive symptoms and liver injury. Patients with digestive symptoms had a trend to develop severe/critical illness.

Role of IFN and Complements System: Innate Immunity in SARS-CoV-2.

The critical role of the innate immune system has been confirmed in driving local and systemic inflammation and the cytokine release storm in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This dysregulated immune response is focused on interferon (IFN) and complement activation, which are crucial for the development of metabolic inflammation, local lung tissue damage, and systemic multi-organ failure. IFNs control viral infections by inducing expression of IFN-stimulated genes (ISGs) that restrict distinct steps of viral replication. Therefore, in this review article, we propose the mechanism of SARS-CoV-2-associated acute respiratory disease syndrome, and assess treatment options by considering IFNs and by targeting IFN-antagonist SARS-CoV-2 virulent gene products. Furthermore, we elaborate on the mechanism of the amplified complement-mediated inflammatory cytokine storm, and propose an antiviral and immunotherapeutic strategy against coronavirus disease 2019 (COVID-19).

Thrombosis and Hemostasis Issues in Cancer Patients with COVID-19.

Coronavirus disease 2019 (COVID-19) is an infectious pandemic disorder caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), a single-stranded RNA β-coronavirus. Virus particles that can be inhaled through the respiratory system and invade lung alveolar cells may cause a limited viral disease. However, in some patients, severe complications, including systemic inflammatory response syndrome, acute respiratory disease syndrome, multiple organ failure, and shock may develop. These presentations are particularly frequent among several risk groups, including older patients, those with hypertension, obesity, cardiovascular, pulmonary and renal diseases, autoimmunity disturbances, and cancer. COVID-19 is associated with severe thrombotic complications, both micro- and macrovascular, substantially including deep vein thrombosis (DVT), pulmonary embolism (PE), primary pulmonary arterial thrombosis, up to disseminate intravascular coagulation (DIC)-like syndrome.[1] [2] [3] [4]

Oxygen-ozone (O2-O3) immunoceutical therapy for patients with COVID-19. Preliminary evidence reported

ObjectiveThis study evaluated the potential efficacy of a novel approach to treat COVID-19 patients, using an oxygen-ozone (O2-O3) mixture, via a process called Oxygen-Ozone- Immunoceutical Therapy. The methodology met the criteria of a novel, promising approach to treat successfully elderly COVID-19 patients, particularly when hospitalized in intensive care units (ICUs) Experimental design: We investigated the therapeutic effect of 4 cycles of O2-O3 in 50 hospitalized COVID-19 subjects suffering from acute respiratory disease syndrome (ARDS), aged more than 60 years, all males and undergoing non invasive mechanical ventilation in ICUs. ResultsFollowing O2-O3 treatment a significant improvement in inflammation and oxygenation indexes occurred rapidly and within the first 9 days after the treatment, despite the expected 14–20 days. A significant reduction of inflammatory and thromboembolic markers (CRP, IL-6, D-dimer) was observed. Furthermore, amelioration in the major respiratory indexes, such as respiratory and gas exchange markers (SatO2%, PaO2/FiO2 ratio), was reported. ConclusionOur results show that O2-O3 treatment would be a promising therapy for COVID-19 patients. It leads patients to a fast recovery from ARDS via the improvement of major respiratory indexes and blood gas parameters, following a relatively short time of dispensed forced ventilation (about one to two weeks). This study may encourage the scientific community to further investigate and evaluate the proposed method for the treatment of COVID-19 patients.

Important Management Considerations In Patients With Pituitary Disorders During The Time Of The Covid-19 Pandemic

Objective: In December 2019, a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused an outbreak of coronavirus disease 2019 (COVID-19) that resulted in a global pandemic with substantial morbidity and mortality. Currently, there is no specific treatment or approved vaccine against COVID-19. The underlying associated comorbidity and diminished immune function of some pituitary patients (whether caused by the disease and its sequelae or treatment with excess glucocorticoids) increases their risk of contracting and developing complications from COVID-19 infection.Methods: A review of studies in PubMed and Google Scholar published between January 2020 to the time of writing (May 1, 2020) was conducted using the search terms ‘pituitary,’ ‘coronavirus,’ ‘COVID-19’, ‘2019-nCoV’, ‘diabetes mellitus’, ‘obesity’, ‘adrenal,’ and ‘endocrine.’Results: Older age and pre-existing obesity, hypertension, cardiovascular disease, and diabetes mellitus increase the risk of hospitalization and death in COVID-19 patients. Men tend to be more severely affected than women; fortunately, most men, particularly of younger age, survive the infection. In addition to general comorbidities that may apply to many pituitary patients, they are also susceptible due to the following pituitary disorder–specific features: hypercortisolemia and adrenal suppression with Cushing disease, adrenal insufficiency and diabetes insipidus with hypopituitarism, and sleep-apnea syndrome and chest wall deformity with acromegaly.Conclusion: This review aims to focus on the impact of COVID-19 in patients with pituitary disorders. As most countries are implementing mobility restrictions, we also discuss how this pandemic has affected patient attitudes and impacted our decision-making on management recommendations for these patients.Abbreviations: ACE = angiotensin-converting enzyme; AI = adrenal insufficiency; ARB = angiotensin receptor blocker; ARDS = acute respiratory disease syndrome; COVID-19 = coronavirus disease 2019; CPAP = continuous positive airway pressure; DI = diabetes insipidus; DM = diabetes mellitus; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2

Attitudinal, regional and sex related vulnerabilities to COVID-19: Considerations for early flattening of curve in Nigeria.

Background: In Nigeria, the policies and interventions due to the COVID-19 pandemic are majorly directed at businesses and relief. There are no clear plans to identify individuals with comorbidities associated with high morbidity and fatality rates. This paper identifies comorbidities associated with high morbidity and fatalities of COVID-19 across countries and vulnerable groups in Nigeria. Methods: Peer-reviewed articles published between 2010 and 2020 retrieved from Google scholar, African Journal Online, EMBASE, Scopus, and MEDLINE/PubMed (central) were systematically reviewed. Results: The pooled prevalence of hypertension is the lowest in North Central Nigeria (22.0%) and the highest in South-Eastern Nigeria (33.6%) while the pooled prevalence of diabetes mellitus (DM) is lowest in North-Western Nigeria (3.0%) and highest in South-Southern Nigeria (9.8%). Significant differences in the frequency of comorbidities (hypertension, DM, cardiovascular disease, cancer, and chronic kidney disease; CKD) and complications (cardiac injury and acute respiratory disease syndrome; ARDS) were observed between fatal and non-fatal cases of COVID-19 (p<0.0001). There were significant correlations between hypertension and ARDS (p=0.002), DM and ARDS (p=0.010), hypertension and (p<0.0001), DM and CKD (p=0.033), and hypertension and DM (p=0.001). Conclusion: High prevalence of comorbidity may be predictive of high COVID-19 morbidity and mortality. Thus, to flatten the curve early intervention funds should be appropriately allocated based on the prevalence of comorbidities in the geopolitical zones. Such high-risk groups should be identified, stratified and actively monitored during treatment to prevent the development or progression of complications such as cardiac injury and ARDS.

Fluid Therapy in COVID-19 Disease: Review

COVID-19 pandemic due to the new corona virus 2019 is an important cause global problems. This infection begins with symptoms such as fever, cough, anorexia, malaise, sore throat, and can progress to acute respiratory disease syndrome (ARDS) and necessitating intensive care unit (ICU) admission with an estimated mortality rate of 3%.There is no confirmed specific antiviral treatment despite different treatment protocols. Supportive care especially fluid therapy plays a very important role in this disease. The aim of this review is to Institute effective strategies for effective fluid therapy in critically ill pediatric patients admitted to ICU. Keywords: COVID-19; Corona virus disease 2019; SARS-CoV-2; Fluids; Child; Intensive care.

Ventilator-associated Events in Children: Controversies and Research Needs.

Ventilator-associated Events in Children: Controversies and Research Needs.

Hiding in Plain Sight: an Approach to Treating Patients with Severe COVID-19 Infection.

Patients with COVID-19 infection are at risk of acute respiratory disease syndrome (ARDS) and death. The tissue receptor for COVID-19 is ACE2, and higher levels of ACE2 can protect against ARDS. Angiotensin receptor blockers and statins upregulate ACE2. Clinical trials are needed to determine whether this drug combination might be used to treat patients with severe COVID-19 infection.

The Role of Computerized Tomography Scan in Diagnosis and Management of Coronavirus Disease 2019 (COVID-19)

Coronavirus disease 2019 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Today we are facing a global epidemic Fever, cough, fatigue, breathlessness, and smell or taste loss are the most frequent clinical symptoms In most cases, the symptoms are mild However, it may occasionally progress to widespread thrombosis, septic shock, or acute respiratory disease syndrome (ARDS) The incubation period is usually about 5 days, but can vary from 2 to 14 days Early quarantine is vital for preventing the complications and rapid spread of the disease Real-time reverse transcription-polymerase chain reaction (RT-PCR) of a nasopharyngeal sample is the standard diagnostic test However, this method is expensive and unavailable in many parts of the country, and has delayed results On the other hand, computerized tomography scan (CT-scan) is widely available and low-cost throughout the country, and provides immediate results with high sensitivity Indeed, in some cases, CT-scan is capable of providing evidence for the disease before detection of viral RNA from upper respiratory samples CT-scan exhibits higher sensitivity, but lower specificity for diagnosis of COVID-19, compared to RT-PCR (sensitivity of 59-78% and 95-98% as well as specificity of approximately 100% and 96% for RT-PCR and chest CT-scan, respectively) Low sensitivity for diagnosis of COVID-19 and ionizing radiation exposure are two major disadvantages of CT-scan, which can be resolved to a large extent by clinical and laboratory correlations and utilizing low-dose CT protocols It seems that CT-scan can be ordered for diagnosis of COVID-19 when PCR test is not feasible, or in case of high clinical suspicion in spite of negative PCR In addition, CT-scan plays a major role in assessing the severity, extent and prognosis of the disease in monitoring the response to treatment, and in diagnosis of complications

The pathophysiology of the haematological manifestations of COVID-19 : a review

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the coronavirus disease 2019 (COVID-19) it causes, are associated with several haematological abnormalities which manifest as some of the clinical syndromes seen in COVID-19. The main organ affected by COVID-19 is the lung, where an intense inflammatory response occurs in the alveoli and the lung vasculature. This may result in severely compromised gaseous exchange consistent with acute respiratory disease syndrome (ARDS). Multiple organ failure and death may ensue. The extent to which SARS-CoV-2 directly affects erythroid, granulocytic and monocytic progenitors is unknown, however related Coronaviridae have previously been shown to infect megakaryocytes and their progenitors. Furthermore, SARS-CoV-2 may directly infect lymphocytes or monocytes causing the production of cytokines and chemokines, which then cause lymphocyte death and lymphopenia. The quantitative changes seen in monocytes and granulocytes are at least partly due to the marked increase in various cytokines also called the “cytokine storm” and the downstream effects of these cytokines. A COVID-19-associated coagulopathy (CAC) may occur, which ranges from a mild derangement of laboratory haemostatic tests, through to sepsis-induced coagulopathy (SIC), and later, frank disseminated intravascular coagulation (DIC). The most common and devastating haemostatic abnormality is widespread thrombosis, which is associated with severe lung inflammation, hypoxia and death. COVID-19 is associated with immune perturbation states namely, immune thrombocytopenia (ITP), Guillain-Barré syndrome, the anti-phospholipid syndrome and a Kawasaki-like syndrome in children. The pathophysiology of the haematological abnormalities seen in COVID-19 is briefly reviewed in this article.

Lactate and Echocardiography Before Veno-Venous Extracorporeal Membrane Oxygenation Support

Lactate has been recognised as a prognostic factor in several critical conditions. Veno-Venous Extracorporeal Membrane Oxygenation (VV-ECMO) is a well-established therapy in patients with Acute Respiratory Disease Syndrome (ARDS) unresponsive to conventional therapy and echocardiography pre ECMO initiation has been recently reported to help in risk stratifying these patients. We assessed whether the detection of hyperlactataemia could be associated with the presence of left ventricle (LV) or right ventricle (RV) dysfunction in 121 consecutive patients with refractory ARDS. The mortality rate was 42.9% (52/121). Higher dosages of norepinephrine and dobutamine were administered to non survivors (p=0.023 and p=0.047, respectively) who showed significantly higher levels of lactate (p=0.002). At echocardiography, non survivors showed higher values of systolic pulmonary artery pressure (sPAP) (p=0.05) and a higher incidence of RV dysfunction (as indicated by lower Tricuspid Annular Plane Excursion (TAPSE)) and RV dilatation (p=0.001). At multivariate logistic regression analysis, the following variables were independent predictors of death: body mass index (BMI) (OR: 0.914, 95%CI 0.857-0.975, p=0.006), RV dilatation (OR: 0.239, 95%CI 0.101-0.561, p=0.001) and lactate (OR: 1.292, 95%CI 1.015-1.645, p=0.038). Lactate values were directly correlated with the simplified acute physiology score (SAPS) II (r=0.38, p<0.001), while they showed an indirect correlation with left ventricular ejection fraction (LVEF) (r=-0.24, p=0.009) and TAPSE (r=-0.21, p=0.024). In refractory ARDS, hyperlactataemia before VVV-ECMO identified a subset of patients at higher risk of death, being an independent predictor of in-Intensive Care Unit (ICU) mortality. Lactate values are mainly related to disease severity (as indicated by SAPS II) and haemodynamic impairment (as inferred by LVEF) and RV failure, as (indicated by TAPSE).

ECLS: Past, present, and future

Extracorporeal life support (ECLS) is the prototype example of translational research. It began in laboratory studies to design, test, and characterize devices for prolonged extracorporeal circulation in the 1960s. The first clinical cases of ECLS for heart and lung failure were in the 1970s. These cases were met with skepticism, but the results in neonatal respiratory failure were encouraging. In the early 1980s, two centers conducted randomized trials in neonates, which demonstrated much higher survival with ECLS, and the term extracorporeal membrane oxygenation (ECMO) was coined. By 1986, there were 18 neonatal ECMO centers and data on 700 cases. These centers formed a consortium (The Extracorporeal Life Support Organization: ELSO) to maintain the registry, define guidelines and techniques, provide education, and hold an annual meeting. In the 1990s, these centers expanded indications to older children with lung and heart failure. ECMO management for post-operative cardiac failure became standard in major pediatric heart centers. A multi-center randomized trial in the UK demonstrated a major survival advantage to ECMO in neonates. A few centers continued to evaluate and improve ECMO and extracorporeal CO2 removal (ECCOR) in adults with 50–60% survival in uncontrolled case series. At the ELSO meeting in 1999, a group met to plan a randomized trial in adult respiratory failure (ARDS). That study was carried out in the UK from 2002 to 2006 (the CESAR trial) using the same study design as the neonatal trial. The results were similar to the neonatal trial but adult intensivists were still skeptical, arguing that the single ECMO center in Leicester was just better at respiratory care than the other non-ECMO centers. During all this time, we used modified pumps, oxygenators, and other equipment designed for cardiac surgery. A new medical profession of “ECMO specialist” developed to manage the ECMO system and patient. The number of specialists determined the number of ECMO cases that could be treated. Around 2008, a few companies made major improvements in these devices and manufactured specific ECMO machines. These machines were much safer, simpler, and reliable than the early ECMO equipment, and patients could be managed for weeks, primarily by the bedside ICU nurse with support from the specialist. This new equipment came along at the same time as the H1N1 flu pandemic of 2008–2009. ECMO was remarkably successful in saving the sickest patients, and adult intensivists scrambled to learn the technology. This was born out by two matched-pairs trials. ECMO for ARDS (acute respiratory disease syndrome) grew rapidly in adult intensive care units (ICU). The use of awake ambulatory ECMO as a bridge to lung transplantation has been expanded to all ECMO patients, in fact, to all ICU patients.1 Currently, ECMO is used for severe heart and lung failure in all ages. Research is focused on improving anticoagulation and devices, defining indications, and new applications like septic shock, ECPR for cardiac arrest, and EDCD to salvage organs for transplantation. Laboratory research has continued as clinical practice proceeded, and it currently includes an artificial placenta for very premature infants and four versions of implantable, wearable lungs for chronic support.2