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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide and has seriously threatened public health by causing significant morbidity and mortality. Patients with coronavirus disease (COVID-19) with preexisting endothelial dysfunction caused by aging, diabetes, hypertension, and obesity are at high risk for life-threatening thromboembolic complications. This suggests a possibility that reduced endothelial nitric oxide (NO) production and NO bioavailability could be a common underlying pathology for the progression of COVID-19. Increasingly, evidence from experimental and clinical studies of SARS-CoV-2 infection shows that NO inhibits the pathogenesis of COVID-19, including virus entry into host cells, viral replication, host immune response, and subsequent thromboembolic complications. Restoring NO bioavailability may have the potential to be a preventive or early-treatment option for COVID-19. This review aims to provide in-depth discussion of NO bioavailability to prevent SARS-CoV-2 infection, particularly by focusing on lifestyle factors such as nitrate-rich diets, physical exercise, and nasal breathing, which could be easily performed on a daily basis to boost NO bioavailability.

Solid organ transplant recipients are at high risk for the development of severe forms of COVID-19. However, the role of immunosuppression in the morbidity and mortality of the immune phenotype during COVID-19 in transplant recipients remains unknown. In this retrospective study, we compared peripheral blood T and B cell functional and surface markers, as well as serum antibody development during 29 cases of mild (World Health Organization 9-point Ordinal Scale (WOS) of 3-4) and 22 cases of severe COVID-19 (WOS 5-8) in solid organ transplant (72% kidney transplant) recipients hospitalized in our center. Patients who developed severe forms of COVID-19 presented significantly lower CD3+ (median 344/mm3 (inter quartile range 197; 564) vs. 643/mm3 (397; 1251), and CD8+ T cell counts (124/mm3 (76; 229) vs. 240/mm3 (119; 435). However, activated CD4+ T cells were significantly more frequent in severe forms (2.9% (1.37; 5.72) vs. 1.4% (0.68; 2.35), counterbalanced by a significantly higher proportion of Tregs (3.9% (2.35; 5.87) vs 2.7% (1.9; 3.45)). A marked decrease in the proportion of NK cells was noted only in severe forms. In the B cell compartment, transitional B cells were significantly lower in severe forms (1.2% (0.7; 4.2) vs. 3.6% (2.1; 6.2). Nonetheless, a majority of transplant recipients developed antibodies against SARS-CoV-2 (77% and 83% in mild and severe forms respectively). Thus, our data revealed immunological differences between mild and severe forms of COVID 19 in solid organ transplant recipients, similar to previous reports in the immunocompetent population., Graphical abstract

BackgroundThe COVID-19 pandemic has resulted in a high death toll. We aimed to describe the place and cause of death during the COVID-19 pandemic.MethodsThis national death registry included all adult (aged ≥18 years) deaths in England and Wales between 1st January 2014 and 30th June 2020. Analyses were based upon ICD-10 codes corresponding to the underlying cause of death as stated on the Medical Certificate of Cause of Death. Daily deaths during COVID-19 pandemic were compared against the expected daily deaths estimated using Farrington surveillance algorithm for daily historical data between 2014 and 2020, by place and cause of death.FindingsBetween 2nd March and 30th June 2020, there was an excess mortality of 57,860 (a proportional increase of 35%) compared with the expected deaths, of which 50,603 (86.2%) were COVID-19 related. Almost half the excess deaths occurred in care homes (25,611 deaths) where deaths were 55% higher than expected. One fifth of the excess deaths occurred in hospital (15,938 deaths; a proportional increase of 21%) with the remainder occurring at home (16,190 deaths; a proportional increase of 39%). At home, only 14% of 16,190 excess deaths were related to COVID-19, with 5,963 deaths due to cancer and 2,485 deaths due to cardiac disease, very few of which involved COVID-19. In care homes or hospices, 61% of the 25,611 excess deaths were related to COVID-19, 5,539 of which were due to respiratory disease and most of these (4,315 deaths) involved COVID-19. In hospital, there were 16,174 fewer deaths than expected which did not involve COVID-19, and there were 4,088 fewer deaths due to cancer and 1,398 fewer deaths due to cardiac disease than expected.InterpretationThe COVID-19 pandemic has resulted in a substantial increase in the absolute numbers of deaths occurring at home and care homes. There was a huge burden of excess deaths occurring in care homes, which were poorly characterised, and were likely to be, at least in part, the result of undiagnosed COVID-19. There was a smaller but important and ongoing excess in deaths at home, particularly from cancer and cardiac disease, which suggests avoidance of hospital care for non-COVID-19 conditions.FundingThe study is unfunded.

Globally, SARS-CoV-2 has emerged as threat to life and economy. Researchers are trying to find a cure against this pathogen but without much success. Several attempts have been made to understand the atomic level details of SARS-CoV-2 in the past few months. However, one review with all structural details for drug and vaccine development has been missing. Hence, this review aims to summarize key functional roles played by various domains of SARS-CoV-2 genome during its entry into the host, replication, repression of host immune response and overall viral life cycle. Additionally, various proteins of SARS-CoV-2 for finding a potent inhibitor have also been highlighted. To mitigate this deadly virus, an understanding of atomic level information, pathogenicity mechanisms and functions of different proteins in causing the infection is imperative. Thus, these structural details would finally pave the way for development of a potential drug/vaccine against the disease caused by SARS-CoV-2.

We report the case of a 10-year-old boy with acute-onset diplopia and ptosis in the right eye. CR was positive for SARS-CoV-2. The patient was managed successfully with corticosteroids. We highlight the need for heightened suspicion of occult COVID-19 infection among children presenting with unusual III nerve palsy.

The breast cancer screening program has continued in Taiwan during the COVID-19 pandemic. Our nationwide data showed that the total number of screenings decreased by 22.2%, which was more pronounced for in-hospital examinations (−37.2%), while outreach showed a 12.9% decrease. This decline in screening participation happened at all levels of hospitals, more significantly at the highest level. Our report revealed that outreach services could maintain relatively stable breast cancer screening under this kind of public health crisis. Building a flexible, outreach system into the community might need to be considered when policymakers are preparing for future possible pandemics., Highlights • Breast cancer screening programs continue in Taiwan during the COVID-19 pandemic. • In-hospital screening rate decreased significantly during the pandemic. • Outreach screening rate decreased but maintained a relatively stable amount of services during the pandemic.

The unexpected emergence of the new Coronavirus disease (COVID-19) has affected more than three hundred million individuals and resulted in more than five million deaths worldwide. The ongoing pandemic has underscored the urgent need for effective preventive and therapeutic measures to develop anti-viral therapy. The natural compounds possess various pharmaceutical properties and are reported as effective anti-virals. The interest to develop an anti-viral drug against the novel severe acute respiratory syndrome Coronavirus (SARS-CoV-2) from natural compounds has increased globally. Here, we investigated the anti-viral potential of selected promising natural products. Sources of data for this paper are current literature published in the context of therapeutic uses of phytoconstituents and their mechanism of action published in various reputed peer-reviewed journals. An extensive literature survey was done and data were critically analyzed to get deeper insights into the mechanism of action of a few important phytoconstituents. The consumption of natural products such as thymoquinone, quercetin, caffeic acid, ursolic acid, ellagic acid, vanillin, thymol, and rosmarinic acid could improve our immune response and thus possesses excellent therapeutic potential. This review focuses on the anti-viral functions of various phytoconstituent and alkaloids and their potential therapeutic implications against SARS-CoV-2. Our comprehensive analysis provides mechanistic insights into phytoconstituents to restrain viral infection and provide a better solution through natural, therapeutically active agents., Graphical Abstract ga1

Introduction The risk of mortality in patients with COVID-19 was found to be significantly higher in patients who experienced thromboembolic events. Thus, several guidelines recommend using prophylactic anticoagulants in all COVID-19 hospitalized patients. However, there is uncertainty about the appropriate dosing regimen and safety of anticoagulation in critically ill COVID-19 patients. Thus, the study aims to compare the effectiveness and safety of standard and escalated dose pharmacological VTE prophylaxis in critically ill patients with COVID-19. Methods A two centers retrospective cohort study including critically ill patients aged ≥ 18-years with confirmed COVID-19 admitted to the ICUs at two tertiary hospitals in Saudi Arabia from March 1st, 2020, until January 31st, 2021. Patients who received either Enoxaparin 40 mg daily or UFH 5000 Unit three times daily were grouped under the “standard dose VTE prophylaxis or higher than standard dose but not as treatment dose ”escalated VTE prophylaxis dose“ The primary outcome was thrombosis, and the secondary outcomes included ICU-related complication (s) Results A total of 758 patients were screened; 565 patients were included in the study. We matched 352 patients using propensity score matching (1:1). The differences in venous thromboembolism (OR 0.75; 95% CI 0.16-3.38; P =0.70) and any case of thrombosis during ICU were more likely to occur (OR 1.22;95%CI 0.52-2.86; P=0.64). In contrast, minor bleeding was associated with the use of escalated VTE prophylaxis dose (OR 3.39; 95% CI 1.08-10.61; P=0.04). There was no difference in the 30-day mortality nor in-hospital mortality between the two groups (HR 1.17;95%CI0.79-1.73; P=0.43 and (HR 1.08;95%CI 0.76-1.53; P=0.83, respectively. Conclusion Escalated-dose pharmacological VTE prophylaxis in critically ill patients with COVID-19 was not associated with VTE, thrombosis, or mortality benefits but led to an increased risk of minor bleeding. This study supports previous study findings regarding optimal dosing VTE pharmacological prophylaxis regimen for critically ill patients with COVID-19.

To explore the recovery of renal function in severely ill coronavirus disease (COVID-19) survivors and determine the plasma metabolomic profile of patients with different renal outcomes 3 months after discharge, we included 89 severe COVID-19 survivors who had been discharged from Wuhan Union Hospital for 3 months. All patients had no underlying kidney disease before admission. At patient recruitment, renal function assessment, laboratory examination, chest computed tomography (CT) were performed. Liquid chromatography–mass spectrometry was used to detect metabolites in the plasma. We analyzed the longitudinally change in the estimated glomerular filtration rate (eGFR) based on serum creatinine and cystatin-c levels using the CKD-EPI equation and explored the metabolomic differences in patients with different eGFR change patterns from hospitalization to 3 months after discharge. Lung CT showed good recovery; however, the median eGFR significantly decreased at the 3-month follow-up. Among the 89 severely ill COVID-19 patients, 69 (77.5%) showed abnormal eGFR (, Graphical abstract Unlabelled Image

Background There are many commercially available automated assays for assessing coronavirus disease 2019 (COVID-19) immune responses; however, owing to insufficient data, their validities remain unknown. Here, we examined antibody responses during acute-phase COVID-19 using four assays that detect anti-spike protein IgM (S-IgM), anti-nucleocapsid protein IgG (N-IgG), anti-spike protein total Ig (S-total Ig), and anti-spike protein IgG (S-IgG). Methods We measured antibody levels in 1154 serum samples collected from 286 hospitalized patients with confirmed COVID-19 by a gene amplification method between February and December 2020 in Japan. Sera from 860 healthcare workers were used as negative controls. Results The antibody positivity rates increased on week 2, peaked, and then started to plateau by the beginning of week 3 after symptom onset. On week 1, there were some significant differences in seropositivity rates between assays (p = 0.032): 14.9% (11.0%–19.4%) for S-IgM and 8.9% (6.0%–12.7%) for N-IgG. The seropositivity for the S-total Ig (10.6% [7.3%–14.6%]) assay was considerably better than that for the S-IgG (6.9% [4.3%–10.4%]) assay, although the difference was not statistically significant (p = 0.150). The levels of S-IgM antibodies and the three others peaked on weeks 3 and 5, respectively. All four assays showed high specificities (>99%). Conclusions All four assays had good specificities and were suitable for seropositivity detection after week 3 of symptom onset. Assays of IgM alone or total Ig (containing IgM) were better than those of IgG alone as an adjunct serological test for early-stage COVID-19 diagnosis, albeit the use of a serological assay alone is insufficient.

Objective To compare prevalence of skin, nose and gingival bleedings after receipt of adeno-vectored or mRNA-vaccines against covid-19. The hypothesis is that milder symptoms indicating altered thrombocyte function may affect a larger proportion of vaccinated individuals than the recently reported severe cases with thrombosis and thrombocytopenia.Design Large, population-based cohort study.Setting Norway, nationwide.ParticipantsMore than 80 000 cohort participants responding to electronic questionnaires about covid-19 vaccination and potential side effects during weeks 11-13, 2021. Response rate 58% (81267/138924), 83% were female, 85% health care workers and 80% were aged 40-55 years. Main outcome measuresSelf-reported episodes of skin, nose and gingival bleedings. Variation in rates by registered vaccine type, age, sex, occupation, previous covid-19 infection and chronic disease. ResultsFour of the 3416 subjects (0.2%) who were vaccinated with a single dose of mRNA vaccine reported skin bleeding as a side effect, as opposed to 163 of 5132 subjects (3.2%) vaccinated with a single dose of the adenovirus-vectored vaccine, OR (odds ratio)=16.0 (95% confidence interval (CI) 7.5-34.1). Corresponding ORs for nose and gingival bleeding were 8.0 (4.0-15.8) and 9.3 (4.3-20.0), respectively.ConclusionsThese findings could potentially indicate that the adenovirus-vectored vaccine may lead to mild bleeding episodes in a larger proportion of vaccinated individuals, and not only in rare cases with documented thrombosis and thrombocytopenia. Studies are needed to understand the possible mechanisms behind these observations, and to establish or refute whether they share similarities with the severe thromboembolic bleeding complications.

Background The coronavirus disease (COVID-19) has afflicted large populations worldwide. Although vaccines aroused great expectations, their side effects on Japanese people and the antibody titer transition after vaccination are unclear. Methods The side effects of the BNT162b2 mRNA COVID-19 vaccine in participants who received vaccination at our center were investigated. Some participants were also surveyed for the antibody titer transition. Results In this study, 983 and 798 Japanese participants responded to the first and second doses, respectively. Side effects occurred in 757 (77.0%) and 715 participants (90.0%) after the first and second doses, respectively. No Grade 4 side effects occurred. The second dose had significantly more side effects than the first dose (p

INTRODUCTION: COVID-19 has radically changed the delivery of healthcare in Australia. Central to a tertiary paediatric institution's (The Royal Children's Hospital Melbourne (RCH) response was a digital health approach comprising a broad suite of informatics and technology solutions including optimising a fully integrated electronic medical record (EMR). METHODS: This comprehensive approach spanned all patient care areas and encompassed a broad range of hospital operations. They included patient triage, registration, COVID-19 screening clinic operations, electronic ordering, prescribing and documentation, telehealth, reporting and analytics and research. DISCUSSION: This paper outlines key aspects of our COVID-19 digital health strategy, highlighting the rapid transition to telehealth and the development of a remote "virtual telehealth" strategy for clinicians which proved popular and allowed true "working from home". CONCLUSION: COVID-19 has inadvertently focussed the spotlight on the utility of digital health for clinical care. The speed and uptake of digital health within this pandemic has been remarkable and unprecedented in both an Australian and global setting. Whilst many of these changes have been beneficial, some may have been rushed or forced with minimal consideration of ongoing governance. Key stakeholders and enablers should be identified for post-pandemic consideration in future digital health implementation and adoption strategies.

Summary Background The impact of the coronavirus disease (COVID-19) pandemic on antimicrobial resistance (AMR) is a major concern. Aim To compare the number of patients and isolation rate of antimicrobial-resistant bacteria before and after the beginning of the COVID-19 pandemic using the comprehensive national surveillance data. Methods We utilized comprehensive surveillance data, collected in the Japan Nosocomial Infections Surveillance programme, which included a total of 16.7 million samples of 5.9 million tested patients from >1300 hospitals. We compared the number of patients and isolation rate of five bacteria between 2019 and 2020, including antimicrobial-susceptible and -resistant bacteria of Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. Findings The number of patients and isolation rate of S. aureus and meticillin-resistant S. aureus decreased slightly; those of S. pneumoniae and penicillin-resistant S. pneumoniae decreased by 60%; and those of third-generation cephalosporin-resistant K. pneumoniae increased. The isolation rate of the remaining bacteria apparently increased, although the number of patients decreased. This was due to a substantial decrease in the total number of tested patients (the denominator of the isolation rate), which was larger than that of the number of patients (the numerator of the isolation rate). Consistent results were obtained when the same data were re-aggregated using the procedure of the World Health Organization Global Antimicrobial Resistance Surveillance System, demonstrating the general importance of this problem. Conclusion Surveillance data during the COVID-19 pandemic must be carefully interpreted based on examination of the numerator, denominator and background factors that affect the denominator.

Graphical abstract, The 2019 novel coronavirus (2019-nCoV; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) has witnessed a rapid and global proliferation since its early identification in patients with severe pneumonia in Wuhan, China. As of 27th May 2020, 2019-nCoV cases have risen to >5 million, with confirmed deaths of 350,000. However, Coronavirus disease (COVID-19) diagnostic and treatment measures are yet to be fully unraveled, given the novelty of this particular coronavirus. Hence, no drug or vaccine has been adapted for treatment, and the accuracy of the current diagnostic tests is debatable. Therefore, existing antiviral agents used for severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) were repurposed for COVID-19, taking their biological features into consideration. This study provides a concise review of the current and emerging detection and supervision technologies for SARS-CoV-2, which is the viral etiology of COVID19, and their performance characteristics, with emphasis on the novel Nano-based diagnostic tests (protein corona sensor array and magnetic levitation) and treatment measures (treatment protocols based on nano-silver colloids) for COVID-19.

Objective To determine the potential association of age-related macular degeneration (AMD), a representative chronic age-related degenerative disease of the retina associated with inflammation and aging, with susceptibility to SARS-CoV-2 infection and severe COVID-19 outcomes. Design Nationwide cohort study with propensity-score matching. Setting Population-based nationwide cohort in Korea. Study population Data were obtained from the Health Insurance Review & Assessment Service of Korea, including all patients older than 40 years who underwent SARS-CoV-2 testing in South Korea between January 1, 2020, and May 15, 2020 (excluding self-referral). Main outcome measures SARS-CoV-2 test positivity was the primary outcome and severe clinical outcome of COVID-19 was the secondary outcome. Results The unmatched cohort consisted of 135,435 patients who were tested for SARS-CoV-2; 4531 (3.3%) tested positive for SARS-CoV-2; 5493 (4.1%) patients had AMD. After propensity score matching, exudative AMD was associated with an increased likelihood of susceptibility to SARS-CoV-2 infection (adjusted odds ratio [aOR], 1.50; 95% confidence interval [CI], 1.03-2.25), and a considerably greater risk of severe clinical outcomes of COVID-19 (aOR, 2.26; 95% CI, 1.02 to 5.26), but not any AMD and non-exudative AMD. Conclusions In a Korean nationwide cohort, our data suggest that clinicians should be aware of the greater risk of susceptibility to severe clinical outcomes of COVID-19 in patients with exudative AMD. Our findings provide an improved understanding of the relationship between the pathogenesis of COVID-19 and chronic neurological disorders.

COVID-19 caused by SARS-CoV-2 is an ongoing global pandemic. SARS-CoV-2 affects the human respiratory tract's epithelial cells, leading to a proinflammatory cytokine storm and chronic lung inflammation. With numerous patients dying daily, a vaccine and specific antiviral drug regimens are being explored. Probiotics are live microorganisms with proven beneficial effects on human health. While probiotics as nutritional supplements are long practiced in different cuisines across various countries, the emerging scientific evidence supports the antiviral and general immune-strengthening health effects of the probiotics. Here, we present an overview of the experimental studies published in the last 10 years that provide a scientific basis for unexplored probiotics as a preventive approach to respiratory viral infections. Based on collated insights from these experimental data, we identify promising microbial strains that may serve as lead prophylactic and immune-boosting probiotics in COVID-19 management.

Background and aims COVID-19 is a pandemic that has affected beyond 100 million and caused nearly 3 million deaths globally. Vitamin D is a known risk factor for COVID-19. Therefore, we aimed to investigate the association of prevalence of vitamin D deficiency and mean vitamin D level with COVID-19 infection and mortality in Asia, predicting with other confounding factors such as median age, obesity, and diabetes. Methods COVID-19 infections and mortalities among the Asian countries were retrieved from the Worldometer website. Information on prevalence of vitamin D deficiency and mean vitamin D values in each Asian country was retrieved through literature searching on PubMed® and Google scholar. The associations between COVID-19 infections and mortalities with prevalence of vitamin D deficiency and mean vitamin D level were explored with correlation coefficients. As a predictive analysis, multiple linear regression was carried out with all confounders. Results Positive correlations were observed for prevalence of vitamin D deficiency with COVID-19 infections (r = 0.55; p = 0.01; R2 = 0.31) and mortalities (r = 0.50; p = 0.01; R2 = 0.25). Moreover, the associations for the COVID-19 infections and mortalities improved to r = 0.76 (p = 0.002; R2 = 0.58) and r = 0.65 (p = 0.03; R2 = 0.42), respectively, after predicting with confounding factors. Similarly, mean vitamin D level had a significant negative correlation with COVID-19 infections (r = −0.77; p = 0.04; R2 = 0.59) and mortalities (r = −0.80; p = 0.03; R2 = 0.63) when combining with confounders. Conclusion Prevalence of vitamin D deficiency is significantly positively associated whereas the mean vitamin D level is significantly negatively associated with both infection and mortality rate of COVID-19 among Asian countries upon predicting with all confounders.

Highlights • SARS-CoV-2 virus was present in the air in the ICU. • Virus may be discharged in aerosol for days after patients test negative. • The finding may be one of the reasons for patients` re-detectable positive. • The clinical guidelines for recovered COVID-19 patients need to be improved., As coronavirus disease 2019 (COVID-19) is spreading worldwide, there have been arguments regarding the aerosol transmission of its causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Moreover, some re-detectable positive (RP) patients have been reported. However, little attention has been given to the follow-up of recovered patients, and there is no environmental evidence to determine whether these patients continue to shed the virus after they test negative. Therefore, with an objective to test the hypothesis of airborne transmission of SARS-CoV-2, it is necessary to 1) determine whether SARS-CoV-2 particles are present in the indoor air and 2) determine whether recovered patients are still shedding virus, thus providing much-needed environmental evidence for the management of COVID-19 patients during the recovery period. In this study, surface and air samples were collected from an intensive care unit (ICU) containing one ready-for-discharge patient. All surface samples tested negative, but the air samples tested positive for SARS-CoV-2. This implies that SARS-CoV-2 particles may be shed in aerosol form for days after patients test negative. This finding may be one of the reasons for the observation of RP patients; therefore, there is a need for improved clinical and disease management guidelines for recovered COVID-19 patients.

Background According to expert consensus, the time interval between Hymenoptera venom immunotherapy (VIT) injections can be extended up to 12 weeks, without significant impact on efficacy and safety. However, the COVID-19 pandemic caused longer delays, and no recommendations are available to manage this huge extension. Objectives Our study aims to provide advice on how to resume VIT safely after a long delay from the last injection considering the potential risk factors for side effects (SE), without starting again with the induction phase. Methods All the patients who delayed VIT due to pandemic were consecutively enrolled in this single-centre study. The time extension was decided according to their risk profile (e.g. long pre-pandemic time interval, severe pre-VIT reaction, older age, multi-treatments), and correlation analyses were performed to find potential risk factors of SE. Results The mean delay from the pre- (7 weeks) to the post-pandemic VIT interval (15.5 weeks) was 8.5 weeks. The total amount of the pre-pandemic VIT maintenance dose was safely administered in one day in 78% of patients, while only three experienced SE, out of 87, and their potential risk factors were identified in bee venom allergy and recent VIT initiation. Conclusions In a real-world setting, long VIT delays may be safe and well-tolerated, but more caution should be paid in resuming VIT in patients with long pre-pandemic maintenance interval, severe pre-VIT reaction, recent VIT initiation, older age, multi-drug treatments, and bee venom allergy. This is useful in any case of long, unplanned, and unavoidable VIT delay., Highlights box What is already known about this topic? The COVID-19 pandemic raised the need to extend venom immunotherapy (VIT) time intervals safely. However, no guidelines are currently available on how to manage long extensions of intervals between VIT administrations (i.e. > 3 months). What does this article add to our knowledge? Our results show that long VIT delay may be tolerated in clinical practice, if key risk factors are considered: bee venom, long time interval between injections, severe pre-VIT reaction, date of VIT initiation, age, multi-treatments. How does this study impact current management guidelines? A safe and effective protocol to resume VIT after a long interruption is useful in case of unexpected delays in treatment. A new build-up phase may be safely avoided in most cases, with compliance and cost advantage.

Highlights • COVID-19 can present varied dermatological manifestations. • Cutaneous small-vessel vasculitis is one of these forms of cutaneous manifestation of COVID-19. • Vesicobullous hemorrhagic lesions can be the clinical presentation. • Most cases of cutaneous vasculitis present in mild cases of COVID-19. • Microvascular thrombosis seems to be part of the pathophysiological process of the cutaneous lesion in COVID-19., We described a case of exuberant cutaneous small-vessel vasculitis in a 27-year-old male with mild CoVID-19 in Brazil. The patient presented painful purpuric papules and vesicobullous lesions with hemorrhagic content located in the larger amount in the lower limbs and, to a lesser extent in the region of the back and upper limbs, saving palms and soles of the feet. Influenza-like syndrome with anosmia and ageusia was reported seven days before the skin lesions. A real-time reverse transcription polymerase chain reaction was positive on a nasopharyngeal swab for SARS-CoV-2. Histopathological study showed leukocytoclastic cutaneous vasculitis affecting small vessels and microthrombi occluding some vessels. The patient presented an improvement in skin lesions by the fifth day of prednisone therapy. This case highlights the importance of the SARS-CoV-2 test in investigating the etiology of cutaneous vasculitis during this pandemic.

Since the beginning of the COVID-19 pandemic, accumulating mutations have led to marked changes in the genetic sequence of SARS-CoV-2. Of these, mutations in the spike (S) protein can alter the properties of the virus, particularly transmissibility and antigenicity. However, it is difficult to detect antigenic variants of the SARS-CoV-2 S protein by immunoassay. Here, we developed an ACE2-based biosensor designed to detect both SARS-CoV-2 S1 mutations and neutralizing antibodies. In "binding mode", the biosensor works by detecting binding of the S protein to an immobilized ACE2 receptor. The ACE2-based biosensor was able to detect S1 proteins of the alpha (500 pg/mL) and beta variants (10 ng/mL), as well as wild-type S1 (10 ng/mL), of SARS-CoV-2. The biosensor distinguished wild-type SARS-CoV-2 S1 from the S1 alpha and beta variants via color differences. In addition, a slight modification to the protocol enabled the ACE2-based biosensor to operate in "blocking mode" to detect neutralizing antibodies in serum samples from COVID-19 patients. Therefore, the ACE2-based biosensor is a versatile test for detecting wild-type S1, S1 mutants, and neutralizing antibodies against SARS-CoV-2. This approach to targeting both the mechanism by which SARS-CoV-2 enters host cells and the subsequent adaptive immune response will facilitate the development of various biosensors against SARS-CoV-2.

The objective of this retrospective study was to identify the clinical risk factor associated with uric acid elevation in coronavirus disease (COVID-19) patients treated with favipiravir. Uric acid elevation was defined as an unexplained increase of ≥1.5 times in the patient's uric acid level from baseline. Twenty-nine COVID-19 patients were included in the study. Uric acid elevation developed during favipiravir therapy in 12 (41.4%) patients and the median onset time was 4.5 days after starting favipiravir. In multiple logistic regression analysis, the favipiravir dosage (adjusted OR = 1.69 [1.02-2.81], P = 0.044) and younger patient age (adjusted OR = 0.91 [0.83-0.99], P = 0.040) were significant clinical risk factors for uric acid elevation. No significant between-group difference was noted in the uric acid elevation and non-elevation groups in the clinical recovery after favipiravir therapy. The uric acid levels of patients administered with favipiravir should be monitored closely.

Objective The objective of this study was to develop a team-based institutional infrastructure for navigating management of a novel disease, to determine a safe and effective approach for performing tracheostomies in patients with COVID-19 respiratory failure, and to review outcomes of patients and healthcare personnel following implementation of this approach. Methods An interdisciplinary Task Force was constructed to develop innovative strategies for management of a novel disease. A single-institution prospective non-randomized cohort study was then conducted on patients with COVID-19 respiratory failure who underwent tracheostomy using an induced bedside apneic technique at a tertiary care academic institution between April 27th, 2020, and June 30th, 2020. Results 28 patients underwent tracheostomy with induced apnea. The median lowest procedural oxygen saturation was 95%. The median number of ventilated days following tracheostomy was 11. There were 3 mortalities (11%) due to sepsis and multiorgan failure; of 25 surviving patients, 100% were successfully discharged from the hospital and 76% are decannulated, with a median time of 26 days from tracheostomy to decannulation (range 12 - 57). There was no symptomatic disease transmission to healthcare personnel on the COVID-19 Tracheostomy Team. Conclusions Patients with respiratory failure from COVID-19 disease may benefit from tracheostomy. This can be completed effectively and safely, without viral transmission to healthcare personnel. Performing tracheostomies earlier in the course of disease may expedite patient recovery and improve ICU resource utilization. Creation of a collaborative Task Force is an effective strategic approach for management of novel disease.

Objective This study aimed to assess the immediate stress and psychological impact experienced by healthcare workers and other personnel during the Coronavirus disease (COVID-19) pandemic. Method The sample consisted of 2554 hospital workers (i.e., physicians, nurses, allied health professionals, and auxiliary staff members) who were working in Yeungnam University Hospital in Daegu, South Korea. The Impact of Event Scale-Revised (IES-R) was administered to the hospital workers twice over a 2 week interval. A high-risk group, identified on the basic of first total IES-R, was assessed further with the Mini International Neuropsychiatric Interview (MINI) and the Clinical Global Impressions-Severity (CGI—S) scale and was offered periodic psychiatric consultations on a telephone. Results The participating nurses and auxiliary staff members had significantly higher IES-R scores (p, Highlights • The healthcare workers reported experiencing high levels of psychological stress during the pandemic period. • Higher levels of stress were reported by the nonmedical staff workers than by the physicians. • These findings underscore the need to provide sufficient information and support to nurses, other staff members. • Psychiatrists will play an important role in implementing rapid and effective psychiatric interventions during a pandemic.

Backgroud Coronavirus disease (COVID-19) is a new respiratory infectious disease, and there is no vaccine currently. Previous studies have found that BCG vaccination can provide extensive protection against respiratory infectious diseases. Methods Herein, we obtained the latest data from the World Health Organization (WHO) as of August 12, 2020, and determined the relationship between three parameters (including the BCG vaccination coverage, human development index (HDI), and transmission classifications) and the incidence rate and mortality of COVID-19. Results The results showed that the morbidity and mortality of COVID-19 in countries with BCG vaccination recommendation were significantly lower than these in countries without BCG vaccination recommendation, and countries with lower HDI have lower morbidity and mortality. In addition, we also found that the mode of virus transmission is also related to the morbidity and mortality of COVID-19. Conclusions Although our data supports the hypothesis that BCG vaccination is beneficial in reducing the morbidity and mortality of COVID-19, the data supporting this result may be inaccurate due to many confounders such as PCR testing rate, population characteristics, and protection strategies, the reliability of this result still needs to be verified by clinical trials., Highlights • The morbidity and mortality of COVID-19 in countries with BCG vaccination recommendation were significantly lower. • The mode of virus transmission is also related to the morbidity and mortality of COVID-19. • The results may be inaccurate due to many confounders, the reliability still needs to be verified by clinical trials. • The role of BCG in COVID-19 should be confirmed by clinical trials.

Due to the outbreak of Severe Acute Respiratory Syndrome coronavirus (SARS-Cov-2), an efficient COVID-19 screening strategy is required for patients undergoing cardiac surgery. The objective of this prospective observational study was to evaluate the role of preoperative computed tomography (CT) screening for COVID-19 in a population of COVID-19 asymptomatic patients scheduled for cardiac surgery. Between the 29th of March and the 26th of May 2020, patients asymptomatic for COVID-19 underwent a CT-scan the day before surgery, with reverse-transcriptase polymerase-chain reaction (RT-PCR) reserved for abnormal scan results. The primary endpoint was the prevalence of abnormal scans, which was evaluated using the CO-RADS score, a COVID-19 specific grading system. In a secondary analysis, the rate of abnormal scans was compared between the screening cohort and matched historical controls who underwent routine preoperative CT-screening prior to the SARS-Cov-2 outbreak. Of the 109 patients that underwent CT-screening, an abnormal scan result was observed in 7.3% (95% confidence interval: 3.2–14.0%). One patient, with a normal screening CT, was tested positive for COVID-19, with the first positive RT-PCR on the ninth day after surgery. A rate of preoperative CT-scan abnormalities of 8% (n = 8) was found in the unexposed historical controls (P > 0.999). In asymptomatic patients undergoing cardiac surgery, preoperative screening for COVID-19 using computed tomography will identify pulmonary abnormalities in a small percentage of patients that do not seem to have COVID-19. Depending on the prevalence of COVID-19, this results in an unfavorable positive predictive value of CT screening. Care should be taken when considering CT as a screening tool prior to cardiac surgery., Graphical Abstract Image, graphical abstract

Background There is inconclusive and controversial evidence of the association between allergic diseases and the risk of adverse clinical outcomes of coronavirus disease 2019 (COVID-19). Objective We sought to determine the association of allergic disorders with the likelihood of a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test result and with clinical outcomes of COVID-19 (admission to intensive care unit, administration of invasive ventilation, and death). Methods A propensity-score–matched nationwide cohort study was performed in South Korea. Data obtained from the Health Insurance Review & Assessment Service of Korea from all adult patients (age, >20 years) who were tested for SARS-CoV-2 in South Korea between January 1, 2020, and May 15, 2020, were analyzed. The association of SARS-CoV-2 test positivity and allergic diseases in the entire cohort (n = 219,959) and the difference in clinical outcomes of COVID-19 were evaluated in patients with allergic diseases and SARS-CoV-2 positivity (n = 7,340). Results In the entire cohort, patients who underwent SARS-CoV-2 testing were evaluated to ascertain whether asthma and allergic rhinitis were associated with an increased likelihood of SARS-CoV-2 test positivity. After propensity score matching, we found that asthma and allergic rhinitis were associated with worse clinical outcomes of COVID-19 in patients with SARS-CoV-2 test positivity. Patients with nonallergic asthma had a greater risk of SARS-CoV-2 test positivity and worse clinical outcomes of COVID-19 than patients with allergic asthma. Conclusions In a Korean nationwide cohort, allergic rhinitis and asthma, especially nonallergic asthma, confers a greater risk of susceptibility to SARS-CoV-2 infection and severe clinical outcomes of COVID-19.

Highlights • Radiomics-based classifier agreed with radiologists for the classification of COVID-19. • Radiomics enables to quantify the CT variation with SARS-CoV-2 positivity & SARS-CoV-2 negativity. • The features identified by multi-classifier can interpret and generalise the CT signs of COVID-19., Purpose To investigate the efficacy of radiomics in diagnosing patients with coronavirus disease (COVID-19) and other types of viral pneumonia with clinical symptoms and CT signs similar to those of COVID-19. Methods Between 18 January 2020 and 20 May 2020, 110 SARS-CoV-2 positive and 108 SARS-CoV-2 negative patients were retrospectively recruited from three hospitals based on the inclusion criteria. Manual segmentation of pneumonia lesions on CT scans was performed by four radiologists. The latest version of Pyradiomics was used for feature extraction. Four classifiers (linear classifier, k-nearest neighbour, least absolute shrinkage and selection operator [LASSO], and random forest) were used to differentiate SARS-CoV-2 positive and SARS-CoV-2 negative patients. Comparison of the performance of the classifiers and radiologists was evaluated by ROC curve and Kappa score. Results We manually segmented 16,053 CT slices, comprising 32,625 pneumonia lesions, from the CT scans of all patients. Using Pyradiomics, 120 radiomic features were extracted from each image. The key radiomic features screened by different classifiers varied and lead to significant differences in classification accuracy. The LASSO achieved the best performance (sensitivity: 72.2%, specificity: 75.1%, and AUC: 0.81) on the external validation dataset and attained excellent agreement (Kappa score: 0.89) with radiologists (average sensitivity: 75.6%, specificity: 78.2%, and AUC: 0.81). All classifiers indicated that "Original_Firstorder_RootMeanSquared" and "Original_Firstorder_Uniformity" were significant features for this task. Conclusions We identified radiomic features that were significantly associated with the classification of COVID-19 pneumonia using multiple classifiers. The quantifiable interpretation of the differences in features between the two groups extends our understanding of CT imaging characteristics of COVID-19 pneumonia.

Coronavirus disease 2019 (COVID-19), which is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared by the World Health Organization (WHO) as a global pandemic on March 11, 2020. SARS-CoV-2 targets the respiratory system, resulting in symptoms such as fever, headache, dry cough, dyspnea, and dizziness. These symptoms vary from person to person, ranging from mild to hypoxia with acute respiratory distress syndrome (ARDS) and sometimes death. Although not confirmed, phylogenetic analysis suggests that SARS-CoV-2 may have originated from bats; the intermediary facilitating its transfer from bats to humans is unknown. Owing to the rapid spread of infection and high number of deaths caused by SARS-CoV-2, most countries have enacted strict curfews and the practice of social distancing while awaiting the availability of effective U.S. Food and Drug Administration (FDA)-approved medications and/or vaccines. This review offers an overview of the various types of coronaviruses (CoVs), their targeted hosts and cellular receptors, a timeline of their emergence, and the roles of key elements of the immune system in fighting pathogen attacks, while focusing on SARS-CoV-2 and its genomic structure and pathogenesis. Furthermore, we review drugs targeting COVID-19 that are under investigation and in clinical trials, in addition to progress using mesenchymal stem cells to treat COVID-19. We conclude by reviewing the latest updates on COVID-19 vaccine development. Understanding the molecular mechanisms of how SARS-CoV-2 interacts with host cells and stimulates the immune response is extremely important, especially as scientists look for new strategies to guide their development of specific COVID-19 therapies and vaccines.

The coronavirus disease of 2019 (COVID-19), which began in Wuhan, China, at the end of 2019, is spreading around the world and causing many deaths, mainly from pneumonia. Currently, there are no specific drugs to treat COVID-19, and existing antiviral drugs are being used as an alternative. One of these is favipiravir, a new type of influenza drug. However, its efficacy, dosage, and duration of administration are still under study. In this case study, we administered favipiravir to patients with COVID-19 and determined the viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the COVID-19 pathogen, using semi-quantitative real-time reverse transcription PCR in sputum samples. We report on two patients in whom the viral load increased again after completion of 10 days of favipiravir treatment and a transient relapse of symptoms was observed.

The coronavirus disease 2019 (COVID-19) pandemic has changed life on a global scale. The numbers of transplantations have plummeted as a result of fear of disease transmission, recipient coronavirus disease 2019 infection, priority shift, and resource limitations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) complicates transplantation because donor testing, (re)allocation of limited resources, and recipient testing may exceed permissible ischemia times. Normothermic machine perfusion (NMP) helps safely prolong liver preservation up to 38 hours. Additional time is essential under the current circumstances. Here we present the case of a 29-year-old liver transplant recipient in whom prolonged liver preservation required for SARS-CoV-2 screening was accomplished through NMP. Donor and recipient test results for SARS-CoV-2 were negative, and intensive care unit capacity was eventually available. The surgical procedure and postoperative course were uneventful. NMP can extend preservation times in liver transplantation while awaiting SARS-CoV-2 test results and available intensive care unit capacity.

Background The COVID-19 pandemic has led to surges of patients presenting to emergency departments (ED) and potentially overwhelming health systems. Objective This study aimed to assess the predictive accuracy of host biomarkers at clinical presentation to the ED for adverse outcome. Methods Prospective observational study of PCR-confirmed COVID-19 patients in the ED of a Swiss hospital. Concentrations of inflammatory and endothelial dysfunction biomarkers were determined at clinical presentation. We evaluated the accuracy of clinical signs and these biomarkers in predicting 30-day intubation/mortality, and oxygen requirement by calculating the area under the receiver operating characteristic curve (AUROC) and by classification and regression tree analysis. Results Of 76 COVID-19 patients included, 24 were outpatients or hospitalized without oxygen requirement, 35 hospitalized with oxygen requirement and 17 intubated/died. We found that soluble triggering receptor expressed on myeloid cells (sTREM-1) had the best prognostic accuracy for 30-day intubation/mortality (AUROC 0.86; 95% CI 0.77-0.95) and interleukin-6 (IL-6) measured at presentation to the ED had the best accuracy for 30-day oxygen requirement (AUROC 0.84; 95% CI 0.74-0.94) .An algorithm based on respiratory rate and sTREM-1 predicted 30-day intubation/mortality with 94% sensitivity and 0.1 NLR. An IL-6-based algorithm had 98% sensitivity and 0.04 negative likelihood ratio (NLR) for 30-day oxygen requirement. Conclusion sTREM-1 and IL-6 concentrations in COVID-19 in the ED have good predictive accuracy for intubation/mortality and oxygen requirement. sTREM-1- and IL-6-based algorithms are highly sensitive to identify patients with adverse outcome and could serve as early triage tools., Capsule summary: To our knowledge, this is the first study evaluating sTREM-1 in the context of COVID-19 risk-stratification. Our results suggested we could use it as triage tool in emergency department.

Background: The high demand for personal protective equipment (PPE) during the novel coronavirus outbreak has created global shortages and prompted the need to develop strategies to conserve supply. Surgical mask PPE have a broad application of use in a pandemic setting, but little is known regarding decontamination interventions to allow for their reuse. Objective: Identify and synthesize data from original published studies evaluating interventions to decontaminate surgical masks for the purpose of reuse. Methods: We searched MEDLINE, Embase, CENTRAL, Global Health, the WHO COVID-19 database, Google Scholar, DisasterLit, preprint servers, and prominent journals from inception to April 8, 2020 for prospective original research on decontamination interventions for surgical mask PPE. Citation screening was conducted independently in duplicate. Study characteristics, interventions, and outcomes were extracted from included studies by two independent reviewers. Outcomes of interest included impact of decontamination interventions on surgical mask performance and germicidal effects. Results: Seven studies met eligibility criteria: one evaluated the effects of heat and chemical decontamination interventions applied after mask use on mask performance, and six evaluated interventions applied prior to mask use to enhance antimicrobial properties and/or mask performance. Mask performance and germicidal effects were both evaluated in heterogenous test conditions across a variety of mask samples (whole masks and pieces or individual mask layers). Safety outcomes were infrequently evaluated. Mask performance was best preserved with dry heat decontamination. Germicidal effects were best in salt-, N-halamine- and nanoparticle-coated masks. Conclusion: There is limited evidence on the safety or efficacy of surgical mask decontamination. Given the heterogenous methods used in the studies to date, we are unable to draw conclusions on the most appropriate, safest intervention(s) for decontaminating surgical masks for the purpose of reuse.

Graphical abstract, Highlights • Explores the pandemic nature, morphology and viral hijacking of COVID-19 against host cells. • Highlights the possibilities of organ failure due to the attack of SARS-CoV2. • Illustrates the risk for COVID-19 attack in comorbid patients and their prognosis under medications. • Discusses the possible therapeutic strategies for the COVID-19., The current pandemic outbreak of COVID-19 originated from Wuhan, China. It is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with significant mortality and morbidity rate. The severe risk factors are commonly detected in patients of older age and with medical comorbidities like cancer and diabetes. Scientists and doctors have scrambled to gain knowledge about the novel virus and its pathophysiology in order to discover possible therapeutic regimens and vaccines for COVID-19. The therapeutic strategies like targeting the viral genome emphasize the promising approach to target COVID-19. Additionally, blocking the receptor, ACE2 via the neutralizing antibodies for viral escape that prevents it from entering into the cells provides another therapeutic regimen. In this review article, we have presented the effect of SARS-CoV-2 infection in comorbid patients and discussed organ failure caused by this virus. Based on the data available from the scientific literature and ongoing clinical trials, we have focused on therapeutic strategies. We hope that we would fill the gaps that puzzled the researchers and clinicians with the best of our knowledge collected for the betterment of the patients for the coming future.

The rapid evolution of the health emergency linked to the spread of severe acute respiratory syndrome coronavirus 2 requires specifications for the rehabilitative management of patients with coronavirus disease 2019 (COVID-19). The symptomatic evolution of patients with COVID-19 is characterized by 2 phases: an acute phase in which respiratory symptoms prevail and a postacute phase in which patients can show symptoms related to prolonged immobilization, to previous and current respiratory dysfunctions, and to cognitive and emotional disorders. Thus, there is the need for specialized rehabilitative care for these patients. This communication reports the experience of the San Raffaele Hospital of Milan and recommends the setup of specialized clinical pathways for the rehabilitation of patients with COVID-19. In this hospital, between February 1 and March 2, 2020, about 50 patients were admitted every day with COVID-19 symptoms. In those days, about 400 acute care beds were created (intensive care/infectious diseases). In the following 30 days, from March 2 to mid-April, despite the presence of 60 daily arrivals to the emergency department, the organization of patient flow between different wards was modified, and several different units were created based on a more accurate integration of patients' needs. According to this new organization, patients were admitted first to acute care COVID-19 units and then to COVID-19 rehabilitation units, post-COVID-19 rehabilitation units, and/or quarantine/observation units. After hospital discharge, telemedicine was used to follow-up with patients at home. Such clinical pathways should each involve dedicated multidisciplinary teams composed of pulmonologists, physiatrists, neurologists, cardiologists, physiotherapists, neuropsychologists, occupational therapists, speech therapists, and nutritionists.

Background The early identification of patients at risk of clinical deterioration is of interest considering the timeline of COVID-19 after the onset of symptoms. Objective The aim of our study was to evaluate the usefulness of testing serum IL-6 and other serological and clinical biomarkers, to predict a short-term negative clinical course of patients with noncritical COVID-19. Methods A total of 208 patients with noncritical COVID-19 pneumonia at admission were consecutively enrolled. Clinical and laboratory findings obtained on admission were analyzed by using survival analysis and stepwise logistic regression for variable selection. Three-day worsening as outcome in a logistic model to generate a prognostic score was used. Results Clinical worsening occurred in 63 patients (16 = died; 39 = transferred to intensive care unit; 8 worsening of respiratory failure). Forty-five of them worsened within 3 days after admission. The risk of clinical worsening was progressively enhanced along with increasing quartiles of IL-6 levels. Multivariate analysis showed that IL-6 (P = .005), C-reactive protein (CRP) (P = .003), and SaO2/FiO2 (P = .014) were the best predictors for clinical deterioration in the first 3 days after admission. The combined score yielded an area under the curve = 0.88 (95% confidence interval: 0.83-0.93). A nomogram predicting the probability of 3-day worsening was generated. The score also showed good performance for 7-day and 14- or 21-day worsening and in predicting death occurring during all the follow-up. Conclusions Combining IL-6, CRP, and SaO2/FiO2 in a score may help clinicians to identify on admission those patients with COVID-19 who are at high risk for a further 3-day clinical deterioration.

Background multiple sclerosis (MS) patients are treated with immunomodulatory treatments that can influence their ability to develop a protective antibody response to the SARS-CoV-2 vaccine. Vaccine efficacy is important for treatment decision and for patients’ reassurance. The main objective is to assess antibody response to SARS-CoV-2 vaccine in MS patients treated with cladribine. Methods Serology response was tested in 97 participants, 67 MS patients and 30 healthy controls (HCs), using two independent methods, 2–3 weeks following the second dose of the BNT162b2 vaccine. Results HCs (n = 30) and MS patients treated with cladribine (n = 32) had 100% positive serology response against the SARS-CoV-2 spike protein following the second vaccine dose (mean S1/S2-IgG and RBD-IgG:284.5 ± 104.9, 13,041±9411 AU/mL and 226.3 ± 121.4, 10,554±11,405 AU/mL respectively). Comparable findings were observed for untreated MS patients, and interferon beta-1a-treated MS patients (mean S1/S2-IgG: 282.1 ± 100.1, 276.9 ± 94.31 AU/mL respectively). No correlation was found between lymphocyte counts, treatment duration, or time between cladribine dose and vaccination, and serology response or antibody titers. Conclusion and relevance Cladribine treated MS patients are able to produce antibodies to the SARS-CoV-2 mRNA vaccine. In the era of the COVID-19 pandemic, it is reassuring and important for both patients and physicians and will allow to develop consensus guidelines.

The spike (S) protein mutations of SARS-CoV-2 are of major concern in terms of viral transmission and pathogenesis. Hence, we developed a PCR-based method to rapidly detect the 6 mutational hotspots (H49Y, G476S, V483A, H519Q, A520S, and D614G) in the S protein and applied this method to analyze the hotspots in the viral isolates from different geographical origins. Here, we identified that there was only the D614G mutation in the viral isolates. As of September 30, 2020, the analysis of 113,381 sequences available from the public repositories revealed that the SARS-CoV-2 variant carrying G614 has become the most prevalent form globally. Our results support recent epidemiological and genomic data demonstrating that the viral infectivity and transmission are enhanced by the S protein D614G mutation., Graphical abstract Unlabelled Image

Background Coronavirus disease 2019 (COVID-19) is an ongoing global pandemic. The ability to predict cardiac injury and analyze lymphocyte immunity and inflammation of cardiac damage in patients with COVID-19 is limited. We aimed to determine the risk factors and predictive markers of cardiac injury in these patients. Methods Data from 124 consecutive hospitalized patients with confirmed COVID-19 were collected. We compared the proportion of cardiovascular disease history in moderate, severe, and critical cases. We obtained high-sensitivity cardiac troponin I (hs-cTn I) results from 68 patients. Patients were divided into two groups based on positive hs-cTn I result: those with cardiac injury (n = 19) and those without cardiac injury (n = 49). Results Compared with the group with moderate disease, hypertension, coronary heart disease, and smoking were more common in severe and critical cases. Diabetes mellitus was most common in the critical group. Age older than 65 years, presence of chronic kidney disease, and lower blood lymphocyte percentage were independent risk factors of cardiac injury. The total T- and B-lymphocyte counts and CD4+ and CD8+ T-cell counts were significantly lower in those with cardiac injury. A minimal lymphocyte percentage, Highlights • Lymphocyte percentage may become a predictive marker for cardiac injury. • Total T and B cells and CD4+ and CD8+ cells decreased in the cardiac injury group. • Interleukin 6 levels increased in patients with cardiac injury. • Cardiac injury is related to lymphocyte immunity dysfunction and inflammation.

Coronavirus 2019 (COVID-19) has globally affected the human mortality rate and economic history of the modern world. According to the World Health Organization, COVID-19 has caused a severe threat to the health of the vulnerable groups, notably the elderly. There is still some disagreements regarding the source of the virus and its intermediate host. However, the spread of this disease has caused most countries to enforce strict curfew laws and close most industrial and recreational centres. This study aims to show the potential positive effects of COVID-19 on the environment and the increase of renewable energy generation in Malaysia. To prevent the spread of this disease, Malaysia enacted the Movement Control Order (MCO) law in March 2020. Implementation of this law led to a reduction in environmental pollution, especially air pollution, in this country. The greenhouse gases (GHG) emission , which was 8 Mt CO2 eq. from January 2020 to March 2020, reduced to, Graphical abstract, Highlights • Show the positive potential effects of COVID-19 on the environment and increase the Renewable Energy Generation in Malaysia. • Reduction in environmental pollution, especially air pollution, in Malaysia. • Reduction in air pollution allowed more sunlight to reach photovoltaic panels and increased renewable energy generation.

The widespread coronavirus SARS-CoV-2 has already infected over 4 million people worldwide, with a death toll over 280,000. Current treatment of COVID-19 patients relies mainly on antiviral drugs lopinavir/ritonavir, arbidol, and remdesivir, the anti-malarial drugs hydroxychloroquine and chloroquine, and traditional Chinese medicine. There are over 2,118 on-going clinical trials underway, but to date none of these drugs have consistently proven effective. Cathepsin L (CatL) is an endosomal cysteine protease. It mediates the cleavage of the S1 subunit of the coronavirus surface spike glycoprotein. This cleavage is necessary for coronavirus entry into human host cells, virus and host cell endosome membrane fusion, and viral RNA release for next round of replication. Here we summarize data regarding seven CatL-selective inhibitors that block coronavirus entry into cultured host cells and provide a mechanism to block SARS-CoV-2 infection in humans. Given the rapid growth of the SARS-CoV-2-positive population worldwide, ready-to-use CatL inhibitors should be explored as a treatment option. We identify ten US FDA-approved drugs that have CatL inhibitory activity. We provide evidence that supports the combined use of serine protease and CatL inhibitors as a possibly safer and more effective therapy than other available therapeutics to block coronavirus host cell entry and intracellular replication, without compromising the immune system., Key messages • There are over 2118 on-going clinical trials for COVID-19 patients, but current results are limited. • Host cell membrane CatL and TMPRSS2 promote coronavirus cell entry by removing the virus surface spike protein S1 subunit. • In host cell endosomes, CatL removes the S1 subunit and promotes viral membrane fusion, viral RNA release, and replication. • At least 7 CatL-selective inhibitors effectively block coronavirus infection of human cells. • At least 10 US FDA-approved drugs exert CatL inhibitory activity. • Combined use of TMPRSS2 inhibitor camostat and CatL inhibitors or FDA-approved CatL inhibitory drugs merits consideration for urgent testing in COVID-19 patients. • Chloroquine-induced endosomal pH increase and protease inactivation inhibit coronavirus infection, but impair human adaptive immunity. • The protease inhibitor cocktail therapy proposed here could block coronavirus infection while sparing human adaptive immunity.