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covid-19

COVID-19 coronavirus (2019-nCoV / SARS-CoV-2)

Introduction

  • outbreak commenced in Dec 2019 originating in Wuhan (China) business operators at the Hua Nan Seafood Wholesale Market, who sold live animals such as poultry, bats, marmots, and wildlife parts
  • with the alpha variant in 2020, 80% of cases are “mild”, 14% severe and 5% were critical
    • in children, only 6% developed severe or critical illness - ie. 94% are “mild”
  • the delta variant dominated 2021 and was much more transmissible
  • the omicron variant has dominated since Dec 2021 and is even more transmissible than Delta but thankfully much less severe although newer Omicron variants B.A4, B.A5 of June 2022 seem to be more Delta-like in severity

minimizing spread from positive cases

  • management of known positive cases:
    • quarantine for 7 days (Omicron)
    • use of PPE for those in contact including prior to commencing CPR
    • contact tracing and testing of contacts at risk
  • reduce risk of unknown positive cases spreading infection
    • manage high risk persons as per positive cases until proven negative
    • self-monitoring for infection - especially of healthcare workers
      • twice daily temp checks for fever
      • monitor for symptoms of Covid
    • self-isolation:
      • for 10-14 days if contact with a positive case or a person at high risk of infection
      • possible Covid symptoms even if Covid swab negative (high false negative rates) until asymptomatic and swab negative
    • health care workers should wear appropriate PPE for ALL patient contacts especially in high risk areas such as EDs:
      • surgical mask + goggles or face shield
      • short-sleeved scrubs to allow regular hand washing to elbows
      • consider hair protection if one does not want to wash hair after shift
    • decontaminate clothing and body after exposure (eg. end of shift for health care workers with any patient contacts)
      • scrubs should be removed at work, placed in bag or at least carried inside out, and laundered appropriately
      • shoes should not be worn into home but should be left outside preferably in the sun
      • have a shower on finishing shift or immediately on arrival home

Incubation period

  • Delta strain appears to have a much shorter incubation period than original Wuhan variant- perhaps 12-24hrs

Diagnosis

  • definitive diagnosis is usually via PCR nasopharyngeal swab
  • a positive Rapid Antigen Test (RAT) nasal swab is probably adequate if pre-test probability is high
  • serology may be needed in equivocal swab result cases

Clinical features of Omicron variant

  • much higher nasopharyngeal growth and viral load but 10x less lung viral load than with Delta variant
  • main features are fever, myalgias and headaches with rhinorrhoea and sneezing
  • 15% of children develop unusual rash
  • viral pneumonitis, anosmia and cytokine storm is much less evident than with Delta

Clinical features of Delta variant

  • children
    • most children have asymptomatic or mild illness
    • some asymptomatic children appear to develop “Covid fingers and toes” - pernio-like painful purple/red papules - esp. adolescents
    • DVT and PEs have even occurred in children as young as 4yrs old after acquiring Covid-19 Delta strain
    • rarely, some children may develop Kawasaki disease which in Italy had a 30x normal prevalence 1)
  • pregnant women
    • pregnancy increases risk of hospitalisation by 5x and 2-3x risk of needing ICU or ventilation, esp. if older than 35yrs, BMI > 30, pre-existing high BP or diabetes
    • Covid-19 infections appear to increase risk of stillbirth, premature delivery, fetal distress, and need for NICU 2)
    • an Indian study published Oct 2021 suggests their 2nd wave of Covid-19 resulted in a 3x increase in miscarriage rates 3)
  • asymptomatic carriers
    • relatively common
  • mild illness
    • the likely order in which the symptoms of the disease first appear — fever, followed by cough, muscle pain, and then nausea, and/or vomiting and diarrhoea
    • bothersome dry cough coming from the chest, low grade fevers (generally in late afternoon or evening) some may have sore throat or diarrhoea
    • some report loss of smell (anosmia) or taste
    • elderly or the immunocompromised may present with atypical symptoms
    • a NY report in April 2020 suggests it may cause a 7-fold increase risk of stroke in adults under aged 50yrs even with mild illness
    • 94% of symptomatic children and 80% of symptomatic adults have only mild symptoms
    • in contrast, influenza is more likely to have high fevers and more severe headache and myalgias
    • it seems even mild cases may have an increased risk, albeit rare, of developing acute disseminated encephalomyelitis (ADEM)
  • diarrhoeal illness
    • occurs in approx 20-50% who present to hospital with Covid-19 and although diarrhoea tends to be an early symptom, those with diarrhoea rather than respiratory symptoms typically have a more delayed presentation to hospitalization
    • tends to be more associated with elevated LFTs and impaired coagulation 4)
  • mild pneumonitis
    • as for mild illness but with SOB (particularly likely to be Covid-19 if this worsens after a week) and CXR changes
    • 20-40% may have no fever on admission to hospital
    • some have “silent hypoxia” with minimal cough or SOB and this is presumably due to a V/Q shunt issue
  • severe pneumonitis
    • as for mild pneumonia but with hypoxia in room air and/or tachypnoea (eg. RR > 30 in adults)
    • this occurs in 5% of symptomatic children and is more likely in infants under 1yr of age 5)
    • as for severe pneumonitis but with hypoxic respiratory failure and CXR or CT scan showing bilateral opacities consistent with pulmonary oedema which is not caused by a cardiac cause or fluid overload
    • patients usually develop SOB by Day 7 post-exposure, and then intubation by day 10-15 possibly followed by death at 2-3 weeks after symptoms begin with a mean time to death from onset of 18 days
    • median time to development of ARDS from hospital admission appears to be 2 days (IQR, 1–4 days)
    • this may be rapidly progressive over hours
    • this occurs in 0.6% of symptomatic children and is more likely in infants under 1yr of age 6)
    • endothelial cell infection and cardiovascular complications
      • of those admitted to ICU, apparently 30-70% develop DVTs and 25% develop PEs
  • delirium
    • the elderly may present primarily with a delirium even without fever or resp. symptoms
    • DVT and PEs have even occurred in children as young as 4yrs old after acquiring Covid-19 Delta strain
  • stroke
    • a minority may present as stroke
  • a variety of skin rashes may occur
  • very rare complications
    • a 10 yr old child has developed orofacial dyskinesia with choreoathetoid movements caused by brainstem encephalitis 7)
    • sepsis occurs in a small minority of patients with severe illness
  • acquired immunity vs subsequent infections (re-infections)
    • natural infection results in strong immunity but this appears to rapidly wane after 3 months and re-infection is possible. Reinfection by SARS-CoV-2 under endemic conditions would likely occur between 3 and 63 months after peak antibody response, with a median of 16 months. 8)
    • vaccinated persons may have breakthrough infections, especially if they have poor immunity, or waning immunity from vaccine
    • infections in vaccinated persons are generally mild and vaccination appears to reduce hospitalisation and mortality rates by ~90%
  • pulmonary aspergillosis in ICU patients
    • coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA)
    • 10% of Covid-19 ICU immunocompetent patients develop invasive aspergillosis, nearly 90% had co-morbidities 9)
  • subacute effects
      • in 1st 4 weeks, 11x risk of PE, 6x risk of atrial arrhythmias, 5x risk of DVT
      • 5x increase in cardiovascular illness in the 1st 6weeks post-Covid- mainly PE and rhythm disturbances
      • 81 per cent more diagnoses of diabetes in the first four weeks of becoming infected, risk of diabetes stayed elevated by 27 per cent for up to 12 weeks
      • risk of new heart conditions began to decline five weeks after infection and returned to baseline levels or lower within 12 weeks to one year
  • long term effects
    • SARS virus patients tended to have impaired lipid metabolism lasting over 12 years after infection and this may be via programming of RAAS to chronically up-regulate ACE/Ang II at the expense of ACE2/Ang-(1-7) in otherwise healthy adolescents and young adults
    • there are concerns it may increase the prevalence of Parkinson's disease in those who lost sense of smell as this would suggest possible neural inflammation which plays an important role in the development of Parkinsons. Prevalence of Parkinsons apparently tripled in the years after the Spanish flu.
    • post ICU syndrome
    • post viral fatigue syndrome
    • permanent organ damage
    • “long term Covid syndrome”
      • possible abnormal smell parosmia where people smell disgusting smells or sulphur or burnt toast smells
      • “brain fog”, chronic fatigue, etc
      • perhaps 10-12% complain they have this and some 2/3rds of these say it impacts their daily living
      • inflammation of the vagus nerve may cause longer term effects of reduced vagal activity such as depression, dysphonia, GOR, tachycardia, orthostatic hypotension and diarrhoea
      • vasculitis can result in vascular events such as stroke (50% higher risk) are raised in the next 12 months even in those who have no risk factors
      • development of mast cell activation syndrome (MCAS) 10)
    • mucormycosis “black fungus”
      • occurs in diabetics at around 12-18 days after recovery from Covid-19 treated with corticosteroids
      • ~50% mortality rate in India with IV amphotericin Rx +/- removal of the infected eye, over 90% mortality untreated
    • long term effects of DVT (eg. venous insufficiency) and PEs (pulmonary hypertension)

Delta Covid-19 adult severity rating

Observation Mild Moderate Severe
SaO2 on room air >95% 92-95% incl. exertional desats <92%
RR 10-25 8-10 and 25-30 < 8 and > 30
HR 50-120 40-50 or 120-140 <40 or >140
GCS 15 15 14 or less

Delta Covid-19 patients at risk of deterioration within 6-12 hours

  • diarrhoea > 4x a day
  • syncope
  • chest pain
  • persistent tachycardia
  • hypotension including symptomatic postural hypotension
  • transient mild hypoxia
  • silent hypoxia without SOB/tachypnoea - more common in elderly
  • confusion

other markers of severe disease

General indications for hospital admission

  • indications for ICU admission for Covid-19
    • “severe” illness as above and warranting intubation
  • indications for general ward admission for Covid-19 (in crisis mode some may be managed by HITH)
    • “severe” illness as above but no indication for intubation or has advanced care directive
    • “moderate disease”
      • RR 20-30;
      • requires oxygen supplementation to maintain SaO2 > 92%
      • mild work of breathing
    • “mild disease” but patient unable to understand or have the resources for self-isolation / clinical plans

Clinical Mx of non-severe illness

  • initial medical assessment to exclude red flags for severity and risk of acute deterioration as above
  • consideration for biologics as below
  • if “mild severity” and appropriate, discharge home as soon as possible with public health community Covid-19 positive streaming services to follow up
    • patient hand out regarding isolation requirement, family advice, and when to seek help etc.
  • if “moderate severity” or red flags then consider hospital admission to monitor and manage

Clinical Mx of non-severe illness with risk factors for progression

oral nirmatrelvir + ritonavir (Paxlovid)

  • consider for those with mild disease within 5 days of onset if at risk (eg age > 65yrs or high risk factors)
  • reduced hospitalisation or death by 88% in outpatient high risk adults
  • C/I include HS, eGFR < 30, severe liver impairment, pregnancy, drugs dependent upon or which induce CYP3A such as fluticasone
  • if C/I, consider IV remdesivir instead
  • ~5% of patients will develop rebound Covid-19 2-8 days after finishing a 7 day course11)

inhaled budesonide

  • according to a large UK study in largely unvaccinated patients, seems to reduce illness duration by 3 days in those:
    • aged over 65yrs
    • aged > 50yrs with co-morbidities

Sotrovimab

  • Monoclonal antibody against spike protein
  • COMET-ICE trial (n= 291, placebo= 292; disease progression occurred in 7% placebo vs 1% Sotrovimab)
  • Single IV infusion
  • Given by day 5 of illness
  • For COVID positive patients over 12 years old WITHOUT an oxygen (supplemental) requirement, who are unvaccinated or partly vaccinated
    • At least one risk factor needed to qualify for Rx:
      1. Age over 54
      2. Diabetes
      3. BMI >30
      4. CKD
      5. CHF
      6. COAD
      7. Mod-to-severe asthma
      8. Pregnancy (category B2)

IV remdesivir

fluvoxamine

  • used in those unable to use the above antiviral / adjunctive agents

Clinical Mx of severe illness

  • see:
  • infection risk precautions - all staff should be vaccinated and must wear fit-tested N95 mask, eye protection (preferably face shield), gown and gloves and practice hand hygiene
  • viral swabs / sputum culture as per local policy
  • standard blood tests including blood cultures and perhaps blood gases
  • CXR
  • consider CTPA to exclude PE if (NB. D-Dimer is NOT useful as it will probably be raised in Covid-19 infection)12):
    • sudden worsening of hypoxia
    • significant drop in BP
    • new onset tachycardia
    • oxygen requirements are disproportionate to the severity of pneumonia on Chest X-Ray
  • general supportive care
  • no maintenance IV fluids unless specific indication
  • IV fluid resuscitation as needed but avoiding fluid overload
    • vaso pressors if BP unresponsive to 3 x boluses of 250mL IV fluids (adults)
  • supplemental low flow 100% oxygen as needed to no higher than 96% sats and lower for those with pre-existing COPD
    • consider awake prone position to increase saturations for those desaturating
    • escalate to high flow oxygen or NIV if SaO2 < 92% despite 6L/min O2 or RR remains > 30/min (adults) and consider referral to ICU as may need early intubation
  • antibiotics generally NOT indicated
    • however, if commenced for suspicion of bacterial infection, they should be stopped after 24-48hrs if no secondary bacterial infection identified and serum procalcitonin levels are not suggestive of bacterial infection
  • assess patient's pre-morbid conditions and prognosis, tailor care as appropriate and discuss this with patient and family, particularly as intubation may be futile for many patients
  • high flow nasal oxygen and BiPAP NIV should be avoided where possible as these create an aerosol dispersion of the virus and increases risk to all those in the room - if needed preferably have patient in negative pressure room or in a Monty hood
  • VTE prophylaxis ASAP unless contra-indicated
  • dexamethasone 6mg daily for 10 days
    • if requires oxygen therapy to maintain SaO2 > 92% AND beyond day 7 of illness
  • consider remdesivir
    • commence within the 1st 7 days of illness only, and only if require oxygen
    • requires govt approval process
    • 200 mg IV as a single dose on day 1, followed by 100 mg IV once daily for 5 days
  • if severe, consider monoclonal antibody biologics such as:
    • Baricitinib or Tocilizumab (generally only indicated in most severe cases and only of benefit if given within 1st 5 days of infection)
    • requires govt approval process
      • Baricitinib
        • inclusion criteria:
          • age ≥ 18 years old
          • COVID-19 confirmed by PCR on NP swab or sputum
          • Evidence of systemic inflammation: CRP ≥ 75 mg/L
          • oxygen saturation (SpO2) ≤ 92% on room air
        • exclusion criteria:
          • unable to tolerate oral/nasogastric administration
          • pregnant or breastfeeding
          • on other biologic treatments
          • active bacterial, fungal or viral infection other than COVID
          • neutropenia or lymphopenia
          • CrCl < 15 mL/min
          • ALT and AST > 5 x upper limit of normal
        • dosage:
          • The standard dose is 4mg orally daily for up to 14 days.
          • Dose adjustment is necessary in renal impairment:
            • CrCl 30 to < 60 mL/min; 2mg daily
            • CrCl 15 to < 30 mL/min; 1mg daily
          • Dose adjustment is not required in mild or moderate hepatic impairment.
      • Tocilizumab
        • as of Sept 2021, use of Tocilizumab is now highly restricted to those with severe disease and unable to use other biologics as there is very limited supplies of Tocilizumab remaining in Australia and further supplies are not expected till at least February 2022.
  • if intubation is deemed appropriate
    • preferably choose a negative pressure room
    • minimize staff and family in the room and place signage to avoid unintended entrance to room
    • pre-oxygenate with 100% oxygen
    • minimize aerosol amount by:
      • avoiding NIV or high flow oxygen if possible (unless in a negative pressure room)
      • avoiding awake fibreoptic procedures
      • using two handed technique for better seal if bag mask ventilation is needed
      • utilizing the most experienced intubator to maximize probability of initial success
      • utilizing video laryngoscopy to increase chance of success
      • avoiding initial ventilations until cuff is inflated
      • avoiding disconnection of the circuit where possible and if needed keep it as brief as possible
      • use the airway circuit and ventilator that will be used in ICU to avoid having to change over circuits
      • using expiratory viral filters to maintain a closed circuit for the virus

Mortality rates and factors

  • cause of death is Acute Respiratory Distress Syndrome (ARDS) in the vast majority of patients who die from Covid-19
  • 94% of deaths are in people with underlying co-morbidities 13)
  • those aged over 64yrs with or without co-mordities were 2-3x more likely to need hospitalization or intensive care compared to 19-64yr olds14)
  • patients can have rapid deterioration over a few hours on day 5 to 11 on symptoms resulting in death if not immediately provided with ventilatory support
  • risk of pneumonitis and thus death is probably related to the degree of expression of ACE2 on pulmonary cells which is known to increase with:
    • age
    • diabetes
    • perhaps with genetic polymorphisms of ACE2
    • human influenza infection induces broader expression of ACE2 in upper airway epithelial cells
    • Covid-19 activated interferon alpha 15)
  • HOWEVER, the situation is complex and it may be that ACE2 and reduction of the activity of AT II is important in the resolution of lung injury and general over-activity of RAS (which may be due to viral binding of ACE2 reducing its actions), and thus there may even be a role for angiotensin II receptor blockers (ARBs) in the Mx of severe cases - research is investigating this
  • case fatality rate (CFR) is estimated to be around 3% overall, but 15% in those aged over 80yrs and 8% in those aged 70-79yrs while around half of those critically ill died and perhaps over 80% of those requiring mechanical ventilation had died within 28 days.
    • CFR was higher in those with premorbid conditions:
      • 10.5% CFR if cardiovascular disease
      • 7.3% CFR if diabetic
      • 6.3% CFR if chronic resp disease
      • 6% CFR if hypertension - it seems this may be related to up-regulation of the ACE2 receptor due to taking ACE inhibitors or angiotensin II receptor blockers (ARBs) in patients with certain ACE2 gene polymorphisms so a theoretical risk reduction strategy is to change to an alternate antihypertensive agent 16)
        • ARBs increase ACE2 receptor numbers by 3-5x
        • current advice is to continue these meds if they are being used to control congestive cardiac failure but as of 19th March 2020, the jury is still out on the risk-benefits of potential loss of BP control when changing to a different antihypertensive when used to Rx hypertension only, however, the main bodies are advising NOT to cease these meds at this stage. 17)18)
      • 5.6% CFR if cancer
    • Men are more likely to die than women
      • in China CFR for men was 2.8% cw 1.7% in women
      • in Italy 71% of deaths have been men
      • in Spain it appears men have died at twice the rate of women
      • in the UK of nearly 11,000 deaths reviewed, males had HR of 1.6 ie. 59% more likely to die than women
    • elderly are at particular risk
      • in the UK of nearly 11,000 deaths reviewed19):
        • age > 80yrs HR 20.6 and 20x more likely to die than those in their 50's and over 100x more likely than those younger than 40
        • age 70-79yrs HR just over 6.1
        • age 60-69yrs HR 2.4
        • age 50-59yrs HR 1.0
        • age 40-49yrs HR 0.3
        • age 18-39yrs HR 0.06
    • race confers less of a risk than being male
      • in the UK of nearly 11,000 deaths reviewed20):
        • black HR 1.48
        • south Asian 1.44
        • white 1.0
    • obesity
      • in the UK of nearly 11,000 deaths reviewed21):
        • BMI > 40 HR 1.92
        • BMI 35-39.9: HR 1.4
        • BMI 30-34.9: HR 1.05
        • BMI < 30: HR 1.0
    • vitamin D deficiency may be a risk factor22)
    • severe illness is also dependent upon the level of cross-reactive antibodies such as:
      • Covid-19 vaccine
      • past exposure to Covid-19
      • past exposures to common cold
      • other vaccines such as DTaP 23)
      • antibodies to food antigens such as milk, gliadin toxic peptide, pea protein, α+β casein, soy, lentil lectin, and roasted almond 24)
    • true fatality rate is thought to be around 0.7%

More Information

Pandemic timeline

covid-19.txt · Last modified: 2022/10/09 20:47 by gary1

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