COVID Towne

COVID-19 AND THE IMMUNE SYSTEM

Class Overview

  • Course: IHL Course, Class of 2029

  • Instructor: Dr. Francina Towne

Purpose of the Lecture

  • Learn the basics of Coronaviruses, COVID-19, and the immune system.

  • Serve as an introductory framework for more detailed discussions on viral infections to follow.

  • Disclaimer:

    • There are still many unknowns regarding COVID-19.

    • This lecture provides a basic overview.

    • Information is current as of the lecture date but may change in the future.

Objectives

  • Describe: Basic similarities and differences between SARS-CoV-1, SARS-CoV-2, and MERS.

  • Discuss: The COVID-19 infection cycle in a cell.

  • Explore: Epidemiology of COVID-19, factors contributing to viral spread, $R_0$ (basic reproduction number), and differences between airborne and droplet transmission.

  • Diagram: Phases and important immune components involved in the immune response to a virus.

  • Outline and Describe: Immune response to COVID-19 in mild, moderate, and severe cases.

Outline

  • Coronavirus Basics

  • COVID-19 Epidemiology

  • COVID-19 and the Immune Response

  • Recent Research on COVID-19

Coronaviridae

  • Definition: Family of viruses known as Coronaviridae.

    • Named for the "Crown" appearance of spike glycoproteins.

    • Characteristics:

    • Enveloped

    • Single-stranded, positive-sense RNA genome

    • Replicates in the cytoplasm

  • Prevalence: Second most prevalent cause of the common cold, with strains such as HCoV-229E and HCoV-OC43 identified.

  • Zoonotic Nature: Infectious diseases transmitted from non-human animals to humans, including SARS-CoV-1, SARS-CoV-2, and MERS-CoV.

Middle East Respiratory Syndrome (MERS)

  • Initial Outbreak: Began in 2012.

  • Reported Cases: Just under 2000 cases as of April 2017.

  • Fatality Rate: Approximately 40%.

  • Transmission: Camels are suspected carriers, but the exact transmission method is unclear.

Severe Acute Respiratory Syndrome 1 (SARS-1)

  • Pathogen: SARS-CoV-1.

  • Initial Outbreak: Began in November 2002.

  • Transmission Source: Traced through civets to cave-dwelling bats.

  • Case Statistics: 8000 cases with 784 deaths, leading to a fatality rate of 9.5%.

  • At-Risk Populations: Mortality rates in those >60 years old approaching 50%.

  • Pathophysiology:

    • Virus binds to ACE-2 receptor for cell entry.

    • Typical incubation period is 2-7 days (maximum up to 10 days).

    • Causes viral pneumonia with resultant damage to alveoli.

    • Virus can also be found in the intestine, liver, and kidney.

    • Acute phase lymphopenia results in the loss of CD4+ and CD8+ T cells.

Severe Acute Respiratory Syndrome 2 (SARS-2)

  • Pathogen: SARS-CoV-2, responsible for COVID-19.

  • Genetic Similarity: Close genetic relationship with SARS-CoV-1.

  • Characteristics: Positive-sense single-stranded RNA virus.

  • Animal Reservoir: Potential intermediate reservoir species such as pangolins derived from bats.

  • Cell Entry: Binds to the ACE-2 receptor for entry into cells.

  • Incubation Period: Typically 2-10 days (14 maximum).

  • Pathophysiology:

    • Causes viral pneumonia with cell damage observed in alveoli.

    • Virus presence noted in the intestine, liver, and kidney.

    • Interaction with the upper respiratory tract is mitigated by the virus's temperature preference compared to common cold viruses.

SARS-CoV-2 Infection Cycle

  • Virus Structure:

    • Enveloped positive-sense single-stranded RNA virus.

    • Genome approximately 30 kb.

    • Key Components:

    • Spike Glycoprotein (S) (S1 & S2)

    • Nucleocapsid (N) - RNA and protein structure

    • Envelope Protein (E)

    • Membrane Protein (M)

  • Infection Process:

    1. Viral attachment to the host cell via the spike protein binding to the ACE2 receptor.

    2. Following proteolytic cleavage by TMPRSS2, membrane fusion occurs, allowing RNA entry.

    3. The virus hijacks host cellular machinery for RNA translation and replication.

    4. Assembled particles are exocytosed from the infected cell.

  • Immune Response: Following infection, SARS-CoV-2 leads to the activation of antigen-presenting cells (APCs) which induce a range of cytokines (e.g., IL-1, IL-6, CXCL-10, TNF-α).

    • Unbalanced pro-inflammatory responses may occur in severe cases, leading to complications.

Overview of COVID-19 Epidemiology

  • Timeline of Cases:

    • Sept 2020: ~200,000 US deaths

    • Sept 2021: ~667,000 US deaths

    • Sept 2022: ~1 million US deaths

    • Sept 2023: ~1.14 million US deaths

    • Sept 2024: ~1.2 million US deaths

  • Impact: Data indicates significant reductions in severe illness, hospitalizations, and death rates.

Viral Transmission

Factors Contributing to Viral Spread

  • Incubation Period: Affects how contagious the virus is.

  • Deadliness: Longer incubation and varying fatality rates impact transmissibility.

    • Basic Reproduction Number ($R_0$): Measures how contagious a virus is.

    • COVID-19 $R_0$ values typically around 2-2.5 (up to 9 for variants like Omicron).

Droplet vs. Airborne Transmission

  • Droplet Transmission: Involves large respiratory droplets that generally travel about 3 feet before settling on surfaces.

  • Airborne Transmission: Involves smaller particles that can remain suspended in air, allowing transmission beyond 6 feet during activities like speaking, singing, or breathing.

Immune Response to COVID-19

Overview of Immune System Components

  • Innate Immunity:

    • Surface Defenses: Physical barriers (skin, mucous) and chemical barriers (enzymes, antimicrobial peptides).

    • Subsurface Cells: Involves macrophages, neutrophils, and natural killer cells (NK cells).

    • Proteins: Complement proteins and various cytokines.

  • Adaptive Immunity:

    • Humoral Immunity: Mediated by B lymphocytes and antibodies that neutralize pathogens and recruit other immune components.

    • Cellular Immunity: Involves T lymphocytes with killer T cells destroying infected cells and helper T cells activating other immune responses.

Progression of the Immune Response

  1. Following SARS-CoV-2 infection, the immune system reacts through various cellular mechanisms.

  2. Type II alveolar cells initiate responses releasing inflammatory signals.

  3. Macrophages and neutrophils generate reactive oxygen species (ROS).

  4. Cytokines attract additional immune cells to the site of infection.

  5. Prolonged inflammation could lead to acute respiratory distress syndrome (ARDS) or systemic inflammatory response syndrome (SIRS).

Analyzing the Immune Response

  • Critical examination of immune system detection points for SARS-CoV-2 (i.e., TLR, NLR, antibodies, T-cells).

Long COVID

  • Definition: A chronic post-infection condition that affects multiple organ systems and lasts for months or years.

  • Symptoms: Include fatigue, brain fog, dizziness, and more.

  • Prevalence: Affects up to 6% of individuals post-infection.

  • Risk Factors: Unvaccinated individuals and those infected before the Omicron variant are more susceptible. Reinfections are associated with higher incidences of long COVID.

COVID Testing and Treatment

Testing Methods

  • RT-PCR Testing:

    • Highly sensitive nucleic acid test detecting viral RNA.

    • Processing time typically between 1-3 days.

  • Antigen Testing:

    • Utilizes lateral flow assays to detect viral proteins.

    • Functions best at high viral loads and offers rapid results.

COVID-19 Treatment

  • Paxlovid:

    • Combination of Nirmatrelvir (Mpro inhibitor) and Ritonavir (which increases plasma concentrations).

  • IL-6 Treatments: High levels of IL-6 observed in severe cases; anti-IL6 monoclonal treatments like Tocilizumab and sarilumab show variable effectiveness but were found critical for certain patients.