Coronavirus Disease 2019 Morbidity Research Articles

Cardiovascular risk factors and clinical outcomes of patients hospitalized with COVID-19 pneumonia in Somalia.

Background:Coronavirus disease-2019 (COVID-19) is a potentially life-threatening illness with no established treatment. Cardiovascular risk factors (CRFs) exacerbate COVID-19 morbidity and mortality.Objective:To determine the prevalence of CRF and clinical outcomes of patients hospitalized with COVID-19 in a tertiary hospital in Somalia.Methods:We reviewed the medical records of patients aged 18 years or older with a real-time polymerase chain reaction (RT-PCR)–confirmed COVID-19 hospitalized at the De Martino Hospital in Mogadishu, Somalia, between March and July 2020.Results:We enrolled 230 participants; 159 (69.1%) males, median age was 56 (41–66) years. In-hospital mortality was 19.6% (n = 45); 77.8% in the intensive care unit (ICU) compared with 22.2%, in the general wards (p < 0.001). Age ⩾ 40 years [odds ratio (OR): 3.6, 95% confidence interval (CI): 1.2–10.6, p = 0.020], chronic heart disease (OR: 9.3, 95% CI: 2.2–38.9, p = 0.002), and diabetes mellitus (OR: 3.2, 95% CI: 1.6–6.2, p < 0.001) were associated with increased odds of mortality. Forty-three (18.7%) participants required ICU admission. Age ⩾ 40 years (OR: 7.5, 95% CI: 1.7–32.1, p = 0.007), diabetes mellitus (OR: 3.2, 95% CI: 1.6–6.3, p < 0.001), and hypertension (OR: 2.5, 95% CI: 1.2–5.2, p = 0.014) were associated with ICU admission. For every additional CRF, the odds of admission into the ICU increased threefold (OR: 2.7, 95% CI: 1.2–5.2, p < 0.001), while the odds of dying increased twofold (OR: 2.1, 95% CI: 1.3–3.2, p < 0.001).Conclusions:We report a very high prevalence of CRF among patients hospitalized with COVID-19 in Somalia. Mortality rates were unacceptably high, particularly among those with advanced age, underlying chronic heart disease, and diabetes.

Safety of conventional immunosuppressive therapies for patients with dermatological conditions and coronavirus disease 2019: A review of current evidence.

The effect of coronavirus disease 2019 (COVID-19) on patients receiving conventional immunosuppressive (IS) therapy has yet to be fully determined; however, research on using IS therapy for treating COVID-19 in acutely ill patients is increasing. While some believe that IS therapy may be protective, others argue that these agents may make patients more susceptible to COVID-19 infection and morbidity and advocate for a more cautious, individualized approach to determining continuation, reduction, or discontinuation of therapy. In this review, we aim to provide an overview of COVID-19 risk in dermatological patients who are receiving conventional IS therapies, including mycophenolate mofetil, methotrexate, cyclosporine, azathioprine, apremilast, JAK inhibitors, and systemic steroids. Additionally, we provide recommendations for management of these medications for dermatological patients during the COVID-19 pandemic. Treatment of dermatological disease during the COVID-19 pandemic should involve shared decision-making between the patient and provider, with consideration of each patient's comorbidities and the severity of the patient's dermatological disease.

One-year Review of COVID-19 in the Arab World.

The coronavirus disease 2019 (COVID-19) has affected almost every country worldwide, including all 22 Arab countries. To the best of our knowledge, this is the first study to follow the prevalence of COVID-19 in all Arab countries. In this review, we aimed to assess the 12-month prevalence of COVID-19 in Arab countries and to compare these findings with other significantly affected countries. World Health Organization, Worldometer, and Ministries of Health websites were used to search for COVID-19 data in all Arab countries. The period covered started from February 2020 to February 2021. In all Arab countries, the median age of the population was 26.25 years. As of March 01, 2021, the total number of confirmed COVID-19 cases in all Arab countries was 4,259,756. Bahrain, Qatar, Lebanon, Kuwait, and United Arab Emirates had the highest reported number of confirmed COVID-19 cases per million population. The total number of COVID-19 deaths was 72,950, with predominance in Lebanon, followed by Tunisia, Jordan, Palestine, and Iraq. In comparison with the topmost affected countries, and based on both the highest number of confirmed and deaths per million population, Arab countries ranked second last before India, with 9,646 and 165 cases, respectively. Among the Arab countries, Qatar, Bahrain, and Lebanon showed the highest number of recovered, confirmed, and death cases per million populations, respectively. The number of confirmed and death cases among all Arab countries triggered significant worries about morbidity and mortality of COVID-19, respectively. However, the younger population in Arab countries may have contributed to fewer COVID-19 deaths in comparison with the topmost affected countries.

Advancing Pediatrics During Turbulent Times.

Advancing Pediatrics During Turbulent Times.

The Effect of Influenza Vaccination on COVID-19 Morbidity, Severity and Mortality: Systematic Review and Meta-Analysis

Coronavirus disease 2019 (COVID-19) pandemic is rapidly developing worldwide with a high mortality rate. In this meta-analysis study, the effect of influenza vaccination on the prevention of COVID-19 and its consequences in patients were investigated. The systematic search for this study was performed from November 2019 to 25 November 2020, in the databases of Medline, PubMed, Scopus, Web of Science, Embase, Ebsco, Cochrane and medRxiv. Search terms used included COVID-19, coronavirus, SARS-CoV-2, covid, influenza, flu, grippe and vaccine. The present study examined the association between influenza vaccination and COVID-19 including COVID-19 infection, mortality, hospitalisation and intensive care unit (ICU) admission. Finally, the pooled estimates for different outcomes were calculated by the software for statistics and data science (STATA) version 15 and I2 was used to determine the heterogeneity. By analysing the data of articles, the pooled estimates of these data indicated that influenza vaccination could lower probability of COVID-19 infection up to 24% (OR = 0.77; 95% CI: 0.65, 0.91), of death up to 32% (OR = 0.68; 95% CI: 0.42, 1.11), of the hospitalisation up to 25% (OR = 0.75; 95% CI: 0.46; 1.23) and of admission to ICU up to 29% (OR = 0.71; 95% CI: 0.40, 1.27). Influenza vaccination can help decrease the COVID-19 infection and reduce hospitalisation and the need for ICU and mortality rates.

Impact of visceral fat on the prognosis of coronavirus disease 2019: an observational cohort study

BackgroundClarification of the risk factors for coronavirus disease 2019 (COVID-19) severity is strongly warranted for global health. Recent studies have indicated that elevated body mass index (BMI) is associated with unfavorable progression of COVID-19. This is assumed to be due to excessive deposition of visceral adipose tissue (VAT); however, the evidence investigating the association between intra-abdominal fat and COVID-19 prognosis is sparse. We therefore investigated whether measuring the amount of intra-abdominal fat is useful to predict the prognosis of COVID-19.MethodsThe present study enrolled 53 consecutive cases of COVID-19 patients aged ≥ 20 years with chest computed tomography (CT) scans. The VAT area, total adipose tissue (TAT) area, and VAT/TAT ratio were estimated using axial CT images at the level of the upper pole of the right kidney. Severe COVID-19 was defined as death or acute respiratory failure demanding oxygen at ≥ 6 L per minute, a high-flow nasal cannula, or mechanical ventilation. The association of VAT/TAT with the incidence of progression to a severe state was estimated as a hazard ratio (HR) using Cox regression analysis. To compare the prediction ability for COVID-19 disease progression between BMI and VAT/TAT, the area under the receiver operating characteristic curve (AUC) of each was assessed.ResultsA total of 15 cases (28.3% of the whole study subjects) progressed to severe stages. The incidence of developing severe COVID-19 increased significantly with VAT/TAT (HR per 1% increase = 1.040 (95% CI 1.008–1.074), P = 0.01). After adjustment for potential confounders, the positive association of VAT/TAT with COVID-19 aggravation remained significant (multivariable-adjusted HR = 1.055 (95% CI 1.000–1.112) per 1% increase, P = 0.049). The predictive ability of VAT/TAT for COVID-19 becoming severe was significantly better than that of BMI (AUC of 0.73 for VAT/TAT and 0.50 for BMI; P = 0.0495 for the difference).ConclusionsA higher ratio of VAT/TAT was an independent risk factor for disease progression among COVID-19 patients. VAT/TAT was superior to BMI in predicting COVID-19 morbidity. COVID-19 patients with high VAT/TAT levels should be carefully observed as high-risk individuals for morbidity and mortality.

School Asthma Care During COVID-19: What We Have Learned and What We Are Learning

The focus of this article is to review school asthma care during coronavirus disease 2019 (COVID-19). Asthma is listed as a risk factor in some guidelines, although children with asthma appear to not be at increased risk of severe respiratory outcomes compared with children without asthma during the pandemic. Differentiating COVID-19 from allergic disease is very difficult in the school-aged children. For school management, there is firm evidence that masks do not exacerbate underlying lung conditions including asthma, and evidence to date supports that children with asthma can learn in-person at school because they do not appear to be at increased risk of COVID-19 morbidity or mortality. For children and adolescents, the COVID-19 vaccine has been demonstrated to be safe and well tolerated. School asthma management includes remaining on prescribed asthma medications. Asthma management, as with management of all pediatric conditions, must also factor in the impact of adverse social determinants and health disparities. Broadly, the pandemic has also served as a call to resource stewardship and innovation and allowed practitioners to consider how this may impact asthma care moving forward.

Gut microbiota in a population highly affected by obesity and type 2 diabetes and susceptibility to COVID-19

Coronavirus disease 2019 (COVID-19) is a disease produced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and it is currently causing a catastrophic pandemic affecting humans worldwide. This disease has been lethal for approximately 3.12 million people around the world since January 2020. Globally, among the most affected countries, Mexico ranks third in deaths after the United States of America and Brazil. Although the high number of deceased people might also be explained by social aspects and lifestyle customs in Mexico, there is a relationship between this high proportion of deaths and comorbidities such as high blood pressure (HBP), type 2 diabetes, obesity, and metabolic syndrome. The official epidemiological figures reported by the Mexican government have indicated that 18.4% of the population suffers from HBP, close to 10.3% of adults suffer from type 2 diabetes, and approximately 36.1% of the population suffers from obesity. Disbalances in the gut microbiota (GM) have been associated with these diseases and with COVID-19 severity, presumably due to inflammatory dysfunction. Recent data about the association between GM dysbiosis and metabolic diseases could suggest that the high levels of susceptibility to SARS-CoV-2 infection and COVID-19 morbidity in the Mexican population are primarily due to the prevalence of type 2 diabetes, obesity, and metabolic syndrome.

COVID-19 and hereditary angioedema: Incidence, outcomes, and mechanistic implications.

Background: Patients with hereditary angioedema (HAE) have been postulated to be at increased risk for coronavirus disease 2019 (COVID-19) infection due to inherent dysregulation of the plasma kallikrein-kinin system. Only limited data have been available to explore this hypothesis. Objective: To assess the interrelationship(s) between COVID-19 and HAE. Methods: Self-reported COVID-19 infection, complications, morbidity, and mortality were surveyed by using an online questionnaire. The participants included subjects with HAE with C1 inhibitor (C1INH) deficiency (HAE-C1INH) and subjects with HAE with normal C1-inhibitor (HAE-nl-C1INH), and household controls (normal controls). The impact of HAE medications was examined. Results: A total of 1162 participants who completed the survey were analyzed, including: 695 subjects with HAE-C1INH, 175 subjects with HAE-nl-C1INH, and 292 normal controls. The incidence of reported COVID-19 was not significantly different between the normal controls (9%) and the subjects with HAE-C1INH (11%) but was greater in the subjects with HAE-nl-C1INH (19%; p = 0.006). Obesity was positively correlated with COVID-19 across the overall population (p = 0.012), with a similar but nonsignificant trend in the subjects with HAE-C1INH. Comorbid autoimmune disease was a risk factor for COVID-19 in the subjects with HAE-C1INH (p = 0.047). COVID-19 severity and complications were similar in all the groups. Reported COVID-19 was reduced in the subjects with HAE-C1INH who received prophylactic subcutaneous C1INH (5.6%; p = 0.0371) or on-demand icatibant (7.8%; p = 0.0016). The subjects with HAE-C1INH and not on any HAE medications had an increased risk of COVID-19 compared with the normal controls (24.5%; p = 0.006). Conclusion: The subjects with HAE-C1INH who were not taking HAE medications had a significantly higher rate of reported COVID-19 infection. Subcutaneous C1INH and icatibant use were associated with a significantly reduced rate of reported COVID-19. The results implicated potential roles for the complement cascade and tissue kallikrein-kinin pathways in the pathogenesis of COVID-19 in patients with HAE-C1INH.

Building capacity of community health centers to overcome data challenges with the development of an agile COVID-19 public health registry: a multistate quality improvement effort.

ObjectiveDuring the coronavirus disease 2019 (COVID-19) pandemic, federally qualified health centers rapidly mobilized to provide SARS-CoV-2 testing, COVID-19 care, and vaccination to populations at increased risk for COVID-19 morbidity and mortality. We describe the development of a reusable public health data analytics system for reuse of clinical data to evaluate the health burden, disparities, and impact of COVID-19 on populations served by health centers.Materials and MethodsThe Multistate Data Strategy engaged project partners to assess public health readiness and COVID-19 data challenges. An infrastructure for data capture and sharing procedures between health centers and public health agencies was developed to support existing capabilities and data capacities to respond to the pandemic.ResultsBetween August 2020 and March 2021, project partners evaluated their data capture and sharing capabilities and reported challenges and preliminary data. Major interoperability challenges included poorly aligned federal, state, and local reporting requirements, lack of unique patient identifiers, lack of access to pharmacy, claims and laboratory data, missing data, and proprietary data standards and extraction methods.DiscussionEfforts to access and align project partners’ existing health systems data infrastructure in the context of the pandemic highlighted complex interoperability challenges. These challenges remain significant barriers to real-time data analytics and efforts to improve health outcomes and mitigate inequities through data-driven responses.ConclusionThe reusable public health data analytics system created in the Multistate Data Strategy can be adapted and scaled for other health center networks to facilitate data aggregation and dashboards for public health, organizational planning, and quality improvement and can inform local, state, and national COVID-19 response efforts.

Comprehensive Review of Cardiovascular Complications of Coronavirus Disease 2019 and Beneficial Treatments.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 and was first reported in December 2019 in Wuhan, China. Since then, it caused a global pandemic with 212,324,054 confirmed cases and 4,440,840 deaths worldwide as of August 22, 2021. The disease spectrum of COVID-19 ranges from asymptomatic subclinical infection to clinical manifestations predominantly affecting the respiratory system. However, it is now evident that COVID-19 is a multiorgan disease with a broad spectrum of manifestations leading to multiple organ injuries including the cardiovascular system. We review studies that have shown that the relationship between cardiovascular diseases and COVID-19 is indeed bidirectional, implicating that preexisting cardiovascular comorbidities increase the morbidity and mortality of COVID-19, and newly emerging cardiac injuries occur in the settings of acute COVID-19 in patients with no preexisting cardiovascular disease. We present the most up-to-date literature summary to explore the incidence of new-onset cardiac complications of coronavirus and their role in predicting the severity of COVID-19. We review the association of elevated troponin with the severity of COVID-19 disease, which includes mild compared to severe disease, in nonintensive care unit compared to intensive care unit patients and in those discharged from the hospital compared to those who die. The role of serum troponin levels in predicting prognosis are compared in survivors and non-survivors. The association between COVID-19 disease and myocarditis, heart failure and coagulopathy are reviewed. Finally, an update on beneficial treatments is discussed.

The Effects of Income Level on Susceptibility to COVID-19 and COVID-19 Morbidity/Mortality: A Nationwide Cohort Study in South Korea.

This study aimed to investigate the association of income level with susceptibility to coronavirus disease 2019 (COVID-19) and COVID-19 morbidity and mortality. Using the Korean National Health Insurance COVID-19 Database cohort, medical claim data from 2015 through 2020 were collected. A total of 7943 patients who were diagnosed with COVID-19 from 1 January 2020 to 4 June 2020 were included. A total of 118,914 participants had negative COVID-19 PCR tests. Income levels were classified by 20th percentiles based on 2019 Korean National Health Insurance premiums. The 20th percentile income levels were categorized into three groups (low, middle, and high). The relationship of income level with susceptibility to COVID-19 and COVID-19 morbidity and mortality was analyzed using logistic regression analysis. A high income level was related to lower odds of COVID-19 infection (adjusted odds ratio (aOR) = 0.79, 95% confidence interval (CI) = 0.75–0.83, p < 0.001). The negative association between income level and COVID-19 infection was maintained in all subgroups. Patients with low income levels were susceptible to COVID-19 infection; however, there was no relation of COVID-19 morbidity and mortality with income level in the Korean population.

Prevalence and mortality of COVID-19 are associated with the L55M functional polymorphism of Paraoxonase 1

IntroductionAccumulating evidence recommends that infectious diseases including coronavirus disease 2019 (COVID-19) are often associated with oxidative stress and inflammation. Paraoxonase 1 (PON1, OMIM: 168,820), a member of the paraoxonase gene family, has antioxidant properties. Enzyme activity of paraoxonase depends on a variety of influencing factors such as polymorphisms of PON1, ethnicity, gender, age, and a number of environmental variables. The PON1 has two common functional polymorphisms, namely, Q192R (rs662) and L55M (rs854560). The R192 and M55 alleles are associated with increase and decrease in enzyme activity, respectively.ObjectiveThe present study was conducted to investigate the possible association of rs662 and rs854560 polymorphisms with morbidity and mortality of COVID-19.MethodsData for the prevalence, mortality, and amount of accomplished diagnostic test (per 106 people) on 25 November 2020 from 48 countries were included in the present study. The Human Development Index (HDI) was used as a potential confounding variable.ResultsThe frequency of M55 was positively correlated with the prevalence (partial r = 0.487, df = 36, p = 0.002) and mortality of COVID-19 (partial r = 0.551, df = 36, p < 0.001), after adjustments for HDI and amount of the accomplished diagnostic test as possible confounders.ConclusionsThis means that countries with higher M55 frequency have higher prevalence and mortality of COVID-19.

Monoclonal antibodies in COVID-19 management: a scoping review

Coronavirus disease 2019 (COVID-19) was declared as pandemic on March 11th 2020 by the world health organization (WHO). Vaccination is for preventing COVID-19 morbidity but when people are infected, treatment is required and even after one and half years the effective cure is yet to be discovered. In this context monoclonal antibodies (mAbs) are promising innovative therapeutic agents in controlling COVID-19 infection. Researchers have found more than 50 mAbs against COVID-19 and they are at different stages of development. Scientists are pacing the research on mAbs. mAbs are innovative therapeutic agents in this context a scoping narrative review was done. At present we have evidences from numerous randomized controlled trials (RCT) on mAbs in effective control of respiratory and coagulation related complications due to COVID-19 infection. Many have got emergency use approval and few of which were withdrawn due to absence of enough evidences or adverse reactions. Examples are bamlanivimab, etesevimab, casirivimab and imdevimab. Other than these many investigational (mAbs) are under scrutiny. With the current evidences the article will give an insight to new and repurposed mAbs which are still under investigation in the management of COVID-19 infections.

COVID-19 mRNA vaccination leading to CNS inflammation: a case series.

The availability of vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), provides hope towards mitigation of the coronavirus disease 2019 (COVID-19) pandemic. Vaccine safety and efficacy has not been established in individuals with chronic autoimmune diseases such as multiple sclerosis (MS). Anecdotal reports suggest that the vaccines may be associated with brain, spinal cord, peripheral nervous system, and cardiac inflammation. Based on the high morbidity and unpredictable course of COVID-19, and the need to achieve herd immunity, vaccination has been recommended for patients with MS. We report clinical and MRI features of seven individuals who received the Moderna (n = 3) or Pfizer (n = 4) SARS-CoV-2 mRNA vaccines. Within one to 21 days of either the first (n = 2) or second (n = 5) vaccine dose, these patients developed neurologic symptoms and MRI findings consistent with active CNS demyelination of the optic nerve, brain, and/or spinal cord. Symptoms included visual loss, dysmetria, gait instability, paresthesias, sphincter disturbance, and limb weakness. Age ranged from 24 to 64 (mean 39.1) years; five were woman (71.4%). The final diagnosis was exacerbation of known stable MS (n = 4, two were receiving disease-modifying therapy at the time of vaccination), new onset MS (n = 2), or new onset neuromyelitis optica (n = 1). All responded to corticosteroid (n = 7) or plasma exchange (n = 1) therapy, with five returning to baseline and two approaching baseline. Large prospective studies are required to further investigate any possible relationship between COVID-19 vaccines and acute CNS demyelination.

Predisposing factors of important invasive fungal coinfections in COVID-19 patients: a review article.

Severe acute respiratory syndrome coronavirus-2 has caused a devastating pandemic lasting for more than a year. To date, 47 million individuals have been infected and 1.2 million individuals have died worldwide. Some of the most important coinfections in patients with coronavirus disease 2019 (COVID-19) are opportunistic invasive fungal infections (OIFIs), which are sometimes not rapidly diagnosed and are often diagnosed after death. Aspergillosis and candidiasis are the most prevalent OIFIs in patients with COVID-19. Mycormycosis, cryptococcosis, and other fungal diseases have also been documented more rarely. This review aimed to summarize factors affecting COVID-19 transmission, prevalence, morbidity, and mortality in Iran as well as to review common OIFIs in patients with COVID-19. Immunological factors, underlying diseases, and social, cultural, and environmental factors can affect COVID-19 transmission. There is a need to improve diagnostic and therapeutic criteria for OIFIs and to optimize management procedures so that patients with OIFIs can receive treatment as rapidly as possible. Screening of patients with confirmed COVID-19 for OIFIs at the treating physician’s discretion could enable early OIFI diagnosis, treatment, and mortality reduction.

Coronavirus Disease 2019 (COVID-19): A Literature Review from a Nursing Perspective.

IntroductionAs the COVID-19 pandemic ravages the world, nursing resources, and capacities play an essential role in disease management. This literature review focuses on the central issues related to the nursing care of patients affected by COVID-19.Material and methodsThis literature review was conducted with an extensive search of databases, including PubMed, Web of Science (WOS), and Scopus, using the keywords “COVID19”, “2019-nCoV disease”, “2019 novel coronavirus infection”, “Nurse”, “NursingCare”, and” Nursing management.” The span of the literature search was between December 01, 2020, and January 12, 2021. A total of 28 original and English-language articles were selected for inclusion in the review.ResultsNursing interventions such as monitoring, oxygen therapy, and the use of Extra Corporeal Membrane Oxygenation (ECMO) in the care of COVID-19 patients, caring for ICU patients with COVID-19, rehabilitation of COVID-19 patients, nurses’ experiences and barriers in the care of patients with COVID-19, and also the ethical challenges in the care of patients with COVID-19, were found to be valuable in managing COVID-19 patients.ConclusionNurses have a pivotal role to play in the care of patients with COVID-19. Therefore, providing comprehensive and quality nursing care supported by experience and research is necessary to successfully reduce the length of hospital stay and decrease the morbidity and mortality rates of COVID-19.

Is there a Relationship between the Blood Group and the Percentage of Lung Involvement in COVID-19‘S Patients?

The Coronavirus Disease 2019 (COVID-19) is spreading rapidly throughout the world. By 9 April 2021, 134,639,017 people have been infected by COVID-19 [1]; moreover, 2,917,974 of these patients have died. There are some factors associated with COVID-19 included age, sex, hypertension, and diabetes [2]. Furthermore, blood group is another factor associated with COVID-19. It was found that COVID-19 positive tests in blood group A were increased and decreased in blood group O, but the association between blood type and increasing COVID-19 morbidity or mortality has not been found [3]. As a faculty member who is teaching students in the main hospital of coronavirus - Tohid hospital - in Sanandaj, Iran. I want to share my experiences in confronting the chest CT of COVID-19 patients. What we saw in chest CT of these patients was the different percentage of lung involvement in blood groups. The percentage of lung involvement in patients with blood group O was noticeably higher than other blood groups. Unfortunately, a high percentage of outpatients with high lung involvement in chest CT were old and were unaware of their blood group, therefore we cannot claim that there is a significant relationship between lung involvement and blood group in COVID-19 patients. To the best of our knowledge, clinical presentations and papers have not yet addressed this issue, therefore proof of this relationship requires clinical studies.

A broadly neutralizing humanized ACE2-targeting antibody against SARS-CoV-2 variants

The successive emergences and accelerating spread of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages and evolved resistance to some ongoing clinical therapeutics increase the risks associated with the coronavirus disease 2019 (COVID-19) pandemic. An urgent intervention for broadly effective therapies to limit the morbidity and mortality of COVID-19 and future transmission events from SARS-related coronaviruses (SARSr-CoVs) is needed. Here, we isolate and humanize an angiotensin-converting enzyme-2 (ACE2)-blocking monoclonal antibody (MAb), named h11B11, which exhibits potent inhibitory activity against SARS-CoV and circulating global SARS-CoV-2 lineages. When administered therapeutically or prophylactically in the hACE2 mouse model, h11B11 alleviates and prevents SARS-CoV-2 replication and virus-induced pathological syndromes. No significant changes in blood pressure and hematology chemistry toxicology were observed after injections of multiple high dosages of h11B11 in cynomolgus monkeys. Analysis of the structures of the h11B11/ACE2 and receptor-binding domain (RBD)/ACE2 complexes shows hindrance and epitope competition of the MAb and RBD for the receptor. Together, these results suggest h11B11 as a potential therapeutic countermeasure against SARS-CoV, SARS-CoV-2, and escape variants.

Hepatic transcriptional effects of simvastatin and the possible impact on COVID-19

Background and Aims: Recent reports show an association between statins therapy and reduction in 28-day all-cause mortality among Coronavirus disease 2019 (COVID-19) patients. This association is poorly understood mechanistically. Hence, we investigated whether simvastatin regulates hepatic expression of genes involved in humoral and innate immune responses, and in the activation of classical pathways of the complement system. Methods: Forty patients eligible for cholecystectomy were randomized to 28-day treatments with simvastatin (80 mg/day), ezetimibe (10 mg/day), combination therapy (simvastatin + ezetimibe), or placebo before surgery. Liver biopsies were collected during the surgical intervention. Pooled RNA libraries were sequenced and RNA-seq reads were mapped to the human genome. Results: A total of 260 genes were differentially expressed by the different treatment regimens. Of particular interest in the statin monotherapy is the downregulation of chemokine ligand 13 (CXCL13), a novel marker of systemic immune activation during acute RNA viral infection. The gene ontology and pathway analyses of the differentially expressed genes further proved the unique immunomodulatory effects of statin mono- and combination therapy. Conclusions: Our pivotal study identifies immunomodulatory effects of a statin that contributes to the understanding of the recently proposed protective role of statin use in the novel coronavirus (SARS-CoV-2) infection and COVID-19 morbidity and mortality disease outcomes.