Updates in COVID 19 31-3-2020

2. COVID-19
Gamal Agmy, MD, FCCP
Professor and Head of Chest Department ,
Assiut University, Egypt

3. COVID-19 (coronavirus disease 2019) is
an infectious disease caused by severe
acute respiratory syndrome coronavirus
2 (SARS-CoV-2), previously known
as 2019 novel coronavirus (2019-nCoV),
a strain of Corona Virus

4. The first cases were seen in Wuhan, China
in December 2019 before spreading globally.
The current outbreak was recognized as a
P a n d e m i c o n 1 1 M a r c h 2 0 2 0 .

5. Most people infected with the COVID-19
virus will experience mild to moderate
respiratory illness and recover without
requiring special treatment. Older people,
and those with underlying medical
problems like cardiovascular disease,
diabetes, chronic respiratory disease, and
cancer are more likely to develop serious
illness.

6. The best way to prevent and slow down
transmission is be well informed about the
COVID-19 virus, the disease it causes and
how it spreads. Protect yourself and others
from infection by washing your hands or
using an alcohol based rub frequently and
not touching your face.

7. The COVID-19 virus spreads primarily
through droplets of saliva or discharge
from the nose when an infected person
coughs or sneezes, so it’s important that
you also practice respiratory etiquette
(for example, by coughing into a flexed
elbow).

8. Terminology
The WHO originally called this illness "novel
coronavirus-infected pneumonia (NCIP)" and
the virus itself had been named "2019 novel
coronavirus (2019-nCoV)
On 11 February 2020, the WHO officially
renamed the clinical condition COVID-19 (a
shortening of COronaVIrus Disease-19) .

9. Terminology
Coincidentally, on the same day, the
Coronavirus Study Group (CSG) of the
International Committee on Taxonomy of
Viruses renamed the virus "severe acute
respiratory syndrome coronavirus 2" (SARS-
CoV-2) .

10. Terminology
The official virus name is similar to SARS-CoV,
the virus strain that caused epidemic Severe
Acute Respiratory Syndrome(SARS) in 2002-
2004, potentially causing confusion . The WHO
has stated it will use "COVID-19 virus" or the
"virus that causes COVID-19" instead of its
official name, SARS-CoV-2, in dealings with the
public.

11. Epidemiology
As of 31 March 2020, 754.948 cases of
COVID-19 have been confirmed worldwide,
having been diagnosed in 203 countries,
with 36.571 confirmed deaths. There are
nine countries with >10,000 confirmed
cases and 27 countries with between 1000
and 10,000 confirmed cases. On 27 March
2020, the USA surpassed China as the
country with the most confirmed cases

12. Epidemiology
The R0(basic reproduction number) of
SARS-CoV-2 has been estimated
between 2.2 and 3.28 , that is each infected
individual, on average, causes between 2-3
new infections.

13. Epidemiology
The Incubation period for COVID-19 was initially
calculated to be ~5 days, which was based on 10 patients
only . An American group performed an epidemiological
analysis of 181 cases, for which days of exposure and
symptom onset could be estimated accurately. They
calculated a median incubation period of 5.1 days, that
97.5% became symptomatic within 11.5 days ( 8.2 to 15.6
days) of being infected, and that extending the cohort to
the 99th percentile results in almost all cases developing
symptoms in 14 days after exposure to SARS-CoV-2

14. Epidemiology
The number of deaths from COVID-19 is 36.571 (31
March), with a case fatality rate of 2-3% . It is speculated
that the true case fatality rate is lower than this, because
many mild cases are not being tested which thus skews
the apparent death rate upwards
A paper published by the Chinese Center for Disease
Control and Prevention (CCDC) analyzed all 44,672 cases
diagnosed up to 11 February 2020. Of these, 1.2% were
asymptomatic and 80.9% were classed as "mild"

15. Epidemiology
Another study looked at clinical characteristics in
COVID-19 positively tested closed contacts of
COVID-19 patients . Approximately 30% of those
COVID-19 positive close contacts never developed
any symptoms or changes on chest CT scans. The
remainder showed changes on CT but ~20%
reportedly developed symptoms during their hospital
course, none of them developed severe disease .
This suggests that a high percentage of COVID-19
carriers are asymptomatic.

16. Epidemiology
In the Chinese population, 55-60% of COVID-19
patients were males and the median age has
been reported between 47 and 59 years
Children seem to be relatively unaffected by this
virus, or indeed other closely-related
coronaviruses with large cohort studies
reporting that 1-2% of COVID-19 patients are
children.

17. Epidemiology
However, there have been cases of critically-ill
children with infants under 12 months likely to be
more seriously affected . A very low number of
pediatric deaths have been reported . In children,
male gender does not seem to be a risk factor .
The incubation period has been reported to
shorter than adults, at about two days .

18. Clinical presentation
COVID-19 typically presents with systemic
and/or respiratory manifestations . Some
individuals infected with SARS-CoV-2 are
asymptomatic and can act as
carriers . Some also experience mild
gastrointestinal or cardiovascular
symptoms, although these are much less
common 1

19. Clinical presentation
Common:
Fever (85-90%)
Cough(65-70%)
fatigue (35-40%)
sputum production
(30-35%)
shortness of breath
(15-20%)
Less common:
Mylagia/arthralgia
(10-15%)
headaches (10-
15%)
sore throat (10-
15%)
chills (10-12%)
pleuritic pain

20. Clinical presentation
Rare:
nausea, vomiting, nasal congestion (<10%),
diarrhoea (<5%)
Palpitation and chest tightness

21. Clinical presentation
Pediatric
In the main, the clinical presentation in children
with COVID-19 is milder than in adults.
Symptoms are similar to any acute chest
infection, encompassing most commonly
pyrexia, dry cough, sore throat, sneezing,
myalgia and lethargy. Wheezing has also been
noted . Other less common (<10%) symptoms
in children included diarrhea, lethargy,
rhinorrhea and vomiting

22. Diagnosis

24. Diagnosis
The definitive test for SARS-CoV-2 is
the real-time reverse transcriptase-
polymerase chain reaction (RT-
PCR) test and is believed to be
highly specific but with sensitivity reported as
low as 60-70% and as high as 95-97% .
Thus, false negatives are a real clinical
problem and several negative tests might be
required in a single case to be confident
about excluding the disease.

25. Laboratory tests
The most common ancillary laboratory
findings in a study of 138 hospitalized
patients were the following :
lymphopenia
increased prothrombin time (PT)
increased lactate dehydrogenase
Mild elevations of inflammatory
markers (CRP and ESR) and D-dimer are
also seen

26. Radiographic features
The primary findings of COVID-19 on chest
radiograph and CT are those of atypical
pneumonia or organizing pneumonia .
Imaging has limited sensitivity for COVID-19,
up to 18% demonstrate normal chest x-rays or
CT when mild or early in the disease course
but this decreases to 3% in severe
disease . Bilateral and/or multilobar
involvement is common

27. Radiographic features
Plain radiograph
may be normal in initial stages
asymmetric patchy or diffuse airspace
opacities have been descibed

28. Halo Sign
CT shows nodular consolidation associated with a halo of ground-glass
opacity (GGO) in both apices resulting from invasive pulmonary
aspergillosis.
This halo represents hemorrhage.
When seen in leukemic patients, is highly suggestive of the diagnosis of
invasive pulmonary aspergillosis.

29. CT Halo Sign

31. Reverse Halo Sign
•Central ground-glass opacity surrounded
by denser consolidation of crescentic or
ring shape, at least 2 mm thick
•First described by Voloudaki in 1996
•Kim in 2003 used the term reverse halo
•Found to be relatively specific for crypto-
genic organizing pneumonia (COP)

32. Reverse Halo Sign
Seen in other conditions:
•Wegener’s granulomatosis
•lymphomatoid granulomatosis
•paracoccidiodomycosis
•neoplastic (metastasis)
•invasive aspergillosis
•lipoid pneumonia

35. Tree-in-Bud Sign
•

36. Secondary lobule
Basic anatomic unit of pulmonary
structure and function.
1-2 cm and is made up of 5-15
pulmonary acini
Supplied by a small bronchiole
(terminal bronchiole) in the
center, that is parallelled by the
centrilobular artery.
Pulmonary veins and lymphatics
run in the periphery
Two lymphatic systems:
 central network
 peripheral network

37. Perilymphatic distribution
Centrilobular distribution
Random distribution

40. Crazy Paving in a patient with Alveolar proteinosis.

41. Radiographic features

42. Radiographic features
CT Typical findings (Radiopaedia)
The primary findings on CT in adults have been
reported :
ground-glass opacities (GGO): bilateral,
subpleural, peripheral
crazy paving appearance (GGOs and inter
/intra-lobular septal thickening)
air space consolidation
bronchovascular thickening in the lesion
traction bronchiectasis

43. Radiographic features
Ultrasound

45. INTERSTITIAL SYNDROME

46. A lines = default normal
 Horizontal echo
reflection at exact
multiples of intervals
from surface to
bright reflector.
 Dry lung OR PNTX
 Decay with depth
 Obliterated by B
pleura A
A
A
A
A
A

49. Tissue pattern representative of Alveolar
Consolidation
Presence of hyperechoic punctiform
imagesrepresentative of air bronchograms
Pleural
effusion
Lower lobe

50. Radiographic features
(Radiopaedia)
CT excluding findings
mediastinal lymphadenopathy
pleural effusions
multiple tiny pulmonary nodules (unlike
many other viral pneumonia )
tree-in-bud appearance
pneumothorax
cavitation

51. Radiographic features
Temporal CT
Four stages on CT have been described :
early/initial stage (0-4 days): normal CT or GGO
only
up to half of patients have normal CT scans within 2 days
of symptom onset
progressive stage (5-8 days): increased GGO and
crazy paving appearance.
peak stage (9-13 days): consolidation
absorption stage (> 14 days): with an improvement in the
disease course, "fibrous stripes" appear and the
abnormalities resolve at 1 month and beyond

52. Radiographic features
Paediatric CT
In a small study of five children that had been
admitted to hospital with positive COVID-19
RT-PCR tests and who had CT chest
performed, only three children had
abnormalities. The main abnormality was
bilateral patchy ground-glass opacities,
similar to the appearances in adults, but less
florid, and in all three cases the opacities
resolved as they clinically recovered .

53. Radiographic features
Pediatric CT
On 18 March 2020, the details of a much larger
cohort of 171 children with confirmed COVID-
19, and evaluated in a hospital setting was
published as a letter in the New England
Journal of Medicine. Ground-glass opacities
were seen in one-third of the total, whereas
almost 16% of children had no imaging
features of pneumonia .

54. Radiographic features
Ultrsound
The following patterns have been observed,
tending to have a bilateral and posterobasal
predominance:
multiple B-lines
ranging from focal to diffuse with spared areas
representative of thickened subpleural
interlobular septa
irregular, thickened pleural line with scattered
discontinuities

55. Radiographic features
Ultrasound
subpleural consolidations
pneumonic consolidation typically associated
with preservation of flow or hyperemia
alveolar consolidation
tissue-like appearance with dynamic and
static air bronchograms
associated with severe, progressive disease
restitution of aeration during recovery
reappearance of bilateral A-lines

58. Egyptian Ministry of Health and
Population
The key +ve CT findings:
1-ground glass opacity 100%
2-Involvement of multiple lobes (100%)
3-Subpleural or peripheral distribution (100%)
4-Consolidations(87.8%)
5-Septal thickening(55.6%)
6-Bronchial dilatation and wall thickening
(55.6%)

59. Egyptian Ministry of Health and
Population
The key -ve CT findings:
1-Pleural effusion 0%
2-Mediastinal lymphadenopathy 0%
3-Lung nodules 0%
4-specific Zonal predominance (variable)

61. Pathology
Etiology:
On 9 January 2020, the World Health Organization
(WHO) confirmed that SARS-CoV-2 was the cause
of COVID-19 (2019-nCoV was the name of the
virus at that time).
It is a member of theBetacoronavirus genus, one
of the genera of the Coronaviridae family of
viruses. Coronaviruses are enveloped single-
stranded RNA viruses that are found in humans,
mammals and birds. These viruses are
responsible for pulmonary, hepatic, CNS, and
intestinal disease.

62. Pathology
Etiology:
As with many human infections, SARS-CoV-2
is zoonotic. The closest animal coronavirus by genetic
sequence is a bat coronavirus, and this is the likely
ultimate origin of the virus . The disease can also be
transmitted by snakes.
Six coronaviruses are known to cause human
disease.Two are zoonoses: the severe acute respiratory
syndrome coronavirus (SARS-CoV) and Middle East
respiratory syndrome coronavirus (MERS-CoV) . both of
which may sometimes be fatal. The remaining four
viruses cause the common cold.

63. Transmission
Although originating from animals, COVID-19 is not considered
a direct zoonosis as its transmission is now primarily
human-to-human. It is primarily transmitted in a similar way to
the common cold, via contact with droplets of infected
individuals' upper respiratory tract secretions, e.g. from
sneezing or coughing .
A recent Bayesian regression model has found that aerosol
and fomite transmission are plausible
Orofecal spread was seen with the SARS epidemic, and
although it remains unclear if SARS-CoV-2 can be transmitted
in this way, there is some evidence for it .

64. Transmission
A recently published cohort study (26 March 2020) could not
rule out the possibility of vertical transmission with 9% of
neonates (n=3/33) developing an early onset SARS-CoV-2
infection despite strict infection control measures during
delivery . However, a retrospective study of nine pregnant
patients infected by SARS-CoV-2 did not show any evidence of
vertical/intrauterine infection . More recent published (20 March
2020) guidance from a joint American-Chinese consensus
panel stated that it remains unclear if vertical transmission
can occur.

65. Complications
In one of the largest studies of hospitalized patients,
reviewing 1,099 individuals across China, the admission rate
to the intensive care unit (ICU) was 5% . In this same study,
6% of all patients required ventilation, whether invasive or
non-invasive.
ICU patients tend to be older with more comorbidities .
Common reported sequelae include the following:
acute respiratory distress syndrome (ARDS): ~22.5% (range
17-29%)

66. Complications
acute cardiac injury: elevated troponin levels
myocardial ischemia
cardiac arrest
secondary infections
sepsis
acute kidney injury (AKI)
multiorgan failure
In a small subgroup of severe ICU cases:
secondary hemophagocytic lymphohistiocytosis (a cytokine
storm syndrome

67. Differential diagnoses
viral pneumonia including :
influenza pneumonia A and B
distribution more along the bronchovascular
bundles
bronchial wall thickening
paramyxovirus pneumonia
cytomegalovirus (CMV) pneumonia
adenovirus pneumonia
SARS-CoV pneumonia
MERS coronavirus
HSV pneumonia
in immunocompromised patients

68. Differential diagnoses
respiratory syncytial virus (RSV) pneumonia
atypical bacterial pneumonia
mycoplasma pneumonia
mainly children and adolescents
bronchial wall thickening
centrilobular nodule
chlamydia pneumonia
​pulmonary edema
interstitial lung disease
cryptogenic organizing pneumonia
chronic eosinophilic pneumonia (CEP)
acute fibrinous organizing pneumonia
rheumatoid arthritis-associated pneumonia

71. Blood from people who recover from coronavirus could provide a treatment
Plasma is being studied as a way to fight off the virus

72. FDA Approves Plasma Treatment for Coronavirus on Conditional
Basis
Survivors Of COVID-19 May Hold The Key For Everyone Else — In
Their Blood
This week, researchers in New York City started collecting blood from
COVID-19 survivors. The hope is that their immunity can be shared with
others.

73. Treatment and prognosis
NSAIDs
Emerging expert opinion is that non-steroidal
anti-inflammatory drugs (NSAIDs) are relatively
contra-indicated in those with COVID-19. This
is based upon several strands of "evidence“ :
1-since 2019 the French government National
Agency for the Safety of Medicines and Health
Products has advised against the routine use of
NSAIDs as antipyretic
2-previous research has shown that NSAIDs
may suppress the immune system

74. Treatment and prognosis
NSAIDs
3-anecdotal reports from France
suggest that young patients on
NSAIDs, otherwise previously fit and
well, developed more severe COVID-
19 symptoms.

75. Treatment and prognosis
NSAIDs
However, it is important to note that
there is currently (March 2020) no
published scientific evidence showing
that NSAIDs increase the risk of
developing COVID-19 or worsen
established disease

76. Prognosis
Progressive deterioration of imaging
changes despite medical treatment is
thought to be associated with poor
prognosis . There is an increased risk of
death in men over the age of 60 years old .
The mortality rate is estimated to be 3.6% .
Early reports show that in some well
patients, the RT-PCR test remains falsely
positive despite an apparent clinical
recovery. This raises the concern that
asymptomatic carriage may occur