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      News & Perspective Drugs & Diseases CME & Education Academy Video Decision Point
      Drugs & Diseases > Infectious Diseases

      Coronavirus Disease 2019 (COVID-19) Clinical Presentation

      Updated: Mar 17, 2023
      • Author: David J Cennimo, MD, FAAP, FACP, FIDSA, AAHIVS; Chief Editor: Michael Stuart Bronze, MD  more...
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      Presentation

      History

      Presentations of COVID-19 range from asymptomatic/mild symptoms to severe illness and mortality. Common symptoms include fever, cough, and shortness of breath. [106]  Other symptoms, such as malaise and respiratory distress, also have been described. [96]

      Symptoms may develop 2 days to 2 weeks after exposure to the virus. [106]  A pooled analysis of 181 confirmed cases of COVID-19 outside Wuhan, China, found the mean incubation period was 5.1 days, and that 97.5% of individuals who developed symptoms did so within 11.5 days of infection. [107]  

      Symptom rebound and viral rebound have been described in patients (with or without antiviral treatment). In untreated patients, those (n = 563) receiving placebo in the ACTIV-2/A5401 (Adaptive Platform Treatment Trial for Outpatients with COIVD-19) platform trial recorded 13 symptoms daily between days 1 and 28. Symptom rebound was identified in 26% of participants at a median of 11 days after initial symptom onset. Viral rebound was detected in 31% and high-level viral rebound in 13% of participants. [108]  

      The following symptoms may indicate COVID-19 [106] :

      • Fever or chills
      • Cough
      • Shortness of breath or difficulty breathing
      • Fatigue
      • Muscle or body aches
      • Headache
      • New loss of taste or smell
      • Sore throat
      • Congestion or runny nose
      • Nausea or vomiting
      • Diarrhea

      Other reported symptoms include the following:

      • Sputum production
      • Malaise
      • Respiratory distress
      • Neurologic (eg, headache, altered mentality) 

      Wu and McGoogan reported that, among 72,314 COVID-19 cases reported to the CCDC, 81% were mild (absent or mild pneumonia), 14% were severe (hypoxia, dyspnea, >50% lung involvement within 24-48 hours), 5% were critical (shock, respiratory failure, multiorgan dysfunction), and 2.3% were fatal. [109] These general symptom distributions have been reconfirmed across multiple observations. [110, 111]

      Clinicians evaluating patients with fever and acute respiratory illness should obtain information regarding travel history or exposure to an individual who recently returned from a country or US state experiencing active local transmission. [112]

      Williamson and colleagues, in an analysis of 17 million patients, reaffirmed that severe COVID-19 and mortality was more common in males, older individuals, individuals in poverty, Black persons, and patients with medical conditions such as diabetes and severe asthma, among others. [113]

      A multicenter observational cohort study conducted in Europe found frailty was a greater predictor of mortality than age or comorbidities. [114]

      Type A blood has been suggested as a potential factor that predisposes to severe COVID-19, specifically in terms of increasing the risk for respiratory failure. Blood type O appears to confer a protective effect. [115, 116]

      Patients with suspected COVID-19 should be reported immediately to infection-control personnel at their healthcare facility and the local or state health department. CDC guidance calls for the patient to be cared for with airborne and contact precautions (including eye shield) in place. [21] Patient candidates for such reporting include those with fever and symptoms of lower respiratory illness who have travelled from Wuhan City, China, within the preceding 14 days or who have been in contact with an individual under investigation for COVID-19 or a patient with laboratory-confirmed COVID-19 in the preceding 14 days. [112]

      A complete or partial loss of the sense of smell (anosmia) has been reported as a potential history finding in patients eventually diagnosed with COVID-19. [19] A phone survey of outpatients with mildly symptomatic COVID-19 found that 64.4% (130 of 202) reported any altered sense of smell or taste. [117] In a European study of 72 patients with PCR results positive for COVID-19, 53 patients (74%) reported reduced olfaction, whereas 50 patients (69%) reported a reduced sense of taste. Forty-nine patients (68%) reported both symptoms. [118]

      Next:

      Physical Examination

      Patients who are under investigation for COVID-19 should be evaluated in a private room with the door closed (an airborne infection isolation room is ideal) and asked to wear a surgical mask. All other standard contact and airborne precautions should be observed, and treating healthcare personnel should wear eye protection. [21]

      The most common serious manifestation of COVID-19 upon initial presentation is pneumonia. Fever, cough, dyspnea, and abnormalities on chest imaging are common in these cases. [119, 120, 121, 122]

      Huang and colleagues found that, among patients with pneumonia, 99% had fever, 70% reported fatigue, 59% had dry cough, 40% had anorexia, 35% experienced myalgias, 31% had dyspnea, and 27% had sputum production. [119]

      Previous
      Next:

      Complications

      Complications of COVID-19 include pneumonia, acute respiratory distress syndrome, cardiac injury, arrhythmia, septic shock, liver dysfunction, acute kidney injury, and multi-organ failure, among others.

      Approximately 5% of patients with COVID-19, and 20% of those hospitalized, experience severe symptoms necessitating intensive care. The common complications among hospitalized patients include pneumonia (75%), ARDS (15%), AKI (9%), and acute liver injury (19%). Cardiac injury has been increasingly noted, including troponin elevation, acute heart failure, dysrhythmias, and myocarditis. Ten percent to 25 percent of hospitalized patients with COVID-19 experience prothrombotic coagulopathy resulting in venous and arterial thromboembolic events. Neurologic manifestations include impaired consciousness and stroke.

      ICU case fatality is reported up to 40%. [110]  

      Long COVID

      As the COVID-19 pandemic has matured, more patients have reported long-term, post-infection sequelae. Most patients recover fully, but those who do not have reported adverse symptoms such as fatigue, dyspnea, cough, anxiety, depression, inability to focus (ie, “brain fog”), gastrointestinal problems, sleep difficulties, joint pain, and chest pain lasting weeks to months after the acute illness. Long-term studies are underway to understand the nature of these complaints. [123]  

      Post-acute sequelae of SARS-CoV-2 (PASC) infection is the medical term for what is commonly called long COVID or "long haulers". The NIH includes discussion of persistent symptoms or organ dysfunction after acute COVID-19 within guidelines that discuss the clinical spectrum of the disease. [124]  

      The UK National Institute for Health and Care Excellence (NICE) issued guidelines on care of long COVID that define the syndrome as: signs and symptoms that develop during or after an infection consistent with COVID-19, continue for more than 12 weeks, and are not explained by an alternative diagnosis. [125]  

      Please see Long COVID-19.

      Future public health implications

      Public health implications for long COVID need to be examined, as reviewed by Datta et al. As with other infections (eg, Lyme disease, syphilis, Ebola), late inflammatory and virologic sequelae may emerge. Accumulation of evidence beyond the acute infection and postacute hyperinflammatory illness is important to evaluate to gain a better understanding of the full spectrum of the disease. [126]  

      Thrombotic manifestations of severe COVID-19 are caused by the ability of SARS-CoV-2 to invade endothelial cells via angiotensin-converting enzyme-2 (ACE-2), which is expressed on the surface of endothelial cells. Subsequent endothelial inflammation, complement activation, thrombin generation, platelet and leukocyte recruitment, and the initiation of innate and adaptive immune responses culminate in immunothrombosis, and can ultimately cause microthrombotic complications (eg, DVT, PE, stroke). [127]  

      Kotecha et al describe patterns of myocardial injury in hospitalized patients with severe COVID-19 who had elevated troponin levels. During convalescence, myocarditis-like injury was observed, with limited extent and minimal functional consequence. However, in a proportion of patients, there was evidence of possible ongoing localized inflammation. Roughly 25% of patients had ischemic heart disease, of which two thirds had no previous history. [128]  

      Reinfection

      COVID-19 reinfection is defined as an infected person who has undergone full vaccination, whether they have had a booster or boosters. According to the CDC, reinfection is COVID-19 infection of an individual with 2 different viral strains that occurs at least 45 days apart. It also may occur when an individual has 2 positive CoV-2 RT-PCR tests with negative tests between the 2 positive tests. [129]

      It is essential to determine reinfection rates to establish the effectiveness of current vaccine prophylaxis. Reinfection in vaccinated and non-vaccinated persons probably is due to a variant. [129, 130]  

      It is important to differentiate reinfection from reactivation or relapse of the virus, which occurs in a clinically recovered person within the first 4 weeks of infection, during which viral RNA testing has remained positive. During relapse, a tiny viral load of dormant virus reactivates, the reason of which often is unclear.

      The only way to prove this state is to show that genetic samples taken at the beginning and at the time of reactivation differ genetically; such testing is unusual at the beginning of a person’s illness.

      For more information, see COVID-19 Reinfections

       

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