Pathophysiology Of Coronavirus Disease 2019 Research Articles

Complement activation and lung injury in Japanese patients with COVID-19: a prospective observational study

Background The production of inflammatory cytokines is reportedly increased in patients with coronavirus disease 2019 (COVID-19), causing the migration of neutrophils and monocytes to lung tissues. This disrupts the air–blood barrier by damaging the bronchial epithelial and vascular endothelial cells. As multiorgan dysfunction in sepsis is considered to be partly caused by complement activation, which can cause lung injury in patients with COVID-19. There are limited studies examining the link between complement activation in patients with COVID-19. This study aimed to AQinvestigate the association of complement activation with the pathophysiology of COVID-19. Twenty-seven patients with COVID-19 were enrolled in this study and classified into two groups depending on the indication for mechanical ventilation. Plasma complement factors (C3a, C5a, Ba, and sC5b-9), complement regulators (sCD59 and factor H), interleukin-6 (IL-6), and syndecan-1 levels were measured using Enzyme-linked immunosorbent assay (ELISA). Results: All complement factors and regulators, IL-6, and syndecan-1 levels were significantly elevated in patients with COVID-19 compared with those in healthy controls. C5a and sC5b-9 levels were decreased significantly in the invasive mechanical ventilation (IMV) group compared with those in the non-IMV group. Syndecan-1 levels were significantly increased in the IMV group compared with those in the non-IMV group. Conclusions: Complement activation is an exacerbating factor for lung injury in patients with COVID-19. Complement factors are nonessential predictors of mechanical ventilation; however, syndecan-1 could be a biomarker of COVID-19 severity in patients.

Insights into COVID-19 pathophysiology from a longitudinal multisystem report during acute infection

The Coronavirus disease 2019 (COVID-19), an illness caused by a SARS-CoV-2 viral infection, has been associated with neurological and neuropsychiatric disorders, revealing its impact beyond the respiratory system. Most related research involved individuals with post-acute or persistent symptoms of COVID-19, also referred to as long COVID or Post-Acute Sequelae of COVID-19 (PASC). In this longitudinal unique report, we aimed to describe the acute supraspinal and corticospinal changes and functional alterations induced by a COVID-19 infection using neuroimaging, neurophysiological and clinical assessment of a participant during acute infection, as compared to three other visits where the participant had no COVID-19. The results favor a multisystem impairment, impacting cortical activity, functional connectivity, and corticospinal excitability, as well as motor and cardiovascular function. The report suggests pathophysiological alteration and impairment already present at the acute stage, that if resolved tend to lead to a full clinical recovery. Such results could be also insightful into PASC symptomatology.

MRNA vaccination reduces the thrombotic possibility in COVID-19: Inflammation risk estimates

Thrombosis is a common clinical feature associated with morbidity and mortality in coronavirus disease-2019 (COVID-19) patients. Cytokine storm in COVID-19 increases patients' systemic inflammation, which can cause multiple health consequences. In this work, we aimed to indicate the effect of Pfizer-BioNTech vaccination on the modulation of monocyte chemoattractant protein-3 (MCP-3), matrix metalloproteinase 1 (MMP-1), and tumor necrosis factor-alpha (TNF-α) levels, and other systemic inflammatory biomarkers that associates with COVID-19 severity in patients who suffers from thrombosis consequences. For this purpose, ninety people were collected from Ibn Al-Nafees Hospital and divided into three groups each of which contained 30 people, 15 of them were venous thromboembolism (VTE) positive and the other were VTE negative. The three groups were non-vaccinated COVID-19, vaccinated COVID-19, and control. The levels of MCP-3 and TNF-α were significantly (p < 0.05) increased in vaccinated and non-vaccinated COVID-19 patients regardless of their thrombosis condition, while MMP-1 level was non-significantly (p > 0.05) higher in vaccinated patients compared to control. MCP-3 and TNF-α were correlated positively with D-dimer (r = 0.544 and r = 0.513, respectively) in non-vaccinated patients, while MMP-1 and TNF-α were correlated positively with D-dimer (r = 0.624 and r = 0.575, respectively) in vaccinated patients. The odds ratio of MCP-3 (2.252), MMP-1 (1.062), and TNF-α (1.360) were reduced in vaccinated patients (2.093, 1.022, and 1.301 for MCP-3, MMP-1, and TNF-α respectively). Thus, MCP-3 plays a vital role in COVID-19 pathophysiology, and vaccination can reduce the risk of developing VTE in COVID-19 patients, and improve the inflammatory condition of patients.

Role of the receptor for advanced glycation end products in the severity of SARS-CoV-2 infection in diabetic patients.

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is a severe disease in older adults and in individuals with associated comorbidities such as diabetes mellitus. Patients with diabetes infected with SARS-CoV-2 are more likely to develop severe pneumonia, hospitalization, and mortality compared with infected non-diabetic patients. During diabetes, hyperglycemia contributes to the maintenance of a low-grade inflammatory state which has been implicated in the microvascular and macrovascular complications associated with this pathology. The receptor for advanced glycation end products (RAGE) is a multi-ligand pattern recognition receptor, expressed on a wide variety of cells, which participates as an important mediator of inflammatory responses in many diseases, including lung diseases. This review highlights the role of RAGE in the pathophysiology of COVID-19 with special emphasis on diabetic patients. These data could explain the severity of the disease, positioning it as a key therapeutic target in the clinical management of this infection.

SARS-CoV-2 Induced Interleukin -18 Response among Presumptive Covid-19 Patients in Kano State, Nigeria

Study’s Novelty/Excerpt This study evaluates Interleukin-18 (IL-18) as a potential biomarker for COVID-19 by comparing its serum levels in COVID-19-positive patients and healthy controls. The research uniquely identifies significantly elevated IL-18 levels in COVID-19 patients, demonstrating a strong statistical association with the infection (t value 6.16, p &lt;0.00010). These findings underscore the potential of IL-18 in the prognosis and clinical management of COVID-19, offering new insights into its role in the disease's pathophysiology and its utility as a biomarker. Full Abstract Coronaviruses have a history of causing severe outbreaks with life-threatening consequences, including Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and the recent coronavirus disease 2019 (COVID-19). COVID-19 first broke out in Wuhan (China) in December 2019). The disease was later declared a pandemic, and so far, more than 222 countries have been affected, with over 771 million confirmed cases and total deaths of over 7.05 million. Some immunological markers were reported elsewhere as directly related to COVID-19 pathophysiology and stand a chance to be considered biomarkers. Interleukin 18 (IL-18) is a proinflammatory cytokine and a member of the interleukin-1 family, produced by macrophages at the early stage of viral infections. However, aberrant IL-18 production can lead to severe pathological injury. Hence, there is a need to assess the feasibility of interleukin -18 as a biomarker for COVID-19. Forty-five individuals diagnosed with COVID-19 and 45 healthy controls screened using a COVID-19 antigen rapid test kit and confirmed by one-step real-time PCR were recruited for this study. Blood samples were collected from the patients and controls, and the samples were analyzed for IL-18 using the ELISA technique. This study revealed a higher level of IL-18 in COVID-19-positive patients (206.42 ± 13.2 pg/mL) compared to the control group (97.96 ± 14.4 pg/mL). Serum level IL-18 was statistically associated with COVID-19 infection (t value 6.16, p &lt;0.00010). The study demonstrates the importance of IL-18 in the COVID-19 cohort, inferentially implying its potential in the prognosis and clinical management of COVID-19.

Favorable Antiviral Effect of Metformin on SARS-CoV-2 Viral Load in a Randomized, Placebo-Controlled Clinical Trial of COVID-19.

Metformin has antiviral activity against RNA viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The mechanism appears to be suppression of protein translation via targeting the host mechanistic target of rapamycin pathway. In the COVID-OUT randomized trial for outpatient coronavirus disease 2019 (COVID-19), metformin reduced the odds of hospitalizations/death through 28 days by 58%, of emergency department visits/hospitalizations/death through 14 days by 42%, and of long COVID through 10 months by 42%. COVID-OUT was a 2 × 3 randomized, placebo-controlled, double-blind trial that assessed metformin, fluvoxamine, and ivermectin; 999 participants self-collected anterior nasal swabs on day 1 (n = 945), day 5 (n = 871), and day 10 (n = 775). Viral load was quantified using reverse-transcription quantitative polymerase chain reaction. The mean SARS-CoV-2 viral load was reduced 3.6-fold with metformin relative to placebo (-0.56 log10 copies/mL; 95% confidence interval [CI], -1.05 to -.06; P = .027). Those who received metformin were less likely to have a detectable viral load than placebo at day 5 or day 10 (odds ratio [OR], 0.72; 95% CI, .55 to .94). Viral rebound, defined as a higher viral load at day 10 than day 5, was less frequent with metformin (3.28%) than placebo (5.95%; OR, 0.68; 95% CI, .36 to 1.29). The metformin effect was consistent across subgroups and increased over time. Neither ivermectin nor fluvoxamine showed effect over placebo. In this randomized, placebo-controlled trial of outpatient treatment of SARS-CoV-2, metformin significantly reduced SARS-CoV-2 viral load, which may explain the clinical benefits in this trial. Metformin is pleiotropic with other actions that are relevant to COVID-19 pathophysiology. NCT04510194.

Determinants of long-lasting postviral COVID-19 and non-COVID-19 olfactory Dysfunction: The sanctuary theory

Since the onset of the Coronavirus disease 2019 (COVID-19) pandemic, the long-lasting postviral olfactory dysfunction (POD) became a prevalent symptom in Western country populations. However, the pathophysiology of long-lasting POD remains poorly understood. The effectiveness of platelet-rich plasma (PRP) injections into the olfactory clefts and recent findings from COVID-19 studies brought new elements in the understanding of the pathophysiology of COVID-19 and non-COVID-19 long-lasting POD. The present hypothesis suggests that the long-lasting POD could be related to a long-lasting silent chronic inflammation in the neuroepithelium due to the persistence of virus antigen into stem cells. The immune response could limit the regenerative and recovery processes, making the olfactory region an incomplete immune sanctuary for some viruses according to some specific pathophysiological phenomena (syncytia formation).

Modulations of Homeostatic ACE2, CD147, GRP78 Pathways Correlate with Vascular and Endothelial Performance Markers during Pulmonary SARS-CoV-2 Infection.

The pathologic consequences of Coronavirus Disease-2019 (COVID-19) include elevated inflammation and dysregulated vascular functions associated with thrombosis. In general, disruption of vascular homeostasis and ensuing prothrombotic events are driven by activated platelets, monocytes, and macrophages, which form aggregates (thrombi) attached to the endothelium lining of vessel walls. However, molecular pathways underpinning the pathological interactions between myeloid cells and endothelium during COVID-19 remain undefined. Here, we tested the hypothesis that modulations in the expression of cellular receptors angiotensin-converting enzyme 2 (ACE2), CD147, and glucose-regulated protein 78 (GRP78), which are involved in homeostasis and endothelial performance, are the hallmark responses induced by SARS-CoV-2 infection. Cultured macrophages and lungs of hamster model systems were used to test this hypothesis. The results indicate that while macrophages and endothelial cells are less likely to support SARS-CoV-2 proliferation, these cells may readily respond to inflammatory stimuli generated by the infected lung epithelium. SARS-CoV-2 induced modulations of tested cellular receptors correlated with corresponding changes in the mRNA expression of coagulation cascade regulators and endothelial integrity components in infected hamster lungs. Among these markers, tissue factor (TF) had the best correlation for prothrombotic events during SARS-CoV-2 infection. Furthermore, the single-molecule fluorescence in situ hybridization (smFISH) method alone was sufficient to determine the peak and resolution phases of SARS-CoV-2 infection and enabled screening for cellular markers co-expressed with the virus. These findings suggest possible molecular pathways for exploration of novel drugs capable of blocking the prothrombotic shift events that exacerbate COVID-19 pathophysiology and control the disease.

Spontaneous Coronary Artery Dissection and COVID-19: A Review of the Literature.

SARS-CoV-2 is responsible for the global coronavirus disease 2019 (COVID-19) pandemic. While the cardiovascular effects of COVID-19 have been thoroughly described, there are limited published studies in the literature establishing a connection between spontaneous coronary artery dissection (SCAD) and COVID-19. Cardiovascular manifestations include, among others, myocarditis, acute myocardial infraction, and thrombosis. In general, SCAD is an uncommon and underdiagnosed cause of acute myocardial infarction (AMI), particularly in younger women and in patients with underlying fibromuscular dysplasia (FMD). Many patients with SCAD often report significant emotional stress, especially in relation with job loss, during the week preceding their cardiac event. Moreover, the COVID-19 pandemic has led to societal stress and increased unemployment, factors that have been associated with cardiovascular morbidity. SCAD emerges as a rare manifestation of coronary artery disease, which a few recent case reports link to COVID-19. The aim of this article is to summarize the relevant data on the pathophysiology of COVID-19 and SCAD along with a review of the reported cases on acute coronary syndrome (ACS) following SARS-CoV2 infection and, thus, to provide insights about the relationship between COVID-19 and SCAD.

Infection Control Practices in Dental Clinics and Dental Care Settings during COVID - 19's Spread: A Comprehensive Review

Coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus, known as severe acute respiratory syndrome. Dental care units and settings face various problems relating to the transmission of disease during treatment and dental operations. The degree to which the healthcare system is ready affects how well coronavirus illness is managed. Blood, saliva, and mixed water droplets possessing the virus cause contamination of equipment used for dental treatment. Both patients and workers may become transmitters and infectors of COVID-19 through direct contact during dental operations. It is possible for dental professionals and patients to contract COVID-19 and spread it to others. The dental care routine is very effective as we discussed below the prevention steps are very effective. All healthcare workers at the dentistry clinics should collaborate to prevent the spread of the COVID-19 virus among patients. The primary aim is to make dental health care providers aware of the pathophysiology of COVID-19 and to increase their preparedness and understanding of this challenge, which will aid in controlling transmission. The information and data that collected will be useful for the dental community in providing effective patient management through evidence-based recommendations for infection control and disinfection protocols.

Severe pediatric COVID-19: a review from the clinical and immunopathophysiological perspectives.

Coronavirus disease 2019 (COVID-19) tends to have mild presentations in children. However, severe and critical cases do arise in the pediatric population with debilitating systemic impacts and can be fatal at times, meriting further attention from clinicians. Meanwhile, the intricate interactions between the pathogen virulence factors and host defense mechanisms are believed to play indispensable roles in severe COVID-19 pathophysiology but remain incompletely understood. A comprehensive literature review was conducted for pertinent publications by reviewers independently using the PubMed, Embase, and Wanfang databases. Searched keywords included "COVID-19 in children", "severe pediatric COVID-19", and "critical illness in children with COVID-19". Risks of developing severe COVID-19 in children escalate with increasing numbers of co-morbidities and an unvaccinated status. Acute respiratory distress stress and necrotizing pneumonia are prominent pulmonary manifestations, while various forms of cardiovascular and neurological involvement may also be seen. Multiple immunological processes are implicated in the host response to COVID-19 including the type I interferon and inflammasome pathways, whose dysregulation in severe and critical diseases translates into adverse clinical manifestations. Multisystem inflammatory syndrome in children (MIS-C), a potentially life-threatening immune-mediated condition chronologically associated with COVID-19 exposure, denotes another scientific and clinical conundrum that exemplifies the complexity of pediatric immunity. Despite the considerable dissimilarities between the pediatric and adult immune systems, clinical trials dedicated to children are lacking and current management recommendations are largely adapted from adult guidelines. Severe pediatric COVID-19 can affect multiple organ systems. The dysregulated immune pathways in severe COVID-19 shape the disease course, epitomize the vast functional diversity of the pediatric immune system and highlight the immunophenotypical differences between children and adults. Consequently, further research may be warranted to adequately address them in pediatric-specific clinical practice guidelines.

Omicron induced distinct immune respiratory transcriptomics signatures compared to pre-existing variants in critically ill COVID-19 patients.

Severe coronavirus disease 2019 (COVID-19) is related to dysregulated immune responses. We aimed to explore the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on the immune response by nasopharyngeal transcriptomic in critically-ill patients. This prospective monocentric study included COVID-19 patients requiring intensive care unit (ICU) admission between March 2020 and 2022. Patients were classified according to VOC (ancestral, Alpha, Delta, and Omicron). Eighty-eight patients with severe COVID-19 were included after matching (on prespecified clinical criteria). Profiling of gene expression markers of innate and adaptive immune responses were investigated by respiratory transcriptomics at ICU admission. Eighty-eight patients were included in the study after matching (ancestral [n = 24], Alpha [n = 24], Delta [n = 22], and Omicron [n = 18] variants). Respiratory transcriptomic analysis revealed distinct innate and adaptive immune profiling between variants. In comparison with the ancestral variant, there was a reduced expression of neutrophil degranulation, T cell activation, cytokines signalling pathways in patients infected with Alpha and Delta variants. In contrast, there was a higher expression of neutrophil degranulation, T and B cells activation, and inflammatory interleukins pathways in patients infected with Omicron. To conclude, Omicron induced distinct immune respiratory transcriptomics signatures compared to pre-existing variants in patients with severe COVID-19, pointing to an evolving pathophysiology of severe COVID-19 in the Omicron era.

Role of glutathione reduction in causation severe complications of coronavirus disease-2019

Abstract Background: Coronavirus is a pandemic disease that emerged in China in 2019 with severe respiratory syndromes in conjunction with organ failure and advanced mortality rate where it has attracted worldwide interest. The pathogenicity of the virus increases by exacerbated oxidative stress that leads to the accumulation of free radicals in the body. Frequently, those free radicals are neutralized by antioxidants, especially glutathione. Objective: Thus, this study aimed to evaluate the role of glutathione in the pathogenicity of the virus alongside certain blood parameters. Materials and Methods: In this study, 90 participants were examined for glutathione levels using a specific enzyme-linked immunosorbent assay (ELISA) kit in addition to the levels of hemoglobin (Hb). Ferritin and vitamin D3 were also measured as they are linked to the level of glutathione in coronavirus disease-2019 (COVID-19). Result: The lowest level of Reduced glutathione in COVID-19 hospitalized patients especially male patients alongside with vitamin D3 and Hb levels. Whereas a significant (P &lt; 0.05) increase in ferritin level was recorded. However, a significant (P &lt; 0.05) increase in ferritin level was recorded. Conclusion: This study showed a significant relationship between glutathione level and disease severity in hospitalized patients with COVID-19, where the depletion of the glutathione level may have a central role in COVID-19 severity and pathophysiology.

Estrogens as a Possible Therapeutic Strategy for the Management of Neuroinflammation and Neuroprotection in COVID-19.

The Coronavirus disease 2019 (COVID-19) affects several tissues, including the central and peripheral nervous system. It has also been related to signs and symptoms that suggest neuroinflammation with possible effects in the short, medium, and long term. Estrogens could have a positive impact on the management of the disease, not only due to its already known immunomodulator effect, but also activating other pathways that may be important in the pathophysiology of COVID-19, such as the regulation of the virus receptor and its metabolites. In addition, they can have a positive effect on neuroinflammation secondary to pathologies other than COVID-19. The aim of this study is to analyze the molecular mechanisms that link estrogens with their possible therapeutic effect for neuroinflammation related to COVID-19. Advanced searches were performed in scientific databases as Pub- Med, ProQuest, EBSCO, the Science Citation index, and clinical trials. Estrogens have been shown to participate in the immune modulation of the response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition to this mechanism, we propose that estrogens can regulate the expression and activity of the Angiotensin-converting enzyme 2 (ACE2), reestablishing its cytoprotective function, which may be limited by its interaction with SARS-CoV-2. In this proposal, estrogens and estrogenic compounds could increase the synthesis of Angiotensin-(1-7) (Ang-(1-7)) that acts through the Mas receptor (MasR) in cells that are being attacked by the virus. Estrogens can be a promising, accessible, and low-cost treatment for neuroprotection and neuroinflammation in patients with COVID-19, due to its direct immunomodulatory capacity in decreasing cytokine storm and increasing cytoprotective capacity of the axis ACE2/Ang (1-7)/MasR.

Host mitochondria: more than an organelle in SARS-CoV-2 infection.

Since December 2019, the world has been facing viral pandemic called COVID-19 (Coronavirus disease 2019) caused by a new beta-coronavirus named severe acute respiratory syndrome coronavirus-2, or SARS-CoV-2. COVID-19 patients may present with a wide range of symptoms, from asymptomatic to requiring intensive care support. The severe form of COVID-19 is often marked by an altered immune response and cytokine storm. Advanced age, age-related and underlying diseases, including metabolic syndromes, appear to contribute to increased COVID-19 severity and mortality suggesting a role for mitochondria in disease pathogenesis. Furthermore, since the immune system is associated with mitochondria and its damage-related molecular patterns (mtDAMPs), the host mitochondrial system may play an important role during viral infections. Viruses have evolved to modulate the immune system and mitochondrial function for survival and proliferation, which in turn could lead to cellular stress and contribute to disease progression. Recent studies have focused on the possible roles of mitochondria in SARS-CoV-2 infection. It has been suggested that mitochondrial hijacking by SARS-CoV-2 could be a key factor in COVID-19 pathogenesis. In this review, we discuss the roles of mitochondria in viral infections including SARS-CoV-2 infection based on past and present knowledge. Paying attention to the role of mitochondria in SARS-CoV-2 infection will help to better understand the pathophysiology of COVID-19 and to achieve effective methods of prevention, diagnosis, and treatment.

Elevated Levels of Cytotoxicity, Cytokines, and Anti-SARS-CoV-2 Antibodies in Mild Cases of COVID-19.

Current evidence shows higher production of cytokines and antibodies against severe acute respiratory coronavirus 2 (SARS-CoV-2) in severe and critical cases of Coronavirus Disease 2019 (COVID-19) in comparison with patients with moderate or mild disease. A recent hypothesis proposes an important role of genotoxicity and cytotoxicity in the induction of the cytokine storm observed in some patients at later stages of the disease. Interestingly, in this study, we report significantly higher levels of interleukin (IL)-1β, IL-6, MCP-1, and IL-4 cytokines in mild COVID-19 patients versus severe cases, as well as a high frequency of karyorrhexis (median [Me] = 364 vs. 20 cells) and karyolysis (Me = 266 vs. 52 cells) in the mucosal epithelial cells of both groups of patients compared with uninfected individuals. Although we observed higher levels of anti-SARS-CoV-2 IgM and IgG antibodies in COVID-19 patients, IgM antibodies were significantly higher only in mild cases, for the N and the S viral antigens. High levels of IgG antibodies were observed in both mild and severe cases. Our results showed elevated concentrations of proinflammatory and anti-inflammatory cytokines in mild cases, which may reflect an active innate immune response and could be related to the higher IgM and IgG antibody levels found in those patients. In addition, we found that SARS-CoV-2 infection induces cytotoxic damage in the oral mucosa, highlighting the importance of studying the genotoxic and cytotoxic events induced by infection and its role in the pathophysiology of COVID-19.

COVID-19 PATHOPHYSIOLOGY PREDICTS THAT ISCHEMIC STROKE OCCURRENCE IS AN EXPECTATION, NOT AN EXCEPTION: A SYSTEMATIC REVIEW

Background: Clinical reports of neurological manifestations associated with severe coronavirus disease 2019 (COVID-19), such as acute ischemic stroke (AIS) are increasing rapidly. However, there are comparatively few studies investigating the potential impact of immunological responses secondary to hypoxia, oxidative stress, and excessive platelet-induced aggregation on the brain.&#x0D; Aim: This study attempted to elucidate potential pathophysiological mechanisms associated with peripheral and consequential neural (central) inflammation leading to COVID-19-related ischemic strokes. &#x0D; Methods: A systematic search strategy was conducted across several electronic reference databases (MEDLINE, Cochrane Library, CINAHL) and included articles published between January 2000 and August 12th, was carried out up to August 15th, 2020. Duplicate publications, review articles, and incomplete articles were excluded.&#x0D; Results: The databases search identified a total of 1.539 articles (Table 1) and resulted in 672 articles after duplicates removed. Of these, 206 articles passed the screening process, resulting in 20 articles for full-text assessment. Among them, 10 articles did not evaluate the outcome of interest and insufficient details. Hence, we found 10 appropriate studies included. &#x0D; Conclusion: This study affirms that the immunological contribution to the pathophysiology of COVID-19 is predictive of the neurological sequelae particularly ischemic stroke, which makes it the expectation rather than the exception.

Analysis of acute COVID-19 including chronic morbidity: protocol for the deep phenotyping National Pandemic Cohort Network in Germany (NAPKON-HAP).

The severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) pandemic causes a high burden of acute and long-term morbidity and mortality worldwide despite global efforts in containment, prophylaxis, and therapy. With unprecedented speed, the global scientific community has generated pivotal insights into the pathogen and the host response evoked by the infection. However, deeper characterization of the pathophysiology and pathology remains a high priority to reduce morbidity and mortality of coronavirus disease 2019 (COVID-19). NAPKON-HAP is a multi-centered prospective observational study with a long-term follow-up phase of up to 36months post-SARS-CoV-2 infection. It constitutes a central platform for harmonized data and biospecimen for interdisciplinary characterization of acute SARS-CoV-2 infection and long-term outcomes of diverging disease severities of hospitalized patients. Primary outcome measures include clinical scores and quality of life assessment captured during hospitalization and at outpatient follow-up visits to assess acute and chronic morbidity. Secondary measures include results of biomolecular and immunological investigations and assessment of organ-specific involvement during and post-COVID-19 infection. NAPKON-HAP constitutes a national platform to provide accessibility and usability of the comprehensive data and biospecimen collection to global research. NAPKON-HAP establishes a platform with standardized high-resolution data and biospecimen collection of hospitalized COVID-19 patients of different disease severities in Germany. With this study, we will add significant scientific insights and provide high-quality data to aid researchers to investigate COVID-19 pathophysiology, pathology, and chronic morbidity.

Increased red blood cell deformation in children and adolescents after SARS-CoV-2 infection

Severe coronavirus disease 2019 (COVID-19) is associated with hyperinflammation, hypercoagulability and hypoxia. Red blood cells (RBCs) play a key role in microcirculation and hypoxemia and are therefore of special interest in COVID-19 pathophysiology. While this novel disease has claimed the lives of many older patients, it often goes unnoticed or with mild symptoms in children. This study aimed to investigate morphological and mechanical characteristics of RBCs after SARS-CoV-2 infection in children and adolescents by real-time deformability-cytometry (RT-DC), to investigate the relationship between alterations of RBCs and clinical course of COVID-19. Full blood of 121 students from secondary schools in Saxony, Germany, was analyzed. SARS-CoV-2-serostatus was acquired at the same time. Median RBC deformation was significantly increased in SARS-CoV-2-seropositive compared to seronegative children and adolescents, but no difference could be detected when the infection dated back more than 6 months. Median RBC area was the same in seropositive and seronegative adolescents. Our findings of increased median RBC deformation in SARS-CoV-2 seropositive children and adolescents until 6 months post COVID-19 could potentially serve as a progression parameter in the clinical course of the disease with an increased RBC deformation pointing towards a mild course of COVID-19.

Inflammasomes: a rising star on the horizon of COVID-19 pathophysiology.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a contagious respiratory virus that is the cause of the coronavirus disease 2019 (COVID-19) pandemic which has posed a serious threat to public health. COVID-19 is characterized by a wide spectrum of clinical manifestations, ranging from asymptomatic infection to mild cold-like symptoms, severe pneumonia or even death. Inflammasomes are supramolecular signaling platforms that assemble in response to danger or microbial signals. Upon activation, inflammasomes mediate innate immune defense by favoring the release of proinflammatory cytokines and triggering pyroptotic cell death. Nevertheless, abnormalities in inflammasome functioning can result in a variety of human diseases such as autoimmune disorders and cancer. A growing body of evidence has showed that SARS-CoV-2 infection can induce inflammasome assembly. Dysregulated inflammasome activation and consequent cytokine burst have been associated with COVID-19 severity, alluding to the implication of inflammasomes in COVID-19 pathophysiology. Accordingly, an improved understanding of inflammasome-mediated inflammatory cascades in COVID-19 is essential to uncover the immunological mechanisms of COVID-19 pathology and identify effective therapeutic approaches for this devastating disease. In this review, we summarize the most recent findings on the interplay between SARS-CoV-2 and inflammasomes and the contribution of activated inflammasomes to COVID-19 progression. We dissect the mechanisms involving the inflammasome machinery in COVID-19 immunopathogenesis. In addition, we provide an overview of inflammasome-targeted therapies or antagonists that have potential clinical utility in COVID-19 treatment.