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By Christian Hoffmann &
Bernd S. Kamps

7 July

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Immunology

O’Callaghan KP, Blatz AM, Offit PA. Developing a SARS-CoV-2 Vaccine at Warp Speed. JAMA, July 6, 2020. Full-text: https://doi.org/10.1001/jama.2020.12190

In this Viewpoint, the authors describe the the five currently leading vaccine candidates, all of which are aimed at inducing antibodies directed against the receptor-binding domain of the surface spike S protein of SARS-CoV-2. These vaccine candidates are messenger RNA-based (Moderna, Pfizer), recombinant vesicular stomatitis virus vectored (MSD) and adenovirus replication-defective vectored (Johnson & Johnson, AstraZeneca). All 5 candidates are undergoing rigorous investigation of their safety profile, including unintended adverse events.

 

Case JB, Rothlauf PW, Chen RE, et al. Neutralizing antibody and soluble ACE2 inhibition of a replication-competent VSV-SARS-CoV-2 and a clinical isolate of SARS-CoV-2. Cell Host Microbe July 01, 2020. Full-text: https://doi.org/10.1016/j.chom.2020.06.021

Using an infectious molecular clone of vesicular stomatitis virus (VSV), researchers replaced the glycoprotein gene (G) with the spike protein of SARS-CoV-2 (VSV-eGFP-SARS-CoV-2) and developed a high-throughput imaging-based neutralization assay at biosafety level 2. This provides a tool for testing inhibitors of SARS-CoV-2 mediated entry under reduced biosafety containment.

 

Dieterle EM, Haslwater D, Bortz RH, et al. A replication-competent vesicular stomatitis virus for studies of SARS-CoV-2 spike-mediated cell entry and its inhibition. Cell July 01, 2020. Full-text: https://doi.org/10.1016/j.chom.2020.06.020

Same direction. This group from the Albert Einstein College in New York have also generated a highly infectious recombinant VSV bearing the SARS-CoV-2 spike glycoprotein S as its sole entry glycoprotein and show that this recombinant virus, rVSV-SARS-CoV-2 S, closely resembles SARS-CoV-2 in its entry-related properties. Another step towards robust, scalable, and readily deployable surrogate viral assays to screen antiviral humoral responses, define correlates of immune protection, and down-select candidate antivirals.

 

Transmission

Morawska L, Milton DK. It is Time to Address Airborne Transmission of COVID-19. Clinical Infectious Diseases, July 6, 2020. Full-text: https://doi.org/10.1093/cid/ciaa939

In their comment, the authors appeal to the medical community and to all relevant national and international bodies to recognize the potential for airborne spread of COVID-19. Given the significant potential for inhalation exposure to viruses in microscopic respiratory droplets (microdroplets) at short to medium distances (up to several meters, or room scale), the authors are advocating for the use of preventive measures. This includes sufficient and effective ventilation (supply clean outdoor air, minimize recirculating air) particularly in public buildings, workplace environments, schools, hospitals, and aged care homes, but also supplement general ventilation with airborne infection control (such as local exhaust, high efficiency air filtration, and germicidal ultraviolet lights). Third, overcrowding has to be avoided, particularly in public transport and public buildings

 

Stubblefield WB, Talbot HK, Feldstein L, et al. Seroprevalence of SARS-CoV-2 Among Frontline Healthcare Personnel During the First Month of Caring for COVID-19 Patients – Nashville, Tennessee. Clin Infect Dis. 2020 Jul 6. PubMed: https://pubmed.gov/32628750. Full-text: https://doi.org/10.1093/cid/ciaa936

Among 249 HCW who worked in hospital units with COVID-19 patients for one month, 19 (7.6%) tested positive for SARS-CoV-2 antibodies. Only 11/19 (57.9%) reported symptoms of a prior illness, suggesting asymptomatic HCW could be an important source of SARS-CoV-2 transmission.

 

Diagnostics

Mei Q, Li J, Du R, et al. Assessment of patients who tested positive for COVID-19 after recovery. Lancet Inf Dis 2020, July 06, 2020. Full-text: https://doi.org/10.1016/S1473-3099(20)30433-3

In this study, 23 (3%) of 651 patients tested positive on a retest for SARS-CoV-2 by RT-qPCR assay in a routine health check. Of note, 52% had IgG anti-viral antibodies and 30% had IgM antibodies, indicating partial immune system recognition of SARS-CoV-2. Of note, 35% of patients had one or more COVID-19-related symptoms, quuestioning the usefulness of viral antibodies in COVID-19 clearance.

 

Clinical

Merkler ASE, Parikh NS, Mir S, et al. Risk of Ischemic Stroke in Patients With Coronavirus Disease 2019 (COVID-19) vs Patients With Influenza. JAMA Neurol. Published online July 2, 2020. Full-text: https://doi.org/10.1001/jamaneurol.2020.2730

Again, it’s NOT a flu. In this retrospective cohort study, 1,916 COVID-19 patients and 1,486 influenza patients (with emergency department visits or hospitalizations) were compared. There were 31 (1.6%; 95% CI, 1.1% – 2.3%) acute ischemic strokes with COVID-19, compared to 3 with influenza (0.2%; 95% CI, 0.0% – 0.6%). After adjustment for age, sex, and race, the likelihood of stroke was almost 8-fold higher with COVID-19 (odds ratio, 7.6; 95% CI, 2.3 – 25.2).

 

Goyal P, Ringel JB, Rajan M, et al. Obesity and COVID-19 in New York City: A Retrospective Cohort Study. Ann Int Med  6 Jul 2020. Full-text: https://www.acpjournals.org/doi/10.7326/M20-2730

More on obesity. In this study of 1,687 adults hospitalized with COVID-19 in New York City, obesity was an independent risk factor for respiratory failure but not for in-hospital mortality. These findings explain the extensive use of invasive mechanical ventilation reported in the US, where the prevalence of obesity exceeds 40%. The risk conferred by obesity was similar across age, sex, and race.

 

Severe COVID-19

Fan E, Beitler JR, Brochard L, et al. COVID-19-associated acute respiratory distress syndrome: is a different approach to management warranted? Lancet Respir Med July 06, 2020. Full-text: https://doi.org/10.1016/S2213-2600(20)30304-0

In their Viewpoint, the authors address ventilation strategies in the context of recent discussions on phenotypic heterogeneity in patients with COVID-19-associated ARDS. Although early reports suggested distinctive features that set it apart from historical ARDS, emerging evidence indicates that the respiratory system mechanics are broadly similar. In the absence of evidence to support a shift away from the current paradigm of ventilatory management, we strongly recommend adherence to evidence-based management, informed by bedside physiology, as resources permit.

 

Treatment

Wang J, Xing S, Ding L, et al. Human IgG neutralizing monoclonal antibodies block SARS-CoV-2 infection. Cell July 01, 2020. Full-text: https://doi.org/10.1016/j.celrep.2020.107918

Forget HCQ, lopinavir, etc. Over the last months, it has become increasingly clear that monoclonal antibodies will be the most promising therapeutic candidates for COVID-19. The authors identified 178 S1 and RBD binding human monoclonal antibodies from the memory B cells of 11 recently recovered patients. Of 8 antibodies showing robust authentic viral neutralizing activities, the best one, 414-1, showed neutralizing IC50 at 1.75 nM. Epitope mapping revealed that the antibodies bound to 3 different RBD epitopes, and epitope B antibody 553-15 could substantially enhance neutralizing abilities of most other neutralizing antibodies.