Adenovirus-mediated Over-Expression of FcγRIIB Attenuates Pulmonary Inflammation and Fibrosis.

Progressive fibrosing interstitial lung diseases (PF-ILDs) result in high mortality and lack effective therapies. The pathogenesis of PF-ILDs involves macrophages driving inflammation and irreversible fibrosis. Fc-gamma receptors (FcγRs) regulate macrophages and inflammation, but their roles in PF-ILDs remain unclear. We characterized the expression of FcγRs and found up-regulated FcγRIIB in human and mouse lungs following exposure to silica. FcγRIIB deficiency aggravated lung dysfunction, inflammation and fibrosis in silica-exposed mice. Using single-cell transcriptomics and in vitro experiments, FcγRIIB was found in alveolar macrophages, where it regulated the expression of fibrosis-related genes Spp1 and Ctss. In mice with macrophage-specific over-expression of FcγRIIB, and in mice treated with adenovirus by intra-tracheal instillation to up-regulate FcγRIIB, silica-induced functional and histological changes were ameliorated. Our data from three genetic models and a therapeutic model suggest that FcγRIIB plays a protective role that can be enhanced by adenoviral over-expression, representing a potential therapeutic strategy for PF-ILDs.

Plant-derived lignans as potential antiviral agents: a systematic review.

Medicinal plants are one of the most important sources of antiviral agents and lead compounds. Lignans are a large class of natural compounds comprising two phenyl propane units. Many of them have demonstrated biological activities, and some of them have even been developed as therapeutic drugs. In this review, 630 lignans, including those obtained from medicinal plants and their chemical derivatives, were systematically reviewed for their antiviral activity and mechanism of action. The compounds discussed herein were published in articles between 1998 and 2020. The articles were identified using both database searches (e.g., Web of Science, Pub Med and Scifinder) using key words such as: antiviral activity, antiviral effects, lignans, HBV, HCV, HIV, HPV, HSV, JEV, SARS-CoV, RSV and influenza A virus, and directed searches of scholarly publisher's websites including ACS, Elsevier, Springer, Thieme, and Wiley. The compounds were classified on their structural characteristics as 1) arylnaphthalene lignans, 2) aryltetralin lignans, 3) dibenzylbutyrolactone lignans, 4) dibenzylbutane lignans, 5) tetrahydrofuranoid and tetrahydrofurofuranoid lignans, 6) benzofuran lignans, 7) neolignans, 8) dibenzocyclooctadiene lignans and homolignans, and 9) norlignans and other lignoids. Details on isolation and antiviral activities of the most active compounds within each class of lignan are discussed in detail, as are studies of synthetic lignans that provide structure-activity relationship information.

Clinical Value of Platelets and Coagulation Parameters in Predicting the Severity of Delta Variant SARS-CoV-2.

INTRODUCTION: The present study aimed to analyze the clinical features and laboratory markers of patients with Delta variant SARS-CoV-2 and explore the role of platelet in predicting the severity of Delta. METHODS: This retrospective, observational study was conducted on 863 patients laboratory-confirmed Delta variant SARS-CoV-2. These cases were sub-classified based on disease severity into mild (n = 304), moderate (n = 537), and severe (n = 22). A series of laboratory findings and clinical data were collected and analyzed during hospitalization. RESULTS: Of 863 hospitalized patients with Delta, the median age was 38 years (interquartile range, 30-51 years) and 471 (54.58%) were male. The most common clinical symptoms mainly included cough, fever, pharyngalgia, expectoration, dyspnea, fatigue, and headache, and the commonest comorbidities were hypertension and diabetes. Among the hematological variables, neutrophil count, red blood cell count, and hemoglobin, were found to be statistically significant with regard to subcategories based of disease severity (p < 0.05). Among coagulation parameters, there was a statistically significant difference in D-dimer, fibrinogen, international normalized ratio, and prothrombin time (p < 0.05). Statistically significant differences were observed in platelet markers including platelet count, large platelet count, and plateletcrit (p < 0.05). Additionally, there was strong correlation between platelet and other parameters with disease severity. Logistical regression analysis and ROC curves showed that D-dimer was a single best marker of disease severity (p = 0.005, p < 0.0001); however, platelet (p = 0.009, p = 0.002) and plateletcrit (p = 0.002, p = 0.001) could also predict severe disease. Platelet was identified as an independent risk factor for severe Delta. CONCLUSION: Low platelet may be a marker of disease severity in Delta variant SARS-CoV-2 and may contribute to determine the severity of patients infected with Delta.

Neutralization sensitivity, fusogenicity, and infectivity of Omicron subvariants.

BACKGROUND: The emergence of SARS-CoV-2 Omicron subvariants has raised questions regarding resistance to immunity by natural infection or immunization. We examined the sensitivity of Delta and Omicron subvariants (BA.1, BA.1.1, BA.2, BA.2.12.1, BA.4/5, and BA.3) to neutralizing antibodies from BBIBP-CorV-vaccinated and BBIBP-CorV- or ZF2001-boosted individuals, as well as individuals with Delta and BA.1 breakthrough infections, and determined their fusogenicity and infectivity. METHODS: In this cross-sectional study, serum samples from two doses of BBIBP-CorV-vaccinated individuals 1 (n = 36), 3 (n = 36), and 7 (n = 37) months after the second dose; BBIBP-CorV- (n = 25) or ZF2001-boosted (n = 30) individuals; and fully vaccinated individuals with Delta (n = 30) or BA.1 (n = 26) infection were collected. The serum-neutralizing reactivity and potency of bebtelovimab were assessed against D614G, Delta, and Omicron subvariants (BA.1, BA.1.1, BA.2, BA.2.12.1, BA.4/5, and BA.3) through a pseudovirus neutralization assay. The fusogenicity and infectivity of D614G, Delta, and Omicron subvariants were determined by cell-cell fusion assay and pseudovirus infection assay, respectively. RESULTS: Omicron subvariants markedly escaped vaccine-elicited neutralizing antibodies after two doses of BBIBP-CorV with comparable efficiency. A third dose vaccination of BBIBP-CorV or ZF2001 increased neutralizing antibody titers and breadth against Delta and three Omicron subvariants. Delta and BA.1 breakthrough infections induced comparable neutralizing antibody titers against D614G and Delta variants, whereas BA.1 breakthrough infections elicited a stronger and broader antibody response against three Omicron subvariants than Delta breakthrough infections. BA.2.12.1 and BA.4/5 are more resistant to immunity induced by breakthrough infections. Bebtelovimab had no significant loss of potency against the Delta and Omicron subvariants. Cell culture experiments showed Omicron subvariants to be less fusogenic and have higher infectivity than D614G and Delta with comparable efficiency. CONCLUSIONS: These findings have important public health implications and highlight the importance of repeated exposure to SARS-CoV-2 antigens to broaden the neutralizing antibody response against Omicron subvariants.

Investigation on the interaction mechanism of different SARS-CoV-2 spike variants with hACE2: insights from molecular dynamics simulations.

Since the COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), SARS-CoV-2 has evolved by acquiring genomic mutations, resulting in the recent emergence of several SARS-CoV-2 variants with improved transmissibility and infectivity relative to the original strain. An underlying mechanism may be the increased ability of the mutants to bind the receptor proteins and infect the host cell. In this work, we implemented all-atom molecular dynamics (MD) simulations to study the binding and interaction of the receptor binding domain (RBD) of the SARS-CoV-2 spike protein singly (D614G), doubly (D614G + L452R and D614G + N501Y), triply (D614G + N501Y + E484K), and quadruply (D614G + N501Y + E484K + K417T) mutated variants with the human angiotensin-converting enzyme 2 (hACE2) receptor protein in the host cell. A combination of multiple analysis approaches elucidated the effects of mutations and the extent of molecular divergence from multiple perspectives, including the dynamic correlated motions, interaction patterns, dominant motions, free energy landscape, and charge distribution on the electrostatic potential surface between the hACE2 and all RBD variants. Moreover, free energy calculations using the MM/PBSA method evaluated the binding affinity between these RBD variants and hACE2. The results showed that the D614G + N501Y + E484K variant possessed the lowest free energy value (highest affinity) compared to the D614G + N501Y + E484K + K417T, D614G + L452R, D614G + N501Y, and D614G mutants. The residue-based energy decomposition also indicated that the energy contribution of residues at the mutation site to the total binding energy was highly variable. The interaction mechanisms between the different RBD variants and hACE2 elucidated in this study will provide some insights into the development of drugs targeting the new SARS-CoV-2 variants.

Rapid Point-of-Care Assay by SERS Detection of SARS-CoV-2 Virus and Its Variants.

Addressing the spread of coronavirus disease 2019 (COVID-19) has highlighted the need for rapid, accurate, and low-cost diagnostic methods that detect specific antigens for SARS-CoV-2 infection. Tests for COVID-19 are based on reverse transcription PCR (RT-PCR), which requires laboratory services and is time-consuming. Here, by targeting the SARS-CoV-2 spike protein, we present a point-of-care SERS detection platform that specifically detects SARS-CoV-2 antigen in one step by captureing substrates and detection probes based on aptamer-specific recognition. Using the pseudovirus, without any pretreatment, the SARS-CoV-2 virus and its variants were detected by a handheld Raman spectrometer within 5 min. The limit of detection (LoD) for the pseudovirus was 124 TU µL-1 (18 fM spike protein), with a linear range of 250-10,000 TU µL-1. Moreover, this assay can specifically recognize the SARS-CoV-2 antigen without cross reacting with specific antigens of other coronaviruses or influenza A. Therefore, the platform has great potential for application in rapid point-of-care diagnostic assays for SARS-CoV-2.

COVID-19 and preventive strategy.

In December 2019, an unprecedented outbreak of the novel coronavirus disease 2019 (COVID-19), an infectious disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) began to spread internationally, now impacting more than 293,750,692 patients with 5,454,131 deaths globally as of January 5, 2022. COVID-19 is highly pathogenic and contagious which has caused a large-scale epidemic impacting more deaths than the severe acute respiratory syndrome (SARS) epidemic in 2002-2003 or the Middle East respiratory syndrome (MERS) epidemic in 2012-2013. Although COVID-19 symptoms are mild in most people, in those with pre-existing comorbidities there is an increased risk of progression to severe disease and death. In an attempt to mitigate this pandemic, urgent public health measures including quarantining exposed individuals and social distancing have been implemented in most states, while some states have even started the process of re-opening after considering both the economic and public health consequences of social distancing measures. While prevention is crucial, both novel agents and medications already in use with other indications are being investigated in clinical trials for patients with COVID-19. The collaboration between healthcare providers, health systems, patients, private sectors, and local and national governments is needed to protect both healthcare providers and patients to ultimately overcome this pandemic. The purpose of this review is to summarize the peer-reviewed and preprint literature on the epidemiology, transmission, clinical presentation, and available therapies as well as to propose a preventive strategy to overcome the present global pandemic.

Atezolizumab With Neoadjuvant Anti-Human Epidermal Growth Factor Receptor 2 Therapy and Chemotherapy in Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: Primary Results of the Randomized Phase III IMpassion050 Trial.

PURPOSE: Combining standard of care (pertuzumab-trastuzumab [PH], chemotherapy) with cancer immunotherapy may potentiate antitumor immunity, cytotoxic activity, and patient outcomes in high-risk, human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. We report the phase III IMpassion050 primary analysis of neoadjuvant atezolizumab, PH, and chemotherapy in these patients. METHODS: Patients with a primary tumor of > 2 cm and histologically confirmed, positive lymph node status (T2-4, N1-3, M0) were randomly assigned 1:1 to atezolizumab/placebo with dose-dense doxorubicin/cyclophosphamide, followed by paclitaxel, and PH. After surgery, patients were to continue atezolizumab/placebo and PH (total: 1 year of HER2-targeted therapy); those with residual disease could switch to ado-trastuzumab emtansine with atezolizumab/placebo. Coprimary efficacy end points were pathologic complete response (pCR; ypT0/is ypN0) rates in intention-to-treat (ITT) and programmed cell death-ligand 1 (PD-L1)-positive populations. RESULTS: At clinical cutoff (February 5, 2021), pCR rates in the placebo and atezolizumab groups in the ITT populations were 62.7% (n = 143/228) and 62.4% (n = 141/226), respectively (difference -0.33%; 95% CI, -9.2 to 8.6; P = .9551). The pCR rates in the placebo and atezolizumab groups in patients with PD-L1-positive tumors were 72.5% (n = 79/109) and 64.2% (n = 70/109), respectively (difference -8.26%; 95% CI, -20.6 to 4.0; P = .1846). Grade 3-4 and serious adverse events were more frequent in the atezolizumab versus placebo group. Five grade 5 adverse events occurred (four neoadjuvant, one adjuvant; two assigned to study treatment), all with atezolizumab. Overall, the safety profile was consistent with that of atezolizumab in other combination studies. CONCLUSION: Atezolizumab with neoadjuvant dose-dense doxorubicin/cyclophosphamide-paclitaxel and PH for high-risk, HER2-positive early breast cancer did not increase pCR rates versus placebo in the ITT or PD-L1-positive populations. PH and chemotherapy remains standard of care; longer follow-up may help to inform the long-term impact of atezolizumab.

Computational Design of Miniprotein Inhibitors Targeting SARS-CoV-2 Spike Protein.

The ongoing pandemic of COVID-19 caused by SARS-CoV-2 has become a global health problem. There is an urgent need to develop therapeutic drugs, effective therapies, and vaccines to prevent the spread of the virus. The virus first enters the host cell through the interaction between the receptor binding domain (RBD) of spike protein and the peptidase domain (PD) of the angiotensin-converting enzyme 2 (ACE2). Therefore, blocking the binding of RBD and ACE2 is a promising strategy to inhibit the invasion and infection of the virus in the host cell. In the study, we designed several miniprotein inhibitors against SARS-CoV-2 by single/double/triple-point mutant, based on the initial inhibitor LCB3. Molecular dynamics (MD) simulations and trajectory analysis were performed for an in-depth analysis of the structural stability, essential protein motions, and per-residue energy decomposition involved in the interaction of inhibitors with the RBD. The results showed that the inhibitors have adapted the protein RBD in the binding interface, thereby forming stable complexes. These inhibitors display low binding free energy in the MM/PBSA calculations, substantiating their strong interaction with RBD. Moreover, the binding affinity of the best miniprotein inhibitor, H6Y-M7L-L17F mutant, to RBD was ∼45 980 times (ΔG = RT ln Ki) higher than that of the initial inhibitor LCB3. Following H6Y-M7L-L17F mutant, the inhibitors with strong binding activity are successively H6Y-L17F, L17F, H6Y, and F30Y mutants. Our research proves that the miniprotein inhibitors can maintain their secondary structure and have a highly stable blocking (binding) effect on SARS-CoV-2. This study proposes novel miniprotein mutant inhibitors with enhanced binding to spike protein and provides potential guidance for the rational design of new SARS-CoV-2 spike protein inhibitors.

Modeling of the Small-Scale Outbreak of COVID-19.

With the improvement of treatment and prevention methods, many countries have the pandemic under control. Different from the globally large-scale outbreak of COVID-19 in 2020, now the outbreak in these countries shows new characteristics, which calls for an effective epidemic model to describe the transmission dynamics. Meeting this need, first, we extensively investigate the small-scale outbreaks in different provinces of China and use classic compartmental models, which have been widely used in predictions, to forecast the outbreaks. Additionally, we further propose a new version of cellular automata with a time matrix, to simulate outbreaks. Finally, the experimental results show that the proposed cellular automata could effectively simulate the small-scale outbreak of COVID-19, which provides insights into the transmission dynamics of COVID-19 in China and help countries with small-scale outbreaks to determine and implement effective intervention measures. The countries with relatively small populations will also get useful information about the epidemic from our research.

Fear of Progression, Anxiety, and Depression in Patients With Advanced Melanoma in the COVID-19 and Post-COVID-19 Era.

Background: The novel coronavirus disease 2019 (COVID-19) pandemic causes great disruption to cancer care services, which might bring about psychological problems and further lower both physical and mental life quality in cancer patients. Until now, very few studies focused on the psychological distress of patients with advanced melanoma before or during the epidemic. This study aimed to elucidate the fear of progression (FoP), anxiety, depression, and related independent predictors in patients with advanced melanoma during the COVID-19 outbreak. Methods: Two hundred and seventy-three patients with unresectable stage III or metastatic melanoma were recruited from February 2020 to November 2021, and completed the Fear of Progression Questionnaire-Short Form (FoP-Q-SF), State Trait Anxiety Inventory (STAI-6), and Patient Health Questionnaire (PHQ-9). Results: One hundred and seventy-four (64.7%) patients experienced heighted FoP (FoP-Q-SF: 39.9 ± 11.0), 198 (72.5%) patients reported elevated anxiety (STAI-6: 13.1 ± 3.0), and 62 (22.7%) patients had increased depression (PHQ-9: 6.4 ± 6.1). In multivariate analysis, illness duration (OR = 0.987 for FoP; OR = 0.984 for depression), cancer stage (OR = 14.394 for anxiety) and disease progression (OR = 1.960 for FoP; OR = 23.235 for anxiety; OR = 1.930 for depression) were independent predictors for FoP, anxiety or depression. Additionally, the high levels of FoP, anxiety and depression were significantly positive correlated with each other (r = 0.466 for FoP and anxiety; r = 0.382 for FoP and depression; r = 0.309 for anxiety and depression). Conclusion: Our study indicates that FoP, anxiety and depression are persisting among patients with advanced melanoma in the COVID-19 and post-COVID-19 era. Effective psycho-oncological interventions are needed for melanoma patients with psychological distress during the ongoing COVID-19 pandemic.

Potential inhibitors for blocking the interaction of the coronavirus SARS-CoV-2 spike protein and its host cell receptor ACE2.

BACKGROUND: The outbreak of SARS-CoV-2 continues to pose a serious threat to human health and social. The ongoing pandemic of COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made a serious threat to public health and economic stability worldwide. Given the urgency of the situation, researchers are attempting to repurpose existing drugs for treating COVID-19. METHODS: We first established an anti-coronavirus drug screening platform based on the Homogeneous Time Resolved Fluorescence (HTRF) technology and the interaction between the coronavirus spike protein and its host receptor ACE2. Two compound libraries of 2,864 molecules were screened with this platform. Selected candidate compounds were validated by SARS-CoV-2_S pseudotyped lentivirus and ACE2-overexpressing cell system. Molecular docking was used to analyze the interaction between S protein and compounds. RESULTS: We identified three potential anti-coronavirus compounds: tannic acid (TA), TS-1276 (anthraquinone), and TS-984 (9-Methoxycanthin-6-one). Our in vitro validation experiments indicated that TS-984 strongly inhibits the interaction of the coronavirus S protein and the human cell ACE2 receptor. Additionally, tannic acid showed moderate inhibitory effect on the interaction of S protein and ACE2. CONCLUSION: This platform is a rapid, sensitive, specific, and high throughput system, and available for screening large compound libraries. TS-984 is a potent blocker of the interaction between the S-protein and ACE2, which might have the potential to be developed into an effective anti-coronavirus drug.

COVID-19 Pandemic and the Operation of a Tertiary Hospital in Tianjin-The Impact of Internet Healthcare on Hospital Business Indicators.

Objective: To explore the impact of the COVID-19 pandemic on hospital business and the contribution of Internet healthcare to hospital operations during the epidemic by analyzing the degree of impact on major business indicators. Methods: The three-year period from 2019 to 2021 was compared and analyzed, and the main medical business indicators such as outpatient and emergency visits, inpatients, operations, patient improvement rate, cure rate and fatality rate in tertiary hospitals were compared and analyzed, and the impact of the epidemic on medical services and hospital operation was analyzed. degree and the impact of Internet medical development on medical service capacity. Results: During the outbreak of COVID-19, the number of hospital outpatient and emergency visits, inpatients, and operations decreased significantly; after the normalization of the epidemic, the main medical business indicators such as outpatient and emergency visits, inpatients, and operations gradually returned to pre-epidemic levels; patient improvement rate, the cure rate and mortality rate and other indicators did not change significantly. During the epidemic period, the number of visits to the Internet outpatient clinic has increased significantly, which has significantly improved the hospital's medical service capacity. Conclusion: With the normalization of epidemic prevention and control, the main business indicators of Tianjin tertiary hospitals have gradually recovered. The operation of Internet medical care during the epidemic has changed the management and operation mode of the hospital to a certain extent, improved the main business indicators of the hospital, and eased the pressure on the hospital's economic operation.

Berbamine hydrochloride potently inhibits SARS-CoV-2 infection by blocking S protein-mediated membrane fusion.

COVID-19 caused by SARS-CoV-2 has posed a significant threat to global public health since its outbreak in late 2019. Although there are a few drugs approved for clinical treatment to combat SARS-CoV-2 infection currently, the severity of the ongoing global pandemic still urges the efforts to discover new antiviral compounds. As the viral spike (S) protein plays a key role in mediating virus entry, it becomes a potential target for the design of antiviral drugs against COVID-19. Here, we tested the antiviral activity of berbamine hydrochloride, a bis-benzylisoquinoline alkaloid, against SARS-CoV-2 infection. We found that berbamine hydrochloride could efficiently inhibit SARS-CoV-2 infection in different cell lines. Further experiments showed berbamine hydrochloride inhibits SARS-CoV-2 infection by targeting the viral entry into host cells. Moreover, berbamine hydrochloride and other bis-benzylisoquinoline alkaloids could potently inhibit S-mediated cell-cell fusion. Furthermore, molecular docking results implied that the berbamine hydrochloride could bind to the post fusion core of SARS-CoV-2 S2 subunit. Therefore, berbamine hydrochloride may represent a potential efficient antiviral agent against SARS-CoV-2 infection.

Clinical characteristics of coronavirus disease 2019 (COVID-19) in patients out of Wuhan from China: a case control study.

BACKGROUND: A large-scale global outbreak of coronavirus disease-19 (COVID-19) out of Wuhan, from China, occurred in January 2020. To examine the clinical characteristics of COVID-19 in infected patients out of Wuhan, from China. METHODS: Thirteen patients were confirmed to be infected with novel coronavirus-2019 (2019-nCoV) between January 27 and February 8, 2020, in Baoji city, Shannxi, northwestern China. Epidemiological and clinical information, and computed to morphology imaging data from all COVID-19 patients were collected; cases were divided into two groups according to the severity of infection (mild or severe). RESULTS: Nine (9/13) COVID-19 patients exhibited mild disease severity, and defined as second-generation human-to-human transmission cases. Most patients (11/13) had a history of travel to or from Wuhan. There were no differences in sex and age between the mild and severe cases (all P > 0.05). A moderate degree of fever (11/13), cough (13/13), and fatigue (8/13) were common symptoms; however, there was no statistical difference between mild and severe cases in this regard (all P > 0.05). Oxyhemoglobin saturation and oxygenation index decreased, and C-reactive protein (CRP) and serum amyloid A (SAA) levels were elevated in all patients with COVID-19 infection, with statistically significant differences between those with severe disease and mild infection (all P < 0.05). Twelve of 13 COVID-19 patients exhibited changes in chest CT imaging features, and time course changes were different between mild and severe cases (all P < 0.05). CONCLUSION: Most cases of COVID-19 infection were second-generation human-to-human transmissions from Wuhan and were mild in severity. The clinical characteristics of COVID-19 varied. Oxyhemoglobin saturation, oxygenation index, CRP and SAA levels, and CT features were reliable parameters to evaluate the severity of COVID-19 infection. However, a few patients with mild COVID-19 disease lacked typical characteristics such as fever and changes in CT imaging features.

Early predictive factors of progression from severe type to critical ill type in patients with Coronavirus Disease 2019: A retrospective cohort study.

BACKGROUND: The current worldwide pandemic of Coronavirus Disease 2019 (COVID-19) has posed a serious threat to global public health, and the mortality rate of critical ill patients remains high. The purpose of this study was to identify factors that early predict the progression of COVID-19 from severe to critical illness. METHODS: This retrospective cohort study included adult patients with severe or critical ill COVID-19 who were consecutively admitted to the Zhongfaxincheng campus of Tongji Hospital (Wuhan, China) from February 8 to 18, 2020. Baseline variables, data at hospital admission and during hospital stay, as well as clinical outcomes were collected from electronic medical records system. The primary endpoint was the development of critical illness. A multivariable logistic regression model was used to identify independent factors that were associated with the progression from severe to critical illness. RESULTS: A total of 138 patients were included in the analysis; of them 119 were diagnosed as severe cases and 16 as critical ill cases at hospital admission. During hospital stay, 19 more severe cases progressed to critical illness. For all enrolled patients, longer duration from diagnosis to admission (odds ratio [OR] 1.108, 95% CI 1.022-1.202; P = 0.013), pulse oxygen saturation at admission <93% (OR 5.775, 95% CI 1.257-26.535; P = 0.024), higher neutrophil count (OR 1.495, 95% CI 1.177-1.899; P = 0.001) and higher creatine kinase-MB level at admission (OR 2.449, 95% CI 1.089-5.511; P = 0.030) were associated with a higher risk, whereas higher lymphocyte count at admission (OR 0.149, 95% CI 0.026-0.852; P = 0.032) was associated with a lower risk of critical illness development. For the subgroup of severe cases at hospital admission, the above factors except creatine kinase-MB level were also found to have similar correlation with critical illness development. CONCLUSIONS: Higher neutrophil count and lower lymphocyte count at admission were early independent predictors of progression to critical illness in severe COVID-19 patients.

Cardiovascular risk and complications associated with COVID-19.

In December 2019, an unprecedented outbreak of pneumonia cases associated with acute respiratory distress syndrome (ARDS) first occurred in Wuhan, Hubei Province, China. The disease, later named Coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO), was caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), and on January 30, 2020, the WHO declared the outbreak of COVID-19 to be a public health emergency. COVID-19 is now a global pandemic impacting more than 43,438,043 patients with 1,158,596 deaths globally as of August 26th, 2020. COVID-19 is highly contagious and has caused more deaths than SARS in 2002-2003 or the Middle East Respiratory Syndrome (MERS) in 2012-2013 combined and represents an unprecedented human affliction not seen since the influenza pandemic of 1918. COVID-19 has been associated with several cardiac complications, including hypercoagulability, acute myocardial injury and myocarditis, arrhythmias, and acute coronary syndromes. Patients with pre-existing cardiovascular disease (CVD) are at the highest risk for myocardial injury and mortality among infected patients. The mechanism by which COVID-infected patients develop cardiac complications remains unclear, though it may be mediated by increased ACE-2 gene expression. Despite initial concerns, there is no evidence that angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy increases risk for myocardial injury among those infected with COVID-19. In the current report, we summarize the peer-reviewed and preprint literature on cardiovascular risks and complications associated with COVID-19, as well as provide insights into its pathogenesis and management.