Diagnostic Considerations

There are four major infections associated with OUD: OUD-IE, epidural abscess, septic arthritis, and osteomyelitis.^[13]Those with OUD-IE and concurrent COVID-19 infection may present with a variety of symptoms, particularly fatigue, fever, shortness of breath, dyspnea, and general malaise, whereas others may experience significant hypoxia. Thus, maintaining broad differential diagnoses should be considered (see Table 2).^[14]

The patient should always be asked about the use of “street antibiotics”. Such use may temporarily interfere with the growth of pathogens from the bloodstream. A prospective cohort study in South Africa demonstrated the positive impact of establishing a protocol to identify organisms involved in patients with IE. This protocol improved identification of organisms by reducing falsely negative blood cultures that would be produced owing to initiation of empiric antibiotics before obtaining blood cultures.^[15]

For example, if one out of three positive cultures were positive for S aureus, it would not be due to contamination but to prior use of “street antibiotics.” Another three sets of blood cultures should then be obtained (see Workup). Diagnostic precision is an important step toward being able to provide "personalized therapeutics" that may improve clinical outcomes. Laboratory markers reflective of acute inflammatory and immune response including CRP, ferritin, and interleukins (ILs) should be considered as we move toward targeted therapies for COVID-19 infection. Risk stratification by understanding the natural history of the COVID-19 infection will be instrumental in determining prognosis. Steps toward understanding the immunology behind COVID-19 infections are beginning to emerge (Table 1).^[7]

Table 2: Likely Causes of Fever and Sepsis Among Persons with OUD During the COVID-19 Pandemic. (Open Table in a new window)

Differential Diagnoses of OUD-IE during the COVID-19 Pandemic

Infectious endocarditis
Deep vein thrombosis/pulmonary embolism
Bacterial pneumonia superimposed on COVID-19 pneumonia
Influenza A, influenza B
Respiratory Syncytial Virus
Osteomyelitis
Abscess formation (eg, spinal abscess)
Renal and splenic embolic infarcts
Hepatitis B, hepatitis C
HIV
Tuberculosis

Workup

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Table 1: Clinical Complication Patterns of COVID-19 Infection

Major Pathological Mechanisms	Definitions	Targeted Pathogenic Pathway	Onset of Symptoms (Days)
Coinfection	Bacterial, fungal, viral co-infection	Interaction of viral specific proteins with host receptors leading to endothelial activation and dysfunction^[7]	6-12
Inflammatory		Endothelitis due to platelet activation^[7]
Type A	↑ CRP ↓ ferritin	IL-6	8-13
Type B	↑ CRP ↑ ferritin	IL-1, IL-6	10-13
Type C	↓ CRP ↑ ferritin	IL- 1	11-16
Thrombotic	DVT, PE	Hypercoagulable state induced by COVID-19 infection^[7]	10-18