COVID-19_Bugando Lecture_v July 2022.pptx
- 1. COVID-19 Overview and Updates Dr.Hamisi Mkindi
- 2. Overview and Goals of Lecture • By the end of this lecture, you should be able to: • Describe the background on COVID-19 • Describe how SARS-CoV-2 is transmitted • Recognize common symptoms and manifestations of COVID-19 • Recognize risk factors that may lead to more severe manifestations • Recognize some important myths and facts on Omicron • Describe the major laboratory tests for diagnosing COVID-19 • Describe treatment options for patients hospitalized with Omicron • Review clinical cases
- 3. COVID-19 • Coronavirus disease 2019 (COVID-19)--highly transmissible disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) • First detected in Wuhan, China in December 2019 • Rapidly became a pandemic (over 576 million total cases and 6.3 million deaths--7/2022) • Symptoms/manifestations: • Fevers, chills, cough • Shortness of breathhypoxic respiratory failure and ARDS • Gastrointestinal (n/v/d) • Neurologic, including loss of smell/taste • Coagulation dysfunction • Cytokine storm syndrome • Multiorgan failure and death 1. https://www.who.int/emergencies/diseases/no vel-coronavirus-2019 2. https://coronavirus.jhu.edu/map.html
- 4. Transmission of SARS-CoV-2 1. Adapted from MITU Presentation by D. Watson-Jones, Feb 2022
- 5. What happens after transmission (1 of 2)? • Virus enters body, binds to ACE2 receptor on cells in upper respiratory tract (nose, mouth, trachea) • Virus enters cells and replicates • People sneeze/cough, causing transmission to continue • In some, the immune system stops the infection here (immunity kicks in ~ 2-4 days) • In others (e.g., not vaccinated), virus moves into lower lungs 1. Adapted from MITU Presentation by D. Watson-Jones, Feb 2022
- 6. What happens after transmission (2 of 2)? • Virus generally moves to lower airways—lots of ACE2 receptors • Inflames lungs + airways swell difficulty breathing, pneumonia • ARDS (fluid builds up in lungs and O2 gas exchange cannot occur) • supplemental oxygen and mechanical ventilation may be required 1. Adapted from MITU Presentation by D. Watson-Jones, Feb 2022
- 7. Common symptoms (review) • Depending on variant/subvariant ( now mostly Omicron), has an an average incubation period of about 2- 3 days (U.S. CDC)—symptoms may occur 2-14 days • Fevers, cough, SOB, chest pain/tightness, fatigue, anosmia/ageusia, rhinorrhea, sore throat, n/v/d, headaches, myalgias, etc. • Severe cases—manifest with pneumonia, ARDS, cytokine storm, coagulation disorder (e.g., DVTs/PEs), multiorgan failure (renal failure, MIS- A, myocarditis, etc.), death 1. Adapted from MITU Presentation by D. Watson-Jones, Feb 2022
- 8. Risk factors and case fatalities • Age • Cancer, particularly solid organ and hematopoietic stem cell transplants • Chronic kidney, liver, lung diseases • Cystic fibrosis • Dementia/neurological conditions, disabilities • Diabetes (type 1 or 2) • Cardiovascular disease, including hypertension, stroke, etc. • HIV • Obesity, smoking (former or current) • Sickle cell disease, tuberculosis • Other conditions, including pregnancy • Case fatality rates (no. deaths/no. of COVID- 19 cases) vary widely, affected by • Number of early or mild diagnoses, demographics and co-morbidities of population, health care capacity (e.g., more deaths if hospital is overwhelmed with cases, not enough ventilators, etc.), cases and deaths not being accurately reported • CFR: Yemen 18%, Norway 0.2%, Burundi 0.2%m Uganda 2.2%, Taiwan 4.4%, Iceland 0.1%, USA 1.2% 1. Adapted from MITU Presentation by D. Watson-Jones, Feb 2022 2. https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with- medical-conditions.html 3. https://coronavirus.jhu.edu/data/mortality
- 13. WHO Quick Myths and Facts • Myth: Omicron only causes mild disease. • Fact: Omicron appears to be less severe than the Delta variant, but it should not be seen as mild. • Myth: Previous infection provides immunity from Omicron. • Fact: Omicron can reinfect people that have previously had COVID-19. • Myth: Vaccines don’t work against Omicron. • Fact: Vaccines offer the best available protection against Omicron. • Myth: Boosters are ineffective against severe disease from Omicron. • Fact: Booster jabs are effective at increasing protection against severe disease from Omicron and all other COVID-19 variants. 1. https://www.euro.who.int/en/health-topics/health- emergencies/pages/news/news/2022/01/the-omicron-variant-sorting-fact-from- myth
- 14. Summary/other knowledge about Omicron • Generally more mild manifestations than Delta—yes • Vaccines and boosters are still effective—yes • Wearing masks and practicing social distancing + hand hygiene are still effective measures from preventing transmission—yes • Certain therapeutics/treatments (e.g., monoclonal antibodies) have been found to be reduced in efficacy against Omicron—yes • Overall, other treatment modalities, such as corticosteroids, are still effective and widely used for moderate-severe cases of Omicron—yes 1. https://www.euro.who.int/en/health-topics/health- emergencies/pages/news/news/2022/01/the-omicron-variant-sorting-fact-from-myth 2. https://www.cdc.gov/coronavirus/2019-ncov/variants/omicron- variant.html?s_cid=11734:omnicron%20variant:sem.ga:p:RG:GM:gen:PTN:FY22
- 15. Overview and Goals of Lecture • By the end of this lecture, you should be able to: Describe the background on COVID-19 Describe how SARS-CoV-2 is transmitted Recognize common symptoms and manifestations of COVID-19 Recognize risk factors that may lead to more severe manifestations Recognize some important myths and facts around Omicron • Describe the major laboratory tests for diagnosing COVID-19 • Describe treatment options for patients hospitalized with Omicron • Review clinical cases
- 16. Diagnostics • Nucleic acid amplification tests (NAATs), such as reverse transcription- polymerase chain reaction (RT-PCR) tests—detects RNA genes • Gold standard for testing—high sensitivity and specificity • Antigen tests—immunoassays that detect presence of viral antigen • Generally similar specificity, but less sensitive than NAATs • Less expensive, generally faster turn around time • Sensitivity generally increases in symptomatic people • Antibody (or serology) tests—used to detect previous infection with SARS-CoV-2 1. Ref: https://www.cdc.gov/coronavirus/2019- ncov/hcp/testing-overview.html
- 17. Therapeutics for patients hospitalized w/ Omicron (per NIH guidelines, 1 of 4)—updated Feb 24, 2022 • Dexamethasone 6 mg (or equivalent) daily for up to 10 days or until discharge • Remdesivir (RDV) 200 mg x 1, then 100 mg on days 2-5 or until discharge • Heparin-–therapeutic vs. prophylactic dose (remember coagulation dysfunction is one of the manifestations of COVID-19) • Supportive care (O2 supplementation, including invasive and non-invasive ventilation, dialysis if needed, etc.) • Others (immunomodulators/monoclonal antibodies)—one of these is sometimes used in conjunction with above to reduce effects of cytokine storm/inflammatory response • Tocilizumab—IL-6 monoclonal antibody (used for various rheumatologic conditions, cytokine release syndrome 2/2 CAR-T cell therapy) • Baricitinib—janus kinase inhibitor (inhibits JAK1 and JAK2; used in rheumatoid arthritis) • Sarulimab—IL-6 monoclonal antibody (used for rheumatoid arthritis; used when Tocilizumab is not available) • Tofacitinib—janus kinase inhibitor (used in rheumatoid arthritis; used when Baricitinib is not available) 1. https://www.covid19treatmentguidelines.nih.gov/management/clinical-management/hospitalized-adults--therapeutic- management/?utm_source=site&utm_medium=home&utm_campaign=highlights
- 18. NIH treatment guidelines, 2 of 4
- 19. NIH treatment guidelines, 3 of 4
- 20. NIH treatment guidelines, 4 of 4
- 21. Therapeutics not covered in this lecture • Outpatient mild COVID-19 disease not requiring oxygen supplementation or hospitalization • Preferred: • Ritonavir-boosted nirmatrelvir (Paxlovid)—careful with drug-drug interaction • Remdesivir—IV, logistical challenge in outpatient setting • Not preferred: Molnupiravir (induces mutagenesis of viral DNA/RNA) or Bebtelovimab (neutralizing human IgG1κ monoclonal antibody targeted against the spike (S) protein of SARS-CoV-2) • Notice: no corticosteroids and anticoagulation recs • Pre-exposure prophylaxis (do not have COVID-19, not have been exposed to someone with COVID-19, and who are immunocompromised enough to not mount an inadequate response to vaccines or who are not able to receive vaccination and booster because of a history of a severe allergic reaction) • Evusheld (tixagevimab plus cilgavimab) 1. https://www.covid19treatmentguidelines.nih.gov/management/clinical-management/nonhospitalized-adults--therapeutic- management/
- 22. Case 1 (1 of 3) • A 35-year man presents with 5 days of shortness of breath and fevers to 39.2C. He was a former smoker (15 pack-year) and had just quit smoking in the last 2 months. He has no other known medical history and has a BMI of 36. He is also not vaccinated against SARS-CoV-2. • On exam, he is febrile, tachypneic, hypoxic to 85% on room air, and unable to finish complete sentences. He receives supplemental O2 via nasal cannula and rapidly requires intubation and mechanical ventilation within 12 hours of admission. 1. Image from: https://radiopaedia.org/cases/covid-19-pneumonia-23?lang=us
- 23. Case 1 (2 of 3) • Q1. What is the most likely diagnosis? What is the gold standard test for proving this diagnosis? • COVID-19; SARS-CoV-2 RT-PCR test. • Q2. How would you classify his presentation? Mild, moderate, or severe? • Severe—very hypoxic and requires rapidly increasing O2 requirements to mechanical ventilation. • Q3. What are his risk factors for severe COVID-19 disease? • Former smoker • Obesity • Not vaccinated or boosted (given global trends, likely with Omicron variant)
- 24. Case 1 (3 of 3) • Q4. The RT-PCR test comes back positive for SARS-CoV-2. How would you manage this patient, according to the NIH guidelines and if drug supply was permitting? • Dexamethasone + remdesivir; would also consider adding tocilizumab or equivalent given his rapidly progressive course and O2 requirements; prophylactic heparin if no e/o VTE. • Q5. Name some potential complications that this patient may experience. • ARDS, renal failure, cytokine storm, multiorgan failure, death--to name several. • Q6. Should this patient get a COVID-19 vaccine if he recovers? • Yes—no contraindication and he should consider getting vaccinated after he recovers and is no longer symptomatic. Previous guidelines recommended waiting at least 90 days after receiving monoclonal antibodies, such as tocilizumab, but more recently the NIH has removed this statement and patients may be considered for vaccination sooner if they recover and have not been vaccinated. 1. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/media-resources/science- in-5/episode-50---do-i-still-need-the-vaccine-if-i-have-covid-19
- 25. Case 2 (1 of 3) • A 65-year man with diabetes and a history of LLE cellulitis, who is vaxxed and boosted with Moderna, presents to the ER with 2 days of rhinorrhea and anosmia. On exam, he is afebrile and hypoxic to 93% on room air, requiring 2L of O2 by nasal cannula. You also notice that he has some erythema and swelling over his LLE without any obvious crepitus. His chest x-ray shows mild bilateral infiltrates. The ER physician also orders a CT scan of his LLE which only shows cellulitis and no deeper soft tissue or bone involvement. • He is admitted to a general Medicine team. A SARS-CoV-2 RT-PCR test is positive and he is begun on dexamethasone, remdesivir, and heparin for DVT prophylaxis. He continues on 2L nasal cannula and overall feels fairly well. 1. Image from: https://www.lecturio.com/concepts/cellulitis/
- 26. Case 2 (2 of 3) • Q1. How would you classify his presentation? Mild, moderate, or severe? • Mild-to-moderate—he is requiring some supplemental oxygen and is being hospitalized with bilateral, albeit mild, infiltrates on his chest x-ray suggesting COVID-19 pneumonia. • Q2. He is already on dexamethasone, RDV, and prophylactic heparin. Would you give him any other therapies for COVID-19? • No—his O2 requirements are stable on 2L NC and he does not meet criteria for the addition of a monoclonal antibody or immunomodulatory like tocilizumab. • Q3. Is he potentially at risk for severe disease? What factors protect him from developing severe disease? • Yes—risk factors are older age and diabetes; he is likely protected against severe disease by his vaccination and booster doses of Moderna (mRNA vaccine).
- 27. Case 2 (3 of 3) • Q4. That left leg—would you start antibiotics? • Yes—it looks like he has cellulitis (and has a history of this). He should be started on antibiotics directed at common skin flora, such as Staphylococcus and Streptococcus species. A 5-7 day course of something like cephalexin (a cephalosporin like ceftriaxone) would likely suffice. Of note, patients with COVID-19 may present concurrently with other disease processes—so just because he has COVID-19 doesn’t mean he cannot have cellulitis or something else. In fact, some patients may present for a completely different diagnosis (e.g., heart failure exacerbation), have no typical symptoms of a viral illness, and are incidentally found to have COVID-19 upon screening. • Q5. By day 5, he is completely weaned off oxygen and feels back to normal. He leg also improves on abx with the erythema significantly receding from the area previously demarcated by the marker. He is ready for discharge to home. According to NIH guidelines, would you continue his dexamethasone and RDV? • No, he is back to normal and guidelines state that you would continue corticosteroids and RDV up until hospital discharge. You may consider finishing the total of 5-7 of antibiotics for his cellulitis (he is on day 5, so perhaps he may need 2 more days of therapy).
- 28. Suggested further reading • Learn about the RECOVERY trial (dexamethasone, tocilizumab), REMAP-CAP trial (tocilizumab, sarulimab)—these drugs have shown a mortality benefit in the treatment of COVID-19. • Learn about the original Remdesivir trial (ACTT-1) (https://www.nejm.org/doi/full/10.1056/nejmoa2007764#null, which shortened time to recovery but no mortality benefit in RDV arm vs. placebo, and more recent PINETREE study which showed that among non-hospitalized patients, a 3-day course of RDV resulted in an 87% lower risk of hospitalization or death when compared to placebo. • Learn about vaccine types and efficacy, including current recommended booster schedules. • Review management guidelines (I presented the NIH guidelines because of my familiarity with them) • Other drugs (e.g., hydroxychloroquine, ivermectin, etc.) have not been shown to be effective and are not recommended by major guidelines—some patients may still believe in these drugs and it is important to know and counsel such patients (may be very difficult).
- 29. Questions or Comments? • Thanks for your attention!