Fatal Coronavirus Disease 2019 Cases Research Articles

Development and validation of nomogram models for severe and fatal COVID-19

BackgroundThe coronavirus disease 2019 (COVID-19) has exhibited escalating contagion and resistance to immunity, resulting in a surge in infections and severe cases. This study endeavors to formulate two nomogram predictive models aimed at discerning patients at heightened risk of severe and fatal outcomes upon hospital admission. The primary objective is to enhance clinical management protocols and mitigate the incidence of severe illness and mortality associated with COVID-19.Methods1600 patients diagnosed with COVID-19 and discharged from Fujian Provincial Hospital were chosen as the subjects of this study. These patients were categorized into three groups: mild group (n = 940), severe group (n = 433), and fatal group (n = 227). The patients were randomly divided into training and validation cohorts in a 7:3 ratio. COVID-19 symptoms were treated as dependent variables, and univariate regression analysis was conducted for the laboratory indicators. Risk factors with p-values greater than 0.05 in the univariate regression analysis were eliminated. The remaining risk factors were then analyzed using direct multiple regression analysis to establish an unadjusted model. Subsequently, risk factors with p-values greater than 0.05 were further removed. Clinical characteristics were added to the model as adjustment factors, and the method of multiple stepwise regression analysis was employed to derive the final fully adjusted model. The severe and fatal COVID-19 models were converted into nomograms, respectively. Receiver operating characteristic (ROC) curves were utilized to evaluate the discrimination of the nomogram models. Calibration was assessed using the Hosmer-Lemeshow test and calibration curves. Clinical benefit was evaluated by decision curve analysis.ResultsCompared to the mild group, individuals in the severe COVID-19 group exhibited significant increases in age, neutrophil (NEU), and lactate dehydrogenase (LDH) levels, alongside notable decreases in lymphocyte (LYM) and albumin (ALB) levels. Nomogram model incorporating age, NEU, LDH, LYM, and ALB demonstrated efficacy in predicting the onset of severe COVID-19 (AUC = 0.771). Furthermore, history of cerebral infarction and cancer, LDH and ALB as risk factors for fatal COVID-19 cases compared to the severe group. The nomogram model comprising these factors was capable of early identification of COVID-19 fatalities (AUC = 0.748).ConclusionsElevated age, NEU, and LDH levels, along with decreased LYM and albumin (ALB) levels, are risk factors for severe illness in hospitalized patients with COVID-19. A history of cerebral infarction and tumors, along with elevated LDH and decreased ALB levels, are risk factors for death in critically ill patients. The nomogram model based on these factors can effectively predict the risk of severe or fatal illness from COVID-19, thereby assisting clinicians in timely interventions to reduce the rates of severe illness and mortality among hospitalized patients. However, the model faces challenges in processing longitudinal data and specific points in time, indicating that there is room for improvement.

SARS-CoV-2 NSP16 promotes IL-6 production by regulating the stabilization of HIF-1α

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of coronavirus disease 2019 (COVID-19). Severe and fatal COVID-19 cases often display cytokine storm i.e. significant elevation of pro-inflammatory cytokines and acute respiratory distress syndrome (ARDS) with systemic hypoxia. Understanding the mechanisms of these pathogenic manifestations would be essential for the prevention and especially treatment of COVID-19 patients. Here, using a dual luciferase reporter assay for hypoxia-response element (HRE), we initially identified SARS-CoV-2 nonstructural protein 5 (NSP5), NSP16, and open reading frame 3a (ORF3a) to upregulate hypoxia-inducible factor-1α (HIF-1α) signaling. Further experiments showed NSP16 to have the most prominent effect on HIF-1α, thus contributing to the induction of COVID-19 associated pro-inflammatory response. We demonstrate that NSP16 interrupts von Hippel-Lindau (VHL) protein interaction with HIF-1α, thereby inhibiting ubiquitin-dependent degradation of HIF-1α and allowing it to bind HRE region in the IL-6 promoter region. Taken together, the findings imply that SARS-CoV-2 NSP16 induces HIF-1α expression, which in turn exacerbates the production of IL-6.

Immunopathogenesis of Lung in Fatal COVID-19 Cases in Erbil, Iraq

Coronavirus disease 2019 (COVID-19) infection is caused by severe acute respiratory syndrome coronavirus-2 (SARS-Cov-2). It is characterized by respiratory distress, multiorgan dysfunction and death in some cases. The host immune response to SARS-CoV-2 appears to play a critical role in disease pathogenesis and clinical manifestation. However the pathological mechanism underling the disease has not been fully defined. Lung autopsy samples from 3 patients with fatal COVID-19 were evaluated using hematoxylin and eosin stain to analyze the histopathological changes. While immunohistochemical (IHC) staining was performed for detecting CD4 in helper T-cells, CD8 in cytotoxic T-cells, CD56 in NK-cells and CD45RO in memory T-cells. Histopathological examination revealed features of diffuse alveolar damage (DAD) with exudate in alveolar space and infiltration of inflammatory cells. Immunohistochemistry staining for CD4 showed weak to positive staining, CD8 showed weak positive staining, CD56 showed negative staining, while CD45RO showed a positive staining. It can be concluded that SARS-CoV-2 virus impaired innate immune response through a decrease in NK cells and adaptive immune response through a decrease in CD8 T cells which is one of the explanations of the destructive nature of SARS-CoV-2 virus.

Pulmonary Co-Infections Detected Premortem Underestimate Postmortem Findings in a COVID-19 Autopsy Case Series.

Bacterial and fungal co-infections are reported complications of coronavirus disease 2019 (COVID-19) in critically ill patients but may go unrecognized premortem due to diagnostic limitations. We compared the premortem with the postmortem detection of pulmonary co-infections in 55 fatal COVID-19 cases from March 2020 to March 2021. The concordance in the premortem versus the postmortem diagnoses and the pathogen identification were evaluated. Premortem pulmonary co-infections were extracted from medical charts while applying standard diagnostic definitions. Postmortem co-infection was defined by compatible lung histopathology with or without the detection of an organism in tissue by bacterial or fungal staining, or polymerase chain reaction (PCR) with broad-range bacterial and fungal primers. Pulmonary co-infection was detected premortem in significantly fewer cases (15/55, 27%) than were detected postmortem (36/55, 65%; p < 0.0001). Among cases in which co-infection was detected postmortem by histopathology, an organism was identified in 27/36 (75%) of cases. Pseudomonas, Enterobacterales, and Staphylococcus aureus were the most frequently identified bacteria both premortem and postmortem. Invasive pulmonary fungal infection was detected in five cases postmortem, but in no cases premortem. According to the univariate analyses, the patients with undiagnosed pulmonary co-infection had significantly shorter hospital (p = 0.0012) and intensive care unit (p = 0.0006) stays and significantly fewer extra-pulmonary infections (p = 0.0021). Bacterial and fungal pulmonary co-infection are under-recognized complications in critically ill patients with COVID-19.

Transcriptional Insights of Oxidative Stress and Extracellular Traps in Lung Tissues of Fatal COVID-19 Cases.

Neutrophil extracellular traps (NETs) and oxidative stress are considered to be beneficial in the innate immune defense against pathogens. However, defective clearance of NETs in the lung of acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients could lead to severe respiratory syndrome infection, the so-called coronavirus disease 2019 (COVID-19). To elucidate the pathways that are related to NETs within the pathophysiology of COVID-19, we utilized RNA sequencing (RNA-seq) as well as immunofluorescence and immunohistochemistry methods. RNA-seq analysis provided evidence for increased oxidative stress and the activation of viral-related signaling pathways in post-mortem lungs of COVID-19 patients compared to control donors. Moreover, an excess of neutrophil infiltration and NET formation were detected in the patients' lungs, where the extracellular DNA was oxidized and co-localized with neutrophil granule protein myeloperoxidase (MPO). Interestingly, staining of the lipid peroxidation marker 4-hydroxynonenal (4-HNE) depicted high colocalization with NETs and was correlated with the neutrophil infiltration of the lung tissues, suggesting that it could serve as a suitable marker for the identification of NETs and the severity of the disease. Moreover, local inhalation therapy to reduce the excess lipid oxidation and NETs in the lungs of severely infected patients might be useful to ameliorate their clinical conditions.

Abstract 14137: SARS-CoV-2 Spike Protein-Induced Inflammation Underlies Proarrhythmia in COVID-19

Cardiac manifestations are common in severe Coronavirus disease 2019 (COVID-19) with rates reported from 2% in non-ICU patients to 59% in non-survivors. Recent CDC data show that COVID-19 patients are at 1.7 higher risk of arrhythmia. AF, which is the most common arrhythmia, is a frequent complication of acute and long COVID-19. It has been reported that the SARS-CoV2 receptor, ACE2, is highly expressed in the heart, leading to the prevalent assumption that infectious virus likely underlies cardiac complications. However, the pathophysiology of cardiac disease in severe COVID-19 has yet to be clarified. We therefore compared the histologic and molecular findings in human cardiac tissue from fatal COVID-19 cases and age-matched controls. Hematoxylin and eosin (H&amp;E) stains revealed histologic changes in the COVID-19 samples, most notably multifocal endothelial cell swelling and degeneration plus microvascular thrombi. Distribution of SARS-CoV2 RNA and nucleocapsid protein expression was investigated by qRT-PCR and in situ hybridization (ISH). Trace amounts of viral RNA and no nucleocapsid protein were detected in the COVID-19 hearts. However, 7/11 COVID-19 hearts were positive for viral spike protein. Further validation by immunohistochemistry (IHC) showed that viral spike protein was detected in all 11 COVID-19 hearts. Co-expression analysis revealed that viral spike protein localized mostly to the ACE2+ interstitial macrophages/pericytes that were activated as evidenced by increased IL6 and TNFα expression. Previously, we identified a novel arrhythmia mechanism wherein inflammation-induced vascular endothelial dysfunction triggers cardiomyocyte structural remodeling, particularly of intercalated disc (ID) components including connexin-43 (Cx43) gap junctions and Na V 1.5 sodium channels, and thereby promotes arrhythmias. We therefore investigated ID structure in our human samples. Both Cx43 and Na V 1.5 showed marked lateral migration in myocytes of COVID-19 hearts, consistent with previous experiments with inflammatory insults in murine hearts. These findings suggest that the viral spike protein, and not direct infection by SARS-CoV2, results in the pathophysiology of cardiac dysfunction in fatal COVID-19.

Vitamin C Deficiency in Blood Samples of COVID-19 Patients.

Coronavirus disease 2019 (COVID-19) is the most notable pandemic of the modern era. A relationship between ascorbate (vitamin C) and COVID-19 severity is well known, whereas the role of other vitamins is less understood. The present study compared the blood levels of four vitamins in a cohort of COVID-19 patients with different severities and uninfected individuals. Serum concentrations of ascorbate, calcidiol, retinol, and α-tocopherol were measured in a cohort of 74 COVID-19 patients and 8 uninfected volunteers. The blood levels were statistically compared and additional co-morbidity factors were considered. COVID-19 patients had significantly lower plasma ascorbate levels than the controls (p-value < 0.001), and further stratification revealed that the controls had higher levels than fatal, critical, and severe COVID-19 cases (p-values < 0.001). However, no such trend was observed for calcidiol, retinol, or α-tocopherol (p-value ≥ 0.093). Survival analysis showed that plasma ascorbate below 11.4 µM was associated with a lengthy hospitalization and a high risk of death. The results indicated that COVID-19 cases had depleted blood ascorbate associated with poor medical conditions, confirming the role of this vitamin in the outcome of COVID-19 infection.

Comprehensive narrative review of real-world COVID-19 vaccines: viewpoints and opportunities.

Currently, people all over the world have been affected by coronavirus disease 2019 (COVID-19). Fighting against COVID-19 is the top priority for all the countries and nations. The development of a safe and effective COVID-19 vaccine is considered the optimal way of ending the pandemic. Three hundred and 44 vaccines were in development, with 149 undergoing clinical research and 35 authorized for emergency use as to March 15 of 2022. Many studies have shown the effective role of COVID-19 vaccines in preventing SARS-CoV-2 infections as well as serious and fatal COVID-19 cases. However, tough challenges have arisen regarding COVID-19 vaccines, including long-term immunity, emerging COVID-19 variants, and vaccine inequalities. A systematic review was performed of recent COVID-19 vaccine studies, with a focus on vaccine type, efficacy and effectiveness, and protection against SARS-CoV-2 variants, breakthrough infections, safety, deployment and vaccine strategies used in the real-world. Ultimately, there is a need to establish a unified evaluation standard of vaccine effectiveness, monitor vaccine safety and effectiveness, along with the virological characteristics of SARS-CoV-2 variants; and determine the most useful booster schedule. These aspects must be coordinated to ensure timely responses to beneficial or detrimental situations. In the future, global efforts should be directed toward effective and immediate vaccine allocations, improving vaccine coverage, SARS-CoV-2 new variants tracking, and vaccine booster development.

Epidemiology of coronavirus disease 2019 (COVID-19) in Japan during the first and second waves.

Following the emergence and worldwide spread of coronavirus disease 2019 (COVID-19), each country has attempted to control the disease in different ways. The first patient with COVID-19 in Japan was diagnosed on 15 January 2020, and until 31 October 2020, the epidemic was characterized by two large waves. To prevent the first wave, the Japanese government imposed several control measures such as advising the public to avoid the 3Cs (closed spaces with poor ventilation, crowded places with many people nearby, and close-contact settings such as close-range conversations) and implementation of "cluster buster" strategies. After a major epidemic occurred in April 2020 (the first wave), Japan asked its citizens to limit their numbers of physical contacts and announced a non-legally binding state of emergency. Following a drop in the number of diagnosed cases, the state of emergency was gradually relaxed and then lifted in all prefectures of Japan by 25 May 2020. However, the development of another major epidemic (the second wave) could not be prevented because of continued chains of transmission, especially in urban locations. The present study aimed to descriptively examine propagation of the COVID-19 epidemic in Japan with respect to time, age, space, and interventions implemented during the first and second waves. Using publicly available data, we calculated the effective reproduction number and its associations with the timing of measures imposed to suppress transmission. Finally, we crudely calculated the proportions of severe and fatal COVID-19 cases during the first and second waves. Our analysis identified key characteristics of COVID-19, including density dependence and also the age dependence in the risk of severe outcomes. We also identified that the effective reproduction number during the state of emergency was maintained below the value of 1 during the first wave.

Distinctive features of SARS-CoV-2-specific T cells predict recovery from severe COVID-19.

Although T cells are likely players in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity, little is known about the phenotypic features of SARS-CoV-2-specific T cells associated with recovery from severe coronavirus disease 2019 (COVID-19). We analyze T cells from 34 individuals with COVID-19 with severity ranging from mild (outpatient) to critical, culminating in death. Relative to individuals who succumbed, individuals who recovered from severe COVID-19 harbor elevated and increasing numbers of SARS-CoV-2-specific T cells capable of homeostatic proliferation. In contrast, fatal COVID-19 cases display elevated numbers of SARS-CoV-2-specific regulatory T cells and a time-dependent escalation in activated bystander CXCR4+ T cells, as assessed by longitudinal sampling. Together with the demonstration of increased proportions of inflammatory CXCR4+ T cells in the lungs of individuals with severe COVID-19, these results support a model where lung-homing T cells activated through bystander effects contribute to immunopathology, whereas a robust, non-suppressive SARS-CoV-2-specific T cell response limits pathogenesis and promotes recovery from severe COVID-19.

Clinical Characteristics and Histopathology of Coronavirus Disease 2019-Related Deaths in African Children.

Globally, very few childhood deaths have been attributed to coronavirus disease 2019 (COVID-19). We evaluated clinical, microbiologic and postmortem histopathologic findings in childhood deaths in whom severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified antemortem or postmortem. Surveillance of childhood deaths was ongoing during the initial COVID-19 outbreak in South Africa from April 14, 2020, to August 31, 2020. All children hospitalized during this time had a SARS-CoV-2 test done as part of standard of care. Postmortem sampling included minimally invasive tissue sampling (MITS) of lung, liver and heart tissue; blood and lung samples for bacterial culture and molecular detection of viruses (including SARS-CoV-2) and bacteria. The cause of death attribution was undertaken by a multidisciplinary team and reported using World Health Organization framework for cause of death attribution. SARS-CoV-2 was identified on antemortem and/or postmortem sampling in 11.7% (20/171) of deceased children, including 13.2% (12/91) in whom MITS was done. Eighteen (90%) of 20 deaths with SARS-CoV-2 infection were <12 months age. COVID-19 was attributed in the causal pathway to death in 91.7% (11/12) and 87.5% (7/8) cases with and without MITS, respectively. Lung histopathologic features in COVID-19-related deaths included diffuse alveolar damage (n = 6, 54.5%), type 2 pneumocyte proliferation (n = 6, 54.5%) and hyaline membrane formation (n = 5, 36.4%). Culture-confirmed invasive bacterial disease was evident in 54.5% (6/11) of COVID-19 attributed deaths investigated with MITS. COVID-19 was in the causal pathway of 10.5% (18/171) of all childhood deaths under surveillance. The postmortem histopathologic features in fatal COVID-19 cases in children were consistent with reports on COVID-19 deaths in adults; although there was a high prevalence of invasive bacterial disease in the children.

SARS-CoV-2 Induces Lymphocytopenia by Promoting Inflammation and Decimates Secondary Lymphoid Organs.

While lymphocytopenia is a common characteristic of coronavirus disease 2019 (COVID-19), the mechanisms responsible for this lymphocyte depletion are unclear. Here, we retrospectively reviewed the clinical and immunological data from 18 fatal COVID-19 cases, results showed that these patients had severe lymphocytopenia, together with high serum levels of inflammatory cytokines (IL-6, IL-8 and IL-10), and elevation of many other mediators in routine laboratory tests, including C-reactive protein, lactate dehydrogenase, α-hydroxybutyrate dehydrogenase and natriuretic peptide type B. The spleens and hilar lymph nodes (LNs) from six additional COVID-19 patients with post-mortem examinations were also collected, histopathologic detection showed that both organs manifested severe tissue damage and lymphocyte apoptosis in these six cases. In situ hybridization assays illustrated that SARS-CoV-2 viral RNA accumulates in these tissues, and transmission electronic microscopy confirmed that coronavirus-like particles were visible in the LNs. SARS-CoV-2 Spike and Nucleocapsid protein (NP) accumulated in the spleens and LNs, and the NP antigen restricted in angiotensin-converting enzyme 2 (ACE2) positive macrophages and dendritic cells (DCs). Furthermore, SARS-CoV-2 triggered the transcription of Il6, Il8 and Il1b genes in infected primary macrophages and DCs in vitro, and SARS-CoV-2-NP+ macrophages and DCs also manifested high levels of IL-6 and IL-1β, which might directly decimate human spleens and LNs and subsequently lead to lymphocytopenia in vivo. Collectively, these results demonstrated that SARS-CoV-2 induced lymphocytopenia by promoting systemic inflammation and direct neutralization in human spleen and LNs.

COVID-19-induced endotheliitis: emerging evidence and possible therapeutic strategies.

The coronavirus disease 2019 (COVID‐19) pandemic, a viral illness caused by the severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), 1 has produced at the time of this writing nearly 33 million cases of infection, with over a million deaths in 235 countries, 2 causing an unprecedented burden on healthcare systems and a severe global socioeconomic crisis. As the pandemic spreads, knowledge on the disease course, as well as potential risk factors and predictors of severity is increasing daily, and initial data from randomised controlled studies have allowed care providers to refine therapeutic strategies. Nonetheless, mortality is markedly elevated among those presenting with severe disease, long‐term sequelae among survivors are unknown, and vaccine‐based therapies currently remain at early stages of development. Most reported cases are asymptomatic or present with mild symptoms; however, 7–26% of hospitalised patients experience severe disease, often requiring admission to intensive care units (ICUs), with progressive multiple organ dysfunction and high mortality. 3 , 4 , 5 Such differences in clinical outcomes have led physicians to initiate diverse pharmacological therapies at various stages of the disease, generating challenges as to the most appropriate therapeutic choice for COVID‐19. In this context, the use of dexamethasone has significantly reduced mortality rates in critically ill patients requiring supplemental oxygen or mechanical ventilation, 6 and remdesivir has demonstrated clinical benefit in hospitalised patients, but with unknown survival benefit to date 7 ; additional effective treatment options are therefore urgently needed. In an initial attempt to provide a uniform and widely reproducible methodology to guide systematic treatment strategies, a three‐stage classification of COVID‐19 has been proposed. 8 The Stage I or ‘early infection’ occurs at the initial establishment of disease with high viral replication, and commonly presents with a range of complaints that can include mild and often non‐specific influenza‐like signs and symptoms. Stage II is the ‘pulmonary phase’, with preferential viral‐mediated injury of the lung parenchyma and this is characterised by shortness of breath, hypoxia and pulmonary infiltrates with some degree of lung inflammation. Stage III is characterised by an exaggerated host immune‐inflammatory response to the virus, leading to acute respiratory distress syndrome (ARDS) and multi‐organ failure (MOF).

Relevance and Clinical Significance of Magnetic Resonance Imaging of Neurological Manifestations in COVID-19: A Systematic Review of Case Reports and Case Series.

We performed a systematic literature review of neuroimaging, predominantly focusing on magnetic resonance imaging (MRI) findings associated with neurological manifestations of coronavirus disease-2019 (COVID-19). We screened articles from PubMed, Google Scholar and Scopus, looking for reports that would potentially have neuroimaging findings in patients with COVID-19. Data analysis was performed with patient-based data based on the availability of clinical characteristics and outcomes for each individual patient from the studies. Chi square and Wilcoxon rank-sum tests were used to report COVID-19 severity and outcomes based on neurological imaging indicators and pathophysiology. A total of 171 patients with COVID-19 having neurological complications, from 134 studies, were identified in our review. The most common neuroimaging finding was ischemic stroke (62, 36.2%) cases, followed by CNS inflammatory disorder (44, 25.7%), and hemorrhagic stroke (41, 24.0%). Around 51% of all the fatal COVID-19 cases had an ischemic stroke. Among patients with ischemic stroke, the mean age of those who suffered from COVID-19 infection was 57.5 years (SD = 15.4) whereas it was 50.7 years (SD = 15.1) among those without stroke/other diagnosis. Fatality was more common in patients with ischemic stroke compared to those with other diagnosis (40% vs. 22%, p = 0.011). The most frequently published neuroimaging findings in patients with COVID-19 were ischemic stroke, CNS inflammatory disorder, and hemorrhagic disorder. In those studies, ischemic stroke was associated with fatality, and was more frequently seen in older patients. Based on our findings, early usage of MRI in COVID-19 patients may be recommended.

Coagulation dysfunction in ICU patients with coronavirus disease 2019 in Wuhan, China: a retrospective observational study of 75 fatal cases.

Coagulation dysfunction in critically ill patients with coronavirus disease 2019 (COVID-19) has not been well described, and the efficacy of anticoagulant therapy is unclear. In this study, we retrospectively reviewed 75 fatal COVID-19 cases who were admitted to the intensive care unit at Jinyintan Hospital (Wuhan, China). The median age of the cases was 67 (62–74) years, and 47 (62.7%) were male. Fifty patients (66.7%) were diagnosed with disseminated intra-vascular coagulation. Approximately 90% of patients had elevated D-dimer and fibrinogen degradation products, which decreased continuously after anticoagulant treatment and was accompanied by elevated albumin (all P<0.05). The median survival time of patients treated with anticoagulant was 9.0 (6.0–14.0) days compared with 7.0 (3.0–10.0) days in patients without anticoagulant therapy (P=0.008). After anticoagulation treatment, C-reactive protein levels decreased (P=0.004), as did high-sensitivity troponin (P=0.018), lactate dehydrogenase (P<0.001), and hydroxybutyrate dehydrogenase (P<0.001). In conclusion, coagulation disorders were widespread among fatal COVID-19 cases. Anticoagulant treatment partially improved hypercoagulability, prolonged median survival time, and may have postponed inflammatory processes and cardiac injury.

Immunoinflammatory, Thrombohaemostatic, and Cardiovascular Mechanisms in COVID-19.

The global coronavirus disease 2019 (COVID-19) pandemic has deranged the recent history of humankind, afflicting more than 27 million individuals to date. While the majority of COVID-19 patients recuperate, a considerable number of patients develop severe complications. Bilateral pneumonia constitutes the hallmark of severe COVID-19 disease but an involvement of other organ systems, namely the cardiovascular system, kidneys, liver, and central nervous system, occurs in at least half of the fatal COVID-19 cases. Besides respiratory failure requiring ventilation, patients with severe COVID-19 often display manifestations of systemic inflammation and thrombosis as well as diffuse microvascular injury observed postmortem. In this review, we survey the mechanisms that may explain how viral entry and activation of endothelial cells by severe acute respiratory syndrome coronavirus 2 can give rise to a series of events including systemic inflammation, thrombosis, and microvascular dysfunction. This pathophysiological scenario may be particularly harmful in patients with overt cardiovascular disease and may drive the fatal aspects of COVID-19. We further shed light on the role of the renin–angiotensin aldosterone system and its inhibitors in the context of COVID-19 and discuss the potential impact of antiviral and anti-inflammatory treatment options. Acknowledging the comorbidities and potential organ injuries throughout the course of severe COVID-19 is crucial in the clinical management of patients affecting treatment approaches and recovery rate.

Transcriptional and proteomic insights into the host response in fatal COVID-19 cases

Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2, has resulted thus far in greater than 933,000 deaths worldwide; yet disease pathogenesis remains unclear. Clinical and immunological features of patients with COVID-19 have highlighted a potential role for changes in immune activity in regulating disease severity. However, little is known about the responses in human lung tissue, the primary site of infection. Here we show that pathways related to neutrophil activation and pulmonary fibrosis are among the major up-regulated transcriptional signatures in lung tissue obtained from patients who died of COVID-19 in Wuhan, China. Strikingly, the viral burden was low in all samples, which suggests that the patient deaths may be related to the host response rather than an active fulminant infection. Examination of the colonic transcriptome of these patients suggested that SARS-CoV-2 impacted host responses even at a site with no obvious pathogenesis. Further proteomics analysis validated our transcriptome findings and identified several key proteins, such as the SARS-CoV-2 entry-associated protease cathepsins B and L and the inflammatory response modulator S100A8/A9, that are highly expressed in fatal cases, revealing potential drug targets for COVID-19.

The first consecutive 5000 patients with Coronavirus Disease 2019 from Qatar; a nation-wide cohort study

BackgroundThere are limited data on Coronavirus Disease 2019 (COVID-19) outcomes at a national level, and none after 60 days of follow up. The aim of this study was to describe national, 60-day all-cause mortality associated with COVID-19, and to identify risk factors associated with admission to an intensive care unit (ICU).MethodsThis was a retrospective cohort study including the first consecutive 5000 patients with COVID-19 in Qatar who completed 60 days of follow up by June 17, 2020. The primary outcome was all-cause mortality at 60 days after COVID-19 diagnosis. In addition, we explored risk factors for admission to ICU.ResultsIncluded patients were diagnosed with COVID-19 between February 28 and April 17, 2020. The majority (4436, 88.7%) were males and the median age was 35 years [interquartile range (IQR) 28–43]. By 60 days after COVID-19 diagnosis, 14 patients (0.28%) had died, 10 (0.2%) were still in hospital, and two (0.04%) were still in ICU. Fatal COVID-19 cases had a median age of 59.5 years (IQR 55.8–68), and were mostly males (13, 92.9%). All included pregnant women (26, 0.5%), children (131, 2.6%), and healthcare workers (135, 2.7%) were alive and not hospitalized at the end of follow up.A total of 1424 patients (28.5%) required hospitalization, out of which 108 (7.6%) were admitted to ICU. Most frequent co-morbidities in hospitalized adults were diabetes (23.2%), and hypertension (20.7%). Multivariable logistic regression showed that older age [adjusted odds ratio (aOR) 1.041, 95% confidence interval (CI) 1.022–1.061 per year increase; P < 0.001], male sex (aOR 4.375, 95% CI 1.964–9.744; P < 0.001), diabetes (aOR 1.698, 95% CI 1.050–2.746; P 0.031), chronic kidney disease (aOR 3.590, 95% CI 1.596–8.079, P 0.002), and higher BMI (aOR 1.067, 95% CI 1.027–1.108 per unit increase; P 0.001), were all independently associated with increased risk of ICU admission.ConclusionsIn a relatively younger national cohort with a low co-morbidity burden, COVID-19 was associated with low all-cause mortality. Independent risk factors for ICU admission included older age, male sex, higher BMI, and co-existing diabetes or chronic kidney disease.