SARS-CoV-2: Difference between revisions

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*Mild: no oxygen
*Mild: no oxygen
*Moderate: supplemental oxygen
*Moderate: low-flow supplemental oxygen
*Severe: non-invasive mechanical ventilation
*Severe: high-flow supplemental oxygen or non-invasive mechanical ventilation
*Critical: invasive mechanical ventilation
*Critical: invasive mechanical ventilation


===Bacterial Coinfection===
===Bacterial Coinfection===


*True coinfection is rare, detected in about 5% of patients[[CiteRef::lansbury2020co]]
*True coinfection with bacterial pneumonia is rare, detected in about 5% of patients at presentation, and complicates about 8% of cases as a secondary infection[[CiteRef::lansbury2020co]]
**See https://www.tarrn.org/covid for a living systematic review
**See https://www.tarrn.org/covid for a living systematic review
*Most commonly [[Mycoplasma pneumonia]], [[Pseudomonas aeruginosa]], and [[Haemophilus influenzae]]
*Most commonly [[Mycoplasma pneumonia]], [[Pseudomonas aeruginosa]], and [[Haemophilus influenzae]]
*Also possibly need to consider [[COVID-19-associated pulmonary aspergillosis|Aspergillus fumigatus]] and even [[Pneumocystis jirovecii]]
*May be at risk of post-infectious or secondary bacterial infections
*Also possibly need to consider [[Aspergillus fumigatus]] and even [[Pneumocystis jirovecii]]


===Complications===
===Complications===
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== Investigations ==
== Investigations ==


* Chest x-ray typically showed diffuse, bilateral mixed interstitial and airspace disease
* CT chest imaging may show:[[CiteRef::simpson2020ra]]
* CT chest imaging may show:[[CiteRef::simpson2020ra]]
** Typical appearance:, classic for COVID-19
** Typical appearance:, classic for COVID-19
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==Diagnosis==
==Diagnosis==


*Rapid antigen testing from NP swab
**Sensitivity depends on circulating variant
*PCR from NP swab
*PCR from NP swab
**Highest sensitivity within 5 days of symptom onset, with decreasing sensitivity as the disease enters the immune-mediated phase
**Highest sensitivity within 5 days of symptom onset, with decreasing sensitivity as the disease enters the immune-mediated phase
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==Management==
==Management==


=== Mild Disease (No Supplemental Oxygen) ===
*For patients no requiring supplemental oxygen, the focus is on supportive care
*For patients not requiring supplemental oxygen, the focus is on supportive care
**[[Remdesivir]] 200 mg IV once followed by 100 mg IV daily for 2 more days may be used within 7 days of symptom onset who have at least one risk factor for disease progression (age ≥60 years, obesity, or other medical conditions)[[CiteRef::gottlieb2021ea]]
*Patients who are high risk for progression to severe disease may benefit from prophylaxis with either 3 days of [[remdesivir]] or 5 days of [[Paxlovid]]
**Consideration of monoclonal antibodies such as [[casirivimab-imdevimab]] (Regeneron), depending on the variant
*Risk factors include age, vaccination status, and the following:
***Use in patients who are anti-spike protein seronegative and within 9 days of symptom onset
**[[Obesity]], with BMI ≥30
***May reduce hospitalization of high risk patients (hypertension, diabetes, chronic lung disease, congestive heart failure, of immunodeficiency) with ARR of 2 to 3%
**[[Diabetes]]
**[[Paxlovid]] may be considered for patients at high risk of progressing to severe disease, within 5 days of symptom onset
**Heart disease, [[hypertension]], or [[heart failure]]
***Management of drug-drug interactions is available [https://www.med.umich.edu/asp/pdf/outpatient_guidelines/Paxlovid-DDI.pdf here]
**Chronic respiratory disease, including [[cystic fibrosis]]
**[[Cerebral palsy]]
**Intellectual disability
**[[Sickle cell disease]]
**[[Chronic kidney disease]] with eGFR ≤60 mL/min
**Liver disease with [[Child-Pugh classification|Child-Pugh]] class B or C
{| class="wikitable"
|+Risk for progression to severe disease
! rowspan="2" |Age (years)
! colspan="3" |Vaccinations
|-
!0 doses
!1 or 2 doses
!3+ doses
|-
|<20
|higher risk if ≥3 risk factors
|standard risk
|standard risk
|-
|20 to 39
|higher risk if ≥3 risk factors
|higher risk if ≥3 risk factors
|standard risk
|-
|40 to 69
|higher risk if ≥1 risk factors
|higher risk if ≥3 risk factors
|standard risk
|-
|≥70
|higher risk
|higher risk if ≥1 risk factors
|higher risk if ≥3 risk factors
|-
|Immunocompromised (regardless of age)
| colspan="3" |higher risk
|-
|pregnancy (regardless of age)
|higher risk
|standard risk
|standard risk
|}

* [[Remdesivir]] 200 mg IV once followed by 100 mg IV daily for 2 more days may be used within 7 days of symptom onset who have at least one risk factor for disease progression (age ≥60 years, obesity, or other medical conditions)[[CiteRef::gottlieb2021ea]]
*[[Paxlovid]] for 5 days may be considered for patients at high risk of progressing to severe disease, within 5 days of symptom onset
**[[Nirmatrelvir-ritonavir]] 300 mg / 100 mg (3 tablets total) twice daily for 5 days
**Needs dose adjustment in renal dysfunction
**Management of drug-drug interactions is available at [https://www.med.umich.edu/asp/pdf/outpatient_guidelines/Paxlovid-DDI.pdf University of Michigan] or [https://www.covid19-druginteractions.org/ University of Liverpool]
**[https://doi.org/10.47326/ocsat.2022.03.58.3.0 Ontario guidelines are available]
*Consider of monoclonal antibodies, depending on the variant
*Can consider [[fluvoxamine]] or inhaled [[budesonide]]
**Evidence for significant benefit is weak
**[[Fluvoxamine]] 100 mg p.o. twice daily for 15 days, started within 7 days of symptom onset
**[[Budesonide]] 800 mcg inhaled twice daily for 14 days

=== Moderate Disease (Low-Flow Supplemental Oxygen) ===
*For patients requiring supplemental oxygen or with oxygen saturation less than 94%:
*For patients requiring supplemental oxygen or with oxygen saturation less than 94%:
**[[Dexamethasone]] 6 mg PO/IV daily for 10 days, which has a mortality benefit
*[[Dexamethasone]] 6 mg PO/IV daily for 10 days, which has a mortality benefit
**[[Remdesivir]] 200 mg IV once on day one followed by 100 mg PO daily for 5-10 days, which has not been shown to have a mortality benefit
*[[Remdesivir]] 200 mg IV once on day one followed by 100 mg PO daily for 5-10 days, which has not been shown to have a mortality benefit
**[[Tocilizumab]] indicated if progressing despite [[dexamethasone]], still requiring oxygen and CRP ≥75 mg/L, per RECOVERY trial
*[[Tocilizumab]] indicated if progressing despite [[dexamethasone]], still requiring oxygen and CRP ≥75 mg/L, per RECOVERY trial
***ARR for 28-day mortality of about 4%
**ARR for 28-day mortality of about 4% in unvaccinated patients
***If tocilizumab is unavailable, then [[baricitinib]] 4 mg p.o. daily for 14 days or until hospital discharge
**If tocilizumab is unavailable, then [[baricitinib]] 4 mg p.o. daily for 14 days or until hospital discharge
*Consider monoclonal antibodies, depending on the variant
**If unvaccinated/no prior infection, declining clinically, and within 9 days of symptom onset, [[casirivimab-imdevimab]] (Regeneron) 8000 mg IV once
*Consider therapeutic anticoagulation with [[LMWH]] for 14 days (stopped at discharge or on transfer to ICU)
*Avoid [[hydroxychloroquine]]/[[chloroquine]], [[lopinavir-ritonavir]]
**May decrease progression to invasive mechanical ventilation


=== Severe or Critical Disease (High-Flow or Mechanical Ventilation) ===
===Anticoagulation===


* Patients requiring ventilatory support, including high-flow nasal oxygen, non-invasive ventilation, invasive mechanical ventilation, or ECMO
*A multiplatform RCT combined ATTACC, REMAP-CAP, and ACTIV-4a looked at therapeutic anticoagulation (compared to prophylactic)
* [[Dexamethasone]] 6 mg p.o./IV daily for 10 days
**Therapeutic anticoagulation with heparin derivatives, using the LMWH typical for the hospital at DVT/PE treatment doses
** Can consider 12 mg dosing in patients unable to receive IL-6 inhibitors
**Duration 14 days, or until discharge if before 14 days
* [[Tocilizumab]] for patients on [[dexamethasone]]
**Helpful in moderately ill patients, regardless of D-dimer value
* Do ''not'' treat with therapeutic anticoagulation, [[remdesivir]], monoclonal antibodies, or [[Paxlovid]]
**Potentially harmful in severely or critically ill patients


=== Strongyloidiasis ===
=== Strongyloidiasis ===
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* Patients should be screened per CATMAT guidelines and treated if appropriate
* Patients should be screened per CATMAT guidelines and treated if appropriate
* For steroid exposure, 10 days of dexamethasone +/- tocilizumab is considered substantial risk
* For steroid exposure, 10 days of dexamethasone +/- tocilizumab is considered substantial risk
* See also [https://www.canada.ca/en/public-health/services/reports-publications/canada-communicable-disease-report-ccdr/monthly-issue/2021-47/issue-7-8-july-august-2021/covid-19-treating-strongyloides-ivermectin-patients.html Ivermectin treatment for ''Strongyloides'' infection in patients with COVID-19] from the CCDR<br />
* See also [https://www.canada.ca/en/public-health/services/reports-publications/canada-communicable-disease-report-ccdr/monthly-issue/2021-47/issue-7-8-july-august-2021/covid-19-treating-strongyloides-ivermectin-patients.html Ivermectin treatment for ''Strongyloides'' infection in patients with COVID-19] from the CCDR

=== Anti-SARS-CoV-2 Monoclonal Antibodies ===

* Effectiveness varies by strain/lineage
* Refer to https://www.covid19treatmentguidelines.nih.gov/tables/variants-and-susceptibility-to-mabs/ for up-to-date table of effectiveness

=== Immunocompromised Patients With Persistent Infection ===

* A few case studies
** [https://doi.org/10.1093/cid/ciac847 10.1093/cid/ciac847]: 60M CLL, got [[Paxlovid]] x5 days; recurred, got [[remdesivir]] x10 days; recurred, got betelovimab; was on concurrent high-dose steroids essentially throughout for organizing pneumonia; finally [[remdesivir]] and [[Paxlovid]] combination to 20 days, with negative NP swab and clinical resolution
** [https://doi.org/10.1093/ofid/ofac382 10.1093/ofid/ofac382]: 44 yo with [[GPA]] and [[hypogammaglobulinemia]] with 5 months of symptomatic infection treated with IVIG, convalescent plasma, and finally [[remdesivir]] to negative NP swab PCR, which took 30 days
** [https://doi.org/10.1093%2Finfdis%2Fjiaa446 10.1093/infdi/jiaa446]: 50M with CLL post-treatment had relapse twice after 10-day courses of [[remdesivir]], finally resolved after infusion of convalescent plasma
** [https://doi.org/10.1136/bcr-2021-244768 10.1136/bcr-2021-244768]: child with [[Primary immunodeficiency|PID]] eventually resolved with multiple courses of [[IVIG]]
** [https://doi.org/10.1093/infdis/jiaa666 10.1093/infdis/jiaa666]: lymphoma with 3 admissions over 4 months, treated with two courses of [[remdesivir]] and convlescent plasma
** [https://doi.org/10.1016/j.ijid.2020.12.050 10.1016/j.ijid.2020.12.050]: follicular lymphoma post treatment with 2 months of COVID, got [[remdesivir]] twice (second time 10 days) as part of trials, as well as IVIG


==Prevention==
==Prevention==
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==Further Reading==
==Further Reading==


=== Review Articles ===
*Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review. ''JAMA''. doi: [https://doi.org/10.1001/jama.2020.12839 10.1001/jama.2020.12839]
*Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review. ''JAMA''. doi: [https://doi.org/10.1001/jama.2020.12839 10.1001/jama.2020.12839]


=== Canadian Guidelines ===
=== Canadian Guidelines ===
*AMMI Canada Practice Point: Treatments for adults with COVID-19 in 2021–2022. ''JAMMI''. 2022;7(3):163-169. doi: [https://doi.org/10.3138/jammi-2022-08-08 10.3138/jammi-2022-08-08]
*[https://covid19-sciencetable.ca/science-briefs/#infectious-diseases-clinical-care Ontario Science Table Clinical Practice Guideline Summary: Recommended Drugs and Biologics in Adult Patients with COVID-19]
*[https://doi.org/10.47326/ocsat.cpg.2022.11.0 Ontario Science Table Clinical Practice Guideline Summary: Recommended Drugs and Biologics in Adult Patients with COVID-19]
*[http://www.bccdc.ca/health-professionals/clinical-resources/covid-19-care/clinical-care/treatments BC COVID-19 Therapeutics Committee (CTC) and COVID-19 Therapeutics Review and Advisory Working Group (CTRAWG) Clinical Practice Guidance]
*[http://www.bccdc.ca/health-professionals/clinical-resources/covid-19-care/clinical-care/treatments BC COVID-19 Therapeutics Committee (CTC) and COVID-19 Therapeutics Review and Advisory Working Group (CTRAWG) Clinical Practice Guidance]


Latest revision as of 19:22, 17 November 2022

Background

Microbiology

  • Coronavirus related to SARS-CoV
  • Virion consists of:
    • Spike glycoprotein (S), which appears to be an important virulence factor
      • Vaccines may target either the full protein or only its distal receptor binding domain
    • Membrane protein (M)
    • Nucleocapsid protein (N)
    • Hemagglutinin esterase (He)
    • Envelope protein (E)

Epidemiology

  • Transmitted mostly by respiratory droplets, with some amount transmission via aerosols and little to no transmission via contact
  • First cases detected Dec 2019 related to likely exposure in wet market in Wuhan, Hubei, China, and declared a pandemic in 2020
  • Secondary household attack rate of 12-17%
  • Possibility of animal reservoirs, including cats (possibly), dogs (unlikely), deer (probably)
    • Difficult to prove transmission to humans
    • Unlikely to contribute to household transmission, since human-to-human transmission is far more likely

Risk Factors for Mortality

Clinical Manifestations

Pregnancy

  • Please refer to a living systematic review on the topic
  • Slightly less reported fever and myalgias
  • Slightly more ICU admissions and mechanical ventilation
    • Risk factors included age, obesity, hypertension, and diabetes
  • With regards to the fetus, there were more preterm deliveries (6%) and more needed NICU admission (25%)

Severity

  • Mild: no oxygen
  • Moderate: low-flow supplemental oxygen
  • Severe: high-flow supplemental oxygen or non-invasive mechanical ventilation
  • Critical: invasive mechanical ventilation

Bacterial Coinfection

Complications

Investigations

  • Chest x-ray typically showed diffuse, bilateral mixed interstitial and airspace disease
  • CT chest imaging may show:2
    • Typical appearance:, classic for COVID-19
      • Peripheral, bilateral ground-glass opacity with out without consolidation or visible intralobular lines (crazy paving)
      • Multifocal rounded GGO with or without consolidation or crazy paving
      • Reverse halo sign or other findings of organizing pneumonia (later finding)
    • Indeterminate appearance:
      • Multifocal, diffuse, perihilar, or unilateral GGO with or without consolidation lacking a specific distribution and are non-rounded or non-peripheral
      • Few very small GGO with a non-rounded and non-peripheral distribution
    • Atypical appearance, which suggests unlikely to be COVID-19:
      • Isolated lobar or segmental consolidation without GGO
      • Discrete small nodules (centrilobular, tree-in-bud)
      • Lung cavitation
      • Smooth interlobular septal thickening with pleural effusion

Diagnosis

  • Rapid antigen testing from NP swab
    • Sensitivity depends on circulating variant
  • PCR from NP swab
    • Highest sensitivity within 5 days of symptom onset, with decreasing sensitivity as the disease enters the immune-mediated phase
    • May be positive long after no longer infectious
  • Diagnostic accuracy of PCR by sample site (below) has a lot of heterogeneity among the studies
Sensitivity Specificity
Upper Respiratory Samples
Oral 56 99
Nasal 76 100
NP 97 100
Nasal 95 100
Saliva 85 100
Mid-turbinate 100 100
Upper Versus Lower Tract
Upper respiratory tract 57 100
Lower respiratory tract 81 100
Single Versus Repeat Testing
Single test 71 100
Repeat testing 100 100
  • Serology (IgM and IgG)
    • Total antibodies have poor sensitivity (51%) in first week, and increases to about 90% by week 3

Management

Mild Disease (No Supplemental Oxygen)

Risk for progression to severe disease
Age (years) Vaccinations
0 doses 1 or 2 doses 3+ doses
<20 higher risk if ≥3 risk factors standard risk standard risk
20 to 39 higher risk if ≥3 risk factors higher risk if ≥3 risk factors standard risk
40 to 69 higher risk if ≥1 risk factors higher risk if ≥3 risk factors standard risk
≥70 higher risk higher risk if ≥1 risk factors higher risk if ≥3 risk factors
Immunocompromised (regardless of age) higher risk
pregnancy (regardless of age) higher risk standard risk standard risk
  • Remdesivir 200 mg IV once followed by 100 mg IV daily for 2 more days may be used within 7 days of symptom onset who have at least one risk factor for disease progression (age ≥60 years, obesity, or other medical conditions)3
  • Paxlovid for 5 days may be considered for patients at high risk of progressing to severe disease, within 5 days of symptom onset
  • Consider of monoclonal antibodies, depending on the variant
  • Can consider fluvoxamine or inhaled budesonide
    • Evidence for significant benefit is weak
    • Fluvoxamine 100 mg p.o. twice daily for 15 days, started within 7 days of symptom onset
    • Budesonide 800 mcg inhaled twice daily for 14 days

Moderate Disease (Low-Flow Supplemental Oxygen)

  • For patients requiring supplemental oxygen or with oxygen saturation less than 94%:
  • Dexamethasone 6 mg PO/IV daily for 10 days, which has a mortality benefit
  • Remdesivir 200 mg IV once on day one followed by 100 mg PO daily for 5-10 days, which has not been shown to have a mortality benefit
  • Tocilizumab indicated if progressing despite dexamethasone, still requiring oxygen and CRP ≥75 mg/L, per RECOVERY trial
    • ARR for 28-day mortality of about 4% in unvaccinated patients
    • If tocilizumab is unavailable, then baricitinib 4 mg p.o. daily for 14 days or until hospital discharge
  • Consider monoclonal antibodies, depending on the variant
  • Consider therapeutic anticoagulation with LMWH for 14 days (stopped at discharge or on transfer to ICU)
    • May decrease progression to invasive mechanical ventilation

Severe or Critical Disease (High-Flow or Mechanical Ventilation)

  • Patients requiring ventilatory support, including high-flow nasal oxygen, non-invasive ventilation, invasive mechanical ventilation, or ECMO
  • Dexamethasone 6 mg p.o./IV daily for 10 days
    • Can consider 12 mg dosing in patients unable to receive IL-6 inhibitors
  • Tocilizumab for patients on dexamethasone
  • Do not treat with therapeutic anticoagulation, remdesivir, monoclonal antibodies, or Paxlovid

Strongyloidiasis

Anti-SARS-CoV-2 Monoclonal Antibodies

Immunocompromised Patients With Persistent Infection

Prevention

Infection Prevention and Control

Healthcare Workers

  • Awaiting results
    • If symptomatic, HCWs should be off work
    • If asymptomatic, HCWs may return to work while awaiting results, depending on the reason for testing and the staffing needs
  • Positive but asymptomatic: in exceptional circumstances, may return to work early

Clearance

  • Non-test based (preferred)
    • Asymptomatic: isolate for 10 days from swab
    • Mild to moderate symptoms in immunocompetent person: 10 days from onset of symptoms, as long as afebrile (without antipyretics) and clinically improving
    • Severe (i.e. ICU-level care) or immunocompromised: 20 days from onset of symptoms, as long as afebrile (without antipyretics) and clinically improving
  • Test based (alternative): 2 negative swabs at least 24 hours apart (if still positive, repeat in 3 to 4 days), as long as afebrile and clinically improving

Further Reading

Review Articles

  • Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review. JAMA. doi: 10.1001/jama.2020.12839

Canadian Guidelines

References

  1. ^  Louise Lansbury, Benjamin Lim, Vadsala Baskaran, Wei Shen Lim. Co-infections in people with COVID-19: a systematic review and meta-analysis. Journal of Infection. 2020;81(2):266-275. doi:10.1016/j.jinf.2020.05.046.
  2. ^  Scott Simpson, Fernando U. Kay, Suhny Abbara, Sanjeev Bhalla, Jonathan H. Chung, Michael Chung, Travis S. Henry, Jeffrey P. Kanne, Seth Kligerman, Jane P. Ko, Harold Litt. Radiological Society of North America Expert Consensus Document on Reporting Chest CT Findings Related to COVID-19: Endorsed by the Society of Thoracic Radiology, the American College of Radiology, and RSNA. Radiology: Cardiothoracic Imaging. 2020;2(2):e200152. doi:10.1148/ryct.2020200152.
  3. ^  Robert L. Gottlieb, Carlos E. Vaca, Roger Paredes, Jorge Mera, Brandon J. Webb, Gilberto Perez, Godson Oguchi, Pablo Ryan, Bibi U. Nielsen, Michael Brown, Ausberto Hidalgo, Yessica Sachdeva, Shilpi Mittal, Olayemi Osiyemi, Jacek Skarbinski, Kavita Juneja, Robert H. Hyland, Anu Osinusi, Shuguang Chen, Gregory Camus, Mazin Abdelghany, Santosh Davies, Nicole Behenna-Renton, Frank Duff, Francisco M. Marty, Morgan J. Katz, Adit A. Ginde, Samuel M. Brown, Joshua T. Schiffer, Joshua A. Hill. Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients. New England Journal of Medicine. 2021. doi:10.1056/nejmoa2116846.

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