Hypertension,medications, and risk of severe COVID‐19: A Massachusetts community‐based observational study

It remains uncertain whether the hypertension (HT) medications angiotensin‐converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) mitigate or exacerbate SARS‐CoV‐2 infection. We evaluated the association of ACEi and ARB with severe coronavirus disease 19 (COVID‐19) as defined by hospitalization or mortality among individuals diagnosed with COVID‐19. We investigated whether these associations were modified by age, the simultaneous use of the diuretic thiazide, and the health conditions associated with medication use. In an observational study utilizing data from a Massachusetts group medical practice, we identified 1449 patients with a COVID‐19 diagnosis. In our study, pre‐infection comorbidities including HT, cardiovascular disease, and diabetes were associated with increased risk of severe COVID‐19. Risk was further elevated in patients under age 65 with these comorbidities or cancer. Twenty percent of those with severe COVID‐19 compared to 9% with less severe COVID‐19 used ACEi, 8% and 4%, respectively, used ARB. In propensity score‐matched analyses, use of neither ACEi (OR = 1.30, 95% CI 0.93 to 1.81) nor ARB (OR = 0.94, 95% CI 0.57 to 1.55) was associated with increased risk of severe COVID‐19. Thiazide use did not modify this relationship. Beta blockers, calcium channel blockers, and anticoagulant medications were not associated with COVID‐19 severity. In conclusion, cardiovascular‐related comorbidities were associated with severe COVID‐19 outcomes, especially among patients under age 65. We found no substantial increased risk of severe COVID‐19 among patients taking antihypertensive medications. Our findings support recommendations against discontinuing use of renin–angiotensin system (RAS) inhibitors to prevent severe COVID‐19.     

COVID‐19 and renin‐angiotensin system inhibition: role of angiotensin converting enzyme 2 (ACE2) ‐ Is there any scientific evidence for controversy?

Renin–angiotensin system (RAS) blockers are extensively used worldwide to treat many cardiovascular disorders, where they are effective in reducing both mortality and morbidity. These drugs are known to induce an increased expression of angiotensin‐converting enzyme 2 (ACE2). ACE2 acts as receptor for the novel SARS coronavirus‐2 (SARS‐CoV‐2) which raising the important issue of possible detrimental effects that RAS blockers could exert on the natural history and pathogenesis of the coronavirus disease‐19 (COVID‐19) and associated excessive inflammation, myocarditis and cardiac arrhythmias. We review the current knowledge on the interaction between SARS‐CoV‐2 infection and RAS blockers and suggest a scientific rationale for continuing RAS blockers therapy in patients with COVID‐19 infection.     

The renin–angiotensin–aldosterone system as a link between obesity and coronavirus disease 2019 severity

Coronavirus disease 2019 (COVID‐19), caused by the severe acute respiratory distress coronavirus 2 (SARS‐CoV2), is a rapidly evolving pandemic challenging the world and posing unprecedented public health issues. Current data show that COVID‐19 is associated with increased disease severity in individuals with obesity. Obesity is usually associated with dysregulated renin–angiotensin–aldosterone (RAAS) axis. RAAS has also been implicated in acute lung injury as well as myocardial injury and has thus attracted interest as a potential regulator of COVID‐19 severity. Whilst research all over the world is still struggling to provide a detailed characterization of the biology of SARS‐CoV2 and its associated disease profile, it has become evident that SARS‐CoV2 uses the membrane‐bound form of angiotensin‐converting enzyme 2 (ACE2) as a receptor for cell internalization. ACE2 is a protective component of the RAAS axis and is downregulated after SARS‐CoV2 infection. The RAAS axis could thus be a link between obesity and COVID‐19 severity; therefore, more accurate understanding of the underlying mechanisms would be needed with the hope of proposing efficient therapeutic interventions.     

SARS‐CoV‐2 infection in patients with a normal or abnormal liver

Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), a novel coronavirus causing coronavirus disease 19 (COVID‐19), with an estimated 22 million people infected worldwide so far although involving primarily the respiratory tract, has a remarkable tropism for the liver and the biliary tract. Patients with SARS‐CoV‐2 infection and no antecedent liver disease may display evidence of cytolytic liver damage, proportional to the severity of COVID‐19 but rarely of clinical significance. The mechanism of hepatocellular injury is unclear and possibly multifactorial. The clinical impact of SARS‐CoV‐2 infection in patients with underlying chronic liver disease, a cohort whose global size is difficult to estimate, has been assessed appropriately only recently and data are still evolving. Patients with cirrhosis are at higher risk of developing severe COVID‐19 and worse liver‐related outcomes as compared to those with non‐cirrhotic liver disease. OLT patients have an intermediate risk. Specific interventions in order to reduce the risk of transmission of infection among this high‐risk population have been outlined by international societies, together with recommendations for modified treatment and follow‐up regimens during the COVID‐19 pandemic. When a vaccine against SARS‐CoV‐2 becomes available, patients with fibrotic liver disease and those with OLT should be considered as prime targets for prophylaxis of COVID‐19, as all other highly susceptible subjects.     

Cardiac and arrhythmic complications in patients with COVID‐19

In December 2019, the world started to face a new pandemic situation, the severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2). Although coronavirus disease (COVID‐19) clinical manifestations are mainly respiratory, major cardiac complications are being reported. Cardiac manifestations etiology seems to be multifactorial, comprising direct viral myocardial damage, hypoxia, hypotension, enhanced inflammatory status, ACE2‐receptors downregulation, drug toxicity, endogenous catecholamine adrenergic status, among others. Studies evaluating patients with COVID‐19 presenting cardiac injury markers show that it is associated with poorer outcomes, and arrhythmic events are not uncommon. Besides, drugs currently used to treat the COVID‐19 are known to prolong the QT interval and can have a proarrhythmic propensity. This review focus on COVID‐19 cardiac and arrhythmic manifestations and, in parallel, makes an appraisal of other virus epidemics as SARS‐CoV, Middle East respiratory syndrome coronavirus, and H1N1 influenza.     

COVID‐19 and heart failure: from infection to inflammation and angiotensin II stimulation. Searching for evidence from a new disease

Patients with cardiovascular disease and, namely, heart failure are more susceptible to coronavirus disease 2019 (COVID‐19) and have a more severe clinical course once infected. Heart failure and myocardial damage, shown by increased troponin plasma levels, occur in at least 10% of patients hospitalized for COVID‐19 with higher percentages, 25% to 35% or more, when patients critically ill or with concomitant cardiac disease are considered. Myocardial injury may be elicited by multiple mechanisms, including those occurring with all severe infections, such as fever, tachycardia, adrenergic stimulation, as well as those caused by an exaggerated inflammatory response, endotheliitis and, in some cases, myocarditis that have been shown in patients with COVID‐19. A key role may be that of the renin–angiotensin–aldosterone system. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infects human cells binding to angiotensin‐converting enzyme 2 (ACE2), an enzyme responsible for the cleavage of angiotensin II into angiotensin 1–7, which has vasodilating and anti‐inflammatory effects. Virus‐mediated down‐regulation of ACE2 may increase angiotensin II stimulation and contribute to the deleterious hyper‐inflammatory reaction of COVID‐19. On the other hand, ACE2 may be up‐regulated in patients with cardiac disease and treated with ACE inhibitors or angiotensin receptor blockers. ACE2 up‐regulation may increase the susceptibility to COVID‐19 but may be also protective vs. angiotensin II‐mediated vasoconstriction and inflammatory activation. Recent data show the lack of untoward effects of ACE inhibitors or angiotensin receptor blockers for COVID‐19 infection and severity. Prospective trials are needed to ascertain whether these drugs may have protective effects.     

Practical management of inflammatory bowel disease patients during the COVID‐19 pandemic: expert commentary from the Gastroenterological Society of Australia Inflammatory Bowel Disease faculty

The COVID‐19 pandemic, caused by the novel coronavirus SARS‐CoV‐2, has emerged as a public health emergency and challenged healthcare systems globally. In a minority of patients, SARS‐CoV‐2 manifests with a severe acute respiratory illness and currently there are insufficient data regarding the virulence of COVID‐19 in inflammatory bowel disease patients taking immunosuppressive therapy. This review aims to summarise the current literature and provide guidance on the management of inflammatory bowel disease (IBD) patients in the context of the COVID‐19 pandemic in the Australasian setting.     

Liver injury during highly pathogenic human coronavirus infections

The severe acute respiratory syndrome coronavirus 2 (SARS‐Cov‐2), the pathogen of 2019 novel coronavirus disease (COVID‐19), has posed a serious threat to global public health. The WHO has declared the outbreak of SARS‐CoV‐2 infection an international public health emergency. Lung lesions have been considered as the major damage caused by SARS‐CoV‐2 infection. However, liver injury has also been reported to occur during the course of the disease in severe cases. Similarly, previous studies have shown that liver damage was common in the patients infected by the other two highly pathogenic coronavirus – severe acute respiratory syndrome coronavirus (SARS‐CoV) and the Middle East respiratory syndrome coronavirus (MERS‐CoV), and associated with the severity of diseases. In this review, the characteristics and mechanism of liver injury caused by SARS‐CoV, MERS‐CoV as well as SARS‐CoV‐2 infection were summarized, which may provide help for further studies on the liver injury of COVID‐19.     

Ten key points about COVID‐19 in children: The shadows on the wall

The pandemic of the new coronavirus disease‐2019 (COVID‐19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), initially described in China, is challenging the health care systems of all countries. Every emerging disease raises many questions with a scarcity of answers since all its characteristics are still being discovered. In the case of SARS‐CoV‐2, most of the literature comes from adult patients. Children seem to be less affected. Pediatric patients diagnosed with COVID‐19 disease usually suffer a mild illness, with a low risk of complications, or mortality. Defining the role of children in the transmission of SARS‐CoV‐2 is critical as some national infection control decisions involving children, such as school closures or social distancing, will probably impact the dynamics of the virus. To aid in the knowledge of COVID‐19 in children, this study presents an expert review of the literature published from 1 January to 28 May 2020, including peer‐reviewed and preprint nonpeer‐reviewed studies, along with some relevant articles afterward, summarizing ten key points that characterize the disease in children.     

Influence of immunosuppression on seroconversion against SARS‐CoV‐2 in two kidney transplant recipients

Solid organ transplant recipients are at risk for infectious complications due to chronic immunosuppression. The outbreak of coronavirus disease 2019 (COVID‐19) in the United States has raised growing concerns for the transplant patient population. We seek to add to the current limited literature on COVID‐19 in transplant recipients by describing the clinical course of two kidney transplant recipients with SARS‐CoV‐2 infection monitored by both RT‐PCR and serology. Through careful adjustment of their immunosuppression regimen, both patients had excellent recovery with intact graft function and development of anti‐SARS‐CoV‐2 antibodies.     

COVID‐19 diagnosis and management: a comprehensive review

Severe acute respiratory syndrome coronavirus (SARS‐CoV)‐2, a novel coronavirus from the same family as SARS‐CoV and Middle East respiratory syndrome coronavirus, has spread worldwide leading the World Health Organization to declare a pandemic. The disease caused by SARS‐CoV‐2, coronavirus disease 2019 (COVID‐19), presents flu‐like symptoms which can become serious in high‐risk individuals. Here, we provide an overview of the known clinical features and treatment options for COVID‐19. We carried out a systematic literature search using the main online databases (PubMed, Google Scholar, MEDLINE, UpToDate, Embase and Web of Science) with the following keywords: ‘COVID‐19’, ‘2019‐nCoV’, ‘coronavirus’ and ‘SARS‐CoV‐2’. We included publications from 1 January 2019 to 3 April 2020 which focused on clinical features and treatments. We found that infection is transmitted from human to human and through contact with contaminated environmental surfaces. Hand hygiene is fundamental to prevent contamination. Wearing personal protective equipment is recommended in specific environments. The main symptoms of COVID‐19 are fever, cough, fatigue, slight dyspnoea, sore throat, headache, conjunctivitis and gastrointestinal issues. Real‐time PCR is used as a diagnostic tool using nasal swab, tracheal aspirate or bronchoalveolar lavage samples. Computed tomography findings are important for both diagnosis and follow‐up. To date, there is no evidence of any effective treatment for COVID‐19. The main therapies being used to treat the disease are antiviral drugs, chloroquine/hydroxychloroquine and respiratory therapy. In conclusion, although many therapies have been proposed, quarantine is the only intervention that appears to be effective in decreasing the contagion rate. Specifically designed randomized clinical trials are needed to determine the most appropriate evidence‐based treatment modality.     

In‐hospital management of persons with haemophilia and COVID‐19: Practical guidance

A new disease (COVID‐19) caused by a coronavirus (SARS‐CoV‐2) that appeared in China at the end of 2019 is currently spreading globally. This emerging virus is mainly responsible for respiratory tract infections and potentially fatal pneumonia, mainly in more frail patients. Persons with haemophilia of variable severity and from all parts of the world will likely be infected and develop COVID‐19. We here propose practical guidance for the in‐hospital specific management of haemophilia persons with COVID‐19 including their possible transfer to the intensive care unit. Rapid identification of the haemophilia status, undelayed and regular liaison with the haemophilia team, proper therapy with factor concentrates or alternative treatments appear instrumental to prevent haemophilia‐related complications in this setting. Information of patients and their families about COVID‐19, psychological support and good appreciation of the impact of haemophilia on therapeutic decisions including end‐of‐life directives are also addressed.     

Pathophysiological mechanisms of liver injury in COVID‐19

The recent outbreak of coronavirus disease 2019 (COVID‐19), caused by the Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) has resulted in a world‐wide pandemic. Disseminated lung injury with the development of acute respiratory distress syndrome (ARDS) is the main cause of mortality in COVID‐19. Although liver failure does not seem to occur in the absence of pre‐existing liver disease, hepatic involvement in COVID‐19 may correlate with overall disease severity and serve as a prognostic factor for the development of ARDS. The spectrum of liver injury in COVID‐19 may range from direct infection by SARS‐CoV‐2, indirect involvement by systemic inflammation, hypoxic changes, iatrogenic causes such as drugs and ventilation to exacerbation of underlying liver disease. This concise review discusses the potential pathophysiological mechanisms for SARS‐CoV‐2 hepatic tropism as well as acute and possibly long‐term liver injury in COVID‐19.     

Human post‐infection serological response to the spike and nucleocapsid proteins of SARS‐CoV‐2

To inform seroepidemiological studies, we characterized the IgG‐ responses in COVID‐19 patients against the two major SARS‐CoV‐2 viral proteins, spike (S) and nucleocapsid (N). We tested 70 COVID‐19 sera collected up to 85 days post‐symptom onset and 230 non‐COVID‐19 sera, including 27 SARS sera from 2003. Although the average SARS‐CoV‐2 S and N‐IgG titers were comparable, N‐responses were more variable among individuals. S‐ and N‐assay specificity tested with non‐COVID‐19 sera were comparable at 97.5% and 97.0%, respectively. Therefore, S will make a better target due to its lower cross‐reactive potential and its' more consistent frequency of detection compared to N.     

Clinical characteristics of COVID‐19 in children: Are they similar to those of SARS?

Although the number of SARS‐CoV‐2 infections has been rising amid the current pandemic of COVID‐19, the low infection rate of SARS‐CoV‐2 in children has been low. By examining the clinical data available in the public domain, the present work clarifies the clinical presentations in children with COVID‐19 in China. Statistical significance tests and adjusted odds ratios estimation were performed on the children (age below 18) and adults (age 18 or above) cohorts in China. SARS‐CoV and SARS‐CoV‐2 shared similar clinical features. Lower respiratory tract infection was less prominent in children as evidenced by the relatively low prevalence in chest pain/discomfort and dyspnea. Similar to SARS, younger children had a less aggressive clinical course, compared with adolescents. While fewer symptoms were observed in children compared to adults, there is not yet sufficient evidence to conclude shorter hospital stay in children.     

Discordant courses of COVID‐19 in a cohabiting couple of lung transplant recipients

COVID‐19 is a novel infectious disease caused by SARS‐CoV‐2 that emerged in late 2019 and which is now a pandemic. Solid organ transplant recipients are perceived to be at increased risk of severe COVID‐19 due to their chronic use of immunosuppressive drugs (ISDs) and to their associated conditions. Scarce data are available on the optimized management of ISDs in these patients and on its impact on presentation, clinical course, viral shedding, and outcome. We report here two cases of COVID‐19 in a cohabiting couple of lung transplant recipients for cystic fibrosis, who had different ISDs management and who developed discordant courses of their disease. Our findings suggest that the degree of their immunosuppression might be a reason for their different course and that ISDs might prove partially protective.     

COVID‐19 and diabetes: Is there enough evidence?

The pandemic of COVID‐19, a disease caused by a novel coronavirus SARS‐CoV‐2, is associated with significant morbidity and mortality. Recent data showed that hypertension, diabetes mellitus, cardiovascular diseases, and chronic obstructive pulmonary disease were the most prevalent comorbidities in COVID‐19 patients. Additionally, data indicate that hypertension, diabetes, and cardiovascular diseases are important risk factors for progression and unfavorable outcome in COVID‐19 patients. There is only limited amount of data regarding follow‐up of these patients, and they provided conflicting results. The main limitation is a small number of participants and particularly those who experienced primary composite outcome (admission in intensive care unit, use of mechanical ventilation, or death). Additionally, the limited number of patients was essential obstacle for performing analysis that would include many confounding factors such as advanced age, smoking status, and obesity and potentially change conclusion. So far, there is no study that demonstrated independent predictive value of diabetes on mortality in COVID‐19 patients, but there are many speculations about the association between diabetes and susceptibility to novel coronavirus, as well as its impact on progression and prognosis of COVID‐19. The aim of this review article was to summarize the current knowledge about the relationship between diabetes and COVID‐19 and its role in outcome in these patients.     

Management of heart failure patients with COVID‐19: a joint position paper of the Chinese Heart Failure Association & National Heart Failure Committee and the Heart Failure Association of the European Society of Cardiology

The coronavirus disease 2019 (COVID‐19) pandemic of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection is causing considerable morbidity and mortality worldwide. Multiple reports have suggested that patients with heart failure (HF) are at a higher risk of severe disease and mortality with COVID‐19. Moreover, evaluating and treating HF patients with comorbid COVID‐19 represents a formidable clinical challenge as symptoms of both conditions may overlap and they may potentiate each other. Limited data exist regarding comprehensive management of HF patients with concomitant COVID‐19. Since these issues pose serious new challenges for clinicians worldwide, HF specialists must develop a structured approach to the care of patients with COVID‐19 and be included early in the care of these patients. Therefore, the Heart Failure Association of the European Society of Cardiology and the Chinese Heart Failure Association & National Heart Failure Committee conducted web‐based meetings to discuss these unique clinical challenges and reach a consensus opinion to help providers worldwide deliver better patient care. The main objective of this position paper is to outline the management of HF patients with concomitant COVID‐19 based on the available data and personal experiences of physicians from Asia, Europe and the United States.     

Use of distinct anti‐hypertensive drugs and risk for COVID‐19 among hypertensive people: A population‐based cohort study in Southern Catalonia,Spain

The use of some anti‐hypertensive drugs in the current COVID‐19 pandemic has become controversial. This study investigated possible relationships between anti‐hypertensive medications use and COVID‐19 infection risk in the ambulatory hypertensive population. This is a population‐based retrospective cohort study involving 34 936 hypertensive adults >50 years in Tarragona (Southern Catalonia, Spain) who were retrospectively followed through pandemic period (from 01/03/2020 to 30/04/2020). Two data sets including demographic/clinical characteristics (comorbidities and cardiovascular medications use) and laboratory PCR codes for COVID‐19 were linked to construct an anonymized research database. Cox regression was used to calculate multivariable hazard ratios (HRs) and estimate the risk of suffering COVID‐19 infection. Across study period, 205 PCR‐confirmed COVID‐19 cases were observed, which means an overall incidence of 586.8 cases per 100 000 persons‐period. In multivariable analyses, only age (HR: 1.03; 95% CI: 1.02‐1.05; P < .001) and nursing home residence (HR: 19.60; 95% CI: 13.80‐27.84; P < .001) appeared significantly associated with increased risk of COVID‐19. Considering anti‐hypertensive drugs, receiving diuretics (HR: 1.22; 95% CI: 0.90‐1.67; P = .205), calcium channel blockers (HR: 1.29; 95%CI: 0.91‐1.82; P = .148), beta‐blockers (HR: 0.97; 95% CI: 0.68‐1.37; P = .844), and angiotensin‐converting enzyme inhibitors (HR: 0.83; 95% CI: 0.61‐1.13; P = .238) did not significantly alter the risk of PCR‐confirmed COVID‐19, whereas receiving angiotensin II receptor blockers was associated with an almost statistically significant reduction risk (HR: 0.67; 95% CI: 0.44‐1.01; P = .054). In conclusion, our data support that receiving renin‐angiotensin‐aldosterone system inhibitors does not predispose for suffering COVID‐19 infection in ambulatory hypertensive people. Conversely, receiving angiotensin II receptor blockers could be related with a reduced risk.     

Understanding immunopathological fallout of human coronavirus infections including COVID‐19: Will they cross the path of rheumatologists?

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection causing coronavirus disease 2019 (COVID‐19) is the biggest pandemic of our lifetime to date. No effective treatment is yet in sight for this catastrophic illness. Several antiviral agents and vaccines are in clinical trials, and drug repurposings as immediate and alternative choices are also under consideration. Immunomodulatory agents like hydroxychloroquine (HCQ) as well as biological disease‐modifying anti‐rheumatic drugs (bDMARDs) such as tocilizumab and anakinra received worldwide attention for treatment of critical patients with COVID‐19. This is of interest to rheumatologists, who are well versed with rational use of these agents. This brief review addresses the understandings of some of the common immunopathogenetic mechanisms in the context of autoimmune rheumatic diseases like systemic lupus erythematosus (SLE) and COVID‐19. Apart from demographic comparisons, the role of type I interferons (IFN), presence of antiphospholipid antibodies and finally mechanism of action of HCQ in both the scenarios are discussed here. High risks for fatal disease in COVID‐19 include older age, metabolic syndrome, male gender, and individuals who develop delayed type I IFN response. HCQ acts by different mechanisms including prevention of cellular entry of SARS‐CoV‐2 and inhibition of type I IFN signaling. Recent controversies regarding efficacy of HCQ in management of COVID‐19 warrant more studies in that direction. Autoantibodies were also reported in severe acute respiratory syndrome (SARS) as well as in COVID‐19. Rheumatologists need to wait and see whether SARS‐CoV‐2 infection triggers development of autoimmunity in patients with COVID‐19 infection in the long run.