Research Insights About Covid-19

We attempt to provide selected highlights in recent research findings

Last Update on 1 December 2020

A. Medicine and Health 

November 2020

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A. Medicine and Health 

November 2020

November 30, 2020 (Nat Commun)

Development of a multi-antigenic SARS-CoV-2 vaccine candidate using a synthetic poxvirus platform

Chiuppesi, F., Salazar, M.d., Contreras, H. et al. 

https://doi.org/10.1038/s41467-020-19819-1

Modified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. The authors constructed a vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. They used this vaccine platform to produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. They also discuss the effectiveness of these sMVA vectors in antibody development and demonstrate the potential of using this platform to develop a vaccine

 

 

November 24, 2020 (NEJM)

A Randomized Trial of Convalescent Plasma in COVID-19 Severe Pneuomnia

Simonovich V.A., Burgos Pratx L.D., Scibona P., et al.

Hospitalized adults with severe COVID-19 pneumonia were randomly assigned in a 2:1 ratio to receive convalescent plasma or placebo. At 30 days, no significant difference in clinical status was noted between the two groups. Overall mortality was 11.43% with placebo and 10.96% with convalescent plasma, a difference that was not significant.

 

 

November 24, 2020 (NEJM)

A Cluster-Randomized Trial of Hydroxycholoroquine for Prevention of COVID-19

Mitjà O., Corbacho-Monné M., Ubals M., et al.

https://doi.org/10.1056/NEJMoa2021801

In a trial involving asymptomatic contacts of patients with PCR–confirmed Covid-19 in Spain, the authors compared the use of hydroxychloroquine with usual care. Postexposure therapy with hydroxychloroquine did not prevent SARS-CoV-2 infection or symptomatic Covid-19 in healthy persons.

 

 

November 19, 2020 (NEJM)

Effect of Hydroxychloroquine in Hospitalized Patients with Covid-19
The RECOVERY Collaborative Group

10.1056/NEJMoa2022926

This randomized, controlled, open-label platform trial compared hydroxychloroquine with usual care in patients hospitalized with COVID-19. The primary outcome tested was 28-day mortality. They found that among 4716 hospitalized adult patients with COVID-19 in the United Kingdom, those who were treated with hydroxychloroquine did not have a lower incidence of death at 28 days than those who received usual care.

 

 

November 19, 2020 (EClinicalMedicine)

Multi-center nationwide comparison of seven serology assays reveals a SARS-CoV-2 non-responding seronegative subpopulation

Kfir Oved, Liraz Olmer, Yonat Shemer-Avni et al.

This multi-centre study performed clinical and analytical validation of seven serology assays to determine their utility and limitations for SARS-CoV-2 diagnosis. The authors found that the commercially available automated immunoassays exhibit significant differences in performance and expected positive predictive values in low prevalence scenarios. They also found that 5% of those with positive SARS-CoV2 PCR were seronegative non-responders, representing a proportion of patients that may be at risk for re-infection.

 

 

November 19, 2020 (PNAS)

Event-specific interventions to minimize COVID-19 transmission

Paul Tupper, Himani Boury, Madi Yerlanov, Caroline Colijn

https://doi.org/10.1073/pnas.2019324117

The authors provided a simple model of COVID-19 transmission at workplaces, events, and other settings. They used data from reported single-event, short-duration outbreaks to estimate the transmission rate, number of contacts, and turnover at events. Using this data, they predicted how many new infections are expected to occur at various events given the presence of a single infectious individual. They also determined which types of interventions will be the most effective in reducing the number of infections: reducing transmission rates (such as with masks), social distancing (reducing the number of people in contact), or bubbling (keeping contact groups small and consistent).

 

November 19, 2020 (JAMA Net. Open)

Pregnancy Outcomes Among Women With and Without Severe Acute Respiratory Syndrome Coronavirus 2 infection

Emily H. Adhikari, Wilmer Moreno, Amanda C. Zofkie et al.

10.1001/jamanetworkopen.2020.29256

This cohort study evaluates the adverse outcomes associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among pregnant women and describes clinical management, disease progression, hospital admission, placental abnormalities, and neonatal outcomes.

 

 

November 18, 2020 (Evaluation & The Health Professions)

Notes from the Field: Effectiveness of Prevention and Control Measures for Imported COVID-19 in Guangming District of Shenzhen

Xiaoliang Chen, Tieqiang Wang, Yang Zhao et al.

https://doi.org/10.1177/0163278720971833

The Guangming District of Shenzhen formulated a mechanism that integrated early identification, early diagnosis, early isolation, and early protection for the COVID-19 epidemic. A district-wide epidemic prevention and control system was established under the major leadership of the district government. The purpose of this paper was to describe the strategies for the control and prevention of the COVID-19 epidemic in Shenzhen Guangming District and the results of the first 50 days from January 20, as of March 13.

 

 

November 16, 2020 (JAMA Int. Med)

Diaphragm Pathology in Critically Ill Patients With COVID-19 and Postmortem Findings from 3 Medical Centers

Zhonghua Shi, Heder J. de Vries, Alexander P. J. Vlaar et al. https://doi.org/10.1001/jamainternmed.2020.6278

This case-control study examines the association of COVID-19 with the respiratory muscles in Dutch critically ill patients. The authors found evidence for ACE-2 expression and SARS-CoV-2 viral infiltration in the diaphragm of a subset of COVID-19–ICU patients. They also an increased expression of genes involved in fibrosis and histological evidence of diaphragmatic fibrosis. They hypothesize that severe diaphragm myopathy associated with COVID-19, may lead to diaphragm weakness and might contribute to ventilator weaning failure, persistent breathlessness, and fatigue in patients with COVID-19 who survive their ICU stay.

 

 

November 12, 2020 (NEJM)

An mRNA Vaccine against SARS-CoV-2 — Preliminary Report

Lisa A. Jackson, Evan J. Anderson, Nadine G. Rouphael et al.

https://doi.org/10.1056/NEJMoa2022483

Two injections of mRNA-1273, a lipid nanoparticle-encapsulated mRNA-based vaccine produced in collaboration with the NIAID that encodes the SARS-CoV2 spike protein, induced anti–SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified in the phase 1 trial. These findings support further development of this vaccine. 

 

 

November 12, 2020 (The Lancet)

Ethnicity and clinical outcomes in COVID-19: A systematic analysis

Shirley Sze, Daniel Pan, Clareece R. Nevill et al.

https://doi.org/10.1016/j.eclinm.2020.100630

The authors performed a systematic review and meta-analysis to explore the relationship between ethnicity and clinical outcomes in COVID-19. After analysing data of more than 18 million patients from 50 studies, they found that individuals of Black and Asian ethnicity are at increased risk of COVID-19 infection compared to White individuals and that Asians may be at a higher risk of ITU admission and death. These findings are of critical public health importance in informing interventions to reduce morbidity and mortality amongst ethnic minority groups.

 

 

November 12, 2020 (JAMA Int. Med.)

Assessment of SARS-CoV-2 RNA Test Results Among Patients Who Recovered From COVID-19 With Prior Negative Results

Flora Marzia Liotti, Giulia Menchinelli, Simona Marchetti et al.

https://doi.org/10.1001/jamainternmed.2020.7570

This study examines positive rt-PCR nasal-oropharyngeal swab results from patients who recovered from COVID-19 with prior negative results. This study highlights that many patients who recovered from COVID-19 may be still positive (albeit at lower levels) for SARS-CoV-2 RNA, but only a minority of the patients may carry a replicating SARS-CoV-2 in the respiratory tract. Further studies are needed to verify whether such patients can transmit the virus.

 

 

November 11, 2020 (Int. J of Stroke)

Stroke in COVID-19: A systematic review and meta-analysis

Stefania Nannoni, Rosa de Groot, Steven Bell et. al.

https://doi.org/10.1177/1747493020972922

COVID-19 is not just a respiratory disease. Here, the authors aimed to characterize the incidence, risk factors, clinical–radiological manifestations, and outcome of COVID-19-associated stroke. They found that acute cerebrovascular diseases are not uncommon in patients with COVID-19, especially in those with severe and have pre-existing vascular risk factors. The pattern of large vessel occlusion and multi-territory infarcts suggests that cerebral thrombosis and/or thromboembolism could be possible causative pathways for the disease.

 

 

November 10, 2020 (JAMA)

Gastrointestinal Complications in Critically Ill Patients With and Without COVID-19

Mohamad El Moheb, Leon Naar, Mathias A. Christensen et. al.

https://doi.org/10.1001/jama.2020.19400

This cohort study compares the incidence of gastrointestinal complications (transaminitis, ileus, Ogilvie syndrome, mesenteric ischemia) among critically ill patients with COVID-19 vs non–COVID-19–induced acute respiratory distress syndrome (ARDS) at a single US academic hospital between March and May 2020. Although limited to a single centre and by the unavailability of inflammatory markers to use for matching, the authors found a higher rate of gastrointestinal complications, including mesenteric ischemia, in critically ill patients with COVID-19 suggesting a distinct phenotype for COVID-19 compared with conventional ARDS.

 

 

November 9, 2020 (PNAS)

The impact of COVID-19 nonpharmaceutical interventions on the future dynamics of endemic infections

Rachel E. Baker, Sang Woo Park, Wenchang Yang, 

https://doi.org/10.1073/pnas.2013182117

Nonpharmaceutical interventions (NPIs), such as social distancing, reduce not only COVID-19 cases but also other circulating infections such as influenza and RSV. The susceptible population for these infections will increase while NPIs are in place. Using models fit to historic cases of RSV and influenza, the authors project large future outbreaks of both diseases may occur following a period of extended NPIs depending on the transmissibility and evolutionary dynamics of circulating strains. These outbreaks, which may reach peak numbers in the winter, could increase the burden to healthcare systems.

 

 

November 7, 2020 (Thrombosis Research)

Prevalence and characteristics of pulmonary embolism in 1042 COVID-19 patients with respiratory symptoms: A nested case-control study

Benjamin Planquette, Alice Le Berre, Lina Khider et al.

https://doi.org/10.1016/j.thromres.2020.11.001

The authors conducted a retrospective nested case-control study in 2 French hospitals to estimate the prevalence of symptomatic pulmonary embolism (PE) in COVID-19 patients and to identify the clinical, radiological or biological characteristics associated with PE. Their results show a PE prevalence of close to 5% in COVID-19 patients. They found that PE appears to be associated with more extensive lung damage and more frequently requires invasive ventilation.

 

 

November 6, 2020 (Science)

Free fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein

Christine Toelzer, Kapil Gupta, Sathish K.N. Yadav et. al.

https://doi.org/10.1126/science.abd3255                                                 

Many efforts to develop therapies against SARS-CoV-2 are focused on the spike (S) protein trimer that binds to the host receptor. Toelzer et al. produced SARS-CoV-2 S in insect cells and determined the structure by cryo-electron microscopy. In their dataset, the closed-form was predominant and was stabilized by binding linoleic acid, an essential fatty acid. A similar binding pocket appears to be present in previous highly pathogenic coronaviruses, and past studies suggested links between viral infection and fatty acid metabolism. The pocket could be exploited to develop inhibitors that trap S protein in the closed conformation.

 

 

November 2, 2020 (PNAS)

Rapid identification of a human antibody with high prophylactic and therapeutic efficacy in three animal models of SARS-CoV-2 infection

Wei Li, Chuan Chen, Aleksandra Drelich, David R. Martinez et al.

https://doi.org/10.1073/pnas.2010197117

Effective therapies are urgently needed for COVID-19. The authors identified a fully human monoclonal germline-like antibody (ab1) from phage-displayed libraries that potently inhibited mouse ACE2-adapted SARS-CoV-2 replication in wild-type BALB/c mice and native virus in transgenic mice expressing human ACE2 as well as in hamsters when administered before virus challenge. Ab1 was highly specific and did not bind to human cell membrane-associated proteins. It also exhibited good developability properties including complete lack of aggregation. Ab1 has potential for prophylaxis and therapy of COVID-19 alone or in combination with other agents.

 

 

Nov 1, 2020 (JAMA Cardio.)

Association of Troponin Levels With Mortality in Italian Patients Hospitalized With Coronavirus Disease 2019: Results of a Multicenter Study

Carlo Mario Lombardi, Valentina Carubelli, Annamaria Iorio et al.

https://doi.org/10.1001/jamacardio.2020.3538

This cohort study of patients with coronavirus disease 2019 who were hospitalized in cardiology units in Italy assesses the association of troponin levels at admission with patient outcomes.

 

 

Nov 1, 2020 (JAMA Int Med.)

Prone Positioning in Awake, Nonintubated Patients With COVID-19 Hypoxemic Respiratory Failure

Alison E. Thompson, Benjamin L. Ranard, Ying Wei et al.

https://doi.org/10.1001/jamainternmed.2020.3030

This cohort study investigates whether the prone position is associated with improved oxygenation and decreased risk for intubation in spontaneously breathing patients with severe COVID-19 hypoxaemic respiratory failure.

 

 

Nov 1, 2020 (JAMA Int Med.)

The Exclusion of Older Persons From Vaccine and Treatment Trials for Coronavirus Disease 2019—Missing the Target

Benjamin K. I. Helfand, Margaret Webb, Sarah L. Gartaganis et al.

https://doi.org/10.1001/jamainternmed.2020.5084

This cross-sectional study evaluates the risk of exclusion for older adults in randomized clinical trials for treatment and vaccine interventions in COVID-19.