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Adv Drug Deliv Rev ; 169: 100-117, 2021 02.
Article in English | MEDLINE | ID: covidwho-966180


To address the COVID-19 pandemic, there has been an unprecedented global effort to advance potent neutralizing mAbs against SARS-CoV-2 as therapeutics. However, historical efforts to advance antiviral monoclonal antibodies (mAbs) for the treatment of other respiratory infections have been met with categorical failures in the clinic. By investigating the mechanism by which SARS-CoV-2 and similar viruses spread within the lung, along with available biodistribution data for systemically injected mAb, we highlight the challenges faced by current antiviral mAbs for COVID-19. We summarize some of the leading mAbs currently in development, and present the evidence supporting inhaled delivery of antiviral mAb as an early intervention against COVID-19 that could prevent important pulmonary morbidities associated with the infection.

Antibodies, Monoclonal/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/therapy , Immunologic Factors/therapeutic use , SARS-CoV-2/drug effects , Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/metabolism , Animals , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/metabolism , Antiviral Agents/chemistry , Antiviral Agents/metabolism , COVID-19/diagnosis , COVID-19/metabolism , Humans , Immunization, Passive , Immunologic Factors/chemistry , Immunologic Factors/metabolism , Protein Structure, Secondary , Protein Structure, Tertiary , SARS-CoV-2/chemistry , SARS-CoV-2/metabolism , Virus Shedding/drug effects , Virus Shedding/physiology
Clin Infect Pract ; 7: 100041, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-753766


BACKGROUND: Cold agglutinins are autoantibodies against RBC antigens, leading to hemolysis at less-than-physiological temperatures through complement fixation. Production can be triggered by infections, resulting in secondary cold agglutinin syndrome (CAS). This syndrome has been classically described in the setting of Mycoplasma pneumoniae infection, as well as with several viral pathogens. CASES: Here, we present two cases of cold agglutinins identified in the context of Covid-19 in critically ill patients treated at our institution. Each case was characterized by little in-vivo hemolysis, but these antibodies complicated laboratory assessment and renal replacement therapy. Management included anticoagulation and warming of dialysis circuit. CONCLUSIONS: Despite minimal in-vivo hemolysis, these antibodies are of clinical significance given their implications for laboratory assessment and renal replacement therapy, particularly with the frequency of multi-organ system dysfunction associated with severe Covid-19.

J Stroke Cerebrovasc Dis ; 29(9): 105010, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-548353


Aneurysmal subarachnoid hemorrhage (SAH) patients require frequent neurological examinations, neuroradiographic diagnostic testing and lengthy intensive care unit stay. Previously established SAH treatment protocols are impractical to impossible to adhere to in the current COVID-19 crisis due to the need for infection containment and shortage of critical care resources, including personal protective equipment (PPE). Centers need to adopt modified protocols to optimize SAH care and outcomes during this crisis. In this opinion piece, we assembled a multidisciplinary, multicenter team to develop and propose a modified guidance algorithm that optimizes SAH care and workflow in the era of the COVID-19 pandemic. This guidance is to be adapted to the available resources of a local institution and does not replace clinical judgment when faced with an individual patient.

Betacoronavirus/pathogenicity , Coronavirus Infections/therapy , Critical Pathways/organization & administration , Delivery of Health Care, Integrated/organization & administration , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Occupational Exposure/prevention & control , Personal Protective Equipment/supply & distribution , Pneumonia, Viral/therapy , Subarachnoid Hemorrhage/therapy , Algorithms , COVID-19 , Clinical Protocols , Coronavirus Infections/diagnosis , Coronavirus Infections/transmission , Coronavirus Infections/virology , Humans , Occupational Exposure/adverse effects , Occupational Health , Pandemics , Patient Safety , Pneumonia, Viral/diagnosis , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Risk Factors , SARS-CoV-2 , Subarachnoid Hemorrhage/diagnosis , Virulence , Workflow