Airborne Viral Diseases: COVID-19

Human Diseases Caused by Viruses and Prions

• Viruses and prions can cause a variety of human diseases, and they can be transmitted through different routes

Airborne Viral Diseases

• Viruses can be transmitted through airborne routes.

COVID-19

• Belongs to the Coronaviridae family and has large (120-150 nm), enveloped viruses.
• Characterized by large spikes protruding from the envelope, creating a corona-like illusion.
• There are 7 coronavirus species that infect people, with 4 causing the common cold (types 229E, NL63, OC43, and HKU1).
• 3 can cause severe, sometimes lethal, respiratory syndromes.
• SARS-CoV caused a severe acute respiratory syndrome (SARS) epidemic in 2003, with 8,098 confirmed cases and 774 deaths.
• MERS-CoV, identified in 2012, causes Middle East respiratory syndrome (MERS), with 2,500 cases and 935 deaths (mortality rate around 34).
• MERS-CoV is transmitted from dromedary camels to humans and can rarely spread person-to-person.
• SARS-CoV-2 key proteins include the spike protein, nucleocapsid protein, and two proteases.
• The spike protein binds to the angiotensin-converting enzyme 2 (ACE2) receptor, making it a basis for many vaccines.
• Roughly 40% of infected individuals are asymptomatic.
• Symptomatic disease has 2 phases.
• The severely ill are mostly in phase 2, experiencing overproduction of pro-inflammatory cytokines like IL-1 and IL-6.
• mRNA-based vaccines introduce a short piece of engineered mRNA into recipient cells, which translates into spike proteins, prompting antibody production.
• There is no cure for COVID-19, making vaccination key.

Measles (Rubeola)

• A highly contagious disease endemic worldwide, preventable by vaccination.
• Incubation period is usually 10 to 14 days, with visible symptoms starting around day 10.
• Symptoms include nasal discharge, cough, fever, headache, and conjunctivitis, intensifying prior to rash onset.
• Caused by the measles virus (MeV or measles morbillivirus), a negative-strand virus from the Paramyxoviridae family.
• Treatment Vaccination with attenuated measles vaccine, often administered in combination with mumps and rubella (MMR vaccine).

Rubella (German Measles)

• First described in Germany in the 1800s and is contagious but mild.
• It is caused by rubella virus (Rubivirus rubellae), an enveloped, positive-strand RNA virus in the Matonavirida family.
• Characterized by a rash of small red spots usually lasting no more than 3 days.
• Infection during the first trimester of pregnancy can be disastrous, leading to fetal death, premature delivery, or congenital rubella syndrome.

Arthropod-Borne Viral Diseases

• Use arthropods as vectors
• Arthropod-borne viruses (arboviruses) are transmitted by bloodsucking arthropods (ticks, mosquitoes, flies) from one vertebrate host to another.
• Multiply in arthropod hosts without causing disease.
• Approximately 150 arboviruses cause illness in humans.
• No antiviral therapy is effective.

Chikungunya Virus

• It is a positive-strand, enveloped RNA virus belonging to the Togaviridae family.
• Aedes aegypti and Aedes albopictus mosquitoes transmit it to humans.
• Symptoms include fever and severe joint pain, headache, muscle pain, joint swelling, and rash.
• Symptoms often resolve in 7 to 10 days.
• No specific medicine to treat, or vaccine to prevent this viral disease.
• Travelers to endemic areas should follow guidelines using insect repellent, wearing long sleeves and pants, and using mosquito netting.

Zika Virus

• A member of the Flaviviridae family, featuring an enveloped capsid and a positive-strand RNA genome.
• Transmitted by various Aedes mosquitoes, including A. africanus, A. aegypti, and A. albopictus.
• Can also be transmitted through bodily fluids, like breast milk and semen.
• Symptoms include mild fever, rash, joint pain, and conjunctivitis, which resolve in 3 to 7 days.
• There is no treatment, only prevention.

Direct Contact Viral Diseases

• Direct contact with an infected person can cause disease through touching, kissing, sexual contact, or contact with body fluids, secretions, or open wounds.

HIV: Direct Contact

• HIV is a positive strand, enveloped RNA virus within the Retrovirida family.
• Approximately one million people die each year from HIV/AIDS.
• An estimated 1.2 million lives are saved annually due to antiretroviral therapy.
• Transmitted by infected blood, semen, vaginal secretions, or breast milk coming into contact with mucous membranes.
• The course of disease can vary greatly once a person is infected.

HIV: Asymptomatic Stage

• In untreated individuals, the asymptomatic stage of HIV infection can last from 6 months to 10 years (or longer in some individuals).
• Levels of detectable HIV in the blood decrease due to virus replication in lymphoid tissues.
• The virus may compromise certain immune functions, such as memory cell responses to common antigens, even before any CD4+ T cell decline.

HIV: Acute Infection Stage

• Occurs 2 to 8 weeks after HIV infection.
• About 70% of individuals experience a brief illness, with symptoms like fever, malaise, headache, weight loss, and lymph node enlargement.
• The virus multiplies rapidly and disseminates to lymphoid tissues.
• An acquired immune response is generated to reduce virus multiplication.
• Blood levels of HIV increase rapidly to 105 to 106 copies of viral RNA per milliliter of plasma.

HIV: Chronic Symptomatic Stage

• Chronic symptomatic stage lasts for months to years.
• Virus multiplication continues, and the number of CD4+ T cells begins to decrease significantly.
• Individuals develop a variety of symptoms, including fever, weight loss, malaise, fatigue, anorexia, abdominal pain, diarrhea, headaches, and lymphadenopathy.
• As CD4+ T-cell numbers decline, patients develop opportunistic infections.

Cold Sores

• Characterized by fluid-filled lesions typically found on the lips or inside the nostrils.
• Caused by pain, itching, or a burning sensation because they reside on or near nerve endings
• Caused by Human alphaherpesvirus 1, commonly known as herpes simplex virus type 1 (HSV-1).
• HSV-1 is usually associated with cold sores or fever blisters. HSV-2 is associated with genital herpes.
• HSV infections may occur in the eyes causing herpetic keratitis
• Active and latent phases occur within an infected host

Cold Sores: Action

• During the active phase, the virus multiplies explosively, and HSV inhibits the host cell's metabolism and degrades host DNA, causing apoptosis and releasing viral progeny.
• May be symptom-free or present as painful blisters containing fluid and infectious virions.
• Latent state - the virus persists for the lifetime of the infected host.
• A virulence factor initiates the latent survival of HSV-1 (trigeminal nerve ganglion).
• Reactivation can be triggered by stressful stimuli like excessive sunlight, fever, trauma, emotional stress, and hormonal changes.
• Once reactivated, the virus travels from the nerve ganglion down a peripheral nerve to epithelial cells, producing another active phase.
• Treatment includes drugs like acyclovir, valacyclovir, and famciclovir, and idoxuridine and trifluridine for herpetic keratitis.

Viral Hepatitides

• Hepatitis is a general term for infection and inflammation of liver cells.
• 11 viruses are recognized as causing hepatitis.
• There are 2 herpesviruses that cause hepatitis, cytomegalovirus (CMV) and Epstein-Barr virus (EBV).
• EBV and CMV cause mononucleosis syndromes, leading to mild, self-resolving forms of hepatitis without permanent liver damage.
• 9 human hepatotropic viruses specifically target liver cells (hepatocytes).
• Only five types of viral hepatitis are well characterized, A-E.
• Hepatitis G and TTV (transfusion-transmitted virus) are more recently discovered.

Hepatitis B

• Caused by hepatitis B virus (HBV), an enveloped virus with a partially double-stranded circular DNA genome.
• HBV uses a reverse transcriptase enzyme to replicate its genome.
• Serum contains 3 distinct antigenic particles, with only one being the mature virion, known as the Dane particle.
• The two other antigenic particles (smaller spherical and larger filamentous) act as decoys for host antibodies.
• The inner nucleocapsid has a core antigen (HBcAg).
• HBV envelope is coated with hepatitis B surface antigen (HBsAg), an indicator of active hepatitis B infection.
• HBsAg is used in large-scale screening of blood for HBV and is the basis for the HBV vaccine.
• Clinical signs of hepatitis B vary, with about 70% of cases being asymptomatic.
• For others, symptoms include fever, loss of appetite, abdominal discomfort, nausea, fatigue, liver tissue degeneration, and hepatocellular carcinoma (liver cancer).

Hepatitis C

• Caused by hepatitis C virus (HCV), which has a 50-nm enveloped virion that contains a single strand of linear RNA.
• Transmitted through contaminated needles, in utero, or organ transplantation and is rarely sexually transmitted.
• Worldwide, hepatitis C is an epidemic, with about 70 million people chronically infected.
• Can cause hepatocellular carcinoma.
• The leading reason for liver transplantation in the United States.
• Six major genotypes, with genotype 1 being the most common.
• Treatment for genotype 1 is with sofosbuvir and ledipasvir (an HCV replication inhibitor).
• A 12-week treatment results in complete cure of the virus.

Hepatitis D

• Caused by the Hepatitis delta virus (HDV).
• There are 8 known genotypes of HDV, with different geographical distributions
• All genotypes can cause acute as well as chronic liver disease.
• HDV is a satellite virus that is dependent on hepatitis B virus to provide the surface protein (HBsAg) for its own replication.
• HDV only replicates in liver cells coinfected with actively replicating HBV.
• HDV is spread to persons who are already infected with HBV (superinfection) or when HBV and the satellite are transmitted together (coinfection).
• Treatment mirrors that of HBV-infected patients.

Food And Water Borne Viral Diseases

• Certain viruses are transmitted via food and water

Hepatitis A (Infectious Hepatitis)

• Usually transmitted by fecal contamination of food or drink, or shellfish that lived in contaminated water.
• Hepatitis A virus (HAV) is an icosahedral, linear, positive-strand RNA virus without an envelope.
• Once in the digestive system, the virus multiplies within the intestinal epithelium, resulting in mild intestinal symptoms.
• Viruses may be found in the blood (viremia) and spread to the liver and reproduces in the liver, enters the bile, and is released into the small intestine which explains why feces are so infectious.
• After about a 4-week incubation period, symptoms develop that include anorexia, general malaise, nausea, diarrhea, fever, chills, and jaundice.
• Most cases resolve in 4 to 6 weeks and yield a strong immunity, and the mortality rate is low.
• Control is achieved through simple hygienic measures, sanitary disposal of excreta, and the HAV vaccine.

Hepatitis E

• Is caused by the Hepatitis E Virus (HEV).
• Genotypes 1 and 2 are implicated in epidemics in countries with limited clean water and sanitation, while genotypes 3 and 4 are found in Europe and in the United States.
• Has a single, positive-strand nonenveloped, RNA viral genome.
• HEV genotypes 1 and 2 are usually associated with feces-contaminated drinking water, whereas genotypes 3 and 4 are transmitted by contaminated food, particularly undercooked pork.
• HEV enters the blood from the gastrointestinal tract, replicates in the liver, is released from hepatocytes into the bile, and is subsequently excreted in the feces.
• Signs and symptoms of HEV include abdominal pain, anorexia, dark urine, fever, enlarged liver, jaundice, malaise, nausea, and vomiting.
• Low fatality rates (1 to 3%), except for pregnant women (15 to 25%), who risk death from fulminant hepatic failure.
• Improving the level of health and sanitation in affected areas prevent HEV infections.

Zoonotic Viral Diseases

• Arise from human-animal interactions

Ebola Virus Disease (EVD)

• Caused by Ebola viruses.
• First recognized near the Ebola River in the Democratic Republic of the Congo in Africa.
• Members of the genus Ebolavirus in the family Filoviridae are a group of filamentous, negative-strand RNA viruses.
• Six Ebola species are known
• Ebola viruses that infect humans are transmitted by contact with body fluids.
• Reston ebolavirus causes diseases only in nonhuman primates and pigs -- it is spread by aerosol transmission.

Viral Hemorrhagic Fever

• Term used to describe the severe, multisystem syndrome seen in Ebola epidemics.
• The host vascular system is damaged leading to vascular leakage of fluids into body tissues.
• Diminished ability to clot (coagulopathy) occurs, leading to bleeding
• Characterized by abrupt fever, headache, joint and muscle aches, sore throat, and weakness, followed by diarrhea, vomiting, and stomach pain.
• Signs of infection include fever, rash, red eyes, bleeding, and hiccups-symptoms alerting of internal hemorrhage

Viral Hemorrhagic Fever: Treatment

• There is no standard treatment for Ebola infection.
• Patients receive supportive therapy consisting of:
  • Balancing patients' fluids and electrolytes
  • Maintaining their oxygen status and blood pressure
  • Treating any complicating infections
• A highly effective vaccine is now used to control outbreaks.

Marburg Disease

• Caused by a Marburgvirus with a genetically unique RNA.
• The Marburgvirus (MARV) is in the Filoviridae family, and it similarly causes a hemorrhagic fever.
• Rare, severe type of hemorrhagic fever that affects both humans and nonhuman primates.
• First recognized in 1967, when hemorrhagic fever outbreaks occurred simultaneously in laboratories.
• The first people infected had been exposed to African green monkeys or their tissues.
• Indigenous to Africa, and the reservoir host is the African fruit bat, Rousettus aegyptiacus.
• Average incubation period for Marburg hemorrhagic fever is 5 to 10 days.
• Symptoms abruptly onset with fever, chills, headache, myalgia, and a maculopapular rash.
• Nausea, vomiting, chest pain, sore throat, abdominal pain, and diarrhea also occur
• Severe symptoms include jaundice, delirium, liver failure, pancreatitis, severe weight loss, shock, and multiorgan dysfunction.
• Treatment is limited to supportive hospital therapy.

Prion Transmitted Diseases

• Caused by abnormally folded proteins

Prion Proteins Transmit Disease

• Prions consist of abnormally folded proteins (PrPSc) that induce normal forms of the protein (PrPC) to fold abnormally.
• Prion diseases, also called transmissible spongiform encephalopathies (TSEs), are fatal neurodegenerative disorders.
• Share clinical and cell biological features with Alzheimer's disease (spongiform braindegeneration).
• Include scrapie, kuru, Creutzfeldt-Jakob disease (CJD), variant Creutzfeldt-Jakob disease (vCJD), Gerstmann-Sträussler-Scheinker disease (GSD), and fatal familial insomnia (FFI).

Prion Diseases: Symptoms

• Scrapie primarily occurs in sheep.
• Kuru was first studied in humans and discovered in the Fore tribe of New Guinea.
• Transmitted by ritual cannibalism where brains and spinal cords were eaten.
• The primary symptom is dementia, accompanied by cerebral ataxia and myoclonus.
• FFI is characterized by abnormal functioning of the autonomic nervous system and sleep disturbances.
• These symptoms appear insidiously in middle to late adult life and last months (CJD, FFI, and kuru) to years (GSD).

CJD (Creutzfeldt-Jakob Disease) Subcategories

• Prion diseases are organized into three subcategories: familial (inherited) types, sporadic types, and acquired types.
• Familial CJD is the result of an inherited mutation within the prion-encoding gene; rare, progresses rapidly, and is always fatal within 1 year
• Sporadic is a spontaneous mutation in the PrPC protein-coding gene is rapidly progressive, moves from depression to physical disability, and 70% of patients die within 6 months
• Acquired CJD occurs through Variant CJD (vCJD) acquired by consuming meat products from a cow with bovine spongiform encephalopathy
• Iatrogenic CJD is acquired from a physician or surgeon, a medical treatment, or diagnostic procedures and is most likely caused by contaminated growth hormones or tissue/organ transplants