COVID-19




Pathopthysiology


Imbalanced host response to SARS-CoV-2 drives development of COVID-19 Cell ****


Clinical Features 

Asymptomatic COVID Infection

https://www.cebm.net/covid-19/covid-19-what-proportion-are-asymptomatic/


Alterations in Smell or Taste in Mildly Symptomatic Outpatients With SARS-CoV-2 Infection


Classification of the cutaneous manifestations of COVID‐19: a rapid prospective nationwide consensus study in Spain with 375 cases BJD ****



Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms


Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan


Testings


Incorporating Test Characteristics Into SARS-CoV-2 Testing Policy—Sense and Sensitivity


Diagnostic Testing for the Novel Coronavirus


Positive RT-PCR Test Results in Patients Recovered From COVID-19


Rates of Co-infection Between SARS-CoV-2 and Other Respiratory Pathogens



Prognostic Risk Prediction Model 




Prediction models for diagnosis and prognosis of covid-19 infection


https://www.cebm.net/covid-19/what-prognostic-clinical-risk-prediction-scores-for-covid-19-are-currently-available-for-use-in-the-community-setting/


Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020 (BMJ)  **


Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19 NEJM **





Estimating clinical severity of COVID-19 

https://www.cebm.net/covid-19/global-covid-19-case-fatality-rates/


Treatment 



Non-pharmaceutical interventions (NPIs) to reduce COVID-19 mortality and healthcare demand 

https://spiral.imperial.ac.uk/bitstream/10044/1/77482/14/2020-03-16-COVID19-Report-9.pdf


Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial (Lancet) XXXX


Mental Health and Additional Implication 

Mental Health Needs of Health Care Workers Providing Frontline COVID-19 Care


The Mental Health Consequences of COVID-19 and Physical Distancing: The Need for Prevention and Early Intervention


Coronavirus Disease 2019 (COVID-19) and Mental Health for Children and Adolescents



 

EBM April 3-April 17



Week 1


  • Group 1. 58 yo AAM presented after headache and subjective fever of 1 month duration. Hx of HSV meningitis (previously treated). He had no sick contacts. Given subjective Fever – COVID-19 tests was done, and was positive. With ID input, we decided it was an asymptomatic COVID-19 infection, and may have had subclinical HSV meningitis that we decided to treat empirically without pursuing LP.  He works in two NH during night shift (1200 +300 individuals remain in those two facility). Given that patient was likely asymptomatic from COVID-19infection, is it necessary to take an aggressive measures to prevent the infection of NH residents and employees? Above case is the clinical scenario for NEJM PAPER 

  • Group 2:  58 yo AAM presented after headache and subjective fever of 1 month duration. Hx of HSV meningitis (previously treated). He had no sick contacts. Given subjective Fever – COVID-19 tests was done, andwas positive. With ID input decided, it was an asymptomatic COVID-19 infection, and may have had subclinical HSV meningitis that we decided to treat empirically without pursuing LP for concern of transimission of infection to healtcare provider.. As a front line healthcare provider there is a risk of transmission of infection, but what are those risks that increases the of transmission of Infection to care providers? Above case is the clinical scenario for paper on risk factors for infection of health care workers. 

  • Group 3. 88 yo CF with hx of HTN, DM, CKD-2 presented  for fever and SOB. T Max of 103.2, HR 112, RR 28, BP 120/80. Requiring 2 L oxygen. CXR shows diffuse infiltrate.  Abx for PNA was started. Results for COVID-19came positive. Doctor, I am scared, what will happen to me? Will I survive this? This is a case scenario for Lancet Article

  • Group 4. 88 yo CF with hx of HTN, DM, CKD-2 presented  from NH for fever and SOB. T Max of 103.2, HR 112, RR 28, BP 114/70. Requiring 2 L oxygen. CXR shows diffuse infiltrate.  COVID-19 tests came positive/ WBC 3.9, CRP 12, Ferritin 508, D-dimer 5.  Over next few hours patient oxygen requirement increased and patient was transferred to ICU for father care .Doctor, Will I survive this? Can you give any medication to prevent the worse outcome  (intubation or prevent death) from COVID-19 infection? Above is the case for Journal for antimicrobial agent paper on Hydrozychloroquin and Azithromycin

Week 2  
  • Group 1  (Initial Clinical Scenario) Macrolide and Azithromycin 68 yo F with PMH of DM2, Obesity, OSA, HTN presented to ED for SOB on 3/25. 2 weeks prior (on 3/10) she was admitted ED for symptoms of non-productive cough associated with SOB, wheezing,  chills, headache, body ache of 2 weeks. Flu test was negative. She was not tested for COVID-19 infection then. No sick contacts then but 3 weeks back had travelled to Michigan. Was diagnosed with possible viral infection and discharged next day. Since discharge her symptoms continued to get worse and she presented now with worsening SOB and weakness. On arrival, she was found to be hypoxemic and is required 2 L oxygen. CRP, 5.9, WBC 3.9, Pat 139. D-dimer elevated. CXR shows diffuse infiltrate. Based on her moderate to severe clinical prevention she was started on Hydroxychloroquine, Azithromycin, and Doxycyline. She completed the 5 days treatment. Clinical Assessment: What is the evidence for the use of Azithromycin or Doxy or combination on treatment of COVID-19 pneumonia?
  • Group 1/ Revised Clinical Scenario as there was no article of macrolide and doxy: 80 yo F with hx of HTN, CAD, DM-2, A fib presents with fever, cough, SOB of 1 week and hemoptysis of 1 day duration. On presentation her T-Max is 100.4, HR 96, RR22, BP 126/72. INR 3.1She is requiring 3 L of oxygen. CXR shows RUL consolidation with evidence of patchy infiltrate elsewhere. CRP 5.2, Ferritin 500, D-dimer 4.3, COVID-19 tests came positive. Clinical assessment for your team. Are there any antiviral (Lopinative/Ritonavir) treatment to help treat COVID-19 Pneumonia.
  • https://www.nejm.org/doi/full/10.1056/NEJMoa2001282?query=featured_coronavirus


  • Week 2/ Diagnostic Tests:  55 yo AAM with Cough, Malaise, Chills of 1-week duration was brought by security personal after Motor Vehicle Chase in early March. COVID-19 test was negative. Flu test was negative. Patient was  discharged back with security personal next day once COVID-19 infection was ruled out with a diagnosis of some viral infection? Clinical Assessment: If the COVID-19 test came negative, how accurate is it to rule out the disease.  
  • Diagnosis of the Coronavirus disease (COVID-19): rRT-PCR or CT? 

  • Group 3 / Surgical Mask:  68 yo F with PMH of DM2, Obesity, OSA, HTN presented to ED for SOB on 3/25. 2 weeks prior (on 3/10) she was admitted ED for symptoms of non-productive cough associated with SOB, wheezing,  chills, headache, body ache of 2 weeks. Flu test was negative. She was not tested for COVID-19 infection then. No sick contacts then but 3 weeks back had travelled to Michigan. Was diagnosed with possible viral infection and discharged next day. Since discharge her symptoms continued to get worse and she presented now with worsening SOB and weakness. On arrival, she was found to be hypoxemic and is required 2 L oxygen. CRP, 5.9, WBC 3.9, Pat 139. D-dimer elevated. CXR shows diffuse infiltrate. Based on her moderate to severe clinical prevention she was started on Hydroxychloroquine, Azithromycin, and Doxycycline. She completed the 5 days treatment. Patient now feels better. Is off of oxygen. Is ambulating in room without need of oxygen. Patient is ready for the discharge and at the time of discharge patient daughter says she is here in town to help her mom for few days and will stay with her until she feels better. She asks if she should wear the mask or is it adequate for her mom to wear masks?Clinical Assessment: Does use of surgical masks by a general public (non-infected) help prevent the transmission of infection?
  • https://www.nature.com/articles/s41591-020-0843-2

  • Group 4 / Duration of isolation68 yo F with PMH of DM2, Obesity, OSA, HTN presented to ED for SOB on 3/25. 2 weeks prior (on 3/10) she was admitted ED for symptoms of non-productive cough associated with SOB, wheezing,  chills, headache, body ache of 2 weeks. Flu test was negative. She was not tested for COVID-19 infection then. No sick contacts then but 3 weeks back had travelled to Michigan. Was diagnosed with possible viral infection and discharged next day. Since discharge her symptoms continued to get worse and she presented now with worsening SOB and weakness. On arrival, she was found to be hypoxemic and is required 2 L oxygen. COVID-19 test came positive. CRP, 5.9, WBC 3.9, Pat 139. D-dimer elevated. CXR shows diffuse infiltrate. Based on her moderate to severe clinical prevention she was started on Hydroxychloroquine, Azithromycin, and Doxycyline. She completed the 5 days treatment.Patient now feels better. Is ambulating in room without need of oxygen. Patient is ready for the discharge and at the time of discharge patient daughter says she is here in town to help her mom for few days and will stay with her until she feels better. She also asks, is her mom clear of any infection now, or when will she be clear of infection? Current CDC recommendations for home self-isolation are: 7 days from symptoms onset AND  3 days since last fever without use of anti-pyretic AND other symptoms have improved. Clinical Assessment: How long should we ask the patient with COVID-19 infection to remain in self-isolation for? 
  • Second case for Group 4 / Duration of Isolation
  • 70 yo F with hx of DM2, HTN, ESRD – on HD cam from HD center after she was noted to have Temp of 101.4 F. RR 24, HR 114, BP 110/80. CRP, D-dimer, Ferritin, LDH all elevated. Pertinent Lab included K of 6.2. Patient was admitted to ICU for urgent HD, and transferred to floor. By Day 5, she is not having any fever, clinically feels ready for discharge, did not require oxygen during the hospital stay, HD center at community where they do HD for COVID-19 patient is identified. She lives in a Group Home and Group Home manager is fearful of her coming back as it will expose other vulnerable patients in their Group Home to the SARS-CoV-2 as they have limited staffing, lack of PPE, and limited space where patient isolation is difficult to maintain? Clinical Assessment: When will it be safe for her to return to group home without putting other residents at group home at risk of infection?
  • https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30195-X/fulltext?fbclid=IwAR0z2mTiZ4D4itGAzVM9WhiNgSYuYlH48MDlYIWXqXqGLn1XdbIwcsk2wM4


 

Week 3

 

  • ACEI/ARB use 
  • 72 yo AAM with hx of HTN (Amlodipine 5 mg, Lisinopril 20 mg, Triamterene/HCTX 37.5 /25 mg ), DM-2, prior stroke on G-tube for feeding comes from NF for fever. TMax 101.4, RR16, HR 123, BP 105/65. COVID-19 test is done and is positive.  O2 sats 93% in 1 L oxygen. Cr 1.7, K 5.8, D-dimer 2.3, LDH 345, Lactic Acid 2.8, Ferritin 318. All BP medications were held, and fluid resuscitation done and Lactic acidosis has since resolved. Repeat K 4.4, Cr 1.3 (baseline 1.1). Repeat BP 120/80. How should we manage ACEI in the setting of COVID-19 Infection?

  • Prone Positioning
  • 72 yo AAM with hx of HTN (Amlodipine 5 mg, Lisinopril 20 mg, Triamterene/HCTX 37.5 /25 mg ), DM-2, prior stroke on G-tube for feeding comes from NF for fever. TMax 101.4, RR16, HR 123, BP 105/65. COVID-19 test is done and is positive.  O2 sats 93% in 1 L oxygen. Cr 1.7, K 5.8, D-dimer 2.3, LDH 345, Lactic Acid 2.8, Ferritin 318. All BP medications were held, and fluid resuscitation done and Lactic acidosis has since resolved. Repeat K 4.4, Cr 1.3 (baseline 1.1). Repeat BP 120/80. What is the evidence of asking patient to be in Prone position to prevent respiratory failure and the need for mechanical ventilation?  

  • Plasma exchange 
  • 70 yr o AAM with hx of HTN, CAD, DM-2 presents with Fever, Cough and SOB. Tmax 103, RR 23. BP 110/60, Pulse 110. O2 saturation 1 L in room air. CRP 12, D-dimer 3.4, Ferritin 718, Xray shows diffuse patchy opacity. Patient is admitted to floor but over the night patient oxygen need accelerates and is transferred to ICU. Patient is intubated and put in prone position. 
  • Now that there is antibody tests being available, we should be quickly identify large number of patients who have recovered from Coronavirus infection. What is the evidence of using convalescent plasma in the care of acutely ill, rapidly worsening patient?

  • COVID-19 and Mental Health 
  • Because of the SARS-CoV-2 virus pandemic, we are living in unprecedented times. All of us are socially distancing ourselves, schools closed, jobs lost. Many patient asked to self quarantine for at least 14 days. Many cities have been locked down for over 2 months, families including children have to remain in confined space for days. Likewise, many healthcare providers have been sick with COVID-19 infection that they got while caring for patients in suboptimal environment.  Many more health care works are either not going to home or are living socially isolated lives to prevent the vulnerable ones / family members from getting infection. Many in the front line have witnessed the war like scenarios. All of them continue to care for COVID-19 patients in the frontlines. There is no sign to when this will end. Clinical assessment: what is the effect of current pandemic and such unprecedent social measures on the mental health of general population, OR patient with prior mental health issues  OR  what is the impact of pandemic on mental health of the front line health care providers?

 


EBM May 8, 15, 22 2020 (Group 2) 

Week 1 / May 8

  • Group 1: 58 yo AAM presented after headache and subjective fever of 1 month duration. Hx of HSV meningitis (previously treated). He had no sick contacts. Given subjective Fever, COVID-19 tests was done, and came positive. We decided it was an asymptomatic COVID-19 infection, and may have had subclinical HSV meningitis and patient was treated empirically.  He works at two NH during night shift (Total residents and staff at those facility is about 1200 and 300 respectively) and continued to work before he came to hospital. Given that patient was likely  an asymptomatic patient from COVID-19infection, is it necessary to take an aggressive measures to screen and prevent the infection of NH residents and staffs. Clinical Assessment: What is the transmission risk of infection at the NH residents and staff and is the symptoms based screening adequate? Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility NEJM
  • Group 2: 70 yo F with hx of DM2, HTN, ESRD – on HD came from Dialysis center after she was noted to have fever. On arrival patient had Temp of 101.4 F, RR 24, HR 114, BP 110/80, Saturating 97% in room air. Test for COVID-19 was positive. CRP, D-dimer, Ferritin, LDH all elevated. Pertinent Lab included K of 6.2. Patient was admitted to ICU for urgent HD, and transferred to floor. By Day 5, she was not having any fever, clinically feels ready for discharge, did not require oxygen during the hospital stay, HD center at community where they do HD for COVID-19 patient is identified. She lives in a Group Home and Group Home manager is fearful of her coming back as it will expose other vulnerable patients in their Group Home to the SARS-CoV-2 as they have limited staffing, lack of PPE, and limited space where patient isolation is difficult to maintain.  Clinical Assessment: When will it be safe for her to return to group home without putting other residents at group home at risk of infection? Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020 (BMJ)
  • Group 3: 57 yo AAM with Hx of HTN, DM-2, CKD was admitted in early March for Fever, Cough, and SOB after not feeling well for over a week. On initial presentation, patient required 3 L oxygen  via NC to maintain oxygen saturation at 93 %. Patient oxygen need deteriorated quickly and required intubation. On Day 3, patient was extubated but continued to require 5 L oxygen. Patient remained in ICU for another 3 days when his oxygen needs started to come down. CRP remained high. Renal function remained stable all along. Patient was transferred to floor on day 6. While in the floor, continued to feel worse due to persistent dry cough. Over next 4 days, patient cough and oxygen need gradually decreased. Finally, on day 11, patient was discharged home after he did well on room air at rest and on ambulation. Clinical Assessment: What are the presenting characteristics, and clinical course of the patient with COVID-19 infection? 
  • Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area JAMA
  • Group 4: 88 yo CF with hx of HTN, DM, CKD-2 presented  from NH for fever and SOB. T Max of 103.2, HR 112, RR 28, BP 114/70. Requiring 2 L oxygen. CXR shows diffuse infiltrate.  COVID-19 tests came positive. WBC 3.9, CRP elevated, Ferritin 508, D-dimer increased.  Over next few hours patient oxygen requirement increased and patient was transferred to ICU. Doctor, Will I survive this - Can you give any medication to prevent the worse outcome  (intubation or prevent death) from COVID-19 infection? Clinical Assessment: Will Remdesevir help prevent intubation or death?
  • Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial (Lancet)

Week 2 / May 15
  • Group 1/ Anti-coagulation and COVID-19 infection: 72 yo AAM with hx of HTN, DM-2, prior stroke (atherosclerotic) on G-tube for feeding comes from Nursing Home for fever. TMax 101.4, RR16, HR 123, BP 105/65. COVID-19 test is done and is positive.  O2 sats 93% in 1 L oxygen. On exam there is no evidence of lower extremity edema, or elevated JVD. Cr 1.7, K 5.8, D-dimer 6.2 mcg/mL (normal < 0.4 mcg/mL), LDH 345, Lactic Acid 2.8, Ferritin 318. All BP medications were held, and fluid resuscitation done and Lactic acidosis has since resolved. Repeat K 4.4, Cr 1.3 (baseline 1.1). Repeat BP 120/80. Patient continues to require 1 L oxygen. No prior hx of VTE. Clinical Assessment: How should anticoagulation management be approached on this patient? 
  • http://www.onlinejacc.org/content/accj/early/2020/05/05/j.jacc.2020.05.001.full.pdf
      
  • Group 2/ Prognostic model: 72 yo AAM with hx of HTN, DM-2, prior stroke on G-tube for feeding comes from Nursing Home for fever. TMax 101.4, RR16, HR 123, BP 105/65. COVID-19 test is done and is positive.  O2 sats 93% in 1 L oxygen. Cr 1.7, K 5.8, D-dimer 6.2, LDH 345, Lactic Acid 2.8, Ferritin 318. All BP medications were held, and fluid resuscitation done and Lactic acidosis has since resolved. Repeat K 4.4, Cr 1.3 (baseline 1.1). Repeat BP 120/80. Clinical Assessment: What models are there to predict the prognosis of a patient with COVID-19 infection?
  • Prediction models for diagnosis and prognosis of covid-19 infection: systematic review and critical appraisal BMJ April 7

  • Group 3 / COVID-19 and Mental Health 
  • Because of the SARS-CoV-2 virus pandemic, we are living in unprecedented times. All of us are socially distancing ourselves, schools closed, jobs lost. Many patient asked to self quarantine for at least 14 days. Many cities have been locked down for over 2 months, families including children have to remain in confined space for days. Likewise, many healthcare providers have been sick with COVID-19 infection that they got while caring for patients in suboptimal environment.  Many more health care works are either not going to home or are living socially isolated lives to prevent the vulnerable ones / family members from getting infection. Many in the front line have witnessed the war like scenarios. All of them continue to care for COVID-19 patients in the frontlines. There is no sign to when this will end. Clinical assessment: what is the impact of current pandemic and such unprecedented social measures on the mental health of general population, OR on patient with prior mental health issues  OR  of the front line health care providers? Please choose one focused question only. 
  • https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2763229


Week 3 / May 22

  • Group 1 / Use of mask by general public  
  • With case approaching 1.5 million and over 84000 deaths, COVID-19 infection has caused dramatic changes to everyone lives. While we desperately wait for public health interventions to work to contain the infection, it is likely, use of mask in the public space including at groceries, public transportation, work place etc will be a new normal until pandemic is controlled. Clinical Assessment: How effective is simple mask (Not N95) in preventing the transmission of COVID-19 infection in the community?
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177146/

  • Group 2 / Plasma exchange 
  • 70 yr o AAM with hx of HTN, CAD, DM-2 presents with Fever, Cough and SOB. Tmax 103, RR 23. BP 110/60, Pulse 110. O2 saturation 1 L in room air. Test for COVID-19 infection is positive. CRP 12, D-dimer 3.4, Ferritin 718, Xray shows diffuse patchy opacity. Patient is admitted to floor but overnight patient oxygen need increased and is transferred to ICU. Patient is intubated and put in prone position. 
  • Now that there is antibody tests being available, we should be able to quickly identify large number of patients who have recovered from Coronavirus infection. Clinical assessment: What is the evidence of using convalescent plasma in the care of acutely ill, rapidly worsening patient with COVID?
  • https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013600/full

  • Group 3 / Prone Positioning
  • 72 yo AAM with hx of HTN (Amlodipine 5 mg, Lisinopril 20 mg, Triamterene/HCTX 37.5 /25 mg ), DM-2, prior stroke on G-tube for feeding comes from NF for fever. TMax 101.4, RR16, HR 123, BP 105/65. Test for COVID-19 test is positive.  O2 sats 93% in 1 L oxygen. Cr 1.7, K 5.8, D-dimer 2.3, LDH 345, Lactic Acid 2.8, Ferritin 318. All BP medications were held, and fluid resuscitation done and Lactic acidosis has since resolved. Repeat K 4.4, Cr 1.3 (baseline 1.1). Repeat BP 120/80. Clinical Assessment: What is the evidence of asking patient to be in Prone position to prevent respiratory failure and the need for mechanical ventilation? 
  • https://www.nejm.org/doi/10.1056/NEJMoa1214103?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200www.ncbi.nlm.nih.gov

  • Group 4 / Herd immunity to help control Infectious Disease 
  • With over 4.4 million cases of COVID-19 worldwide including 302,000 death worldwide (as of 5/15), there is no sign on how this pandemic will eventually end. If we are extremely lucky, we will have vaccine by 2021. Despite multiple ongoing clinical trials, we will be even more lucky if we have an effective treatment. Most likely scenario is we will continue to have pandemic until we have a herd immunity at which time it may only remain in small communities without causing large scale infection. Hence, it eventually may come down to building herd immunity (ideally through vaccine, if not, by having infection). As a student of medicine, we have to understand public health interventions are the treatment of pandemic. Clinical assessment: What is the science on  Herd immunity in controlling spread of infectious disease?
  •  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164482/

 

 

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