COVID-19 - Differential Diagnosis

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The symptoms of COVID-19 infection are similar to those of other cold and flu viruses.  The severity of illness ranges from mild illness, in most cases, to serious illness seen in about 16% of cases.  Symptoms develop about 2-14 days after viral exposure. According to theCDC, symptoms typically include cough, shortness of breath/difficulty breathing or at least two of the following symptoms: fever, chills, repeated shaking with chills, myalgias, headache, sore throat, and/or new loss of taste or smell. As these symptoms are very similar to other cold and flu viruses, patients are being screened for COVID-19 if they meet additional modifiers, including recent travel and/or exposure to an individual infected with COVID-19.

Currently, a 2019-nCoV rRT-PCR Diagnostic Panel is available to test patients for the virus.  However, the turn-around time is not immediate as the test must be sent to the CDC for analysis. CT scan has been found to be positive for ground glass opacities in 88% of individuals with coronavirus and is being used in some cases when COVID-19 is highly suspected as an additional screening tool.  The decision of when to use CT is often made on a very individualized basis by the hospital epidemiologist in conjunction with the treating pulmonologist/intensivist. 

Overall, the differential diagnosis is very broad given the non-specific signs and symptoms. A rapid respiratory viral pathogen panel via nasopharyngeal swab may help detect the presence of a respiratory virus.  Some potential respiratory pathogens may include (those tested on a respiratory pathogen panel noted with an *):

·       Adenovirus

·       Coronavirus* (Coronavirus detected on RPP is NOT COVID-19)

·       Chlamydia pneumoniae*

·       Influenza*

·       Human metapneumovirus (HmPV)*

·       Human rhinovirus/enterovirus*

·       Legionella pneumophilia

·       Mycoplasma pneumoniae* 

·       Parainfluenza*

·       Pneumocystis jirovecii (in immunocompromised hosts)

·      Respiratory syncytial virus (RSV)*

·       Rhinovirus (common cold)

·       Streptococcus pneumoniae

·      Infectious mononucleosis

·       Acute HIV

·       Primary viral or bacterial pneumonia

In addition to the common respiratory illnesses above, the differential can be very broad if the patient presents with other signs and symptoms, or if the symptoms persist and do not follow the typical clinical course.  In these cases, the differential may include non-infectious disorders such as vasculitis and dermatomyositis. 

Additional non-infectious diagnoses that can be considered include:

  • Pulmonary: Pulmonary edema, Pulmonary embolism, COPD exacerbation, Asthma, Pulmonary hypertension/Cor pulmonale, ARDS, pneumonitis
  • Cardiac: Acute Coronary syndrome, CHF, valvular disease
  • Other: Tumor, Acute Chest Syndrome (from Sickle Cell Disease)

Lastly, if patients have returned from international travel, the destination must be taken into consideration with symptoms and timing of presentation.  In these settings, illnesses such as malaria and dengue must be considered. 


Bordi Licia, Nicastri Emanuele, Scorzolini Laura, Di Caro Antonino, Capobianchi Maria Rosaria, Castilletti Concetta, Lalle Eleonora, on behalf of INMI COVID-19 study group and Collaborating Centers2. Differential diagnosis of illness in patients under investigation for the novel coronavirus (SARS-CoV-2), Italy, February 2020. Euro Surveill. 2020;25(8):pii=2000170.

Cascella M, Rajnik M, Cuomo A, et al. Features, Evaluation and Treatment Coronavirus (COVID-19) [Updated 2020 Mar 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from:

Correlation of Chest CT and RT-PCR Testing in Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases

Tao Ai, Zhenlu Yang, Hongyan Hou, Chenao Zhan, Chong Chen, Wenzhi Lv, Qian Tao, Ziyong Sun, Liming Xia. Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China (T.A., Z.Y., C.Z.,C.C., L.X.), and Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China (H.H., Z.S.), Department of Artificial Intelligence, Julei Technology Company, Wuhan, 430030, China (W.L.), Division of Imaging Processing, Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands (Q.T.). Published Online:Feb 26 2020

Julie Grishaw, ACNP

Senior Editor, McGraw-Hill Education