RNA Viruses Phase 2 - Jan 22, 2025 PDF

RNA Viruses Phase 2 - Jan 22, 2025 Rod Russell @RodRussell99 [email protected]  Learning Objectives Describe the symptoms, diagnosis and treatment of 10612 common RNA viruses  “Some” of the Viruses RNA Viruses DNA...

RNA Viruses Phase 2 - Jan 22, 2025 Rod Russell @RodRussell99 [email protected]  Learning Objectives Describe the symptoms, diagnosis and treatment of 10612 common RNA viruses  “Some” of the Viruses RNA Viruses DNA Viruses Emerging Viruses Respiratory Viruses Coronaviruses (OC43 229E) Adenovirus Avian influenza Adenovirus Enterovirus HHV-1/HSV-1 - Oral herpes Chikungunya virus Coronaviruses HAV HHV-2/HSV-2 - Genital herpes Dengue virus Entero/Rhino HCV HHV-3/VZV - chicken pox/shingles Ebola virus Human metapneumovirus HEV HHV-4/EBV Hantavirus Influenza A HIV HHV-5/CMV MERS Influenza B HTLV Parvovirus/fifth/slapped cheek Monkeypox Parainfluenza Human metapneumovirus Nipah virus RSV Influenza A SARS Influenza B SARS-CoV-2 Measles West Nile virus MERS Zika Mumps Norovirus Parainfluenza Polio Rhinoviruses Rotavirus RSV Rubella (German Measles) SARS SARS-CoV-2  Common Cold Symptoms Problem – clinically, they all present mostly the same way… – Sneezing – Stuffy nose So as a doctor, what do you – Runny nose do for these patients? – Sore throat - Rarely treated… (unhappy parents!) – Coughing - Inhalers are being prescribed more now – Post-nasal drip - Recommend monitoring symptom – Watery eyes severity – Fever (rare) - Breathing and temperature is key – Chills (rare) - Watch for rashes Source: CDC  Coronaviruses Background Coronaviruses are a family of enveloped positive-sense, single- stranded RNA viruses They have the largest genomes of all RNA viruses (~30kb) Infect humans, other mammals, some birds, livestock and pets Account for 10-15% of upper respiratory tract infections  Nidovirales Coronaviridae Nidoviruses are named for the nested subgenomic mRNAs generated during infection Enveloped viruses 100-150nm RNA genomes Gorbalenya, AE 2006 Virus Research 117:17 Slide provided by Dr. Susan Weiss, U Penn  Types of infections from coronaviruses Respiratory (human OC43, 229E; avian IBV) Brain (neurotropic MHV, demyelinating) Liver (MHV) GI (procine TGEV, avian IBV, MHV) From Matt Frieman Slide provided by Dr. Susan Weiss, U Penn  Human coronaviruses: timeline SARS-CoV-2 COVID-19 Common cold SARS-CoV MERS-CoV >7M deaths OC43 812 deaths HKU1; Pneumonia 866 deaths CFR 1% (Originally 2-3%) 229E CFR 10% NL63; Croup CFR 34% Influenza: 250,000 - 500,000/yr 1980 2002 2004/2005 2012 2019 Slide modified from Dr. Susan Weiss, U Penn  Human Metapneumovirus Can cause upper and lower respiratory disease – Affects all ages, but especially young children and older adults Symptoms include cough, fever, nasal congestion, can progress to bronchitis or pneumonia No specific treatment No vaccine Source: CDC  Respiratory syncytial virus (RSV) Usually causes mild, cold-like symptoms Most people recover in 1-2 weeks, but can be serious in infants and older adults due to inflammation in the airways Symptoms include runny nose, decreased appetite, coughing, sneezing, fever, wheezing “Almost all children will have had RSV by their second birthday.” Vaccine (mRESVIA; mRNA) available in Canada for adults over 60 No specific treatment Source: CDC  Influenza 75-95% of influenza infects are influenza A, the others 5-25% are B Infects nose, throat and lungs Can cause mild to severe illness Symptoms: fever (not everyone), cough, sore throat, runny/stuffy nose, muscle ache, headache, fatigue, sometimes vomiting and diarrhea Source: CDC  Influenza Flu patients become more susceptible to bacterial infections Cytokine storm syndrome results from an excessive inflammatory response that can aggravate respiratory failure and lead to systemic organ failure. Source: CDC  Influenza Orthomyxoviridae have segmented genomes, which allows for reassortment that generates strains with different HA/NA combinations. – This helps to maintain prevalence within the human population. – Also impacts vaccine design and effectiveness from year to year. Source: CDC Influenza  Rotavirus Double-stranded RNA virus of the Reoviridae family Symptoms include watery diarrhea, vomiting, fever, abdominal pain No virus-specific treatment 2-dose vaccine available Source: CDC  Norovirus Single-stranded RNA virus of the Caliciviridae family Symptoms include diarrhea, vomiting, nausea, stomach pain No virus-specific treatment No vaccine Source: CDC Measles Virus Symptoms – Begin 10-14 days post-exposure – 4 day fever – 3C’s (cough, coryza [head cold, fever, sneezing], conjunctivitis) – Typical rash Diagnosis – Fever for at least 3 days and 1 of the 3C’s – Confirmed by presence of MV antibodies or RNA from respiratory samples Measles Virus Complications – Diarrhea – Pneumonia – Bronchitis – Brain inflammation (rarely subacute sclerosing panencephalitis) and corneal ulceration Measles Virus Treatment – No virus-specific treatment – Symptoms are treated Ibuprofen Airway dilators if necessary Vitamin A to reduce risk of blindness  Human Immunodeficiency Virus Etiological agent responsible for AIDS AIDS was discovered in 1981 – How? HIV was discovered in 1984 Currently approximately 40 million people living with HIV infection - 50,000 in Canada No vaccine available – Why not? ~30 drugs currently in use – RT, Protease, Entry and Integrase Inhibitors Acute HIV Infection  Chronic HIV Infection Symptoms of chronic HIV/AIDS – Nausea – Vomiting – Persistent Diarrhea – Rapid weight loss – Rashes, sores, lesions – Persistent infections – Neurological – memory loss, confusion Course of Disease  Therapy Nucleoside Analogue Reverse Transcriptase Inhibitors (NRTI) Nonnucleoside Analogue Reverse Transcriptase Inhibitors (NNRTI) Protease Inhibitors (PI) Binding and Fusion Inhibitors Integrase Inhibitors Latency-Reversing Agents  Therapy Therapeutic response – Decreased viral load – Slow but steady increase in CD4+ T cells and return of immune function – Disappearance of symptoms Therapeutic Failure – Selection of resistant virus – Increased viral load – Decline in CD4+ T cells and loss of immune function  HIV in 2019 “Chronic manageable disease” Infected individuals with access to therapy are dying of the same things uninfected people are dying of… We’ve identified elite controllers – Maintained low viral load for years (10-20) without ever having ART (antiretroviral treatment)  Hepatitis C Virus 70-85% get chronic infection if untreated, some resolve 15-20% progress to hepatocellular carcinoma  Statistics For HCV Estimated 71 million infected worldwide 270,000 Canadians are infected with HCV – 0.8% of the population – 2-4 people/100,000 3,200 to 5,000 new cases per year Routes of Infection  Chronic HCV Fatigue Muscle aches Loss of apatite Weakness Weight loss Blood clotting problems Liver-specific complications – Cirrrhosis – Fibrosis – Hepatocellular carcinoma  HCV Treatment IFN + Ribavirin is the only treatment available – limited efficacy due to genotype specificity – poor tolerance Protease Inhibitors available since 2011 Polymerase Inhibitors now available NS5A Inhibitors now available Polymerase/5A cocktails now showing 99% cure rates in clinical trials and as high as 95% in real world treatment HCV Treatment 2020: The Year of the Virus https://www.nobelprize.org/prizes/medicine/2020/summary/  Why is Chronic HCV so important? Virus discovered in 1989 Meant the blood supply was tainted with HCV until 1990 when an HCV test was available What does this mean? Currently 250,000 Canadians have HCV and 40-70% of them don’t know it. When do we treat HCV? When should we treat HCV? HCV Elimination Dr. Cindy Whitten Dr. Jennifer Dr. Peter Daley Leonard