AUTHORS
Luke Erdahl, DO, Department of Emergency Medicine, Boonshoft School of Medicine, Wright State University, Dayton, OH
Michael Ballester, MD, Assistant Professor, Emergency Medicine, Program Director, Emergency Medicine, Boonshoft School of Medicine, Wright State University, Dayton, OH
PEER REVIEWER
Larissa I. Velez, MD, Associate Dean for Graduate Medical Education, Professor and Vice Chair for Education, Michael P. Wainscott Professorship in Emergency Medicine, Department of Emergency Medicine, UT Southwestern Medical Center, Dallas, TX
EXECUTIVE SUMMARY
- Pneumonia is an infection of the alveoli characterized by fever, cough, and pulmonary infiltrate.
- Prior to COVID-19, the most common pathogens found in adults hospitalized with pneumonia were rhinovirus, influenza, and Streptococcus pneumoniae.
- The identification of a pathogen is increased in severe cases of pneumonia and when multiple detection techniques are used.
- Blood cultures are not recommended for routine cases of pneumonia.
- SARS-CoV-2 and influenza testing is recommended when either is prevalent in the community.
- Healthy patients with suspected bacterial community-acquired pneumonia and who are otherwise suitable for
discharge can be treated with a course of oral antibiotics for five to seven days. - Patients with comorbidities who are appropriate for discharge should be treated with either an amoxicillin/clavulanic acid or a cephalosporin in addition to treatment with a macrolide or doxycycline for seven days.
- The concept of healthcare-associated pneumonia is not useful to identify patients at increased risk for infection from drug-resistant organisms.
- Scoring tools can be used to support clinical judgment in determining patients with a low mortality risk who may be appropriate for outpatient treatment.
- The effectiveness of monoclonal antibodies and antivirals is subject to change because of the potential development of resistance to newer variants.
Pneumonia is an infection of the alveoli of the lungs, as compared to bronchitis, which is inflammation of the conducting airways. Alveolar infection results in inflammation that disrupts normal pulmonary function, producing impaired gas exchange. Pneumonia can be caused by bacteria, viruses, or fungi. Pathogens can infect the lung parenchyma through three routes: inhalation, aspiration, or hematogenous spread.1 The severity of pneumonia can vary from mild illness to severe, life-threatening disease.
The Infectious Diseases Society of America (IDSA) defines pneumonia as meeting three criteria: 1) the presence of a pulmonary infiltrate on chest X-ray or computed tomography (CT); 2) at least one of the following signs or symptoms: cough, abnormal temperature, leukocytosis, or leukopenia; and 3) lack of a more appropriate alternative diagnosis.2
Pneumonia can be classified into community-acquired pneumonia (CAP) and nosocomial pneumonia. In CAP, the infection is initiated outside the hospital, and in nosocomial pneumonia the infection is acquired in the hospital. Nosocomial pneumonia includes both hospital-associated pneumonia (HAP) and ventilator-associated pneumonia (VAP). Hospital-acquired pneumonia is defined as pneumonia occurring more than 48 hours after hospitalization — which was not incubating at time of admission. Ventilator-associated pneumonia is defined as pneumonia occurring greater than 48 hours after intubation and initiation of mechanical ventilation.
Another category of pneumonia, healthcare-associated pneumonia or HCAP, was created to potentially identify patients with pneumonia who had recent contact with the healthcare system and would be suspected to be at higher risk for infection from drug-resistant organisms. The following patient categories were included in the HCAP definition: pneumonia in a nursing home patient; pneumonia in a patient who had been hospitalized within the past 90 days; or a patient who received infusion therapy, wound care, dialysis, or had been exposed to a family member with a multidrug-resistant organism in the past 30 days. Recent review of HCAP patients found that this definition was overly sensitive and correlated poorly with the identification of drug-resistant organisms.2 Categorizing patients with HCAP resulted in inappropriately broad antibiotic coverage, with increased adverse reactions and pressure on further drug-resistant bacteria selection. Thus, the term HCAP has been retired from clinical use.
Epidemiology
Pneumonia is one of the most frequent principal diagnoses in hospitalizations in adults in the United States.3 CAP accounts for more than 4.5 million outpatient and emergency room visits annually in the United States.4 Prior to 2000, the most common pathogens found in CAP were S. pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Chlamydia pneumoniae, and respiratory viruses (influenza viruses A or B, parainfluenza viruses 1 to 3, respiratory syncytial virus, and adenovirus).
The prevalence of COVID-19, the clinical disease caused by the SARS-CoV-2 virus, has changed the landscape of pneumonia. COVID-19 typically is a respiratory infection, with pneumonia and respiratory failure the most common cause of death. The COVID-19 pandemic was declared a national emergency by the United States on March 13, 2020.5 At the time of this publication, COVID-19 has resulted in 996,000 deaths in the United States. Despite the rise in COVID-19 cases, bacterial pneumonia continues to be prevalent.
A study conducted in Louisville, KY, as a representation of the population of the United States, analyzed the incidence, epidemiology, and mortality of CAP between 2014 and 2016.6 In this study, the age-adjusted annual incidence of hospitalization from pneumonia was 649 cases per 100,000 adults. Patients older than 65 years were more than three times more likely to be hospitalized with CAP compared to nonelderly adults. Patients with a prior diagnosis of chronic obstructive pulmonary disease (COPD) had a hospitalization rate that was nine times more than the average rate. All-cause mortality for hospitalized adult patients with CAP was 6.5% during hospitalization, 13% at 30 days, 23.4% at six months, and 30.6% at one year.6 Nine percent of hospitalized patients were hospitalized again in the same year.6
This study cross referenced census data to determine who is at a higher risk for pneumonia. Increased frequency of CAP hospitalizations correlated with areas of Black or African American race, low income, and a high percentage of elderly population. Although the incidence was higher for areas where African American/Black population was prevalent, the study found the incidence of pneumonia was similar between whites and African Americans overall, suggesting a social/housing impact may be greater than ethnicity.6
Etiology
In a study conducted between 2010 and 2012 at five hospitals in Chicago and Nashville, 2,259 patients hospitalized with radiographic evidence of pneumonia underwent a culture of blood, urine, and sputum for the causative agent.7 A pathogen was detected in 38% of the cases: one or more viruses in 23%, bacteria in 11%, and both bacterial and viral pathogens in 3%. The most common infectious organisms identified were human rhinovirus in 9%, influenza virus in 6%, and S. pneumoniae in 5%. This indicates that in the majority of these hospitalized patients, a pathogen was not identified, and when one was, most cases were viral.7
The detection rate of pathogens is increased in severe cases and when multiple detection techniques are used. In a study of 275 patients with severe CAP from China in 2018 to 2019 using multiple microbial detection techniques, a pathogen was identified in 72%.
Currently, the most common bacterial causes of CAP include S. pneumoniae, H. influenzae, Mycoplasma pneumoniae, Legionella species, C. pneumoniae, and Moraxella catarrhalis. Therefore, the initial antibiotic therapy recommended by the IDSA guidelines is empirically targeted to cover these organisms.2
A patient’s past medical history also may present clues to the diagnosis of pneumonia and potentially aid in determining the underlying pathogen. Vaccination status for pneumococcal pneumonia, influenza, and COVID-19 is an important historical element to gather. Patients with asplenia or compromised humoral immunity are at risk for infection with encapsulated bacteria, such as H. influenzae and S. pneumoniae. Neutropenic patients are at risk for infections with gram-negative bacilli and fungi such as Aspergillus. Patients with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) or patients with impaired T-cell immunity have increased risk of opportunistic pathogens, including viruses, intracellular bacteria, acid-fast bacteria, and fungi.8
Pathophysiology
Pneumonia develops when alveolar defenses are unable to eliminate pathogens, allowing them to multiply and produce an inflammatory reaction. The lower respiratory tract was previously thought to be sterile; however, new research has shown the presence of an innate microbiome. Polymerase chain reaction (PCR) testing of alveolar samples has identified small quantities of intact or remnant microbiologic genetic material.9 As in other locations with an innate microbiome, the alveolar microbiome contributes to healthy function and resistance to infection. Factors altering this pulmonary microbiome, such as antibiotic use, recent hospitalization, and steroid use, put the patient at increased risk for pneumonia.8,10
The body protects against respiratory infection through several mechanisms. Immunoglobulin A (IgA) antibodies located on mucous membranes bind pathogens as they enter the upper airway.11 Coughing helps protect the lower respiratory tract by clearing particulates and pathogens. Mucociliary clearance is critical in clearing pathogens from the lower respiratory tract. Any factors that affect a patient’s ability to protect their respiratory tract will predispose the patient to pneumonia. Smoking causes squamous metaplasia of the pseudostratified epithelium and loss of the ciliary elevator that clears the lower respiratory tract, especially in patients with COPD. Gross or microscopic aspiration caused by impaired swallowing can lead to increased frequency of pathogens entering the lower respiratory tract.12,13 Pneumonia can occur if a pathogen reaches the alveoli with a sufficient inoculum to overwhelm the host’s immune response.8
Clinical Features
Pneumonia can have variable clinical presentations. Typical symptoms associated with pneumonia include fever, cough, production of or change in sputum, chills, and night sweats.14 Additionally, patients may complain of chest pain, pleuritic chest pain, or shortness of breath. Patients may have associated symptoms as well, such as nausea, vomiting, and diarrhea. Elderly patients may present with a change in function or mental status. COVID-19 infection has been associated with a change in (or loss of) taste or smell. Headache, muscle or body aches, and fatigue also can be signs of influenza or COVID-19 pneumonia. Conversely, both rhinorrhea and sore throat have a negative predictive value for pneumonia.14
Vital sign abnormalities are common and are associated with an increased likelihood of pneumonia.14 Hypoxia, detected by pulse oximetry, makes the diagnosis of pneumonia more likely, but a normal value does not exclude it. Physical examination findings indicative of pneumonia include adventitious lung sounds, such as wheezes, rales, and rhonchi. Diminished breath sounds unilaterally or in a lung field also may indicate pneumonia.14,15
Historical Elements
Past medical and social history is useful for the emergency provider in assessing the risk for CAP. There is increased incidence of CAP among men, the elderly, and the immunocompromised. Additionally, patients with comorbidities are at increased risk for CAP, specifically: chronic heart disease, chronic lung disease, diabetes mellitus, cerebrovascular disease, Parkinson’s disease, epilepsy, dementia, HIV, chronic kidney disease (CKD), and chronic liver disease. All these comorbidities increase the risk of CAP by two to four.16
Social determinants of health also influence the risk of developing pneumonia. Screening patients for specific factors may assist the provider in detecting those at a greater risk. Smoking tobacco, alcohol consumption, being underweight, a large household size (greater than 10 individuals), regular contact with children, and a lower level of education were associated with an increased risk of CAP.16
Additional information important to gather includes recent hospitalization and/or administration of parenteral antibiotics, recent travel, exposure to known sick contacts, previous history of pneumonia or pulmonary infections, and history of intrathoracic surgery. Assessing patients’ comorbidities, such as chronic heart, lung, or endocrine disease, is used to select initial empiric antimicrobial therapy.
Diagnostic Studies
The hallmark clinical finding of pneumonia is a pulmonary infiltrate on radiographic studies.6 (See Figure 1.) Chest X-ray is an appropriate diagnostic study for the initial evaluation for the patient with suspected pneumonia. Ideally a two-view study should be obtained: a posterior-anterior and lateral chest radiographs. The clinician may consider a portable single anterior-posterior chest radiograph at initial evaluation to decrease exposure of ancillary staff to potentially infectious patients, or with unstable patients who are not safe to transport to a separate area. The sensitivity and specificity of chest radiographs for detection is good and adequate in most clinical circumstances. CT imaging has significantly increased specificity and sensitivity for pneumonia when compared with plain radiographs. However, the routine use of CT imaging to evaluate for pneumonia has drawbacks, including increased radiation exposure, higher healthcare cost, and more use of limited resources.17
Figure 1. Lobar Consolidation in an Elderly Patient with Suspected Bacterial Community-Acquired Pneumonia |
 |
Consider a chest CT for further evaluation in certain clinical scenarios, such as patients with multiple comorbidities. Another scenario may include caring for a patient for whom a high clinical suspicion for pneumonia is present despite a negative chest X-ray. CT imaging of the chest also can be considered in patients with unclear etiology for either symptoms and in whom a definitive diagnosis of pneumonia would change management. CT imaging of the chest also reveals additional information about pneumonia, which may change management, including pneumonia that appears unifocal on chest radiograph but is multifocal when evaluated with CT.
CT also has been shown to be a powerful tool to reduce the overdiagnosis of pneumonia and use of unnecessary antimicrobials.18,19 In a 2015 study from France, ED providers were asked to classify the likelihood a patient had pneumonia based on chest radiograph. Following this, a chest CT was obtained, and researchers quantified the frequency of change in diagnosis or management. CT showed a pulmonary infiltrate in 33% of the patients without infiltrate on chest X-ray. Additionally, CT excluded pneumonia in 29.8% of patients with a positive chest X-ray.20
This study did note that patients with more indeterminate findings on chest X-ray were more likely to have a changed diagnosis based on CT imaging. Those who were classified as intermediate probability of pneumonia on chest X-ray had a 76.7% chance of changing diagnosis based on CT imaging of the chest. In the subset of patients where clinicians rated chest X-ray findings as having a high degree of certainty for pneumonia, 17% of cases changed diagnosis based on CT imaging. Therefore, if there is uncertainty about a definitive diagnosis, CT is more likely to provide additional actionable information and may affect patient disposition and/or the decision to administer or continue antibiotics.18,20
Additionally, CT imaging can be helpful, especially in cases with a broad differential diagnosis. In this scenario, CT may identify underlying pulmonary edema, pulmonary embolism, or pericardial effusion. This additional information can aid in targeting management of patients who present with a similar clinical picture to pneumonia.
Radiographic Imaging in COVID-19
COVID-19 pneumonia has distinctive features that can help identify COVID-19 vs. other causes of viral pneumonia. The most common abnormal chest radiograph findings in patients with COVID-19 pneumonia include bilateral infiltrates, ground glass opacities, or unilateral infiltrate.21 Radiographic findings more specific to COVID-19 infection include peripheral infiltrate distribution, ground glass opacities, fine reticular opacities, and vascular thickening. Pneumonia caused by COVID-19 is less likely to have central and peripheral distribution, pleural effusion, or lymphadenopathy.22,23
Chest CT has demonstrated improved sensitivity for diagnosing COVID-19 pneumonia compared to chest radiograph. A difference in radiology interpretation of the chest X-ray vs. a chest CT is as high as 52%, including 13% of patients who tested positive for SARS-CoV-2 via PCR and had a normal chest radiograph but demonstrated bilateral ground glass opacities on chest CT. This radiographic information is clinically relevant, since the presence of bilateral infiltrates or ground glass opacities has been shown to be associated with a higher rate of intubation, greater number of inpatient days, and a higher mortality rate.21
Chest CT is not required for routine COVID-19 patients but may be beneficial in certain clinical scenarios. Consider obtaining a chest CT in patients with suspected COVID-19 when the likelihood of a diagnosis of COVID-19 is questionable, to risk stratify and assess prognosis, and to evaluate for additional pathology. Classic findings for COVID-19 on chest CT has a high positive predictive value for COVID-19, up to 85%, which can be used in conjunction with information such as a COVID-19 antigen test or pending PCR test.24
If there is suspicion for the development of non-COVID-19 infection, chest CT could reveal findings such as focal opacities, lobar consolidation, centrilobular tree-in-bud opacities, and pleural effusions, which are more common in bacterial pneumonia than COVID-19.25 Additionally, findings on chest CT, including bronchiectasis, severe parenchymal involvement, and subtle changes to vascular structures, may serve as an independent predictor of poor patient outcome and aid in determining the appropriate level of care.24 Chest CT is advantageous if there is suspicion of noninfectious complications of COVID-19, such as venous thromboembolism.26
Additional Testing
Laboratory testing often is used to augment clinical decision making for patients with pneumonia. Laboratory testing, including viral antigen testing, blood cultures, and inflammatory markers, may provide additional information regarding diagnosis, management, and disposition.
The IDSA currently recommends molecular testing for COVID-19 in all symptomatic patients with pneumonia. Patients diagnosed with CAP are likely to have symptoms that would overlap with pneumonia caused by SARS-CoV-2, such as fever, cough, and dyspnea. Therefore, molecular testing for COVID-19 should be ordered for patients with suspected CAP with typical symptoms.2
Differentiating between bacterial and viral pneumonia can be a challenging task. Inflammatory markers, such a C-reactive protein and procalcitonin, have been studied for their ability to distinguish between viral and bacterial infections. However, the American College of Emergency Physicians (ACEP) clinical policy recommends against using C-reactive protein and/or procalcitonin to determine if an adult patient has viral vs. bacterial pneumonia, specifically in regard to administration of antimicrobials or for disposition decision making.27 Influenza testing should be obtained on patients with CAP when influenza is prevalent in the community.2
The IDSA recommends not obtaining blood cultures in patients who will be managed in the outpatient setting or for a routine, otherwise healthy hospitalized patient.2 (See Table 1.) Blood cultures are recommended in patients who are septic, in septic shock, or who meet criteria for severe CAP. (See Table 2 and Figure 2.) The IDSA recommends obtaining blood cultures in patients with a history of previous documented infection with methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas. Also consider obtaining blood cultures in patients with previous hospitalizations who received parenteral antibiotics in the last 90 days.2
Table 1. Indication for Ordering Blood Cultures2 | |
Blood Cultures Indicated |
Blood Cultures Not Indicated |
|
|
CAP: community-acquired pneumonia; MRSA: methicillin-resistant Staphylococcus aureus | |
Table 2. Criteria for Severe Community-Acquired Pneumonia2,53 | |
Severe community-acquired pneumonia = 1 major or 3 minor criteria | |
Major Criteria: Any 1 criterion |
Minor Criteria: 3 or more criteria |
|
|
WBC: white blood cells; PLT: platelets | |
Figure 2. Patient with Severe Pneumonia |
 |
The patient presented with hypoxemia and in respiratory distress, requiring bilevel positive airway pressure (BiPAP) and intensive care unit hospitalization. The patient had positive polymerase chain reaction testing for SARS-CoV-2. During hospitalization, patient also had positive sputum and blood cultures for Streptococcus pneumoniae and sputum cultures positive for Acinetobacter baumannii. |
The IDSA recommends blood cultures if antimicrobial treatment is empirically targeting MRSA or Pseudomonas. According to this recommendation, it is reasonable to obtain blood cultures in patients treated with an agent, such as piperacillin/tazobactam, cefepime, or vancomycin, since these agents are chosen for the empiric coverage of MRSA and Pseudomonas.
According to the 2019 IDSA guidelines for pneumonia, urine Legionella antigen and pneumococcal antigen testing is not routinely recommended. Consider obtaining Legionella and pneumococcal antigen testing when indicated by increased risk factors, such as a recent outbreak of Legionella, recent travel, or in adults with severe CAP.
Bacterial Coinfection in COVID-19
Patients with COVID-19 also can be coinfected with bacterial respiratory pathogens. In an observational study of 989 patients and a meta-analysis with 3,834 patients, the rate of bacterial coinfection in hospitalized patients with COVID-19 was 7%.28,29 The most common bacterial pathogens in patients with coinfection at the time of hospitalization were Streptococcus pneumoniae and Staphylococcus aureus.30,31 Patients with hospital-acquired bacterial superinfections were likely to be caused by Pseudomonas aeruginosa and Escherichia coli. Intensive care unit (ICU) patients were more likely to have such coinfections (14%).31 Patients also were found to have coinfection with M. pneumonia, C. pneumonia, and H. influenzae.31,32 Sepsis was more prevalent in coinfected individuals, and patients with coinfection were more likely to die.31,32
The IDSA and the Centers for Disease Control and Prevention (CDC) do not recommend the routine use of empiric antibiotics for patients with confirmed COVID-19.31 The IDSA describes objective findings that increase the concern for bacterial superinfection, such as a rise in leukocyte counts, lobar consolidation on chest X-ray, evidence of necrotizing infection on chest imaging, and recrudescence of fever after initial defervescence.31 Since patients requiring ICU hospitalization are more likely to have coinfection, to have increased mortality, and to be infected with drug-resistant organisms, it is reasonable to treat COVID-19 patients requiring ICU hospitalization with parenteral antibiotics. Providers should pay attention to the above risk factors for bacterial coinfection when considering empiric antibiotic use.
Management
Outpatient Management of Healthy Patients
Otherwise healthy patients with suspected bacterial CAP and who are otherwise suitable for discharge can be treated with a course of oral antibiotics. There is not sufficient evidence based on randomized controlled trials to definitively show superiority of any one specific antibiotic regimen. Randomized controlled trials of specific regimens have difficulty proving superiority because of the relatively small incidence of important outcomes, such as mortality and/or treatment failure, and, therefore, are difficult reach adequate power.2,33 Most importantly, patients with CAP who are appropriate for outpatient treatment generally do well regardless of the specific antibiotic regimen chosen.
According to the IDSA and American Thoracic Society (ATS) guidelines, CAP patients without comorbidities should be treated with amoxicillin 1 g orally (PO) three times daily (TID). If the patient is allergic or unable to tolerate amoxicillin, doxycycline 100 mg PO twice a day (BID) is an acceptable choice as well. (See Table 3.) In areas where pneumococcal resistance to macrolides is less than 25%, azithromycin 500 mg once followed by azithromycin 250 mg PO daily for four days, or clarithromycin 500 mg PO BID is acceptable. Always consider the antibiogram of your practice region.2
Table 3. Outpatient Community-Acquired Pneumonia Treatment2 | |
Outpatient CAP treatment, healthy patient |
OR
OR
OR
|
CAP: community-acquired pneumonia; PO: per os; TID: three times per day; BID: two times per day | |
The duration of antibiotic therapy should be no less than five days and guided by clinical improvement. Several studies outlined in the 2019 IDSA CAP guidelines comparing duration of therapy from five to 10 days of treatment with beta lactams and fluroquinolones showed similar efficacy with shorter courses of therapy (five to seven days). Signs of clinical improvement include resolution of vital sign abnormalities, ability to eat, and normal mentation. Patients who fail to achieve clinical improvement in five days are associated with worse clinical outcomes, and this should prompt a re-evaluation for resistant pathogens and/or alternate sources of infection.
Outpatient Management for Patients with Comorbidities
In some cases, CAP patients with comorbidities still may be suitable for discharge with treatment using oral antibiotics. These patients require more broad-spectrum antibiotic coverage. Comorbidities prompting increased antibiotic coverage include diabetes mellitus, alcoholism, malignancy, asplenia, or chronic diseases of the heart, lung, liver, or kidney. If these patients are appropriate for discharge, they should be treated with either an amoxicillin/clavulanic acid or a cephalosporin in addition to treatment with a macrolide or doxycycline. Treatment regimens are outlined in Table 4 and, again, should be no less than five days and guided by clinical improvement. Refer to the disposition section for more information on who may be appropriate for outpatient management.2
Table 4. Outpatient Community-Acquired Pneumonia Treatment for Patients with Comorbidities2 | ||||
Outpatient CAP treatment, patient with comorbidities | ||||
Amoxicillin/ clavulanate OR Amoxicillin/ clavulanate OR Amoxicillin/ clavulanate OR Cefpodoxime 200 mg BID OR Cefuroxime 500 mg PO BID |
AND |
Doxycycline OR Azithromycin |
OR |
Monotherapy Levofloxacin 750 mg PO daily OR Moxifloxacin PO OR Gemifloxacin |
PO: per os; TID: three times per day; BID: two times per day | ||||
These patients also can be managed appropriately with monotherapy with a respiratory fluoroquinolone, such as levofloxacin. Specific adverse effects of fluoroquinolones and discussion of this evidence is beyond the scope of this article. However, because of adverse effects of tendon rupture, aortic aneurysm, and peripheral neuropathy, fluoroquinolones should be used with caution.34
Aspiration Pneumonia
The IDSA does not recommend additional antibiotic coverage beyond standard empiric treatment for CAP if suspected aspiration is present. (See Figure 3.) The 2019 ATS/IDSA pneumonia guidelines cite previous studies from the 1970s showing high rates of anerobic organisms from transtracheal sampling obtained from patients late in their disease course.2 These factors may have contributed to a higher likelihood of identifying anerobic organisms. More recent studies noted decreased rates of anerobic organisms. In a sample of 95 elders with severe aspiration pneumonia, anerobic bacteria were identified in 16% of cases, and in 55% of these cases, aerobic gram-negative bacteria were identified in conjunction with anaerobes.35 The most frequently encountered anaerobes were Prevotella and Fusobacterium.35 Additional antibiotic coverage may be warranted if a lung abscess or empyema is suspected or confirmed, but this is a conditional recommendation, with an overall low quality of evidence.2
Figure 3. Aspiration Pneumonia in a Patient with Recent COVID-19 |
 |
Debris is seen within the right lower lobe bronchus. |
Inpatient CAP
Patients with CAP who require hospitalization can be managed appropriately with one of multiple available antibiotic regimens. For patients with non-severe CAP, the IDSA recommends antibiotics, including beta lactams or cephalosporins, in addition to treatment with a macrolide. Monotherapy with a fluoroquinolone may be appropriate for a patient hospitalized with non-severe CAP, but monotherapy with a fluoroquinolone is not appropriate for patients hospitalized with severe pneumonia. Specific antibiotic regimens are outlined in Tables 5 and 6.
Table 5. Treatment of Patients with Non-Severe Pneumonia Who Require Hospitalization2 | ||||
Inpatient CAP treatment – non-severe | ||||
Ampicillin/sulbactam 1.5 g to 3 g IV q6h OR Cefotaxime 1g to OR Ceftriaxone 1 g to OR Ceftaroline 600 mg IV q12h |
AND |
Azithromycin IV OR Clarithromycin IV OR Doxycycline |
OR |
Monotherapy Levofloxacin 750 mg PO daily OR Moxifloxacin PO |
CAP: community-acquired pneumonia; IV: intravenous; PO: per os; BID: two times per day | ||||
Table 6. Treatment of Patients with Severe Pneumonia Who Require Hospitalization2 | ||
Inpatient Pneumonia Treatment: Severe Pneumonia | ||
Ampicillin/sulbactam 1.5 g to 3 g q6h IV OR Cefotaxime 1 g to 2 g IV q8h OR Ceftriaxone 1 g to 2 g IV daily OR Ceftaroline 600 mg IV q12h |
AND |
Azithromycin 500 mg IV daily OR Clarithromycin 500 mg IV q12h OR Levofloxacin 750 mg IV or PO daily OR Moxifloxacin 400 mg IV or PO daily |
IV: intravenous; PO: per os | ||
Deciding who needs coverage for drug-resistant organisms while trying to maintain antibiotic stewardship is a challenging task. The IDSA guidelines note the strongest risk factors for MRSA or Pseudomonas include any history of prior respiratory isolation with either MRSA or Pseudomonas, or hospitalization in the past 90 days requiring parenteral antibiotics. Patients with these risk factors should be covered for MRSA and/or Pseudomonas.
Appropriate coverage for MRSA includes vancomycin 15 mg/kg IV q12 hours or linezolid 600 mg IV q12 hours. Appropriate coverage for Pseudomonas includes either piperacillin/tazobactam 4.5 g IV q6 hours, cefepime 2 g IV q8 hours, ceftazidime 2 g IV q8 hours, meropenem 1 g IV q8 hours, or imipenem 500 mg IV q6 hours. The IDSA recommends seven days of antimicrobial therapy.36 Dual therapy from different classes for pseudomonal coverage in VAP/HAP should be used only when suspected resistance rates are greater than 10%.2
The 2019 ATS/IDSA guidelines for the treatment of CAP recommend that individual hospital and healthcare centers create a program to routinely obtain blood cultures and sputum culture to establish risk factors for drug-resistant organisms that are specific to a practice area. This is guided by previous studies attempting to identify specific reliable risk factors for drug-resistant organisms finding highly variable results based on location. Once there is more information on what constitutes increased risk for resistant organisms in a specific area, centers will be able to establish more accurate protocols for treatment of patients at risk for drug-resistant infection.
In the interim, the IDSA recommends initiating coverage for MRSA and Pseudomonas initially with de-escalation as appropriate if microbiological results do not demonstrate evidence of MRSA or Pseudomonas in nasal PCR, blood cultures, or other cultures.
Intensive care hospitalization is warranted for patients requiring mechanical ventilation or vasopressor support. The ACEP clinical policy recommends using the 2007 IDSA criteria for severe pneumonia to determine which patients are most appropriate for ICU hospitalization as outlined in Table 2.27
Corticosteroids
The ATS/IDSA guidelines do not recommend the use of corticosteroids routinely for the treatment of bacterial pneumonia or influenza. If corticosteroids are otherwise indicated, such as in a patient with an acute COPD or asthma exacerbation, it still is appropriate to prescribe them in conjunction with antimicrobial therapy.2
A Cochrane review of 17 randomized control trials in 2017 evaluated patients with severe and non-severe CAP who received corticosteroid therapy.37 This meta-analysis showed improved outcomes in patients with severe CAP who were treated with corticosteroids. Most studies used corticosteroid doses equivalent to
40 mg to 50 mg of prednisone per day, for five to 10 days. Patients with severe CAP were shown to have reduced mortality with a number needed to treat (NNT) of 18 patients.
This analysis also found that patients with CAP admitted to the ICU had a reduced length of ICU and hospital stay when treated with corticosteroids. Conversely, there was no benefit or harm shown for patients with non-severe CAP who received corticosteroids. Patients treated with corticosteroids were more likely to have hyperglycemia, but there was no significant difference between groups in the rate of superinfections, gastrointestinal, neuropsychiatric, or cardiac adverse events.37
Additionally, corticosteroids also should be initiated in patients with persistent hypotension refractory to vasopressors and fluid resuscitation, according to 2021 Surviving Sepsis guidelines.37,38
Influenza
The ATS/IDSA guidelines recommend that patients with CAP who test positive for influenza and are hospitalized be treated with anti-influenza treatment, such as oseltamivir, regardless of duration of illness.2 The guidelines also recommend that ambulatory patients with CAP due to influenza also be treated with oseltamivir regardless of duration of illness, but note that this is a conditional recommendation with a low quality of evidence. It is noted that there may be additional benefit if this therapy is started within 48 hours of symptom onset.2 Oseltamivir should be administered at a dose of 75 mg PO BID for five days.24,39
COVID-19 Pneumonia
The management of COVID-19 pneumonia is a rapidly changing field. There still is a significant knowledge gap on the optimal management of COVID-19. The most current information on recommended COVID-19 treatment modalities and antiviral therapy can be found at: https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/
Ambulatory Management of COVID-19 Pneumonia
Monoclonal antibody therapy may reduce viral replication in the upper and lower respiratory tract.40 SARS-CoV-2 variants developed increasing resistance to the initial monoclonal antibodies, so starting in April 2021, combination therapy was recommended.
“Among ambulatory patients with mild to moderate COVID-19 at high risk for progression to severe disease, the IDSA guideline panel suggests bamlanivimab/etesevimab, casirivimab/imdevimab (REGEN-COV®), or sotrovimab (Xevudy®) rather than no neutralizing antibody treatment.”41 Factors to determine which patients should receive monoclonal antibody therapy may vary by institutional drug availability, patient comorbidities, and currently circulating strain(s) of SARS-CoV-2. Specific criteria that were used in the clinical trial for bamlanivimab/etesevimab include: age ≥ 65 years, body mass index (BMI) ≥ 35 kg/m2, chronic kidney disease, diabetes, immunosuppressive disease, immunosuppressant treatment, or age ≥ 55 years with cardiovascular disease, hypertension, chronic pulmonary disease, or other chronic respiratory diseases.42
The evidence supporting individual monoclonal antibody treatments varies. Bamlanivimab/etesevimab demonstrated an absolute mortality reduction of 1.9% in patients with mild to moderate COVID-19 infection.41 Ambulatory patients with at least one risk factor for severe disease treated with casirivimab/imdevimab had reduced relative risk of hospitalization but no change in mortality.43 Ambulatory patients with COVID-19 and at least one risk factor for severe disease treated with sotrovimab had reduced hospitalizations or death.44
The treatment arms for bamlanivimab/etesevimab, casirivimab/imdevimab, or sotrovimab all had reduced serious adverse events when compared to placebo.41 The IDSA guidelines note that this is an area with a need for continued research, especially regarding new neutralizing antibodies and new SARS-CoV-2 variants.41
Hospital Management of COVID-19 Pneumonia
COVID-19 pneumonia causes significant hypoxemia. Patients requiring greater than 6 liters per minute (LPM) via nasal cannula to maintain arterial oxygenation can be treated with either high flow nasal cannula (HFNC) or noninvasive ventilation (NIV) such as bilevel positive airway pressure (BiPAP) or continuous positive airway pressure (CPAP). More research still needs to be done to prove if one of these modalities is superior. Consider available resources and how the patient tolerates the chosen supplemental oxygen modality. Patients with hypercapnia may have additional benefit of increased minute ventilation from BiPAP over HFNC.45,46
Choosing the exact timing of when to intubate a patient with COVID-19 is difficult. In the early stages of the pandemic, providers considered early intubation to avoid the aerosolization of viral material that occurs with noninvasive ventilatory measures. However, intubating all patients who may have otherwise tolerated NIV results in unnecessary intubations, increased used of critical care resources, and decreased supply of available ventilators.46 Consider intubation of patients with COVID-19 pneumonia who have rapid progression over hours, persistent need for high FIO2, progressing respiratory failure, hemodynamic instability, or multiorgan failure.46
In patients with COVID-19 pneumonia who require supplemental oxygen or mechanical ventilation, glucocorticoids can improve mortality. A study done in U.K. hospitals through the National Health Service randomized patients to receive either usual care or usual care plus dexamethasone. The dose of dexamethasone used was 6 mg once daily, PO or IV.47 They noted that patients who received dexamethasone and required either supplemental oxygen or mechanical ventilation had a mortality benefit at 28 days. Patients who did not require supplemental oxygen or mechanical ventilation had no clear benefit.47 The IDSA guidelines recommend dexamethasone 6 mg IV or PO daily for 10 days for patients who require mechanical ventilation or in those with oxygen saturations less than or equal to 94% on room air.48
Patients with severe COVID-19 pneumonia may benefit from prone positioning based on data extrapolated from treatment of acute respiratory distress syndrome (ARDS), where prone positioning reduces mortality in moderate to severe ARDS.49,50 Prone positioning improves oxygenation by minimizing ventilation perfusion mismatch, improving respiratory mechanics, and decreasing right ventricular strain.51 At this time, there is a lack of specific research demonstrating mortality benefit of prone positioning in COVID-19.52
The IDSA guidelines recommend against the use of hydroxychloroquine, combination hydroxychloroquine and azithromycin, lopinavir/ritonavir, or bamlanivimab monotherapy. They recommend against the use of convalescent plasma outside a clinical trial on ambulatory patients. They also recommend against the use of ivermectin outside the context of a clinical trial.41
At this time, more research needs to be done to determine if any treatments for COVID-19 are time sensitive and have additional benefit if initiated rapidly.
Disposition
Determining the appropriate disposition for a patient with pneumonia is of utmost importance. Patient disposition should be determined by a complete evaluation of the patient, incorporating clinical judgment, vital signs, examination, laboratory studies, imaging studies, as well as social considerations. Scoring tools also can be used to supplement this decision-making process.
Several scoring tools may be used to aid in appropriate disposition. The Pneumonia Severity Index (PSI) and CURB-65 decision aids are explicitly mentioned in the ACEP clinical policy as acceptable tools to support clinical judgment in determining patients with low mortality risk who may be appropriate for outpatient treatment.27 (See Table 7.) The ATA/IDSA guidelines also recommend using a support tool to aid in disposition decision making.2 The ACEP clinical policy notes that PSI is supported by a larger body of evidence and is preferred over other guidelines. However, the PSI includes 20 elements of data with variable point values that can be time consuming to obtain and complete. Because of this, it is impractical to complete without online tools. CURB-65 is easier to calculate and includes only five historical/vital sign elements and a blood urea nitrogen (BUN), and each element is equally weighted with one point.
Table 7. Clinical Elements of Pneumonia Severity Scores54,55 | |
PSI/PORT Score: Pneumonia Severity Index for CAP elements
|
CURB-65 Score for Pneumonia Severity Elements
|
PSI/PORT: pneumonia severity index; CAP: community-acquired pneumonia; CHF: congestive heart failure; BUN: blood urea nitrogen; BP: blood pressure | |
In any event, clinical judgment should always be considered in addition to any scoring tool to determine patient disposition. Any patient who meets criteria for severe pneumonia should be hospitalized. Any patient who is hypoxemic or shows signs of end organ damage should be hospitalized. A study published in 2008 compared scoring tools to clinical judgment and highlighted the value of a clinician in weighing the most appropriate disposition.45 The authors noted that 56 (32%) of 174 patients in the study had a disposition that varied from that recommended by the PSI score, with 49 (86%) of the differences due to low-risk patients (who were appropriate for outpatient management, according to PSI) being admitted to the hospital. The most common element causing this difference was hypoxemia. These patients had a significant length of stay of five days on average. This suggests that clinical judgment outperformed the PSI in these cases by identifying patients who required a significant duration of treatment in the hospital.45
Summary
Community-acquired pneumonia is a leading infectious cause of hospitalization and mortality, with increased prevalence during the current COVID-19 pandemic. It is important to focus on appropriate testing, prompt treatment, and disposition to improve outcomes and maximize efficient use of limited resources during this global pandemic.
References
- Cline DM, Ma JO, Cydulka RK, et al. Tintinalli’s Emergency Medicine Manual, 7th ed. McGraw-Hill Medical; 2012.
- 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:e45-e67.
- Pfuntner A, Wier LM, Stocks C. Most frequent conditions in U.S. hospitals, 2011: Statistical brief #162. Healthcare Cost and Utilization Project (HCUP). Agency for Healthcare Research and Quality; 2013.
- Ramirez JA. Overview of community-acquired pneumonia in adults. UpToDate. Updated April 15, 2022. https://www.uptodate.com/contents/overview-of-community-acquired-pneumonia-in-adults
- Biden J. A letter on the continuation of the national emergency concerning the Coronavirus Disease 2019 (COVID-19) pandemic. The White House. Feb. 24, 2021. https://www.whitehouse.gov/briefing-room/statements-releases/2021/02/24/a-letter-on-the-continuation-of-the-national-emergency-concerning-the-coronavirus-disease-2019-covid-19-pandemic/
- Ramirez JA, Wiemken TL, Peyrani P, et al. Adults hospitalized with pneumonia in the United States: Incidence, epidemiology, and mortality. Clin Infect Dis 2017;65:1806-1812.
- Jain S, Self WH, Wunderink RG, et al. Community-acquired pneumonia requiring hospitalization among U.S. adults.
N Engl J Med 2015;373:415. - Aleem MS, Sexton R, Akella J. Pneumonia in an immunocompromised patient. Updated July 31, 2021. In: StatPearls [Internet]. StatPearls Publishing; 2022 Jan.
- Dickson RP, Erb-Downward JR, Martinez FJ, Huffnagle GB. The microbiome and the respiratory tract. Annu Rev Physiol 2016;78:481-504.
- Hanada S, Pirzadeh M, Carver KY, Deng JC. Respiratory viral infection-induced microbiome alterations and secondary bacterial pneumonia. Front Immunol 2018;9:2640.
- de Sousa-Pereira P, Woof JM. IgA: Structure, function, and developability. Antibodies (Basel) 2019;8:57.
- Martino R, Foley N, Bhogal S, et al. Dysphagia after stroke: Incidence, diagnosis, and pulmonary complications. Stroke 2005;36:2756-2763.
- Rigden HM, Alias A, Havelock T, et al. Squamous metaplasia is increased in the bronchial epithelium of smokers with chronic obstructive pulmonary disease. PLoS One 2016;11:e0156009.
- Rosh AJ, Newman DH. Diagnosing pneumonia by medical history and physical examination. Ann Emerg Med 2005;46:465.
- Wipf JE, Lipsky BA, Hirschmann JV, et al. Diagnosing pneumonia by physical examination: Relevant or relic? Arch Intern Med 1999;159:1082-1087.
- Torres A, Peetermans WE, Viegi G, Blasi F. Risk factors for community-acquired pneumonia in adults in Europe: A literature review. Thorax 2013;68:1057-1065.
- Syrjälä H, Broas M, Suramo I, et al. High-resolution computed tomography for the diagnosis of community-acquired pneumonia. Clin Infect Dis 1998;27:358-363.
- Prendki V, Scheffler M, Huttner B, et al. Low-dose computed tomography for the diagnosis of pneumonia in elderly patients: A prospective, interventional cohort study. Eur Respir J 2018;51:1702375.
- Garin N, Marti C, Carballo S, et al. Rational use of CT-scan for the diagnosis of pneumonia: Comparative accuracy of different strategies. J Clin Med 2019;8:514.
- Claessens YE, Debray MP, Tubach F, et al. Early chest computed tomography scan to assist diagnosis and guide treatment decision for suspected community-acquired pneumonia. Am J Respir Crit Care Med 2015;192:974-982.
- Marco CA, Repas SJ, Studebaker H, et al. Radiographic findings of SARS-CoV-2 infection. J Am Coll Emerg Physicians Open 2021;2:e12399.
- Bai HX, Hsieh B, Xiong Z, et al. Performance of radiologists in differentiating COVID-19 from non-COVID-19 viral pneumonia at chest CT. Radiology 2020;296:E46-E54.
- Chung M, Bernheim A, Mei X, et al. CT imaging features of 2019 novel coronavirus (2019-nCoV). Radiology 2020;295:202-207.
- Machnicki S, Patel D, Singh A, et al. The usefulness of chest CT imaging in patients with suspected or diagnosed COVID-19: A review of literature. Chest 2021;160:652-670.
- Zhou J, Liao X, Cao J, et al. Differential diagnosis between the coronavirus disease 2019 and Streptococcus pneumoniae pneumonia by thin-slice CT features. Clin Imaging 2021;69:318-323.
- Espallargas I, Rodríguez Sevilla JJ, Rodríguez Chiaradía DA, et al. CT imaging of pulmonary embolism in patients with COVID-19 pneumonia: A retrospective analysis. Eur Radiol 2021;31:1915-1922.
- American College of Emergency Physicians. Community-acquired pneumonia. ACEP Clinical Policy, Community-Acquired Pneumonia. October 2020. https://www.acep.org/patient-care/clinical-policies/community-acquired-pneumonia/
- Garcia-Vidal C, Sanjuan G, Moreno-García E, et al; COVID-19 Researchers Group. Incidence of co-infections and superinfections in hospitalized patients with COVID-19: A retrospective cohort study. Clin Microbiol Infect 2021;27:83-88.
- Lansbury L, Lim B, Baskaran V, Lim WS. Co-infections in people with COVID-19: A systematic review and meta-analysis.
J Infect 2020;81:266-275. - Cucchiari D, Pericàs JM, Riera J, et al. Pneumococcal superinfection in COVID-19 patients: A series of 5 cases. Med Clin (Barc) 2020;155:502-505.
- COVID-19 Real Time Learning Center. CDC and IDSA. Co-Infection and Antimicrobial Stewardship. Last Updated: June 22, 2021. https://www.idsociety.org/covid-19-real-time-learning-network/disease-manifestations--complications/co-infection-and-Antimicrobial-Stewardship/#KL
- Pérez-Lazo G, Silva-Caso W, Del Valle-Mendoza J, et al. Identification of coinfections by viral and bacterial pathogens in covid-19 hospitalized patients in Peru: Molecular diagnosis and clinical characteristics. Antibiotics (Basel) 2021;10:1358.
- Pakhale S, Mulpuru S, Verheij TJM, et al. Antibiotics for community‐acquired pneumonia in adult outpatients. Cochrane Database Syst Rev 2014;10:CD002109.
- Mathews B, Thalody AA, Miraj SS, et al. Adverse effects of fluoroquinolones: A retrospective cohort study in a South Indian tertiary healthcare facility. Antibiotics 2019;8:104.
- El-Solh AA, Pietrantoni C, Bhat A, et al. Microbiology of severe aspiration pneumonia in institutionalized elderly. Am J Respir Crit Care Med 2003;167:1650-1654.
- Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 2016;63:e61-e111. [Published correction appears in Clin Infect Dis 2017;64:1298] [Published correction appears in Clin Infect Dis 2017;65:1435] [Published correction appears in Clin Infect Dis. 2017;65:2161].
- Stern A, Skalsky K, Avni T, et al. Corticosteroids for pneumonia. Cochrane Database Syst Rev 2017;12:CD007720.
- Evans L, Rhodes A, Alhazzani W, et al. Surviving Sepsis Campaign: International guidelines for management of sepsis and septic shock 2021. Crit Care Med 2021;49:e1063-e1143.
- Genentech. TAMIFLU® (oseltamivir phosphate) highlights of prescribing information. Reference ID: 3235738. Food and Drug Administration. 2012. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021087s062lbl.pdf
- Jones BE, Brown-Augsburger PL, Corbett KS, et al. LY-CoV555, a rapidly isolated potent neutralizing antibody, provides protection in a non-human primate model of SARS-CoV-2 infection. bioRxiv. Posted Oct. 1, 2020.
- Infectious Diseases Society of America. IDSA Guidelines on the Treatment and Management of Patients with COVID-19. Last updated Jan. 18, 2022. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/
- Eli Lilly and Company. Fact sheet for health care providers emergency use authorization of bamlanivimab and etesevimab. Literature revised Jan. 24, 2022. https://www.fda.gov/media/145802/download
- Regeneron Pharmaceuticals. Fact Sheet for Health Care Providers Emergency Use Authorization (EUA) of REGEN-COV® (casirivimab and imdevimab). Revised December 2021. https://www.fda.gov/media/145611/download
- Gupta A, Gonzalez-Rojas Y, Juarez E, et al. Early treatment for Covid-19 with SARS-CoV-2 neutralizing antibody sotrovimab. N Engl J Med 2021;385:1941-1950.
- Seymann G, Barger K, Choo S, et al. Clinical judgment versus the Pneumonia Severity Index in making the admission decision. J Emerg Med 2008;34:261-268.
- Anesi GL. COVID-19: Respiratory care of the nonintubated hypoxemic adult (supplemental oxygen, noninvasive ventilation, and intubation). UpToDate. Last updated Feb. 16, 2022. https://www.uptodate.com/contents/covid-19-respiratory-care-of-the-nonintubated-hypoxemic-adult-supplemental-oxygen-noninvasive-ventilation-and-intubation?topicRef=127419&source=see_link#H1608378004
- RECOVERY Collaborative Group; Horby P, Lim WS, Emberson JR, et al. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med 2021;384:693-704.
- Infectious Diseases Society of America. IDSA guidelines on the treatment and management of patients with COVID-19. Last updated March 14, 2022. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management
- Munshi L, Del Sorbo L, Adhikari NKJ, et al. Prone position for acute respiratory distress syndrome. A systematic review and meta-analysis. Ann Am Thorac Soc 2017;14(Supplement_4):S280-S288.
- Guérin C, Reignier J, Richard JC, et al; PROSEVA Study Group. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med 2013;368:
2159-2168. - Koulouras V, Papathanakos G, Papathanasiou A, Nakos G. Efficacy of prone position in acute respiratory distress syndrome patients: A pathophysiology-based review. World J Crit Care Med 2016;5:121-136.
- Qadri SK, Ng P, Toh TSW, et al. Critically ill patients with COVID-19: A narrative review on prone position. Pulm Ther 2020;6:233-246.
- Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44(Suppl 2):S27-S72.
- Fine MJ. PSI/PORT Score: Pneumonia Severity Index for CAP. https://www.mdcalc.com/psi-port-score-pneumonia-severity-index-cap#creator-insights
- Macfarlane J. CURB-65 Score for Pneumonia Severity. https://www.mdcalc.com/curb-65-score-pneumonia-severity
Pneumonia is an infection of the alveoli of the lungs. Alveolar infection results in inflammation that disrupts normal pulmonary function, producing impaired gas exchange. Pneumonia can be caused by bacteria, viruses, or fungi. Pathogens can infect the lung parenchyma through three routes: inhalation, aspiration, or hematogenous spread. In community-acquired pneumonia, the infection is initiated outside the hospital. The prevalence of COVID-19, the clinical disease caused by the SARS-CoV-2 virus, has changed the landscape of pneumonia.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content