Thread by @drsubramanians

Starting a series on clinical Pearls I am gathering in #COVID19 patients based on experiences of many experts

Will add as we go along

Feel free to add your own observations/experiences

#covidclinicalpearls /1

Anosmia is likely the most specific #COVID19 related symptom
30% of patients have anosmia as their 1st symptom
#covidclinicalpearls /2

Around 90% of patients have fever.
50% maybe afebrile at the time of presentation
Fever tends to be very resistant to routine measures in hospitalized patients
There is no consensus that NSAIDs are to be avoided in #COVID2019 patients

#covidclinicalpearls /3

Viral shedding is greatest at the time of symptom onset and declines over the course of several days
50% of patients keep shedding after complete resolution of symptoms
Viral shedding can continue for as much as 24 days

#COVID2019
#covidclinicalpearls /4

Lymphopenia is common in #COVID2019 > 80% patients
Leukopenia is seen in 1/3 of patients
Its associates with poor outcomes and poor surivival.
Recovery with Lym % > 20% at Day10 of symptoms is a + outcome marker
Lym % of <5% = poor prognosis

#covidclinicalpearls /5

Lymphopenia timeline in #COVID19

LYM% < 20% are pre-severe type
At TLM-2
If LYM% > 20% those are reclassified as “moderate”
If 5% < 20% = “severe”
If < 5% = “critical”

#covidclinicalpearls /6

Diagnosis by PCR testing has upto 30% false negative rate #COVID19
Sampling early in disease course will have lower sensitivity
CT Chest has BETTER predictive value in cases where CT findings are high probability even if PCR swab negative

#covidclinicalpearls /7

Average time from initial negative to positive PCR swab test is 5 days

Do NOT rule out #COVID19 with ONE pharyngeal swab.

Sensitivity of CT in patients with positive CT & negative PCR is 97%

#covidclinicalpearls /8

#CT Chest in #COVID19

Early #groundglass abnormality in early disease,

followed by “crazy paving,”

finally increasing consolidation

Typically peripheral
#covidclinicalpearls /9

Temporal changes of CT findings in #COVID19

Note #groundglass predominant early

#covidclinicalpearls /10

Respiratory support
#COVID19

AVOID
- Noninvasive ventilations #NPPV
- High flow O2 #HFNC

due to high risk to healthcare workers due to aerosols.

EARLY intubation

#covidclinicalpearls /11

For #intubation in #COVID19

Only Experts intubate
AVOID bag-mask ventilations
Use PEEP valve if needed
Gentle bagging via supraglottic device preferred if needed

Always use rapid sequence intubation - rocuronium preferred by some

#covidclinicalpearls /12

If using #NPPV #NIV in #COVID2019 (#Ventilator in short supply)

Use a full face mask or helmet
Use a filter for the leak port
Use a HME Filter to provide additional safety from aerosol

Set Alarms for patient disconnect

#covidclinicalpearls /13

If using #HFNC (preferred to #NIV) in #COVID19
Use preferably low flow rates (30-40L/min) have lower rates of aerosolization
Always increase FiO2 to max before increasing flow rate >30L/min
Reassess at 1 hr and 3 hr intervals for possible intubation

#covidclinicalpearls /14

Use of Venturi mask
#COVID19
if patient requires >8L/min NC
Non humidified
Uptitrate to FiO2 35%
Then increase flow rate if needed to 12 L/min

#covidclinicalpearls /15

For mechanical #ventilation in #COVID19 #ICU

Tidal volume 6ml/kg IBW
PEEP 5 if BMI <35
(10 if BMI >35)

Avoid HIGH PEEP
#COVID19 ARDS is atypical with normal compliance & high PEEP may do more harm than good

#covidclinicalpearls /16

Use ARDSnet LOW PEEP table as a guide but try to maintain as low a PEEP as feasible early in #COVID19 disease

#covidclinicalpearls /17

#COVID19 #ARDS is atypical
Compliance tends to normal-high
Hence high PEEP strategy may not improve oxygenation

#covidclinicalpearls / 17

#proning #prone #ventilation in #COVID19 #ARDS

General consensus is to prone early
Suggest prone ventilation in non-intubated patients in early lung injury
Awake patient may lie in prone position for 12-16hrs a day

#covidclinicalpearls /18

#proning in #COVID19
#ARDS

Prone positioning of patients with relatively high compliance results in a modest benefit at the price of a high demand for stressed human resources

Be judicious and reassess benefits of prone #ventilation

#covidclinicalpearls /19

#COVID19 #ARDS

High reintubation rates

Glottic edema/stridor common after extubation

Leak test before extubation is critical
Delayed extubation (longer than typical) may help extubation failures

#covidclinicalpearls /20

#COVID19 #ARDS
Nitric oxide has anti viral effect invitro

Initiate iNO in refractory cases at 20ppm

If repeat ABG in 2 hrs PaO2 ⬆️10% continue - if not ⬆️iNO to 80ppm - if still no ⬆️PaO2 stop

Alternative consider #epoprostenol

#covidclinicalpearls /21

#Covid_19 UK group reports wedge infarcts/pulmonary thrombosis & prevalence of pulmonary embolism.

Role for Anticoagualtion?

In patients with coagulopathy or D Dimer >6X high use of LMWH was associated with reduced mortality (40% vs 64%)
#COVID19

#covidclinicalpearls /22

#ECMO
in #Covid_19
It’s “rarely necessary”

Several concerns for use - including potential for lymphopenia and worse outcomes

Very limited role /if any
#covidclinicalpearls /23

#fluidmanagement in #COVID19

Do NOT give routine 30cc/kg resuscitation IVF

Restrict Fluids

Limit use of maintenance IVF

Do not use ⬆️Lactate to trigger IVF

Avoid diuretic use (—> AKI)

Avoid large + fluid balance

#covidclinicalpearls /24

#troponin in #Covid_19

Increase rapidly from D14
Steady rise from D4 to D22 is seen in non survivors

Fulminant myocarditis has been described

Cardiogenic shock important cause of death ~30% of deaths

#covidclinicalpearls /25

Gattinoni et al describe 2 phenotypes in #COVID2019 respiratory failure

Type L /Type H

Type L : early, normal compliance, low V:Q.
Type H : high elastance & high right to left shunt

For type L caution using high PEEP

#covidclinicalpearls /26

#renal failure in #Covid_19 is fortunately rare 1-5% of all hospitalized patients

RRT needed in 5-20% of ICU cases
100% mortality in patients needing RRT in one large series

Reports of frequent clotting of circuit in CVVHD- use LMWH eary #covid19

#covidclinicalpearls /27

Co-infection rates can be high with #COVID19

Stanford group reports 22% coinfection rates with other viral infections in 49 #Covid_19 patients

#covidclinicalpearls /28

Bacterial superinfection in #COVID19 rates are low 10-20%

#MRSA is typically not seen as with #influenza

#Azithromycin use with #Hydroxycloroquine has been shown to be effective ...

#covidclinicalpearls /29

Use of #hydroxychloriquine and #Azithromycin was studied in 20 patients with #Covid_19 - showed significant reduction in viral carriage on Day6 vs controls

Evidence favoring use of #Azithromycin gaining

Caution due to QTc interval

#covidclinicalpearls /30

Criticism for Gautret et al #hydroxycholoroquine trial for #COVID19

Viral load higher in control group

AND

6 patients in HCQ group were excluded from analysis - 5 would have been considered #Covid_19 failures

Thus NO clear evidence for Azithro

#covidclinicalpearls /31

UPenn protocol

#Hydroxychoroquine use is NOT recommended in

non-hospitalized patients and
hospitalized with mild disease
and
no risk factors

#Covid_19

#covidclinicalpearls /32

#antiviral use in #Covid_19

#Remdesevir is the only agent with universal consensus

This is algorithm at Brigham & Women’s

#covidclinicalpearls /33

#Antiviral #Covid_19

#Lopinavir #Ritonavir combo could be useful

Cao et al (NEJM) considered a negative study

However trial DID show
▪️28 day mortality was lower
▪️~50% Shorter ICU Stay (6 vs 11 days)

Randomized only on D13 so likely too late

#covidclinicalpearls /34

#Antiviral #Covid_19

#Triple-therapy with

#Remdesivir
#Ritonavir
#Lopinavir

+ #interferon
+ #Hydroxychloroquine

🔹Is in clinical trials
🔹 Can be tried in center where available in moderate /severe disease or high risk #COVID19 patients

#covidclinicalpearls /35

#Covid_19 IV Ig described in one case series by Cao. 5days 25g/d in 3 severe pts. More data needed

#chestpulmonary

#covidclinicalpearls /37

Convalescent plasma in #Covid_19 #ARDS

Donors
🔹asymptomatic x10d
🔹Ab titer >1:1000(Elisa) & >1:40 (neutral)
ALL 5 recovered
This is the most promising #treatment for #COVID19

All hospitals must initiate protocols for plasma pheresis from survivors

#covidclinicalpearls /38

A new study now casts doubt on efficacy of #Hydroxychloroquine and #Azithromycin
80% of patients in this study had no viral clearance on D5-6 after therapy

#covidclinicalpearls /39

pdf.sciencedirectassets.com/272288/AIP/1-s…

I don’t know who needs to hear this

#Covid_19 #pneumonia #ARDS is NOT #HAPE ; nor similar to it.

#covidclinicalpearls /40

Extensive Intravascular microthrombosis is seen in autopsy in #Covid_19

#Dipyridamole has been shown to decrease D Dimer levels and clinical benefit in 1 study

#covidclinicalpearls /41

#tocilizumab is being tried in critically ill patients with #covid_19

15 patients with severe #covid19 & ⬆️ #IL6 levels (2X - 90X normal)

10 of 15 improved
3 of 4 that received only single dose died

onlinelibrary.wiley.com/doi/epdf/10.10…

#covidclinicalpearls /42

#SARSCoV2 infects AEC2 thru ACE2 receptor➡️destruction of epithelial cells ➡️release of virus➡️activate the innate immune system➡️release ⏫cytokines incl #IL6 Adaptive immunity also activated by dendritic cells

#Covid_19 molecular pathogenesis & #IL6

#covidclinicalpearls /42

#Tocilizumab in #COVID19
21 #Covid_19 patients 17 severe & 4 critical

All patients improved -19 discharged ~ avg D13

75% ⬇️ lowered FiO2 levels
CT improvement in 90%

#covidclinicalpearls /43

A clinical trial for #sarilumab another #IL6 blocker in #Covid_19 is currently underway;

Attractive alternative to #Tocilizumab for #COVID19

#Sarilumab higher #IL6 R binding affinity vs #Tocilizumab

#covidclinicalpearls /44

Maximal #IL6 highly predictive of respiratory failure in #COVIDー19

For #IL6 ≥ 80pg/ml, risk of respiratory failure was 92%

Sound rationale for #Tocilizumab #sarilumab in #COVID19

#covidclinicalpearls / 45

Patients at risk for #CytokineStorm in #COVIDー19 should be identified with serum biomarkers

#DDimer
#Ferritin
#LDH
#IL6

If ⬆️ start #Tocilizumab early + #steroids + #anticoag (for ⬆️DDimer)

#covidclinicalpearls / 46

#COVID19 #Yale protocol suggests following lab tests

Every 12 hours #DDimer #troponin

Every 24 hours #Ferritin CBC PT/PTT fibrinogen; EKG

Every 48 hours #cytokine panel

#covidclinicalpearls / 47

#Hydroxychloroquine and #Azithromycin combinations in #Covid_19 - more data from France - this is likely the 3rd study (pre-publication) Raoult et al

▫️91.7% positive clinical outcome & virologic cure
▫️NO cardiac toxicity
▫️1061 patients; 5 deaths

#covidclinicalpearls /48

#remdesevir in #COVIDー19 respiratory failure
53 patients
17/30 (57%) on vent extubated,
3/4 on ECMO weaned off

Overall 13% mortality
Mortality for those on vent 18% (much lower than historic controls)
Not a RCT but excellent results #covid19

#covidclinicalpearls /49

#pregnancy in #COVID19
Spanish algorithm

Mild #COVID__19 illness - bimonthly fetal growth ultrasounds and Doppler.

Vaginal delivery via induction of labour favoured to avoid unnecessary surgical complications unless septic shock/MSOF

#covidclinicalpearls /50

#Pathology in #COVID19 autopsy findings

Thrombotic microangiopathy restricted to the lungs.

Small vessel thrombus formation in the lung periphery in many cases with foci of alveolar hemorrhage.

No secondary infection

#Covid_19
#covidclinicalpearls /51

#COVID__19 Lab markers provide important insight into prognosis & hence need to be monitored closely even in patients who appear stable.

#DDimer #ferritin #IL6 #lymphocyte % #LDH

#covid19

#covidclinicalpearls /52

#COVID__19 CNS manifestations including #CVA #stroke are reported

Case series from #Wuhan describes 6 cases /214 presenting with ischemic stroke / hemiplegia & 16 with impaired LOC

Patients may not manifest typical symptoms of #covid19 infection

#covidclinicalpearls / 53

#Hydroxychloroquine in #covid19 story gets murkier everyday.

#HCQ vs supportive care compared in 63 #COVID__19 pts

#Hydroxychloroquine associated with a need for ⬆️respiratory support & ⬆️risk for intubation by D5

Mortality HCQ 4/31 (vs 1/32)

#covidclinicalpearls /54

#COVID__19 High prevalence of thromboembolism even in patients receiving prophylaxis.
Dutch series 184 ICU #COVID19 patients

31% incidence of #thrombotic complication
#Pulmonaryembolism was the most frequent thrombotic complication (n=25)

#covidclinicalpearls /55

#COVID19 Just ~ 20% of patients who died in #Wuhan received mechanical #ventilation !

Partly related to shortage of vents (?)
Also underscores #COVID__19 patients can deteriorate quickly. Need to monitor closely & intervene early

#covidclinicalpearls / 56

Cough in patients with #COVID__19 tends to be especially severe & often resistant to standard #antitussive measures.
#Morphine 2.5 - 5mg q4 suggested in these #COVID19 patients.

#covidclinicalpearls / 57

#COVID19

3 phase model of pathogenesis

Stg1 : early infection
#Antiviral

Stg 2 Pulm involvement 2A without & 2B with hypoxia
#Steroid use in 2B

Stg 3 #CytokineStorm & systemic #HLH
#Steroid #Tocilizumab

#covidclinicalpearls / 58

Biggest risk factors associated with severity of #COVID19 pneumonia are Age > 70; Adiposity #Obesity BMI > 40 & #Asian ethnicity

Obesity & OSA are associated with ⬆️ #IL6 levels & may be ➡️exaggerated #CytokineStorm in #COVID__19

#covidclinicalpearls /59

#Bloodgroup analysis of #COVID19 from China appear to show
A predilection for #blood group A (38% cases; OR 1.28)
&
A relative protection with blood group O (25% of cases; OR 0.68)

Similar distribution seen with #SARS previously

#covidclinicalpearls / 60

#Obesity a major risk for serious #COVID19 infection

More data showing morbidity in #Covid_19 esp age < 60yrs is significantly modulated by #obesity OR 3.6

#ACE2 expresses in adipocytes & expression is ⬆️ in obesity ➡️ >> risk of severe illness.

#covidclinicalpearls / 61

Protecting #HealthWorkers in #COVID19 rooms includes using #oxygen including #highflow and #NIV in ways that minimize aerosol dispersion & potential infection.
#O2 via NRB better than nasal canula
#NPPV via helmet with air tight cushion works best

#covidclinicalpearls / 62

Correct placement of high flow oxygen nasal canula #HFNC & bag mask ventilation in patients with #COVID19

Important to prevent aerosol dispersion & protect #HealthWorkers in #Covid_19

#covidclinicalpearls / 63

Yet another #Fail #Hydroxycloroquine study in #COVID19 also from France from 4 centers

NO difference in ICU admission, ARDS or Mortality in #covid_19

medrxiv.org/content/10.110…

#covidclinicalpearls / 64

#Hydroxychloroquine in #COVID19 another #FAIL

150 hospitalized #Covid_19 RCT - #HCQ vs SOC
Day28 viral negative conversion rate was not different 85.4% vs 81.3%.

No difference in symptoms alleviation rate D28

30% adverse events in HCQ; 2 SAE.

#covidclinicalpearls / 65