COVID-19 Treatment and Long-term Effects

COVID-19 Treatment and Long-term Effects

• Presentation topics include layers of defense against infection, treatments, vaccines, and long COVID.
• Principles of virus infection control include removing reservoirs (like animals), interrupting transmission (with hygiene, masks, and isolation), and increasing host resistance (by vaccination, passive immunisation, and antivirals).
• The Swiss cheese model illustrates multiple layers of defense against viral infection. Each layer represents a preventative measure, and a successful infection occurs when all layers are penetrated.
• Therapies can target host responses (like inflammation, thrombosis, and ARDS) or the virus directly (with antivirals and antibody therapies).

COVID-19 Therapies

• Therapies targeting host responses include immunosuppressive drugs and antithrombotic therapies.
• Therapies targeting the virus include antivirals that disrupt viral replication.
• Host-targeted agents and virus-targeted agents are listed including spike inhibitors, PLpro (protease) inhibitors, Mpro inhibitors, NSP12 inhibitors, NSP13 inhibitors, NSP14 inhibitors, NSP15 inhibitors, NSP16 inhibitors, nucleocapsid inhibitors, cytokine inhibitors, JAK inhibitors, ACE2 inhibitors, host protease inhibitors, glucocorticoids, and anticoagulants.
• COVID-19 treatments can be preventative strategies (like distancing, masks, and hand sanitation), therapeutic options (like repurposed antivirals, novel antivirals, and repurposed antimalarials), and management strategies (like monoclonal antibodies, supportive therapies, and corticosteroids).
• Antibody-based therapies, like those targeting the interaction between the spike protein and ACE2, are crucial for preventing infection. This includes several classes of antibodies with various mechanisms.

Repurposing of Known Treatments

• Hydroxychloroquine is shown not to have clinical benefits.
• There's no significant mortality impact from lopinavir.
• Dexamethasone reduced deaths by up to one-third.
• Tocilizumab reduces mortality in hospitalized COVID-19 patients.
• Azithromycin does not have clinical benefits.

COVID-19 Vaccines

• Spikevax (Moderna), Comirnaty (Pfizer/BioNTech), Nuvaxovid (Novavax), Vaxzevria (AstraZeneca/Oxford), Janssen COVID-19 Vaccine (Johnson & Johnson), and Valneva (Valneva) are currently approved in the UK.
• Vaccine types include mRNA vaccines, vector vaccines, protein subunit vaccines, and inactivated virus vaccines.
• Several aspects of vaccine effectiveness were discussed for testing in response to omicron variants, and data on vaccine efficacy.

COVID-19 Current Situation in England

• Data on vaccinations, cases, deaths, and hospitalizations and virus tests were reported in England.
• Infection rates often follow seasonal patterns including a peak during winter.
• Vaccinations have shown significant coverage in the population.

COVID-19 Antivirals

• Antivirals, such as nirmatrelvir-ritonavir (Paxlovid), are used to treat COVID-19, focusing on inhibiting viral replication through protease activity.

• Several antiviral targets are highlighted including NSP12, and others.

COVID-19 Targeting the Viral Lifecycle- Convalescent Plasma, Polyprotein processing and Replication, Polymerase

• Convalescent plasma from survivors can be used to provide antibodies.
• Polyprotein processing is a critical step in viral replication which includes the activity of PLpro and Mpro, the main protease.
• RdRp inhibitors target RNA replication and polymerases.
• Different approaches are utilized to interrupt replication, including nucleoside analogs and non-nucleoside analogs. This can cause termination or mutations.
• Remdesivir and Molnupiravir (and others) are examples of antivirals disrupting viral replication and polymerases leading to interruption in viral growth.