Sound Science Before Quick Judgement Regarding RAS Blockade in COVID-19

Clinical journal of the American Society of Nephrology: CJASN

Matthew A. Sparks, Andrew South, Paul Welling, J. Matt Luther, Jordana Cohen, James Brian Byrd, Louise M. Burrell, Daniel Batlle, Laurie Tomlinson, Vivek Bhalla, Michelle N. Rheault, María José Soler, Sundar Swaminathan and Swapnil Hiremath 

Abstract

There has been much speculation in journals as well as social and traditional media about a link between popularly used classes of drugs that inhibit the renin-angiotensin system (RAS) and novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) infection or coronavirus disease 2019 (COVID-19) disease severity. After examining the available evidence, we advise that inhibitors of the RAS pathway should be continued in patients with COVID-19 who are taking these drugs for evidence-based indications. The putative link between SARS-CoV-2 angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) can be rationalized by the biology of virus entry. The spike protein of SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) as a receptor to enter type II pneumocytes or enterocytes (and likely, other cells).

Keywords

angiotensinrenin angiotensin systemvirology, hypertension, ACE inhibitors, COVID-19, severe acute respiratory syndrome coronavirus 2, Renin-Angiotensin System, Angiotensin-Converting Enzyme Inhibitors

Translating COVID-19 Pandemic Surge Theory to Practice in the Emergency Department: How to Expand Structure

Disaster Medicine and Public Health Preparedness
27 March 2020, pp. 1-33

Matteo Paganini, Andrea Conti, Eric Weinstein, Francesco della Corte and Luca Ragazzoni 

Abstract

Multiple professional societies, nongovernment and government agencies have studied the science of sudden onset disaster mass casualty incidents to create and promote surge response guidelines. The COVID-19 pandemic has presented the health care system with challenges that have limited science to guide the staff, stuff and structure surge response.

This study reviewed the available surge science literature specifically to guide an Emergency Department's surge structural response using a translational science approach to answer the question: How does the concept of sudden onset mass casualty incident (MCI) surge capability apply to the process to expand COVID-19 Pandemic surge structure response?

The available surge structural science literature was reviewed to determine the application to a pandemic response. The on-line ahead of print and print COVID-19 scientific publications, as well as grey, literature were studied to learn the best available COVID-19 surge structural response science. A checklist was created to guide the Emergency Department team's COVID-19 surge structural response.

Keywords

COVID-19, SARS-CoV-2, Surge Capacity, Pandemics, Translational Science

Quantitative Detection and Viral Load Analysis of SARS-CoV-2 in Infected Patients

Clinical Infectious Diseases

Yu, Fengting; Yan, Liting; Wang, Nan; Yang, Siyuan; Wang, Linghang; Tang, Yunxia; Gao, Guiju; Wang, Sa; Ma, Chengjie; Xie, Ruming; Wang, Fang; Tan, Chianru; Zhu, Lingxiang; Guo, Yong; Zhang, Fujie 

Abstract

Background

Coronavirus disease 2019 (COVID-19) has become a public health emergency. The widely used reverse transcription PCR (RT-PCR) method has limitations for clinical diagnosis and treatment.

Methods

A total of 323 samples from 76 COVID-19 confirmed patients were analyzed by droplet digital PCR (ddPCR) and RT-PCR based two target genes (ORF1ab and N). Nasal swabs, throat swabs, sputum, blood, and urine were collected. Clinical and imaging data were obtained for clinical staging.

Results

In 95 samples tested positive by both methods, the cycle threshold (Ct) of RT-PCR was highly correlated with the copy numbed of ddPCR (ORF1ab gene, R2 = 0.83; N gene, R2 = 0.87). 4 (4/161) negative and 41 (41/67) single-gene positive samples tested by RT-PCR were positive according to ddPCR with viral load ranging from 11.1 to 123.2 copies/test. Then the viral load of respiratory samples was compared and the average viral load in sputum (17429 ± 6920 copies/test) was found to be significantly higher than in throat swabs (2552 ± 1965 copies/test, p < 0.001) and nasal swabs (651 ± 501 copies/test, p < 0.001). Furthermore, the viral load in the early and progressive stages were significantly higher than that in the recovery stage (46800 ± 17272 vs 1252 ± 1027, p < 0.001) analyzed by sputum samples.

Conclusions

Quantitative monitoring of viral load in lower respiratory tract samples helps to evaluate disease progression, especially in cases of low viral load.

Keywords

COVID-19, SARS-CoV-2, RT-PCR, ddPCR, Viral load

Spotlight on Jails: COVID-19 Mitigation Policies Needed Now

Clinical Infectious Diseases

Wurcel, Alysse G.; Dauria, Emily; Zaller, Nicholas; Nijhawan, Ank; Beckwith, Curt; Nowotny, Kathryn; Brinkley-Rubinstein, Lauren 

Dear Editor,

In response to the COVID-19 pandemic, healthcare institutions and public health experts are mobilizing to develop mitigation protocols based on the experiences of other countries, including China, South Korea, and Italy. Compared to these countries, the US has a higher incarceration rate, with 10.6 million people booked into jails each year.2 Jails pose a unique set of challenges to COVID-19 prevention, detection, and management mitigation that deserves immediate attention.

Spinal Anaesthesia For Patients With Coronavirus Disease 2019 And Possible Transmission Rates In Anaesthetists: Retrospective, Single-Centre, Observational Cohort Study

British Journal of Anaesthesia

Zhong, Qi; Liu, Yin Y.; Luo, Qiong; Zou, Yu F.; Jiang, Hai X.; Li, Hui; Zhang, Jing J.; Li, Zhen; Yang, Xin; Ma, Min; Tang, Li J.; Chen, Ying Y.; Zheng, Feng; Ke, Jian J.; Zhang, Zong Z.

 

Abstract

Background: The safety of performing spinal anaesthesia for both patients and anaesthetists alike in the presence of active infection with the novel coronavirus disease 2019 (COVID-19) is unclear. Here, we report the clinical characteristics and outcomes for both patients with COVID-19 and the anaesthetists who provided their spinal anaesthesia.

Methods: Forty-nine patients with radiologically confirmed COVID-19 for Caesarean section or lower-limb surgery undergoing spinal anaesthesia in Zhongnan Hospital, Wuhan, China participated in this retrospective study. Clinical characteristics and perioperative outcomes were recorded. For anaesthesiologists exposed to patients with COVID-19 by providing spinal anaesthesia, the level of personal protective equipment (PPE) used, clinical outcomes (pulmonary CT scans), and confirmed COVID-19 transmission rates (polymerase chain reaction [PCR]) were reviewed.

Results: Forty-nine patients with COVID-19 requiring supplementary oxygen before surgery had spinal anaesthesia (ropivacaine 0.75%), chiefly for Caesarean section (45/49 [91%]). Spinal anaesthesia was not associated with cardiorespiratory compromise intraoperatively. No patients subsequently developed severe pneumonia. Of 44 anaesthetists, 37 (84.1%) provided spinal anaesthesia using Level 3 PPE. Coronavirus disease 2019 infection was subsequently confirmed by PCR in 5/44 (11.4%) anaesthetists. One (2.7%) of 37 anaesthetists who wore Level 3 PPE developed PCR-confirmed COVID-19 compared with 4/7 (57.1%) anaesthetists who had Level 1 protection in the operating theatre (relative risk reduction: 95.3% [95% confidence intervals: 63.7–99.4]; P<0.01).

Conclusions: Spinal anaesthesia was delivered safely in patients with active COVID-19 infection, the majority of whom had Caesarean sections. Level 3 PPE appears to reduce the risk of transmission to anaesthetists who are exposed to mildly symptomatic surgical patients.

Keywords

Epidemiology

Syndromic Panels or the Panels' Syndrome? A Perspective Through the Lens of Respiratory Tract Infections

Clinical Microbiology and Infection

Zanella, Marie-Céline; Meylan, Pascal; Kaiser, Laurent 

To the Editor,

We thank Brendish et al for their interest in our commentary and they rightly point out that it was not a systematic review. Our main intention was to provide food for thought and discussion regarding the use of panel assays in the light of some relevant publications. In particular, we aimed at discussing the limitations of their analytical aspects and clinical validation. We respectfully disagree with the statement that “The authors suggest that the increasing use of rapid, automated, syndromic molecular panels for respiratory viruses (RVs) should be abandoned in favor of more limited PCR testing for RVs”. As microbiologists and clinicians, we rather suggest that we have the responsibility to promote diagnostic stewardship in order to integrate these new technologies in clinical management, while considering their strengths and limitations. We also highlight the value of a multiple-step approach of testing that does not necessarily preclude their use.

Keywords

Epidemiology

Molecular characterization of SARS-CoV-2 from the first case of COVID-19 in Italy

Clinical Microbiology and Infection

Capobianchi, Maria Rosaria; Rueca, Martina; Messina, Francesco; Giombini, Emanuela; Carletti, Fabrizio; Colavita, Francesca; Castilletti, Concetta; Lalle, Eleonora; Bordi, Licia; Vairo, Francesco; Nicastri, Emanuele; Ippolito, Giuseppe; Maria Gruber, Cesare Ernesto; Bartolini, Barbara

 

To the Editor,

On January 29, 2020, two Chinese spouses (patient 1, female; patient 2, male), coming to Italy as tourists from Hubei province, were hospitalized at the National Institute for Infectious Diseases “L. Spallanzani”, Rome, with fever and respiratory symptoms. SARSCoV-2 diagnosis was accomplished using real-time RT-PCR on a nasopharyngeal swab and sputum for patient 1 and on a nasopharyngeal swab for patient 2, collected 1 day after symptom onset. Partial sequencing confirmed both patients to be infected with SARS-CoV-2

Keywords

Clinical aspects, diagnosis, treatment

Molecular characterization of SARS-CoV-2 in the first COVID-19 cluster in France reveals an amino-acid deletion in nsp2 (Asp268Del)

Clinical Microbiology and Infection

Bal, Antonin; Destras, G.; Gaymard, Alexandre; Bouscambert-Duchamp, Maude; Valette, Martine; Escuret, Vanessa; Frobert, Emilie; Billaud, G.; Trouillet-Assant, Sophie; Cheynet, V.; Brengel-Pesce, Karen; Morfin, Florence; Lina, Bruno; Josset, Laurence 

To the Editor

In December 2019, a novel coronavirus emerged in China, causing outbreaks of pneumonia [1]. The virus was subsequently identified as a betacoronavirus and named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is responsible for the coronavirus disease 2019 (COVID-19) pandemic which includes asymptomatic upper and lower respiratory tract infections. Among the first European cases of COVID-19, six were associated with a cluster of transmissions in the French Alps in late January 2020 [2]. The index case of this cluster travelled from Singapore to France and went back to the United Kingdom (UK) where he tested positive for SARS-CoV-2 on February 6th. Here, we aimed to investigate the French cases related to this cluster using metagenomic next-generation sequencing (mNGS) analysis.

Keywords

Virology, immunology

Is There an Association Between COVID-19 Mortality and the Renin-Angiotensin System—a Call for Epidemiologic Investigations

Clinical Infectious Diseases

Hanff, Thomas C.; Harhay, Michael O.; Brown, Tyler S.; Cohen, Jordana B.; Mohareb, Amir M. 

Abstract

Mortality from coronavirus disease 2019 (COVID-19) is strongly associated with cardiovascular disease, diabetes, and hypertension. These disorders share underlying pathophysiology related to the renin-angiotensin system (RAS) that may be clinically insightful. In particular, activity of the angiotensin-converting enzyme 2 (ACE2) is dysregulated in cardiovascular disease, and this enzyme is used by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to initiate the infection. Cardiovascular disease and pharmacologic RAS inhibition both increase ACE2 levels, which may increase the virulence of SARS-CoV-2 within the lung and heart. Conversely, mechanistic evidence from related coronaviruses suggests that SARS-CoV-2 infection may downregulate ACE2, leading to toxic overaccumulation of Angiotensin II that induces acute respiratory distress syndrome and fulminant myocarditis. RAS inhibition could mitigate this effect. With conflicting mechanistic evidence, we propose key clinical research priorities necessary to clarify the role of RAS inhibition in COVID-19 mortality that could be rapidly addressed by the international research community.

Keywords

COVID-19, SARS-CoV-2, Angiotensin-Converting Enzyme 2, Renin-Angiotensin System, Cardiovascular Disease

Self-Reported Olfactory And Taste Disorders In SARS-Cov-2 Patients: A Cross-Sectional Study

Clinical Infectious Diseases: An Official Publication Of the Infectious Diseases Society of America

Giacomelli, Andrea; Pezzati, Laura; Conti, Federico; Bernacchia, Dario; Siano, Matteo; Oreni, Letizia; Rusconi, Stefano; Gervasoni, Cristina; Ridolfo, Anna Lisa; Rizzardini, Giuliano; Antinori, Spinello; Galli, Massimo 

Dear Editor,

We read with interest the paper by Wang et al [1] describing the clinical features of 69 patients with Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infection in Wuhan, China. The authors provide a detailed description of major signs and symptoms of overt disease [2, 3], but fail to give an account of minor symptoms that may be present at earlier stage of the infection.

Keywords

COVID-19, SARS-CoV-2, Surge Capacity, Pandemics, Translational Science

Using Psychoneuroimmunity Against COVID-19

Brain, Behavior, and Immunity

Kim, Sung-Wan; Su, Kuan-Pin 

Abstract

The worldwide outbreak of coronavirus disease 2019 (COVID-19) raises concerns of widespread panic and anxiety in individuals subjected to the real or perceived threat of the virus. Compared to general populations, patients who are institutionalized in a closed unit are also very vulnerable to COVID-19 infection and complications. This crisis touched on difficult issues of not only psychiatric care and ethics, but also psychological impacts to psychiatric care givers. In this Viewpoint, we address both physical and biopsychosocial aspects of this infection, as well as the psychoneuroimmunity of preventive strategies of healthy lifestyle, regular exercise, balanced nutrition, quality sleep and a strong connection with people. Social distancing and wearing masks might help us from pathogen exposure, yet such these measures also prevent us from expressing compassion and friendliness. Therefore, all forms of psychological support should be routinely implemented not only to consider psychological resilience but also to enhance psychoneuroimmunity against COVID-19.

Keywords

Epidemiology

COVID-19, SARS And MERS: Are They Closely Related?

Clinical Microbiology and Infection

Petrosillo, Nicola; Viceconte, Giulio; Ergonul, Onder; Ippolito, Giuseppe; Petersen, Eskild 

Abstract

Background

The 2019 novel coronavirus (SARS-CoV-2) is a new human coronavirus which is spreading with epidemic features in China and other Asian countries with cases reported worldwide. This novel Coronavirus Disease (COVID-19) is associated with a respiratory illness that may cause severe pneumonia and acute respiratory distress syndrome (ARDS). Although related to the Severe Acute Respiratory Syndrome (SARS) and the Middle East Respiratory Syndrome (MERS), COVID-19 shows some peculiar pathogenetic, epidemiological and clinical features which have not been completely understood to date.

Objectives

We provide a review of the differences in terms of pathogenesis, epidemiology and clinical features between COVID-19, SARS and MERS.

Sources

The most recent literature in English language regarding COVID-19 has been reviewed and extracted data have been compared with the current scientific evidence about SARS and MERS epidemics.

Content

COVID-19 seems not to be very different from SARS regarding its clinical features. However, it has a fatality rate of 2.3%, lower than SARS (9.5%) and much lower than MERS (34.4%). It cannot be excluded that because of the COVID-19 less severe clinical picture it can spread in the community more easily than MERS and SARS. The actual basic reproductive number (R0) of COVID-19 (2-2.5) is still controversial. It is probably slightly higher than the R0 of SARS (1.7-1.9) and higher than MERS (<1),. The gastrointestinal route of transmission of SARS-CoV-2, which has been also assumed for SARS-CoV and MERS-CoV, cannot be ruled out and needs to be further investigated.

Implications

There is still much more to know about COVID-19, especially as concerns mortality and capacity of spreading on a pandemic level. Nonetheless, all of the lessons we learned in the past from SARS and MERS epidemics are the best cultural weapons to face this new global threat.

Keywords

Coronavirus, COVID-19, Emerging infections, MERS, SARS