Introduction: no data are provided about the effect of triple combination therapy with Lopinavir/Ritonavir (LPN/RTN), hydroxychloroquine (HQ) and azithromycin (AZT) on corrected QT (QTc) interval and arrhythmic risk, in COVID-19 patients. This study aims to describe the incidence of extreme QTc interval prolongation among COVID-19 patients on this experimental treatment and to identify the clinical features associated with extreme QTc prolongation. Materials and methods: data of 87 COVID-19 patients, treated with triple combination including LPN/RTN, HQ and AZT, were analyzed. QT interval was obtained by the tangent method and corrected for heart rate using Bazett’s formula. Extreme QTc interval prolongation was considered an absolute QTc interval ≥ 500 ms or an increase in QTc intervals of 60 milliseconds or greater (ΔQTc ≥ 60 milliseconds) compared with baseline. Results: Hypertension (66.7%) and diabetes (25.3%) were the most prevalent cardiovascular comorbidities. 20 patients (23%) showed extreme QTc interval prolongation; No clinical, electrocardiographic or pharmacological characteristics have been associated to extreme QTc prolongation, except the history of ischemic stroke (P= 0,007). One torsade de pointes (TdP) in patient with QTc extreme prolongation (QTc: 560 ms) after 5 days of therapy was recorded. Conclusions: We observed a high incidence of extreme QTc interval prolongation among COVID-19 patients on triple combination therapy. The incidence of malignant arrhythmias seems to be low, a careful electrocardiographic monitoring would be advisable.

A document by Jacqueline Montoya, written on Authorea.

Aims: Variability of ACE2 expression encoded by the ACE2 gene may be important for susceptibility and clinical outcomes of SARS-CoV-2 infection. This study was aimed to identify potential single nucleotide polymorphisms (SNPs) of ACE2 relevant to SARS-CoV-2 infection and predictively assigned risk phenotypes. Methods: Literature was searched in different databases to identify the SNPs of ACE2 that may regulate ACE2 expression in different human tissues relevant to either SARS-CoV-2 or SARS-CoV infection. Allele and genotype information of rs2285666 SNP of ACE2 was obtained from the 1000 Genomes project Phase III in line with Fort Lauderdale principles and phenotypes were assigned accordingly based on carrying characteristics ACE2 allele. Results: About 16 SNPs of ACE2 as potential venture for susceptibility to SARS-CoV-2 infection was identified from the literature. Predicted high-risk phenotypes of ACE2 expressor due to carrying rs2285666 SNP of ACE2 was highly prevalent in East Asia (40.7%; 95% CI 36%-45%), followed by South Asia (36.8%; 95% CI 33%-41%), America (22.8%; 95% CI 18%-27%), Europe (14.5%; 95% CI 11%-18%) and Africa (12.3%; 95% CI 10%-15%), respectively. In total, ~25% of the world population participated in the 1000 Genomes project was predictively identified as being at high-risk for SARS-CoV-2 infection due to carrying rs2285666 ACE2 genetic polymorphism. Conclusion: Identification of high-risk phenotypes for SARS-CoV-2 infection through screening of ACE2 genetic polymorphisms may be valuable for SARS-CoV-2-related COVID-19 prevention and treatment in the population. Customized DNA microarray techniques or next generation sequencing may holistically advance this newly evolving research area of infection genetics.

Abstract. The Controlled Human Infection Model and specifically the Human Viral Challenge Model are not dissimilar to standard clinical trials while adding another layer of complexity and safety considerations. The models deliberately infect volunteers, with an infectious challenge agent (CA) to determine the effect of the infection and the potential benefits of the experimental interventions. The Human Viral Challenge Model studies can shorten the time to assess the efficacy of a new vaccine or treatment by combining this with the assessment of safety. The newly emerging SARS-COV-2 virus is highly contagious and the cause pandemic disease COVID-19. An urgent race in is on to develop a new vaccine against this virus in a timeframe never attempted before. The use of the Human Viral Challenge Model has been proposed to accelerate the development of the vaccine. In the early 2000’s the authors successfully developed a pathogenic Human Viral Challenge Model for another virus for which there was no effective treatment and established it to evaluate potential therapies and vaccines against Respiratory Syncytial Virus. The authors feel that the experience gained in the development of that model can help with the development of a COVID-19 HVCM and describe it here. Word count: 197

This letter is meant to inform the community of pediatricians/pediatric intensivists that we suspect SARS-CoV-2 to cause life-threatening bronchiolitis in infants and we therefore suggest maintaining a high level of suspicion of COVID-19, irrespective of an initially negative SARS-CoV-2 RT-PCR testing, when other causes of bronchiolitis are unidentifiable in young children.

Dear Editor:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious infectious disease of international concern that spreads mainly from person to person through respiratory droplets.1,2 As of July 2020, outbreaks are being reported in China, the country where the pandemic started and in which it was thought initially to be controlled.3 In a similar manner, in other countries like Peru, instead of being controlled, the pandemic is increasing in severity and prevalence. Until July 6, 2020, > 11 million cases had been confirmed across the world, with > 300 000 cases and > 10 000 deaths in Peru.4It is necessary to adopt intentional and thoughtful acts to control the SARS-CoV-2 pandemic. Social distancing measures, minimization of personal contacts, and hand sanitization are effective in limiting the community spread of SARS-CoV-2.1 However, there are social variables that cannot be controlled in Peru, such as lower level education and poor socioeconomic status in a significant percentage of the population5; these factors are related to the morbidity and mortality attributable to COVID 19 infection.6The Centers for Disease Control and Prevention (CDC) describes a list of risk factors for SARS-CoV-2 infection that includes poverty and crowding2. Likewise, a UK-based study investigated the role of ethnicity and socioeconomic position in the development of SARS-CoV-2 infection. They found that socioeconomic deprivation and lack of qualifications were consistently associated with a higher risk of confirmed infection6. Further, reports have shown higher mortality from infectious diseases in patients with a low level of education7. To our knowledge, no studies in Peru have investigated the relationships among the level of education, the socioeconomic status, SARS-CoV-2 infection, and the severity and mortality of the infection, however, statistical findings show a higher frequency of low educational level in people who have died as a result of infection by the virus SARS-CoV-2(Figure 1)Health outcomes are closely related to the educational level. Some types of health behaviors, such as smoking, heavy alcohol drinking, physical inactivity, and unhealthy diet, are expected to mediate the impact of educational level on the incidence of non-communicable diseases8. It is also remarkable that the total prevalence of overweight and obesity in Peru is 60.2% in the total population9. Moreover, lower levels of education are related to higher incidence and prevalence of cardiovascular and cerebrovascular disease, cancer, diabetes, hypertension, and chronic respiratory disease8. Patients with these diseases are at an increased risk of severe illness from COVID-19 because of lower levels of immune cells and high cytokine levels in the body fluids1,2.Educational inequalities in these chronic diseases are mediated by the patient’s socioeconomic status. As expected, low income level and unstable job status that may be linked to low educational level are reasonably predicted to raise the risk of these diseases8. In Peru, > 1/3rd of the population lives in the urban capital, Lima; however, a substantial population still lives in rural areas, with limited access to medical care, chronic disease treatment, and education. These rural residents are often poorer and less educated than their urban counterparts10.Another important factor that influences the characteristics of the COVID-19 pandemic is population density;1 the population density in Peru is 25 people per square kilometer, with a substantial density in the rural population11. Some studies have shown a significant positive linear relationship of population density with number of cases, deaths, and case-fatality rate of SARS-CoV-2. Moreover, there is a significant positive correlation between the number of medical supplies and population density, suggesting that this variable and the lack of medical equipment are key factors that explain the morbidity and mortality of COVID-1912.By 2019, 87% of Peruvians had health insurance coverage;13 however, the quality of health services in the hospitals of the Ministry of Health, in regular situations, is perceived to be low14. The pandemic hit Peru when the country was in the process of improving health services and denoted significant deficiencies across the health system, revealing the need for urgent actions. The lack of equipment, supplies, and medications translates into poor quality of care and plays an important role in the health consequences of the COVID-19 pandemic.In conclusion, we highlight the importance of eliminating the inequality in the coverage of health services and continuing to improve the education for the Peruvian population to control social factors and enable optimal management of the COVID-19 pandemic.

To the Editor,Reported COVID-19 cases usually refer to acute infections diagnosed by PCR and underestimate the true prevalence of disease. Seroprevalence studies provide a more accurate picture as antibodies can be detected in mild or asymptomatic cases who otherwise remain undiagnosed. The majority of seroprevalence studies to date were carried out in developed countries.The first COVID-19 case in Malaysia was reported on January 25, 2020, and the main wave occurred between early March and mid-April. With a national movement control order instituted on March 18, aggressive testing and public health measures, 8,354 cases had been reported as of June 30, 2020,1 or 0.03% of the population. As of June 6, most restrictions had been lifted as part of a phased recovery. We aimed to determine SARS-CoV-2 seroprevalence in residual serum samples collected at a teaching hospital serving Kuala Lumpur and Selangor state, which together have reported 4,483 cases (51.9% of national cases), or 0.05% of the combined population.1We retrieved 816 serum samples sent for diagnostic testing for non-respiratory infections (mainly dengue) and archived at -20°C. These were divided into periods according to dates of collection: pre-pandemic (June-August 2019, n=228), main wave (January 29 to April 14, 2020, n=327) and post-wave (April 15 to June 6, 2020, n=261). For each period, between 17-65 samples were included from every 10-year age group (<10, 10-19, 20-29, 30-39, 40-49, 50-59, 60-69, and >70 years). The samples were from 368 females and 448 males.Samples were first screened with an in-house indirect ELISA detecting IgG to SARS-CoV-2 receptor binding domain (RBD), and shown to be 100% sensitive for samples collected from 14 days post-onset of illness.2 Screen-seropositive samples were confirmed with a highly sensitive and specific (99.3-100%) surrogate viral neutralization test (sVNT; cPass, GenScript, USA) based on total antibody-mediated blockage of ACE2 receptor-RBD interaction,3,4 which has received provisional authorisation from the Singapore Health Sciences Authority. A two-step testing process of screening and confirmation is useful for low-prevalence settings where seropositives have a low predictive value.4These two assays were evaluated in our laboratory with the 228 (ELISA) or 26 (sVNT) pre-pandemic serum samples as negative controls and 35 samples collected from PCR-confirmed COVID-19 patients at least 16 days post-onset of illness. Sensitivity and specificity rates for the screening ELISA were 97.1% and 88.6%, respectively. For the confirmatory sVNT assay, sensitivity and specificity rates were 100%, after increasing the inhibition cut-off from 20% to 25%, as suggested by the manufacturer after assessing background reactivity in our setting. Crude seroprevalence rates are reported with 95% exact binomial confidence intervals (CI) approximated with Poisson distribution. This study was approved by the University Malaya Medical Centre medical ethics committee (no. 2017116-5794).A total of 46 (7.8%) main wave and post-wave samples screened positive, of which 3 were confirmed by sVNT. Two were from the main wave (seroprevalence 0.6%; 95% CI, 0.07-2.2%) and 1 from the post-wave period (0.4%, 95% CI, 0.01-2.1%) (Figure 1). Two were from males aged in their 20s with previous diagnoses of COVID-19. The third was from a 65-year-old man with a 7-day history consistent with COVID-19, who was not tested for SARS-CoV-2. As rates for the main wave and post-wave periods were similar, they were combined to give a crude seroprevalence rate of 0.5% (95% CI, 0.1-1.5%). Using 2019 age- and gender-stratified population data for Kuala Lumpur and Selangor from the Department of Statistics, Malaysia (http://pqi.stats.gov.my/searchBI.php), a direct age-standardised seroprevalence rate was calculated as 0.4% (95% CI, 0-0.93%).This study is potentially limited by bias arising from use of residual inpatients serum. However, residual serum does provide similar estimates of seroprevalence to cohort studies5 and is a convenient option when preliminary data is needed during a lockdown. The rate may also be underestimated because antibodies may take 2 weeks to appear and may be undetectable in mild or asymptomatic cases.The age-standardised seroprevalence of 0.4% for Kuala Lumpur and Selangor found in this study is higher than the period prevalence of confirmed cases of 0.05%. This is consistent with other seroprevalence studies revealing >5 times more COVID-19 infections than are reported.6 As this was a single centre study, a more extensive national serosurvey is necessary to confirm our preliminary indication that Malaysia has experienced limited SARS-CoV-2 transmission to date. With little herd immunity, Malaysia remains highly susceptible to COVID-19 as we emerge from lockdown. Continued vigilance in surveillance and public health measures are critical pending availability of an effective vaccine.

Background: The 2019 novel coronavirus disease (COVID-19) has been reported as pandemy and the number of patients continues to rise. Based on recent data, cardiac injury is a prominent feature of the disease, leading to increased morbidity and mortality.In the present study we aimed to evaluate myocardial dysfunction using transthoracic echocardiography (TTE) and tissue Doppler imaging (TDI) in hospitalized COVID-19 patients. Methods and Results: We recruited 30 patients (56.7 % male, 55.80±14.949 years) who were hospitalized with the diagnosis COVID-19 infection. We analyzed left ventricular (LV) and right ventricular (RV) conventional and TDI parameters at the time of hospitalization and during the course of the disease. Patients without any cardiac disease and with preserved LV ejection fraction (EF) were included.TTE examination was performed and all the variables were recorded and analyzed retrospectively. We observed that both LV and RV conventional echocardiographic parameters were similar when the day of admission to the hospital was compared to the 5th day of the disease. Regarding TDI analysis, we demonstrated significant impairment in LV septal and lateral deformation (p˂.001) .In the correlation analysis no marked correlation was observed between impairment in LV deformation and inflammation biomarkers. Conclusion: Cardiac involvement is an important feature of the COVID-19 infection but the exact mechanism is still undefined. Echocardiography is an essential technique to describe myocardial injury and provide new concepts for the possible definitions of cardiac dysfunction.

Dear Editor,We read the article on possible effects of BCG vacaccine in COVID-19 management should be discouraged and restricted to research purpose only.2

Introduction We reviewed the types of monoclonal antibodies being repurposed for COVID-19 therapeutics, the clinical outcomes and adverse effects so as to provide evidence the bedside physicians, the health policy-makers and the general public could employ in the COVID-19 management protocol. Methods This systematic review was conducted following the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The Joanna Briggs Institute’s critical appraisal checklists for evaluation of the quality of studies were employed to assess the quality of the different types of primary studies included in the review. Results Our search strategy identified 396 potentially relevant articles which decreased to 322 after duplicates were removed. 281 articles were screened out due to lack of relevance. The full text of the remaining 41 relevant papers were retrieved for full text evaluation after which only 19 studies from eight countries met our eligibility criteria and were included in the review. Majority (42%) of the studies emanated from Italy. Also, 94.7% of the studies used tocilizumab. A total of 698 patients were included in all the studies with a male/female ratio of 1.94:1. 78.9% of the studies stated patients’ co-morbidities which include hypertension (80%), diabetes mellitus (73.3%), cardiovascular disease (53.3%) and obesity (26.7%). 75.9% of the patients recovered. Adverse effects reported included viral myocarditis, bacteraemia, candidaemia and invasive aspergillosis. Conclusion Monoclonal antibodies, especially tocilizumab and eculizumab hold some promise in the treatment of the disease but controlled clinical trials using them as monotherapy are needed to further evaluate this finding.

Introduction. Locking the humanity in their homes, COVID-19 forced people to use the technology at hand to keep informed about the outbreak and to keep close to their loved ones. During this time, even if physical health is theoretically unaffected, keeping calm and sane can be challenging. The aim of this research was to evaluate whether exposure to COVID-19 information available in the digital space has a different impact on the mental condition of Romanian medical staff, compared to general population, particularly searching for depression and anxiety symptoms. Materials and methods. An online survey was conducted from April 6 to 16, 2020 within the Romanian users of Social Media platforms. The questionnaire assessed depression with the WHO-Five Well-Being Index, anxiety with the Generalized Anxiety Disorder Scale and Social Media exposure by asking how often the respondents saw COVID-19 related information on the most popular Social Media channels in Romania. Information about: gender, age, educational level, occupation, area of living and risk category was also collected. The risk categories were defined as no risk, medium risk, and medical staff. Results. Almost 90% of the 402 participants received daily through at least one Social Media channel information related to the COVID-19 outbreak. The Social Media Exposure significantly associated with the risk group only for Facebook and LinkedIn. However, exposure to information regarding COVID-19 was neither associated with anxiety nor depression. No significant association was identified neither between age class and self-assessed anxiety nor self-assessed depression. The self-assessment of depression was significantly more frequent as compared to self-assessment of anxiety. Conclusion. The results of this research are opposite to most of the already published literature. Depression and anxiety could not be correlated with the context of lockdown and excessive COVID-19-related information.

Coronavirus disease 2019, an infectious viral disease caused by severe acute respiratory syndrome coronavirus 2 has been declared a global pandemic by World Health Organisation. The race to find an effective cure for it is on. Most of the candidate drugs in various clinical trials are being re-purposed but none has been approved as at date. It is pertinent for the bedside physicians to understand the mechanisms of action of these agents and their peculiar adverse effects so they are properly guided on the risk/benefit of the drugs they choose in managing COVID-19 patients. In this review, we aimed to review the mechanisms of action and adverse effects of the major drugs in clinical trials for COVID-19 therapeutics. Clinicaltrials.gov, the international clinical trials platform of the WHO, the EU clinical trials register and the Cochrane Central Register of Controlled Trials were searched for registered clinical trials. Studies in therapeutic trials were considered eligible for the work. Frequency table was made for the most common trialled drugs and the mechanisms of actions and adverse effects of the selected drugs were reviewed. 10 studies were selected for review in a descending order of their frequency in different therapeutic trials and these are ritonavir, lopinavir, chloroquine/hydroxychloroquine, interferon, remdesvir, favipravir, umifenovir, darunavir, tocilizumab and methylprednisolone. The bedside physicians need to understand the mechanisms of action of these agents and their peculiar adverse effects so they are properly guided on the risk/benefit of the drugs they choose in managing COVID-19 patients.

Background: The COVID19 pandemic gripped every nation’s healthcare system and provisions on all levels. In cardiac and aortic surgery, as it is with most specialities, elective surgeries were halted. Aims of the study: We captured reflections, contingencies, and current practices across of high-volume centres in cardiac and aortic surgery globally. We also aimed this study to assess decision on prioritization of the surgical patients, the need for personal protection equipment and choice of preoperative investigations in current dynamic and fluid climate. Methods: A validated web-based questionnaire was constructed and was circulated to the international surgeons amongst high volume cardiac and aortic surgery centres. Their intrinsic feedback on decision making, impact of the lockdown and perspectives for the future ahead us all were noted. Mixed method approach was constructed. Qualitative data analysis was introduced to signify the impact globally. Results: Overall, 23 centers from 18 countries participated in this international study. 91.7% of the respondents stopped operating on elective patients during the pandemic. Majority of the surgeons agreed that acute aortic dissection (87.1%) should be operated as emergency procedure and stable triple vessel disease (87.1%) to be considered as elective procedure. Three-fifth (60%) of the respondents relied on CT chest as a preoperative screening modality. Conclusion: In the present climate where there is paucity of evidence, this will give an interim consensus for the cardiac surgeons. With the increase in cumulative number of COVID19 patients, careful utilization of the resources regarding hospital beds and manpower is of paramount importance.

Introduction: COVID-19 is a global catastrophic event that causes severe acute respiratory syndrome. The mechanism of the disease remains unclear, and hypoxia is one of the main complications. There is no currently approved protocol for treatment. The microbial threat as induced by COVID-19 causes the activation of macrophages to produce a huge amount of inflammatory molecules and nitric oxide (NO). Activation of macrophages population into a pro-inflammatory phenotype induces a self-reinforcing cycle. Oxidative stress and NO contribute to this cycle, establishing a cascade inflammatory state that can kill the patient. Interrupting this vicious cycle by a simple remedy may save critical patients’ lives. Methods: Nitrite, nitrate (the metabolites of NO), methemoglobin, and prooxidant-antioxidant-balance levels were measured in 25 ICU COVID-19 patients and 25 healthy individuals. As the last therapeutic option, five patients were administered methylene blue-vitamin C-N-acetyl Cysteine (MCN). Results: Nitrite, nitrate, methemoglobin, and oxidative stress were significantly increased in patients in comparison to healthy individuals. Four of the five patients responded well to treatment. Discussion: NO, methemoglobin and oxidative stress may play a central role in the pathogenesis of critical COVID-19 disease. MCN treatment seems to increase the survival rate of these patients. Considering the vicious cycle of macrophage activation leading to deadly NO, oxidative stress, and cytokine cascade syndrome; the therapeutic effect of MCN seems to be reasonable. Accordingly, a wider clinical trial has been designed. It should be noted that the protocol is using the low-cost drugs which the FDA approved for other diseases.

Background and Purpose Previously we reported our hypothesis that the high distribution of antiviral drugs in the lung is a key factor that results in reducing viral loads in COVID-19 patients. So far, chloroquine, lopinavir, hydroxychloroquine, azithromycin, favipiravir, ribavirin, darunavir, remdesivir, and umifenovir have been tested in COVID-19 clinical trials. Here we validate our hypothesis by comparing the pharmacokinetics profiles of these drugs and their capabilities of reducing viral load in clinical trials. Experimental approach The RNA-seq data were obtained from public database and re-analyzed and visualized by Single Cell Portal and Seurat. The tissue/plasma ratio of antiviral drugs were calculated by AUC or Mean values that were compiled from publications. Key Results High expression of both ACE2 and TMPRSS2 makes the lung and intestine vulnerable to SARS-CoV-2. Hydroxychloroquine, chloroquine, and favipiravir, which were highly distributed to the lung, were reported to reduce viral loads in respiratory tract of COVID-19 patients. Conversely, drugs with poor lung distributions, including lopinavir/ritonavir, umifenovir and remdesivir, were insufficient to inhibit SARS-CoV-2 replication. Lopinavir/ritonavir might inhibit SARS-CoV-2 in the GI tract according to their distribution profiles. Conclusion and Implications The antiviral drugs should be distributed straight to or accumulate in the lung for reducing viral loads in respiratory tract of COVID-1 9 patients. Additionally, to better evaluate antiviral drugs that target the intestine, the stool samples should also be collected for viral RNA test in the future.

Introduction: A rapidly evolving evidence suggests that smell dysfunction is a common symptom in COVID-19 infection with paucity of data on its duration and recovery rate. Objectives: delineate the different patterns of olfactory disorders recovery in patients with COVID-19. Methods: This cross-sectional cohort study included 96 patients with olfactory complaint confirmed to be COVID-19 positive with recent onset of anosmia. All patients were inquired for smell recovery patterns using self-assessment questionnaires. Results: ninety six patients completed the study with mean age 34.26±11.91 years. Most patients had sudden anosmia 83%. Loss of smell was accompanied by nonspecific inflammatory symptoms as low-grade fever (17%) and generalized body ache (25%). Nasal symptoms were reported by 33% of patients. Some patients reported comorbidities as D.M (16%), hypertension (8%) or associated allergic rhinitis (25%), different patterns of olfactory recovery showed 40 patients experiencing full recovery (33.3%) while, 32 patients showed partial recovery (41.7%) after a mean of 11 days while 24 patients (25 %) showed no recovery within one month from onset of anosmia. Conclusion: The sudden olfactory dysfunction is a common symptom in patients with COVID-19. Hyposmia patients recover more rapidly than anosmic ones while the middle age group carried the best prognosis in olfactory recovery. Females possess better potentiality in regaining smell after recovery and the association of comorbidities worsen the recovery rate of olfactory dysfunction in patients with COVID19.

Background: Coronavirus disease 2019 (COVID-19), a newly erupted respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has swept across the most of countries. The laboratory characteristics of COVID-patients accompanied with cancer and the risk factors for disease progression and survival of this particular population were few reported. Methods: We enrolled 585 confirmed COVID-19 patients admitted to our hospitals with measured interleukin-6 level on admission. Laboratory tests and outcome were extracted from electronic medical records. Data was divided to cancer group and non-cancer group to explorer the risk factors of progression and survival. Findings: A total of 44 patients with different cancer type (cancer group) and 487 patients without cancer (non-cancer group) were included. Cancer group had significant higher levels of NEUT, NLR, IL-6, and CRP than non-cancer group, but lymphocyte count and ALB were lower. Cancer group showed significantly higher progression rate (42·1% vs 22·5%) and mortality (27·27% vs 11·91%) than non-cancer group. Elevated IL-6 and CRP were the risk factors associated with progression among moderate patients and death in-hospital (all p<0·05) in non- cancer group. This correlation was not observed in caner group. Interpretation: IL-6, CRP, NEUT, and NLR were elevated in COVID-19 patients with cancer, with lower level of LYMP and ALB. IL-6 and CRP were positively correlated with progression and poor outcome in patients without cancer. As one of combined diseases, despite malignancy history did not directly affect the prognosis of COVID-19, but it could play a role in the poorer outcome through release of IL-6 and CRP.

The current COVID-19 global pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of probable bat origin, has highlighted the ongoing need for a One Health response to emerging zoonotic disease events, which are significantly increasing over time. Understanding the human-animal interface and its relevance to disease transmission remains a critical control point for many emerging zoonoses. Determination of the susceptibility of various animal species to infection with SARS-CoV-2 and the role of animals in the epidemiology of the disease will be critical to informing appropriate human and veterinary public health responses to this pandemic. A scoping literature review was conducted to collect, evaluate and present the available research evidence regarding SARS-CoV-2 infections in animals. Experimental studies have successfully demonstrated SARS-CoV-2 infection and transmission in cats, ferrets, hamsters, bats and non-human primates under experimental settings. Dogs appear to have limited susceptibility to SARS-CoV-2, while other domestic species including pigs and poultry do not appear susceptible. Naturally occurring SARS-CoV-2 infections in animals appear uncommon, with 14 pets, 8 captive big cats and an unreported number of farmed mink testing positive to date. Infections typically appear asymptomatic in dogs, while clinical signs of respiratory and/or gastrointestinal disease tend to be mild to moderate in felines, and severe to fatal in mink. Most animal cases have been infected by close contact with COVID-19 patients. In domestic settings, viral transmission is self-limiting, however in high density animal environments there can be sustained between-animal transmission. To date, two potential cases of animal-to-human transmission are being investigated, on infected mink farms. Given the millions of COVID-19 cases worldwide and ongoing potential for further zoonotic and anthroponotic viral transmission, further research and surveillance activities are needed to definitively determine the role of animals in community transmission of SARS-CoV-2.

In the context of the current COVID-19 pandemic, what are the lessons clinical pharmacology could learn to improve our teaching practice and involvement in research and ethics committees to make sure we are better prepared for the next emergency. Is there something in the light of the hydroxychloroquine hype that we as clinical pharmacologists or our professional societies could have done better? We propose updating the way we teach about drug development, rules and ethics of off-label prescribing and critical appraisal of primary sources when guidelines and top-level evidence are not available. Clinical pharmacology should play a leading role in the future re-definition of processes and guidelines for emergencies such as the one we faced in 2020.

There is growing evidence that climatic factors could influence the evolution of the current COVID-19 pandemic. Here, we build on this evidence base, focusing on the southern hemisphere summer and autumn period. The relationship between climatic factors and COVID-19 cases in New South Wales, Australia was investigated during both the exponential and declining phases of the epidemic in 2020, and in different regions. Increased relative humidity was associated with decreased cases in both epidemic phases, and a consistent negative relationship was found between relative humidity and cases. Overall, a decrease in relative humidity of 1% was associated with an increase in cases of 7-8%. Overall, we found no relationship with between cases and temperature, rainfall or wind speed. Information generated in this study confirms humidity as a driver of SARS-CoV-2 transmission.

Background and Purpose. Since the onset of COVID-19 many clinical trials of drugs and/or vaccines are continuing and new ones are introduce daily. Yet the international research process failed to develop a preventative vaccine or potent therapeutic drugs for relieving the severity of the disease. Therefore, at present the best recommendation to people to slow the spread of the disease is; please stay at home and maintain social distancing! Experimental approach. Many aspects of pharmacotherapeutic mechanism of action of some previously approved drugs with anti-inflammatory effects, such as colchicine, in various disorders is not fully understood. Therefore, many potential therapeutic uses for these drugs and its analogues can be imagined. In this hypothesis article, an attempt has been made to evaluate some potential therapeutic effects of colchicine that may be benefit against COVID-19. Key Results. Prophylactic therapy with colchicine regulates the innate inflammatory response by blocking intracellular signaling pathways. This can inhibit respiratory alveolar destruction following COVID-19 pneumonia, which is the main cause of ARDS and death in these patients. Conclusion and Implications Since the macrophage and granulocytes are the main pro-inflammatory mediators in the lung, it seems application of therapeutic doses of colchicine, before the onset of respiratory problems, will protect the lung against severe damages and respiratory failure in COVID-19 patients. Obviously, many clinical trials are required to prove the validity of this claim.

A patient with dacryocystitis who had a regular ophthalmology visit canceled the regular visit with a COVID-19 pandemic. After that, serious deterioration was observed and emergency evisceration was performed. Even during COVID-19 pandemic, so it is necessary to continue regular eye examinations and infection treatment.

Corona virus spread easily and rapidly over countries and caused COVID-19 disease with several organ damage. Lymphopenia and elevation NLR, LDH and CRP in covid 19 patients could be a predictive factor, and when they become deeper during hospitalization show the patients to need ICU admission.

Dear Dr Harky et. al,We appreciate your inquiry regarding our case report. Dr Harky et. al suggested that TEVAR for a Marfan patient could be an unnecessary approach even during the COVID-19 pandemic.We believe in this particular case, the endovascular approach was fully justified as the patient had clear signs of end organ ischemia at presentation. He presented with extreme right leg ischemia with diffuse numbness. There was no detectable distal arterial flow of the right extremity by a Doppler and physical evaluation. Contrast computed tomography scan showed a completely occluded right common iliac artery and diminished flow to the right renal and celiac arteries due to the compression of the true lumen from the false lumen. Preoperative creatinine was elevated to 1.2 mg/dl. She was also suffering ongoing right kidney malperfusion.It was during the time when COVID-19 epidemic started spreading rapidly in New York City. Our hospital beds were filled with COVID-19 patients and there was a shortage of medical supplies with no ventilators immediately available. It was important to reduce exposure of the individual to the hospital environment and minimize length of stay and ventilator needs. As such, we chose to proceed with TEVAR to minimize the risk of lung injury which can occur in open repair. Postoperative respiratory failure is a major issue in open thoracic aortic repair [1]. The patient did not have a risk of respiratory comorbidities but we believed that this pandemic placed all patients at risk for contracting COVID-19 and subsequent acute respiratory distress [2].Due to the high risk of spinal cord ischemia in this particular patient, we performed TEVAR with a distal bare metal component to preserve the blood flow into spinal cord arteries [3]. The initial clinical treatment plan was to perform the TEVAR as a bridge to open repair. We obviously will need to follow-up with her carefully and if any signs of failure of TEVAR is detected, open repair will ultimately be required.Dr Harky et. al suggested axillary femoral artery bypass to rescue the ischemic leg, however, this patient also suffered malperfsuion of the renal and celiac arteries, so further intervention was required.Thank you for your insightful suggestions.References1) Khan FM, Naik A, Hameed I, et al. Open repair of descending thoracic and thoracoabdominal aortic aneurysms: a meta-analysis. Ann Thorac Surg . 2020;S0003-4975(20)30865-1.2) Bai Y, Yao L, Wei T, et al. Presumed Asymptomatic Carrier Transmission of COVID-19. JAMA.  2020;323:1406–7.3) Lombardi JV, Cambria RP, Nienaber CA, et al. Five-year results from the study of Thoracic Aortic Type B Dissection Using Endoluminal Repair (STABLE I) study of endovascular treatment of complicated type B aortic dissection using a composite device design. J Vasc Surg. 2019; 70:1072-81.