Reply to Kesici et al. and Zeng et al.: Blocking the virus and reducing the inflammatory damage in COVID-19

Duan, Kai; Liu, Bende; Li, Cesheng; Zhang, Huajun; Takata, Yasuyuki; Qu, Jieming; Zhou, Min; Chen, Li; Zhu, Chen; Zhang, Xinxin; Yang, Xiaoming

doi:10.1073/pnas.2007408117

Cited by 29 publications

(22 citation statements)

References 10 publications

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“…Convalescent plasma of COVID-19 survivors is being used as a direct approach to combat SARS-CoV-2 infection in severe COVID patients (21,22). This is one of the simplest approaches for using polyclonal neutralizing antibodies from convalescent patients, providing passive immunization.…”

Section: Neutralizing Antibodies Against Sars-cov-2mentioning

confidence: 99%

“…Importantly, several options are proposed to treat or mitigate COVID-19 disease (18)(19)(20). Increasingly, convalescent serum of individuals recovered from COVID-19 is becoming a treatment of choice (21,22). Understanding the exact nature of the CoV ′ s S protein interaction with the h ACE2 receptor molecule is essential to understand how the treatment with passiveimmunization may be effective in humans in neutralizing the virus from adhering and entering the epithelial target cells, thereby controlling the infection.…”

Section: Introductionmentioning

confidence: 99%

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Blocking of the High-Affinity Interaction-Synapse Between SARS-CoV-2 Spike and Human ACE2 Proteins Likely Requires Multiple High-Affinity Antibodies: An Immune Perspective

Khatri

Dongen

2020

Front. Immunol.

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The pandemic of Coronavirus Disease 2019 (COVID-19) caused by SARS-CoV-2 has induced global eagerness to develop vaccines and therapeutics for treating COVID-19, including neutralizing antibodies. To develop effective therapeutic antibodies against SARS-CoV-2, it is critical to understand the interaction between viral and host's proteins. The human ACE2 (h ACE2) protein is the crucial target for the SARS-CoV's Spike protein that allows the virus to adhere to host epithelial cells. X-ray crystal structures and biophysical properties of protein-protein interactions reveal a large interaction surface with high binding-affinity between SARS-CoV-2 and h ACE2 (18 interactions), at least 15-fold stronger than between SARS-CoV-1 and h ACE2 (eight interactions). This suggests that antibodies against CoV-1 infection might not be very efficient against CoV-2. Furthermore, interspecies comparisons indicate that ACE2 proteins of man and cat are far closer than dog, ferret, mouse, and rat with significant differences in binding-affinity between Spike and ACE2 proteins. This strengthens the notion of productive SARS-CoV-2 transmission between felines and humans and that classical animal models are not optimally suited for evaluating therapeutic antibodies. The large interaction surface with strong affinity between SARS-CoV-2 and h ACE2 (dG−12.4) poses a huge challenge to develop reliable antibody therapy that truly blocks SARS-CoV-2 adherence and infection. We gauge that single antibodies against single epitopes might not sufficiently interfere with the strong interaction-synapse between Spike and h ACE2 proteins. Instead, appropriate combinations of high-affinity neutralizing antibodies against different epitopes might be needed, preferably of IgA-class for optimal and prolonged activity at epithelial layers of respiratory and intestine tracts.

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Section: Neutralizing Antibodies Against Sars-cov-2mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Blocking of the High-Affinity Interaction-Synapse Between SARS-CoV-2 Spike and Human ACE2 Proteins Likely Requires Multiple High-Affinity Antibodies: An Immune Perspective

Khatri

Dongen

2020

Front. Immunol.

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“…Therefore, it cannot be guaranteed that the improvement in the symptoms was due only to this intervention as the patients received additional drugs, such as corticosteroids and antivirals, that may have influenced the improvement of the condition. On the other hand, they agreed that the study published by Shen et al provides sufficient evidence for large clinical trials involving the administration of convalescent plasma to critically ill patients with COVID-19 (19,44,93,94).…”

Section: Convalescent Plasmamentioning

confidence: 82%

“…The authors stated that there was a significant improvement in oxygen saturation after 3 days, a decrease in C-reactive protein, varied absorption of lung lesions in radiological exams after 7 days and undetectable viral load in 7 patients without any serious side effect. However, they highlighted the need for randomized clinical trials with the purpose of defining the ideal dose and the best time for administration of convalescent plasma (19).…”

Section: Convalescent Plasmamentioning

confidence: 99%

“…It belongs to the same beta subgroup of viruses that caused severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) in the past decades, sharing 80% and 50% of their genome, respectively (1). Since the first cases of the novel coronavirus disease (COVID- 19) reported in Wuhan (China) in late 2019, more than 80,000 cases have been reported in China alone. According to the World Health Organization (WHO), the epidemic COVID-19 peaked between late January and early February 2020 in China and the rate of new cases declined substantially in early March (2).…”

Section: Introductionmentioning

confidence: 99%

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Therapeutic Options Against the New Coronavirus: Updated Clinical and Laboratory Evidences

et al. 2020

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The pandemic caused by the new coronavirus (SARS-Cov-2) has encouraged numerous in vitro studies and clinical trials around the world, with research groups testing existing drugs, novel drug candidates and vaccines that can prevent or treat infection caused by this virus. The urgency for an effective therapy is justified by the easy and fast viral transmission and the high number of patients with severe respiratory distress syndrome who have increasingly occupied intensive care hospital beds, leading to a collapse in health systems in several countries. However, to date, there is no sufficient evidence of the effectiveness of any researched therapy. The off-label or compassionate use of some drugs by health professionals is a reality in all continents, whose permission by regulatory agencies has been based on the results of some clinical trials. In order to guide decision-making for the treatment of COVID-19, this review aims to present studies and guidelines on the main therapies that have been and are currently being tested against SARS-CoV-2 and to critically analyze the reported evidences.

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COVID-19 in the Pediatric Population—Review and Current Evidence

Rabinowicz

Leshem

Pessach

2020

Curr Infect Dis Rep

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Purpose of Review Coronavirus disease 2019 (COVID-19) pandemic has major health and economic impacts. We review disease characteristics in children. Recent Findings Children comprise 1-2% of the diagnosed cases, and typically suffer mild disease. The median age of infected children is 3.3-11 years, and male/female ratio is 1.15-1.55. Common symptoms in children include upper respiratory symptoms (26-54%), cough (44-54%), fever (32-65%), and gastrointestinal (15-30%) symptoms. Substantial proportion (4-23%) are asymptomatic. Death rates are up to 0.7%. Risk factors associated with severe disease are neonatal age group, male gender, lower respiratory tract disease, and pre-existing medical conditions. Vertical transmission was reported. Multisystem inflammatory syndrome (MIS), characterized by fever, multisystem organ involvement, and laboratory markers of inflammation, causes critical illness in > 50% of cases and is increasingly reported from endemic countries. Indirect effects of the coronavirus epidemic include higher rates of psychiatric morbidities, education loss, unhealthy lifestyle changes, and increased child neglect. Vaccines are in clinical trials and immunogenicity has not yet been shown in children. Summary Overall, COVID-19 has lower incidence and causes milder disease in children compared with adult patients. MIS is a rare severe complication more common in children. More data on the efficacy and safety of antivirals in children are needed.

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Reply to Kesici et al. and Zeng et al.: Blocking the virus and reducing the inflammatory damage in COVID-19

Cited by 29 publications

References 10 publications

Blocking of the High-Affinity Interaction-Synapse Between SARS-CoV-2 Spike and Human ACE2 Proteins Likely Requires Multiple High-Affinity Antibodies: An Immune Perspective

Blocking of the High-Affinity Interaction-Synapse Between SARS-CoV-2 Spike and Human ACE2 Proteins Likely Requires Multiple High-Affinity Antibodies: An Immune Perspective

Therapeutic Options Against the New Coronavirus: Updated Clinical and Laboratory Evidences

COVID-19 in the Pediatric Population—Review and Current Evidence

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