Medicine / Special Report

Vol. 5, NO. 1 / April 2020

Therapeutic Options for the Treatment of COVID-19

The Editors

Letters to the Editors

In response to “Therapeutic Options for the Treatment of COVID-19”

← SARS-CoV-2: Research Guide

The following list of papers and articles will be updated regularly and is offered here as a resource for researchers and interested readers.


  • The Innate Immune System: Fighting on the Front Lines or Fanning the Flames of COVID-19?

    Julia L. McKechnie and Catherine A. Blish / May 19, 2020

    The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has had devastating global impacts and will continue to have dramatic effects on public health for years to come. A better understanding of the immune response to SARS-CoV-2 will be critical for the application and development of therapeutics. The degree to which the innate immune response confers protection or induces pathogenesis through a dysregulated immune response remains unclear. In this review, we discuss what is known about the role of the innate immune system during SARS-CoV-2 infection, suggest directions for future studies, and evaluate proposed COVID-19 immunomodulating therapeutics.

    Julia L. McKechnie and Catherine A. Blish, "The Innate Immune System: Fighting on the Front Lines or Fanning the Flames of COVID-19?," Cell Host & Microbe (2020), doi:10.1016/j.chom.2020.05.009.

  • Cross-Neutralization of SARS-CoV-2 by a Human Monoclonal SARS-CoV Antibody

    Dora Pinto et al. / May 18, 2020

    SARS-CoV-2 is a newly emerged coronavirus responsible for the current COVID-19 pandemic that has resulted in more than 3.7 million infections and 260,000 deaths as of 6 May 2020. Vaccine and therapeutic discovery efforts are paramount to curb the pandemic spread of this zoonotic virus. The SARS-CoV-2 spike (S) glycoprotein promotes entry into host cells and is the main target of neutralizing antibodies. Here we describe multiple monoclonal antibodies targeting SARS-CoV-2 S identified from memory B cells of an individual who was infected with SARS-CoV in 2003. One antibody, named S309, potently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 by engaging the S receptor-binding domain. Using cryo-electron microscopy and binding assays, we show that S309 recognizes a glycan-containing epitope that is conserved within the sarbecovirus subgenus, without competing with receptor attachment. Antibody cocktails including S309 along with other antibodies identified here further enhanced SARS-CoV-2 neutralization and may limit the emergence of neutralization-escape mutants. These results pave the way for using S309- and S309-containing antibody cocktails for prophylaxis in individuals at high risk of exposure or as a post-exposure therapy to limit or treat severe disease.

    Dora Pinto et al., "Cross-Neutralization of SARS-CoV-2 by a Human Monoclonal SARS-CoV Antibody," Nature (2020), doi:10.1038/s41586-020-2349-y.

  • A SARS-CoV-2 Protein Interaction Map Reveals Targets for Drug Repurposing

    David Gordon et al. / April 30, 2020

    The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 2.3 million people, killed over 160,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven clinical efficacy, nor are there vaccines for its prevention, and these efforts are hampered by limited knowledge of the molecular details of SARS-CoV-2 infection. To address this, we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), identifying 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds). Screening a subset of these in multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the Sigma1 and Sigma2 receptors. Further studies of these host factor targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19.

    David Gordon et al., “A SARS-CoV-2 Protein Interaction Map Reveals Targets for Drug Repurposing,” Nature (2020), doi:10.1038/s41586-020-2286-9.

  • Vaccines for SARS-CoV-2: Lessons from Other Coronavirus Strains

    Eriko Padron-Regalado / April 23, 2020

    The emergence of the strain of coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and its impact on global health have made imperative the development of effective and safe vaccines for this lethal strain. SARS-CoV-2 now adds to the list of coronavirus diseases that have threatened global health, along with the SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome) coronaviruses that emerged in 2002/2003 and 2012, respectively. As of April 2020, no vaccine is commercially available for these coronavirus strains. Nevertheless, the knowledge obtained from the vaccine development efforts for MERS and SARS can be of high value for COVID-19 (coronavirus disease 2019). Here, we review the past and ongoing vaccine development efforts for clinically relevant coronavirus strains with the intention that this information helps in the development of effective and safe vaccines for COVID-19. In addition, information from naturally exposed individuals and animal models to coronavirus strains is described for the same purpose of helping into the development of effective vaccines against COVID-19.

    Padron-Regalado, Eriko, “Vaccines for SARS-CoV-2: Lessons from Other Coronavirus Strains,” Infectious Diseases and Therapy (2020), doi:s40121-020-00300-x.

  • Rapid Development of an Inactivated Vaccine for SARS-CoV-2 (Preprint)

    Qiang Gao et al. / April 19, 2020

    The COVID-19 pandemic caused by SARS-CoV-2 has brought about an unprecedented crisis, taking a heavy toll on human health, lives as well as the global economy. There are no SARS-CoV-2-specific treatments or vaccines available due to the novelty of this virus. Hence, rapid development of effective vaccines against SARS-CoV-2 is urgently needed. Here we developed a pilot-scale production of a purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc), which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats and non-human primates. These antibodies potently neutralized 10 representative SARS-CoV-2 strains, indicative of a possible broader neutralizing ability against SARS-CoV-2 strains circulating worldwide. Immunization with two different doses (3?g or 6 ?g per dose) provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without any antibody-dependent enhancement of infection. Systematic evaluation of PiCoVacc via monitoring clinical signs, hematological and biochemical index, and histophathological analysis in macaques suggests that it is safe. These data support the rapid clinical development of SARS-CoV-2 vaccines for humans.

    Gao, Qiang et al., “Rapid Development of an Inactivated Vaccine for SARS-CoV-2,” BioRxiv (2020), doi:10.1101/2020.04.17.046375.

  • A Large-scale Drug Repositioning Survey for SARS-CoV-2 Antivirals (Preprint)

    Laura Riva et al. / April 17, 2020

    The emergence of novel SARS coronavirus 2 (SARS-CoV-2) in 2019 has triggered an ongoing global pandemic of severe pneumonia-like disease designated as coronavirus disease 2019 (COVID-19). To date, more than 2.1 million confirmed cases and 139,500 deaths have been reported worldwide, and there are currently no medical countermeasures available to prevent or treat the disease. As the development of a vaccine could require at least 12-18 months, and the typical timeline from hit finding to drug registration of an antiviral is >10 years, repositioning of known drugs can significantly accelerate the development and deployment of therapies for COVID-19. To identify therapeutics that can be repurposed as SARS-CoV-2 antivirals, we profiled a library of known drugs encompassing approximately 12,000 clinical-stage or FDA-approved small molecules. Here, we report the identification of 30 known drugs that inhibit viral replication. Of these, six were characterized for cellular dose-activity relationships, and showed effective concentrations likely to be commensurate with therapeutic doses in patients. These include the PIKfyve kinase inhibitor Apilimod, cysteine protease inhibitors MDL-28170, Z LVG CHN2, VBY-825, and ONO 5334, and the CCR1 antagonist MLN-3897. Since many of these molecules have advanced into the clinic, the known pharmacological and human safety profiles of these compounds will accelerate their preclinical and clinical evaluation for COVID-19 treatment.

    Laura Riva et al., "A Large-scale Drug Repositioning Survey for SARS-CoV-2 Antivirals," bioRxiv (2020), doi:10.1101/2020.04.16.044016

  • Multidrug Treatment with Nelfinavir and Cepharanthine Against COVID-19 (Preprint)

    Hirofumi Ohashi et al. / April 15, 2020

    Antiviral treatments targeting the emerging coronavirus disease 2019 (COVID-19) are urgently required. We screened a panel of already-approved drugs in a cell culture model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and identified two new antiviral agents: the HIV protease inhibitor Nelfinavir and the anti-inflammatory drug Cepharanthine. In silico modeling shows Nelfinavir binds the SARS-CoV-2 main protease consistent with its inhibition of viral replication, whilst Cepharanthine inhibits viral attachment and entry into cells. Consistent with their different modes of action, in vitro assays highlight a synergistic effect of this combined treatment to limit SARS-CoV-2 proliferation. Mathematical modeling in vitro antiviral activity coupled with the known pharmacokinetics for these drugs predicts that Nelfinavir will facilitate viral clearance. Combining Nelfinavir/Cepharanthine enhanced their predicted efficacy to control viral proliferation, to ameliorate both the progression of disease and risk of transmission. In summary, this study identifies a new multidrug combination treatment for COVID-19.

    Hirofumi Ohashi et al., “Multidrug treatment with nelfinavir and cepharanthine against COVID-19,” bioRxiv (2020), doi:10.1101/2020.04.17.046375.

  • Drug Evaluation During the COVID-19 Pandemic

    Benjamin Rome and Jerry Avorn / April 14, 2020

    The search for a treatment for Covid-19 is testing our country’s ability to quickly develop, test, and deploy medications, presenting both opportunities and challenges to our drug-assessment apparatus. Several aspects of the U.S. response raise serious concerns, highlighting how the processes for evaluating and approving drugs can go awry during a public health crisis.
    The global pandemic has put pressure on clinicians and the Food and Drug Administration (FDA) to act swiftly to make medications available to patients. When very limited observational and anecdotal evidence raised the possibility that the antimalarial drugs chloroquine and hydroxychloroquine may have activity against SARS-CoV-2, President Donald Trump quickly began celebrating the promise of their widespread use, stating on national television that he had a “hunch” that such therapy was effective and that the drugs could be a “game changer” in addressing the pandemic. More recently, he openly encouraged patients to take the drugs and suggested he might do so himself, despite having tested negative for the virus.
    After Trump’s initial assertions, the FDA — still facing criticism that its delays in approving testing kits for the virus hindered prevention efforts — issued an Emergency Use Authorization (EUA) on March 28 that allowed for use of the drugs to treat patients with Covid-19. Although the EUA’s scope was limited to permitting distribution of chloroquine and hydroxychloroquine from a federal stockpile, its issuance was widely yet incorrectly reported by Trump and others as meaning that the FDA had approved the drugs for this indication. The Centers for Disease Control and Prevention (CDC) went so far as to publish doses of chloroquine and hydroxychloroquine for use in patients with Covid-19, though it later removed them from its website. Meanwhile, serious concerns have been raised about the adequacy of the available studies of these drugs.

    Benjamin Rome and Jerry Avorn, “Drug Evaluation During the COVID-19 Pandemic,” The New England Journal of Medicine (2020), doi:10.1056/NEJMp2009457.

  • Preventing COVID-19-induced Pneumonia with Anticytokine Therapy

    Giovanni Monteleone, Pier Carlo Sarzi-Puttini, and Sandro Ardizzone / April 6, 2020

    Immune-mediated disorders are a group of disabling conditions that affect millions of individuals worldwide. These pathologies include, but are not limited to, rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, and inflammatory bowel diseases. Each of these diseases has a unique epidemiology and pathophysiology, despite sharing several pathways of tissue damage, which rely on an excessive cytokine response. Indeed, cytokine blockers, such as infliximab, adalimumab (anti-tumor necrosis factor [TNF]), and ustekinumab (anti-interleukin [IL]-12/IL-23 [p40 subunit]), used for the treatment of psoriasis, rheumatoid arthritis, and inflammatory bowel diseases, are used with success for inducing and maintaining remission. Unfortunately, however, the use of these therapies enhances the risk of bacterial and viral infections, and of viral reactivation in cases with previous viral infection. With the recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the increasing incidence of associated coronavirus disease 2019 (COVID-19) in countries where immune-mediated disorders are frequent, the use of these drugs poses major challenges for clinicians. Studies so far suggest that most patients infected with SARS-CoV-2 remain asymptomatic or develop mild symptoms, but approximately 15–20% of patients develop severe respiratory distress syndrome or septic shock. The treatment of these critically ill patients is particularly difficult, as no specific antiviral drug or vaccine is currently recommended.

    Giovanni Monteleone, Pier Carlo Sarzi-Puttini, and Sandro Ardizzone, “Preventing COVID-19-induced Pneumonia with Anticytokine Therapy,” The Lancet Rheumatology (2020), doi:10.1016/S2665-9913(20)30092-8.

  • Awake Tracheal Intubation in a Suspected COVID-19 Patient with Critical Airway Obstruction

    Imran Ahmad et al. / April 6, 2020

    We report the airway management of a patient suspected of being COVID-19 positive with impending airway obstruction requiring urgent surgical tracheostomy. To our knowledge, this is the first reported case of an awake tracheal intubation in a suspected COVID?19 positive patient. Various modifications were put in place during the awake tracheal intubation and surgical tracheostomy procedures to minimise aerosol generation from the patient, such as avoiding high flow nasal oxygen, establishing conscious sedation with remifentanil prior to commencing airway topicalisation and avoiding trans?tracheal local anaesthetic infiltration. A multidisciplinary team discussion prior to performing the case highlighted aspects of both the airway management and the surgical procedure where particular care and modifications are required. There is a lack of national guidance for awake tracheal intubation and tracheostomy in COVID?19 cases. This report nevertheless addresses the key procedural modifications required.

    Imran Ahmad et al., “Awake Tracheal Intubation in a Suspected COVID-19 Patient with Critical Airway Obstruction,” Anesthesia Reports, doi:10.1002/anr3.12041.

  • Any Possible Role of Phosphodiesterase Type 5 Inhibitors in the Treatment of Severe COVID19 Infections? A Lesson from Urology

    Fabrizio Dal Moro and Ugolino Livi / April 6, 2020

    One of the most challenging characteristics of the novel pandemic of COVID19, is that there are various degrees of severity of symptoms, from asymptomatic to life-threatening forms.
    As recently reported by Zhang et al., considering the biochemical parameters, elevated levels of infection-related biomarkers and inflammatory cytokines (such as IL-6), neutrophilia and lymphocytopenia (as well as low CD3+ and CD4+ T-cell counts) seem to be correlated to the most severe cases of the infection.
    In an attempt to identify some prognostic parameters, there are some clinical factors significantly correlated with higher risks of acute respiratory distress syndrome (ARDS) and death, such as being in an older age group, high fever, and comorbidities. Focusing attention on the last groups of factors, recent studies confirmed a strong correlation between the severity of infection caused by COVID19 and the presence of hypertension. In our experience almost all COVID19 patients with severe ARDS are hypertensive (unpublished data).
    Several studies demonstrated a strong correlation between hypertension and Nitric Oxide (NO): a high level of blood pressure is a pathological condition characterized by endothelial dysfunction, in which NO availability is impaired with concomitant increased release of IL-6 by the dysfunctional endothelium.

    Fabrizio Dal Moro and Ugolino Livi, “Any Possible Role of Phosphodiesterase Type 5 Inhibitors in the Treatment of Severe COVID19 Infections? A Lesson from Urology,” Clinical Immunology 214 (2020), doi:10.1016/j.clim.2020.108414.

  • Intensive Care Management of Coronavirus Disease 2019 (COVID-19): Challenges and Recommendations

    Jason Phua et al. / April 6, 2020

    As coronavirus disease 2019 (COVID-19) spreads across the world, the intensive care unit (ICU) community must prepare for the challenges associated with this pandemic. Streamlining of workflows for rapid diagnosis and isolation, clinical management, and infection prevention will matter not only to patients with COVID-19, but also to health-care workers and other patients who are at risk from nosocomial transmission. Management of acute respiratory failure and haemodynamics is key. ICU practitioners, hospital administrators, governments, and policy makers must prepare for a substantial increase in critical care bed capacity, with a focus not just on infrastructure and supplies, but also on staff management. Critical care triage to allow the rationing of scarce ICU resources might be needed. Researchers must address unanswered questions, including the role of repurposed and experimental therapies. Collaboration at the local, regional, national, and international level offers the best chance of survival for the critically ill.

    Jason Phua et al., “Intensive Care Management of Coronavirus Disease 2019 (COVID-19): Challenges and Recommendations,” The Lancet Respiratory Medicine (2020), doi:10.1016/S2213-2600(20)30165-X.

  • Front Line COVID-19 Critical Care Consortium Urges Immediate Adoption of Early Intervention Protocol to Prevent Mortality and Reduce the Need for Ventilators from COVID-19 Disease

    Umberto Meduri et al. / April 6, 2020

    Five leading critical care specialists, who together have formed the Front Line COVID-19 Critical Care Consortium, have released a protocol for treating patients who arrive in hospitals with COVID-19. Based on available research, the experience in China reflected by the Shanghai expert commission, and their decades-long professional experiences in Intensive Care Units around the country, the five experts strongly urge fellow physicians to immediately adopt a change in strategy by delivering powerful therapies earlier in the disease course, prior to admission to the ICU or the need for a mechanical ventilator. Based on early experiences with this more aggressive approach, they predict that early adoption of the protocol will reduce ICU admissions, obviate the need for mechanical ventilators, and most importantly, save many lives.

    Umberto Meduri et al., “Front Line COVID-19 Critical Care Consortium Urges Immediate Adoption of Early Intervention Protocol to Prevent Mortality and Reduce the Need for Ventilators from COVID-19 Disease,” Front Line COVID-19 Critical Care Consortium (2020).

  • Mechanical Ventilator Milano (MVM): A Novel Mechanical Ventilator Designed for Mass Scale Production in Response to the COVID-19 Pandemic (Preprint)

    Cristiano Galbiati et al. / March 31, 2020

    We present here the design of the Mechanical Ventilator Milano (MVM), a novel mechanical ventilator designed for mass scale production in response to the COVID-19 pandemics, to compensate for the dramatic shortage of such ventilators in many countries. This ventilator is an electro-mechanical equivalent of the old, reliable Manley Ventilator. Our design is optimized to permit large scale production in short time and at a limited cost, relying on off-the-shelf components, readily available worldwide from hardware suppliers. Operation of the MVM requires only a source of compressed oxygen (or compressed medical air) and electrical power. The MVM control and monitoring unit can be connected and networked via WiFi so that no additional electrical connections are necessary other than the connection to the electrical power.
    At this stage the MVM is not a certified medical device. Construction of the first prototypes is starting with a team of engineers, scientists and computing experts. The purpose of this paper is to disseminate the conceptual design of the MVM broadly and to solicit feedback from the scientific and medical community to speed the process of review, improvement and possible implementation.

    Cristiano Galbiati et al., “Mechanical Ventilator Milano (MVM): A Novel Mechanical Ventilator Designed for Mass Scale Production in Response to the COVID-19 Pandemic,” arXiv:2003.10405(2020).

  • COVID-19 in Critically Ill Patients in the Seattle Region — Case Series

    Pavan Bhatraju / March 30, 2020

    BACKGROUND
    Community transmission of coronavirus 2019 (Covid-19) was detected in the state of Washington in February 2020. METHODS We identified patients from nine Seattle-area hospitals who were admitted to the intensive care unit (ICU) with confirmed infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Clinical data were obtained through review of medical records. The data reported here are those available through March 23, 2020. Each patient had at least 14 days of follow-up.
    RESULTS
    We identified 24 patients with confirmed Covid-19. The mean (±SD) age of the patients was 64±18 years, 63% were men, and symptoms began 7±4 days before admission. The most common symptoms were cough and shortness of breath; 50% of patients had fever on admission, and 58% had diabetes mellitus. All the patients were admitted for hypoxemic respiratory failure; 75% (18 patients) needed mechanical ventilation. Most of the patients (17) also had hypotension and needed vasopressors. No patient tested positive for influenza A, influenza B, or other respiratory viruses. Half the patients (12) died between ICU day 1 and day 18, including 4 patients who had a do-not-resuscitate order on admission. Of the 12 surviving patients, 5 were discharged home, 4 were discharged from the ICU but remained in the hospital, and 3 continued to receive mechanical ventilation in the ICU.
    CONCLUSIONS
    During the first 3 weeks of the Covid-19 outbreak in the Seattle area, the most common reasons for admission to the ICU were hypoxemic respiratory failure leading to mechanical ventilation, hypotension requiring vasopressor treatment, or both. Mortality among these critically ill patients was high.

    Pavan Bhatraju, “COVID-19 in Critically Ill Patients in the Seattle Region — Case Series,” New England Journal of Medicine (2020), doi:10.1056/NEJMoa2004500.

  • The Modelling of COVID19 Pathways Sheds Light on Mechanisms, Opportunities and on Controversial Interpretations of Medical Treatments (Preprint)

    Maria Luisa Chiusano / March 25, 2020

    The new coronavirus (2019-nCoV or SARS-CoV2), inducing the current pandemic disease (COVID-19) and causing pneumoniae in humans, is dramatically increasing in epidemic scale since its first appearance in Wuhan, China, in December 2019. The first infection from epidemic coronaviruses in 2003 fostered the spread of an overwhelming amount of related scientific efforts. The manifold aspects that have been raised, as well as their redundancy offer precious information that has been underexploited and needs to be critically re-evaluated, appropriately used and offered to the whole community, from scientists, to medical doctors, stakeholders and common people. These efforts will favour a holistic view on the comprehension, prevention and development of strategies (pharmacological, clinical, etc.) as well as common intervention against the new coronavirus spreading. Here we describe a model that emerged from our analysis that was focused on the Renin Angiotensin System (RAS) and the possible routes linking it to the viral infection. because the infection is mediated by the viral receptor on human cell membranes Angiotensin Converting Enzyme (ACE2), which is a key component in RAS signalling. The model depicts the main pathways determining the disease and the molecular framework for its establishment, and can help to shed light on mechanisms involved in the infection. It promptly gives an answer to some of the controversial, and still open, issues concerning predisposing conditions and medical treatments that protect from or favour the severity of the disease (such as the use of ACE inhibitors or ARBs/sartans), or to the sex related biases in the affected population. The model highlights novel opportunities for further investigations, diagnosis and appropriate intervention to understand and fight COVID19.

    Maria Luisa Chiusano, “The Modelling of COVID19 Pathways Sheds Light on Mechanisms, Opportunities and on Controversial Interpretations of Medical Treatments,” arXiv:2003.11614 (2020).

  • COVID-19: Melatonin as a Potential Adjuvant Treatment

    Rui Zhang et al. / March 23, 2020

    This article summarizes the likely benefits of melatonin in the attenuation of COVID-19 based on its putative pathogenesis. The recent outbreak of COVID-19 has become a pandemic with tens of thousands of infected patients. Based on clinical features, pathology, the pathogenesis of acute respiratory disorder induced by either highly homogenous coronaviruses or other pathogens, the evidence suggests that excessive inflammation, oxidation, and an exaggerated immune response very likely contribute to COVID-19 pathology. This leads to a cytokine storm and subsequent progression to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and often death. Melatonin, a well-known anti-inflammatory and anti-oxidative molecule, is protective against ALI/ARDS caused by viral and other pathogens. Melatonin is effective in critical care patients by reducing vessel permeability, anxiety, sedation use, and improving sleeping quality, which might also be beneficial for better clinical outcomes for COVID-19 patients. Notably, melatonin has a high safety profile. There is significant data showing that melatonin limits virus-related diseases and would also likely be beneficial in COVID-19 patients. Additional experiments and clinical studies are required to confirm this speculation.

    Rui Zhang et al., “COVID-19: Melatonin as a Potential Adjuvant Treatment,” Life Sciences, no. 117,583 (2020), doi:10.1016/j.lfs.2020.117583.

  • Interpretation of Expert Recommendations on Medical Nutrition for Patients with Novel Coronavirus Pneumonia

    Kaiying Yu and Hanping Shi / March 17, 2020

    At present, the new type of coronavirus pneumonia (referred to as new coronary pneumonia) is prevalent. The elderly with poor basic nutritional status and chronically ill patients are more critically ill after infection, highlighting the importance of nutritional treatment. In order to further promote the rehabilitation of patients, improve the treatment effect, and reduce mortality, the Parenteral and Enteral Nutrition Branch of the Chinese Medical Association (CSPEN) has put forward the following 10 recommendations for medical nutrition therapy for patients with new coronary pneumonia. The principles, methods, energy, protein, fat, non-protein energy supply ratio, fluid volume, micronutrients, immunonutrients, and monitoring of the effects of nutritional treatment are now interpreted to facilitate the application of clinicians in the treatment of new coronary pneumonia.

    Kaiying Yu and Hanping Shi, “Interpretation of Expert Recommendations on Medical Nutrition for Patients with Novel Coronavirus Pneumonia [《关于新型冠状病毒肺炎患者的医学营养治疗专家建议》解读],” National Medical Journal of China 100, no. 10 (2020): 724–28, doi:10.3760/cma.j.cn112137-20200205-00196.

  • Possibility of Disinfection of SARS-CoV-2 (COVID-19) in Human Respiratory Tract by Controlled Ethanol Vapor Inhalation (Preprint)

    Tsumoru Shintake / March 13, 2020

    Viruses such as SARS-CoV-2 and Influenza are lipophilic, enveloped viruses, and are relatively easy to inactivate by exposure to alcohols. The envelope mainly consists of the lipid bilayer, taken from the host cells at assembly/budding stage of the viral life cycle. Therefore the constitution of the lipid bilayer should be common in all SARS, MERS and influenza viruses, even after mutations, and thus these closely-related viruses will be disinfected by exposure to ethanol with the same concentration. Existing experimental data indicate that an ethanol concentration of 30~40 v/v% is sufficient to inactivate Influenza-A viruses in solution.
    The author suggests that it may be possible to use alcoholic beverages of 16~20 v/v%concentration for this disinfection process, such as Whisky (1:1 hot water dilution) or Japanese Sake, because they are readily available and safe (non-toxic). By inhaling the alcohol vapor at 50~60°C (122~140°F) through the nose for one or two minutes, it will condense on surfaces inside the respiratory tract; mainly in the nasal cavity. The alcohol concentration will be intensified to ~36v/v% by this process, which is enough to disinfect the corona virus on the mucous membrane. In this situation, our respiratory tract essentially works as an alcohol distillation apparatus (a condenser). This method also provides more moisture into respiratory tract, and helps to clean the inside of the nasal cavity by stimulating blowing of the nose, and also makes the mucous escalator work actively so that the self-clearing mechanism in the trachea will remove viruses faster.
    An alternative prompt method is also discussed. We use 40 v/v% whisky or similar alcohol, dripping on a gauze, inhale the vapor slowly at room temperature. This method works well for the front part of the nasal cavity. This is suitable for clinical workers, because they may need to use prompt preventative measures at any time.

    Tsumoru Shintake, “Possibility of Disinfection of SARS-CoV-2 (COVID-19) in Human Respiratory Tract by Controlled Ethanol Vapor Inhalation,” arXiv:2003.12444 (2020).

  • Analysis of Bronchoscope-Guided Tracheal Intubation in 12 Cases with COVID-19 under the Personal Protective Equipment with Positive Pressure Protective Hood (Preprint)

    Shuijiang Cai et al. / March 5, 2020

    Tracheal intubation is an independent risk factor for respiratory infections. Retrospective analysis of anesthesia, intubation methods, complications, and body temperature and nucleic acid test results of 12 patients with new-type coronavirus pneumonia under tracheal intubation under positive pressure filter hood and tertiary protection. Under midazolam + propofol + morphine / fentanyl sedative analgesia, anesthesia, all 12 patients successfully and successfully completed tracheal intubation under the guidance of bronchoscopy without serious complications. Nine medical staff did not develop fever, and the nucleic acid test of the throat swab was negative. During tracheal intubation of patients with new type of coronavirus pneumonia, medical staff did not develop infection under positive pressure filter hood and tertiary protection. Wearing protective equipment can complete the operation safely and smoothly.

    Shuijiang Cai et al., “Analysis of Bronchoscope-Guided Tracheal Intubation in 12 Cases with COVID-19 under the Personal Protective Equipment with Positive Pressure Protective Hood正压式头罩的三级防护下新型冠状病毒肺炎经支气管镜引导气管插管12例临床分析,” Chinese Journal of Tuberculosis and Respiratory Diseases (2020), doi:10.3760/cma.j.cn112147-20200222-00153.

  • A Systematic Review of Lopinavir Therapy for SARS Coronavirus and MERS Coronavirus—A Possible Reference for Coronavirus Disease-19 Treatment Option

    Tian-Tian Yao et al. / February 27, 2020

    In the past few decades, coronaviruses have risen as a global threat to public health. Currently, the outbreak of coronavirus disease-19 (COVID-19) from Wuhan caused a worldwide panic. There are no specific antiviral therapies for COVID-19. However, there are agents that were used during the severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) epidemics. We could learn from SARS and MERS. Lopinavir (LPV) is an effective agent that inhibits the protease activity of coronavirus. In this review, we discuss the literature on the efficacy of LPV in vitro and in vivo, especially in patients with SARS and MERS, so that we might clarify the potential for the use of LPV in patients with COVID-19.

    Tian-Tian Yao et al., “A Systematic Review of Lopinavir Therapy for SARS Coronavirus and MERS Coronavirus—A Possible Reference for Coronavirus Disease-19 Treatment Option,” Journal of Medical Virology (2020), doi:10.1002/jmv.25729.

  • Clinical Course and Outcomes of Critically Ill Patients with SARS-CoV-2 Pneumonia in Wuhan, China: A Single-centered, Retrospective, Observational Study

    Xiaobo Yang et al. / February 24, 2020

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia is a newly recognised illness that has spread rapidly throughout Wuhan (Hubei province) to other provinces in China and around the world.
    As of Feb 19, 2020, the total number of patients has risen sharply to 74?283 in the mainland of China, with 2009 (2·7%) deceased. The clinical spectrum of SARS-CoV-2 pneumonia ranges from mild to critically ill cases. Previous studies have only described the general epidemiological findings, clinical presentation, and clinical outcomes of patients of SARS-CoV-2 pneumonia.
    However, specific information characterising critically ill patients remains unknown.
    The data on the clinical characteristics and outcomes of critically ill patients with SARS-CoV-2 infection are scarce, but are of paramount importance to reduce mortality. In this study, we investigated critically ill patients with confirmed SARS-CoV-2 pneumonia who were admitted to Wuhan Jin Yin-tan hospital. The baseline SARS-CoV-2-associated morbidity and mortality data from this study will be of considerable value for the early identification of individuals who are at risk of becoming critically ill and who are most likely to benefit from intensive care treatment.

    Xiaobo Yang et al., “Clinical Course and Outcomes of Critically Ill Patients with SARS-CoV-2 Pneumonia in Wuhan, China: A Single-centered, Retrospective, Observational Study,” The Lancet Respiratory Medicine (2020), doi:10.1016/S2213-2600(20)30079-5.

  • More than 80 Clinical Trials Launch to Test Coronavirus Treatments

    Amy Maxmen / February 15, 2020

    As HIV drugs, stem cells and traditional Chinese medicines vie for a chance to prove their worth, the World Health Organization attempts to bring order to the search.

    Amy Maxmen, “More than 80 Clinical Trials Launch to Test Coronavirus Treatments,” Nature News, February 15, 2020.

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As the year draws to a close, we are delighted to present our second annual Christmas Chrestomathy, highlighting the essays that best represent our aims, ambitions, attitudes, and even our animadversions.
Medicine SARS-CoV-2: Research Guide
The Editors
A curated selection of abstracts and links to research papers and articles pertaining to SARS-CoV-2, COVID-19, and the current worldwide crisis. (108 articles, updated May 11, 2020.)
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SARS-CoV-2: Research Guide
The Editors
A curated selection of abstracts and links to research papers and articles pertaining to SARS-CoV-2, COVID-19, and the current worldwide crisis. (108 articles, updated May 11, 2020.)
Outsmarting the Virus
John Hewitt
Variants in the SARS-CoV-2 virus control infectivity, severity, and immunity. Against this hydra, the best modes of defense are multipronged. John Hewitt takes stock of currently available therapies.
History and Risk
Vaclav Smil
The 1918–1919 flu pandemic is not the best point of reference as the world deals with the COVID-19 outbreaks. And the West will likely not make adequate provisions for the next pandemic.
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