Pneumonia

Dr Coraline
• Pneumonia in general
• Community acquired pneumonia
• Covid pneumonia
 Pneumonia
• Pneumonia is defined as inflammation of the substance of the lungs. It is usually
caused by bacteria but can also be caused by viruses and fungi.
• Community-acquired pneumonia
• Hospital-acquired pneumonia (sometimes called ‘healthcare-associated pneumonia’)
• Aspiration pneumonia
• Pneumonia in immunocompromised patient
• Ventilator-acquired pneumonia
Hospital-acquired:
• Defined as >48h after hospital admission. Most commonly Gram-negative enterobacteria or
Staph. aureus. Also Pseudomonas, Klebsiella, Bacteroides, and Clostridia.
• Treatment ; Aminoglycoside IV + antipseudomonal penicillin IV or 3rd-generation
cephalosporin
Aspiration:
• Those with stroke, myasthenia, bulbar palsies, decreased consciousness (eg postictal or
intoxicated), oesophageal disease (achalasia, refl ux), or poor dental hygiene risk aspirating
oropharyngeal anaerobes.
• Treatment ; Cephalosporin IV + metronidazole IV
Immunocompromised patient:
• Strep. pneumoniae, H. infl uenzae, Staph. aureus, M. catarrhalis, M. pneumoniae, Gram -ve
bacilli and Pneumocystis jirovecii (formerly named P. carinii, ). Other fungi, viruses (CMV,
HSV), and mycobacteria.
 Community acquired pneumonia (CAP)
• Community-acquired pneumonia (CAP), an infection of the lung parenchyma that
occurs in persons outside of a hospital setting, is associated with high
morbidity and mortality.
• In 2016, pneumonia was the primary diagnosis in more than 1.7 million
patient visits to emergency departments in the United States. A recent study
projected that CAP results in 1.5 million hospitalizations of adults in the U.S.
annually, with about one in three CAP patients dying within 1 year.
 Risk factors for community-acquired pneumonia

• Age: <16 or >65 years

• Co-morbidities: HIV infection, diabetes mellitus, chronic kidney disease, malnutrition,
recent viral respiratory infection
• Other respiratory conditions: cystic fibrosis, bronchiectasis, chronic obstructive
pulmonary disease, obstructing lesion (endoluminal cancer, inhaled foreign body)
• Lifestyle: cigarette smoking, excess alcohol, intravenous drug use
• Iatrogenic: immunosuppressant therapy (including prolonged corticosteroids)
 Causes
• Typical organisms: Streptococcus pneumoniae (commonest), Haemophilus influenzae, Moraxella
catarrhalis.
• Atypicals: Mycoplasma pneumoniae, Staphylococcus aureus, Legionella species, and Chlamydia.
• Gram-negative bacilli, Coxiella burnetii and anaerobes are rarer .

• Viruses account for up to 15%.

• Flu may be complicated by community-acquired MRSA pneumonia.
 Specific pneumonias
Pneumococcal pneumonia
• The commonest bacterial pneumonia. Affects all ages, but is commoner in the
elderly, alcoholics, post-splenectomy, immunosuppressed, and patients with chronic
heart failure or pre-existing lung disease.
• Clinical features: Fever, pleurisy, herpes labialis.
• CXR shows lobar consolidation.
• If mod/severe, check for urinary antigen.
• Treatment: amoxicillin, benzylpenicillin, or cephalosporin.
Staphylococcal pneumonia
• May complicate influenza infection or occur in the young, elderly, intravenous drug
users, or patients with underlying disease, eg leukaemia, lymphoma, cystic fibrosis
(CF).
• It causes a bilateral cavitating bronchopneumonia.
• Treatment: flucloxacillin ± rifampicin,
• MRSA: contact lab; consider vancomycin.
Klebsiella pneumonia
• Rare. Occurs in elderly, diabetics, and alcoholics.
• Causes a cavitating pneumonia, particularly of the upper lobes, often drug resistant.
• Treatment: cefotaxime or imipenem.
Pseudomonas
• A common pathogen in bronchiectasis and CF.
• It also causes hospital-acquired infections, particularly on ITU or after surgery.
• Treatment: antipseudomonal penicillin, ceftazidime, meropenem, or ciprofloxacin +
aminoglycoside.
• Consider dual therapy to minimize resistance.
Mycoplasma pneumoniae
• Occurs in epidemics about every 4yrs.
• It presents insidiously with flu-like symptoms (headache, myalgia, arthralgia)
followed by a dry cough.
• CXR: reticular-nodular shadowing or patchy consolidation often of one lower lobe,
and worse than signs suggest.
• Diagnosis: PCR sputum or serology. Cold agglutinins may cause an autoimmune
haemolytic anaemia.
• Complications: Skin rash (erythema multiforme), Stevens–Johnson syndrome,
meningoencephalitis or myelitis; Guillain–Barré syndrome.
• Treatment: Clarithromycin (500mg/12h) or doxycycline (200mg loading then 100mg
OD) or a fluroquinolone (eg ciprofloxacin or norfloxacin).
Legionella pneumophila
• Colonizes water tanks kept at <60°C (eg hotel air-conditioning and hot water
systems) causing outbreaks.
• Flu-like symptoms (fever, malaise, myalgia) precede a dry cough and dyspnoea.
• Extra-pulmonary features include anorexia, D&V, hepatitis, renal failure, confusion,
and coma.
• CXR shows bi-basal consolidation.
• Blood tests may show lymphopenia, hyponatraemia, and deranged LFTS.
• Urinalysis may show haematuria.
• Diagnosis: Urine antigen/culture.
• Treatment: fluoroquinolone for 2–3wks or clarithromycin. 10% mortality
Chlamydophila pneumoniae
• The commonest chlamydial infection.
• Person-to-person spread, biphasic illness: pharyngitis, hoarseness, otitis, followed
by pneumonia.
• Diagnosis: Chlamydophila complement fixation test, PCR invasive samples.
• Treatment: Doxycycline or clarithromycin.
Chlamydophila psittaci
• Causes psittacosis, an ornithosis acquired from infected birds (typically parrots).
• Symptoms include headache, fever, dry cough, lethargy, arthralgia, anorexia, and
D&V.
• Extra-pulmonary features are legion but rare, eg meningo-encephalitis, infective
endocarditis, hepatitis, nephritis, rash, splenomegaly.
• CXR shows patchy consolidation.
• Diagnosis: Chlamydophila serology.
• Treatment: doxycycline or clarithromycin.
Pneumocystis pneumonia

• Causes pneumonia in the immunosuppressed (eg HIV).

• It presents with a dry cough, exertional dyspnoea, decreased PaO2, fever, bilateral
crepitations.
• CXR may be normal or show bilateral perihilar interstitial shadowing
• Diagnosis: Visualization of the organism in induced sputum, bronchoalveolar
lavage, or in a lung biopsy specimen.
• Drugs: High-dose co-trimoxazole,(or pentamidine by slow IVI for 2–3 weeks.
Steroids are beneficial if severe hypoxaemia.
• Prophylaxis is indicated if the CD4 count is <200≈106/L or after the 1st attack.
 Clinical features
Symptoms
• a dry or productive cough, sometimes with haemoptysis
• breathlessness
• fevers, which, if swinging, may indicate empyema
• chest pain may be experienced, commonly pleuritic in nature
and due to inflammation of the pleura; a pleural rub may be
heard early on in the illness
• extrapulmonary features
 Extrapulmonary features of community-
acquired pneumonia
• Myalgia, arthralgia and malaise are common, particularly in infections caused
by Legionella and Mycoplasma
• Myocarditis and pericarditis are cardiac manifestations of infection, most
commonly in Mycoplasma pneumonia
• Headache is common in Legionella pneumonia. Meningoencephalitis and
other neurological abnormalities also occur but are much less common
 Extrapulmonary features of community-
acquired pneumonia
• Abdominal pain, diarrhoea and vomiting are common. Hepatitis can be a feature of
Legionella pneumonia
• Labial herpes simplex reactivation is relatively common in pneumococcal
pneumonia
• Other skin rashes, such as erythema multiforme and erythema nodosum, are found
in Mycoplasma pneumonia. Stevens–Johnson syndrome is a rare and potentially
life-threatening complication of pneumonia
Signs:
• Pyrexia,
• Cyanosis,
• Confusion (can be the only sign in the elderly—may also be hypothermic),
• Tachypnoea,tachycardia, hypotension,
• signs of consolidation (reduced expansion, dull percussion, increased tactile
vocal fremitus/vocal resonance, bronchial breathing), and a pleural rub.
 Investigations in community-acquired pneumonia

Blood
Full blood count
• Very high (> 20 × 109/L) or low (< 4 × 109/L) white cell count
• Neutrophil leucocytosis > 15 × 109/L: suggests bacterial aetiology
• Haemolytic anaemia: occasional complication of Mycoplasma
Erythrocyte sedimentation rate/C-reactive protein
• Non-specifically elevated
 Investigations in community-acquired pneumonia

Urea and electrolytes

• Urea > 7 mmol/L (~20 mg/dL): marker of severity
• Hyponatraemia: marker of severity

Liver function tests

• Abnormal if basal pneumonia inflames liver
• Hypoalbuminaemia: marker of severity
 Investigations in community-acquired pneumonia

Blood culture
• Bacteraemia: marker of severity
Cold agglutinins
• Positive in 50% of patients with Mycoplasma
Arterial blood gases
• Measure when SaO2 < 93% or when clinical features are severe, to assess ventilatory failure
or acidosis
 Investigations in community-acquired pneumonia

Chest X-ray
• Lobar pneumonia
• Patchy opacification evolves into homogeneous consolidation of affected lobe
• Air bronchogram (air-filled bronchi appear lucent against consolidated lung tissue) may be
present
• Bronchopneumonia
• Typically patchy and segmental shadowing
 Investigations in community-acquired pneumonia

• Complications
• Para-pneumonic effusion, intrapulmonary abscess or empyema
• Staphylococcus aureus
• Suggested by multilobar shadowing, cavitation, pneumatoceles and abscesses

Pleural fluid
• Always aspirate and culture when present in more than trivial amounts, preferably with
ultrasound guidance
 Investigations in community-acquired pneumonia

Sputum
Sputum samples
• Gram stain, culture and antimicrobial sensitivity testing
Oropharynx swab
• Polymerase chain reaction for Mycoplasma pneumoniae and other atypical pathogens

Urine
• Pneumococcal and/or Legionella antigen
 Chest X-ray
• Radiological abnormalities can lag behind clinical signs.
• A normal chest X-ray on presentation should be repeated after 2–3 days if CAP is
suspected clinically.
• The chest X-ray must be repeated 6weeks later to rule out an underlying bronchial
malignancy causing pneumonia due to bronchial obstruction.
 Blood tests
Strep. pneumoniae
• White cell count is usually >15 × 59/L (90% leucocytosis neutrophils).
• Inflammatory markers are significantly elevated: erythrocyte sedimentation rate (ESR) >100 mm/h;
CRP>100 mg/L.
Mycoplasma
• White cell count is usually normal. In the presence of anaemia, haemolysis should be ruled out (direct
Coombs’ test and measurement of cold agglutin)
Legionella
• There is lymphopenia without marked leucocytosis, hyponatraemia, hypoalbuminaemia and high serum levels
of liver aminotransferases.
 Causes of slow-resolving pneumonia
Incorrect or incomplete antimicrobial Complication of community-acquired
treatment pneumonia
• Underlying antibiotic resistance • Parapneumonic pleural effusion
(exudative)
• Inadequate dose/duration
• Non-adherence • Empyema
• Malabsorption • Lung abscess
 Management
• The most important aspects of management include oxygenation,
fluid balance and antibiotic therapy. In severe or prolonged illness,
nutritional support may be required.

• Initial management and assessment should follow the guidelines for

management of sepsis, particularly when a patient appears to have a
moderate to severe pneumonia.
 General management
Oxygen
• Supplemental oxygen should be administered to maintain saturations between 94% and 98%
(provided the patient is not at risk of carbon dioxide retention, due to loss of hypoxic drive
in COPD).
• In patients with known COPD, oxygen saturations should be maintained between 88% and
92%.
Intravenous fluids
• These are required in hypotensive patients showing any evidence of volume depletion and
hypotension.
Antibiotics
• The first dose of antibiotic should be administered within 1 hour of identifying any high-risk
criteria and treatment should not be delayed while investigations are awaited.
• Parenteral antibiotics should be switched to oral once the temperature has settled for a
period of 24 h, provided there is no contraindication to oral therapy.
• If patients fail to respond to initial treatment, microbiological advice should be sought and
alternative diagnoses considered.
• The antibiotic regimen should be adjusted specifically once culture and sensitivity results are
available.
Thromboprophylaxis
If the patient is admitted for >12 h, subcutaneous low-molecular-weight heparin
should be prescribed and thromboembolus deterrent (TED) stockings should be
fitted, unless contraindications exist.

Physiotherapy
Chest physiotherapy is not needed unless sputum retention is an issue.
Nutritional supplementation
Need is assessed by a dietician, particularly in severe disease.
Analgesia
Simple analgesia, such as paracetamol or an NSAID, helps treat pleuritic pain, thereby
reducing the risk of further complications due to restricted breathing because of pain
(e.g. sputum retention, atelectasis or secondary infection).
 Pneumococcal vaccine
• At-risk groups:
• All adults ≥ 65yrs old.
• Chronic heart, liver, renal, or lung conditions.
• Diabetes mellitus not controlled by diet.
• Immunosuppression, eg impaired spleen function, AIDS, or on chemotherapy or
prednisolone >20mg/d, cochlear implant, occupation risk (eg welders), CSF fluid leaks.
• Vaccinate every 5yrs.
• CI: Pregnancy, lactation, increased T°, previous anaphylaxis to vaccine or one of its
components.
 Causes of slow-resolving pneumonia
Underlying neoplastic lesion or other lung Alternative diagnosis
disease
• Pulmonary thromboembolic disease
• Obstructing lesion • Cryptogenic organizing pneumonia
• Bronchoalveolar cell carcinoma • Eosinophilic pneumonia
• Bronchiectasis • Pulmonary haemorrhage
• Tuberculosis
 Complications of CAP
• Para-pneumonic effusion – common
• Empyema
• Retention of sputum causing lobar
collapse
• Pneumothorax, particularly with
Staphylococcus aureus
• Suppurative pneumonia/lung abscess
• Type I respiratory failure
• Deep vein thrombosis and pulmonary
embolism
• Septicaemia
• ARDS, renal failure, multi-organ failure
• Ectopic abscess formation (Staph. aureus)
• Hepatitis, pericarditis, myocarditis,
meningoencephalitis
• Arrhythmias (e.g. atrial fibrillation)
• Pyrexia due to drug hypersensitivity
Respiratory failure
• Type I respiratory failure (PaO2 <8kPa) is relatively common.
• Treatment is with high-flow (60%) oxygen.
• Transfer the patient to ITU if hypoxia does not improve with O2 therapy or PaCO2
rises to >6kPa.
• Be careful with O2 in COPD patients; check ABGS frequently, and consider elective
ventilation if rising PaCO2 or worsening acidosis.
• Aim to keep SaO2 at 94–98%, PaO2 ≥8kPa.
Hypotension
• May be due to a combination of dehydration and vasodilation due to sepsis.
• If systolic BP is <90mmHg, give an intravenous fl uid challenge of 250mL
colloid/crystalloid over 15min. If BP does not rise, consider a central line and give
IV fluids to maintain the systolic BP >90mmHg.
• If systolic BP remains <90mmHg despite fluid therapy, request ITU assessment for
inotropic support.
Atrial fibrillation
• Common in the elderly.
• It usually resolves with treatment of the pneumonia.
• ß-blocker or digoxin may be required to slow the ventricular response rate in the short term.
Pleural effusion
• Inflammation of the pleura by adjacent pneumonia may cause fluid exudation into the
pleural space. If this accumulates faster than it is reabsorbed, a pleural effusion develops. If
small, it may be of no consequence. If larger and patient symptomatic, or infected
(empyema), drainage is required.
Empyema
• Pus in the pleural space.
• It should be suspected if a patient with a resolving pneumonia develops a recurrent
fever.
• CXR indicates a pleural effusion. The aspirated pleural fluid is typically yellow and
turbid with a pH <7.2, ↓glucose, and ↑LDH.
• The empyema should be drained using a chest drain, inserted under radiological
guidance.
• Adhesions and loculation can make this difficult.
Lung abscess
• A cavitating area of localized, suppurative infection within the lung
• Causes: Inadequately treated pneumonia,Aspiration (eg alcoholism, oesophagealobstruction,
bulbar palsy), Bronchial obstruction (tumour, foreign body), Pulmonary infarction, Septic
emboli (septicaemia, right heart endocarditis, IV drug use), Subphrenic or hepatic abscess.
• Look for: finger clubbing; anaemia;
• Empyema develops in 20–30%.
• CXR: cavity, often with a fluid level.
• Consider CT scan to exclude obstruction, and bronchoscopy to obtain diagnostic
specimens.
• Treatment: Antibiotics as indicated by sensitivities; continue until healed (4–6 wks).
• Postural drainage. Repeated aspiration, antibiotic instillation, or surgical excision
• may be required.
Septicaemia
• May occur as a result of bacterial spread from the lung parenchyma into the
bloodstream.
• This may cause metastatic infection, eg infective endocarditis, meningitis.
• Treat with IV antibiotic according to sensitivities.
Pericarditis and myocarditis
• May also complicate pneumonia.
Jaundice
• This is usually cholestatic, and may be due to sepsis or secondary to antibiotic
therapy (particularly flucloxacillin and co-amoxiclav).
• The updated guidelines do not recommend routine collection of sputum Gram
stain and culture or blood cultures in CAP patients who are treated in the outpatient
setting.

• In the inpatient setting, it is recommended that pretreatment sputum Gram stain

with culture and blood cultures be obtained only in patients with severe CAP ,those
being empirically treated for MRSA or P aeruginosa, and those with strong risk
factors for these pathogens.
• Testing for pneumococcal urinary antigen and Legionella urinary antigen is recommended for
inpatients suspected of having severe CAP; testing for Legionella is also recommended if
epidemiologic factors (e.g., an outbreak) suggest the possibility of infection.

• In both the inpatient and the outpatient setting, testing for influenza is recommended when
influenza viruses are circulating in the community.
• The use of procalcitonin is not recommended to determine the need for initial antibiotic
therapy in patients with CAP, and empirical antibiotic therapy should be initiated in adults
with clinically suspected and radiographically confirmed CAP regardless of serum
procalcitonin levels.
 Outpatient Setting
• For patients without comorbid conditions or risk factors for drug-resistant
pathogens, monotherapy with amoxicillin, doxycycline, or a macrolide (azithromycin
or clarithromycin) is recommended.
• However, owing to resistance-related factors, macrolide monotherapy went from
being a strong recommendation in the previous guidelines to a conditional
recommendation in the new guidelines.
• A macrolide should not be used if the local rate of resistance of pneumococcus is
greater than 25%, and in the U.S., the average rate of pneumococcal resistance to
macrolides is about 30%.
 Inpatient setting
• The standard recommended empirical regimen for inpatients with nonsevere
pneumonia is a beta-lactam plus a macrolide or a respiratory fluoroquinolone alone.
• In patients in whom the use of both macrolides and fluoroquinolones is
contraindicated, a beta-lactam may be used in combination with doxycycline as an
alternative empirical regimen.
• The recommended empirical regimen for inpatients diagnosed with severe
pneumonia is combination therapy with a beta-lactam plus a macrolide or a beta-
lactam plus a fluoroquinolone.
• An empirical antimicrobial agent with activity against MRSA and/or P
aeruginosa should be added in all inpatients with prior respiratory isolation of
the pathogen, as well as in patients having severe pneumonia with recent
hospitalization and receipt of parenteral antibiotics (within the past 90 days)
in addition to the presence of locally validated risk factors.
• In all cases, antimicrobial therapy may be deescalated after 48 hours (with
discontinuation of coverage for MRSA or P aeruginosa) if cultures for these
pathogens remain negative.
 Newly Approved Agents
1. Lefamulin
a bacterial protein synthesis inhibitor
CAP caused by S pneumoniae, methicillin-susceptible S aureus (MSSA), H
influenzae, Legionella pneumophila, M pneumoniae, and C pneumoniae.
A dosage of 150 mg IV every 12 hours or 600 mg orally every 12 hours with
dosage adjustment required for patients with hepatic impairment.
may prolong the QT interval
may cause fetal harm
2. Delafloxacin
a fluoroquinolone antibiotic
CAP caused by S pneumoniae, MSSA, selected gram-negative pathogens
(Klebsiella pneumoniae, Escherichia coli, P aeruginosa, H
influenzae, Haemophilus parainfluenzae), and atypical microorganisms (C
pneumoniae, L pneumophila, M pneumoniae)
• a dosage of 300 mg IV every 12 hours or 450 mg orally every 12 hours,
with adjustment required for patients with severe renal impairment.
 Duration of Therapy

• Patients with CAP should be treated for a minimum of 5 days, with antibiotic
therapy continued until the patient achieves clinical stability.
• Validated measures of clinical stability include resolution of vital sign
abnormalities (heart rate, respiratory rate, blood pressure, oxygen saturation, and
temperature); ability to eat; and normal mental status.
• Most patients achieve clinical stability within 48 to 72 hours after therapy initiation,
a 5-day course typically is sufficient.
• CAP due to suspected or proven MRSA or P aeruginosa should be treated for 7 days.
In CAP patients whose symptoms resolve within 7 days, routine follow-up chest
imaging is not recommended.
• Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of
adults with community-acquired pneumonia. An official clinical
practice guideline of the American Thoracic Society and Infectious
Diseases Society of America. Am J Respir Crit Care
Med. 2019;200(7):e45-e67.
Covid Pneumonia
• The most striking characteristic of the disease is its heterogeneity, ranging from no symptoms to
critical illness.
• Older age, male sex, race (particularly Black, Hispanic, and South Asian), and comorbidities
(including hypertension, diabetes, cardiovascular disease, chronic pulmonary disease, chronic
kidney disease, cancer, and chronic liver disease) have been associated with worse outcomes.
• Genetic factors may play a part as well, with blood type A associated with a higher risk for severe
disease.
• A common characteristic of SARS-CoV-2 is asymptomatic transmission, which is likely the cause of
rampant spread and transmission.
 Epidemiology & pathogenesis
• The COVID-19 pandemic has exploded since cases were first reported in China in
December 2019. As of December 14, 2021, more than 270 million cases of COVID-19—
caused by SARS-CoV-2 infection—have been reported globally, including more than 5.3
million deaths.
• The probability of serious COVID-19 disease is higher in people aged ≥60 years, those
living in a nursing home or long-term care facility, and those with chronic medical
conditions.
• The percentage of patients who died was 12 times higher among those with reported
medical conditions (19.5%) than among those without medical conditions (1.6%), and the
percentage of those who were hospitalized was 6 times higher among those with reported
medical conditions (45.4%) than among those without medical conditions (7.6%).

• The mortality rate was highest in those aged >70 years, regardless of the presence of
chronic medical conditions.

• Among those with available data on health conditions, 32% had cardiovascular disease, 30%
had diabetes, and 18% had chronic lung disease. Other conditions that may lead to a high
risk for severe COVID-19 include cancer, kidney disease, liver disease (especially in patients
with cirrhosis), obesity, sickle cell disease, and other immunocompromising conditions.
Transplant recipients and pregnant people are also at a higher risk of severe COVID-19.
 Structure of SARS -CoV-2
• SARS-CoV-2 is a positive sense, single stranded RNA enveloped virus in the Betacoronavirus
genus.
• Bats and pangolins may be the animal hosts of SARS-CoV-2 as there is a >90% gene
homology to the SARS-CoV-2 found to infect humans.
• In light of the current pandemic, researchers first compared SARS-CoV-2 with the previous
endemic SARS-CoV (2002-03) and MERS-CoV (2012).
• SARSCoV- 2 has overlapping genetic sequences with SARSCoV and MERS-CoV, with 79%
and 50% homology, respectively.
 The S protein is also important
• for binding to the angiotensin converting enzyme 2
Structure of SARS -CoV-2 (ACE2) receptor, which is the point of entry of the
virus to the human and animal host.
• a major contributor to the immunogenic response;
therefore the S protein is the target of most vaccines.
The M protein is a transmembrane protein important in
viral pathogenesis.
The E protein is to play a role in viral replication and
infectivity.
The N protein allows for regulation of viral RNA
replication, transcription, and synthesis.
Transmitted primarily
• via respiratory droplets( large – 3 ft , small – 6 ft)
• Hand to mucus membrane contact

• Viable for 3 days on solid(Plastic ,porcelain, steel)

• Infection can be spread by asymptomatic , presymptomatic and symotomatic
carriers.
 SARS -CoV-2 invasion and replication in cells

• Older age and male sex of the host are also determinants of S protein-ACE2 binding
efficiency.
• ACE2 receptors are highly expressed in the upper respiratory tract of humans.
• Proteolytic cleavage of the S protein by serine proteases including transmembrane protease
serine 2 (TMPRSS2), cathepsin L, and furin, are required for binding to the ACE2 receptor.
• Similar to the ACE2 receptor, protease expression varies by tissue type and location, with a
high expression in the nasal and bronchial epithelium.
• In addition, human epithelial cells that line mucosal surfaces and cover organs such as
conjunctiva, gastrointestinal tract, liver, and kidney also express ACE2 and TMPRSS2.
 SARS -CoV-2 mutations

• SARSCoV- 2 mutated variants include

B.1.1.7 (UK variant),
P.1 (Brazilian variant), and
B.1.351 (South African variant).
• The primary region of mutation for these variants is in the spike protein.
• The B.1.1.7 variant has a greater rate of infectivity and spread, which may be related to
binding affinity to the ACE2 receptor.
 Host response

• Over the first few days after SARS-CoV infection, activation of toll-like receptors (TLR 3, 7,
and 8) by pathogen recognition receptors (PRRs) induces transcriptional upregulation of
interferons (type I and III interferons) and recruitment of leukocytes.
• Case and observational studies in patients with SARS-CoV-2 showed early detection of
specific IgA and IgM antibodies (within five days) and late detection of specific IgG
antibodies (after 14 days).
• In addition, disease severity has recently been shown to drive an enhanced antibody
response, which correlates with clinical outcomes.
• Clinical observation of lymphopenia has been apparent since the start of the covid-19
pandemic and may be associated with worsening disease.
• An adequate T cell response (both CD4+ and CD8+ T cells) directed toward SARS-CoV-2
has been shown to be associated with milder disease.
• Aging is well established to be associated with failure of regeneration of naive T cells and T
cell activation.
• Early descriptions of covid-19 included development of a cytokine storm as a harbinger for
clinical deterioration.
• More recent studies comparing serum cytokine measurements with other known cytokine
mediated diseases such as sepsis and cytokine release syndrome have noted that covid-19
patients’ serum cytokine levels were substantially lower.
• As a result, the direct role of cytokines in disease pathogenesis has been challenged.
• Autopsy studies of patients who have died from severe SARS CoV-2 infection reveal
presence of alveolar wall injury and diffuse alveolar damage consistent with ARDS.
• However, compared with classic ARDS, autopsy studies also indicate higher thrombus
burden in pulmonary capillaries, which suggests a greater pathogenic role of thrombotic and
microangiopathic vasculopathy in covid-19 related ARDS
• Studies collectively show that thromboembolism occurs more frequently and is associated
with a higher mortality in patients with covid-19.
• Additional studies are needed to delineate the direct clinical consequences of increased
thrombosis and its association with mortality in covid-19,
Pathophysiology
• The estimated incubation period for COVID-19 is up to 14 days from the time of
exposure, with a median incubation period of 4 to 5 days.
• Doubling time - 6-7 days
• High viral sheeding occurs early disease course and prolong shedding noted

• The spectrum of illness can range from asymptomatic infection to severe pneumonia
with acute respiratory distress syndrome and death.
81% of cases were reported to be mild ,
14% were severe and
5% were critical.

• In a report United States,

70% of patients experienced fever, cough, or shortness of breath,
36% had muscle aches, and
34% reported headaches.
• Other reported symptoms have included diarrhea, dizziness, rhinorrhea, anosmia, dysgeusia, sore
throat, abdominal pain, anorexia, and vomiting.

• Neurological manisfestations ; dizziness, agitation , weakness ,seizure or findings suggestive of

stroke including trouble with speech or vision ,sensory loss or problems with balance when standing
and walking .

• In older and immunocompromised patients , reduced alertness, reduced mobility , diarrhoeaa , loss
of appetite , confusion and absence of fever.
 Complications
• Acute complications
1. Venous Thromboembolism ( 20-31%)
2. Cardiovascular complications such as heart failure , AC$ , myocardial injury
(5-31%) , arrhythmias
3. Acute Kidney Injury ;11%
4,. Acute Liver Injury such as elevated ALT(26%), AST (37%), total bilirubin
(18%), decreased albumin (45%)
5. Neurology complications ; 36-57%
6. Pancreatic injury ; 17%
7. Septic shock; 4-8 %
8. ARDS ; 8% ( the leading cause of mortality )
9. Immune thrombocytopenia
10. Cytokine release syndrome
11. Autoimmune hemolytic anaemia
• The abnormalities seen in chest X-rays of patients with COVID-19 vary, but bilateral
multifocal opacities are the most common.
• The abnormalities seen in computed tomography of the chest also vary, but the most
common are bilateral peripheral ground-glass opacities, with areas of consolidation
developing later in the clinical course of COVID-19.
• Imaging may be normal early in infection and can be abnormal in the absence of
symptoms.

• Common laboratory findings in patients with COVID-19 include leukopenia and

lymphopenia. Other laboratory abnormalities have included elevated levels of
aminotransferase, C-reactive protein, D-dimer, ferritin, and lactate dehydrogenase.
 Management
• Depend on disease severity
• Symptomatic / supportive management at home in asymptomatic / mild patients
• Admit patients with moderate to sever disease
• Supportive management in hospital
… Oxygen therapy
… Fluid management
…VTE prophylaxis
…Respiratory support ( HFNO , NIV .IV )
 Management of epidemic
• Prevention
Safe public health practice – Vaccine , WASH (water, sanitation and hygiene) and infection
prevention and control measures, universal precautions
Surveillance systems of WHO ,CDC, community health
• Containment
Isolation of sick persons, contact tracing and quarantine of exposed persons
• Non pharmacological interventions
Personal – hand hygiene , cover cough, stay away from the sick person and avoid face
Social - Social distancing , cancelling mass gatherings/ non essential activities
Environmental – Cleaning measures
• https://www.covid19treatmentguidelines.nih.gov/