Coronavirus Disease 2019 (COVID-19) Clinical Presentation

Updated: Jan 23, 2021
  • Author: David J Cennimo, MD, FAAP, FACP, AAHIVS; Chief Editor: Michael Stuart Bronze, MD  more...
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Presentation

History

Presentations of COVID-19 have ranged from asymptomatic/mild symptoms to severe illness and mortality. Common symptoms have included fever, cough, and shortness of breath. [13] Other symptoms, such as malaise and respiratory distress, have also been described. [33]

Symptoms may develop 2 days to 2 weeks following exposure to the virus. [13] A pooled analysis of 181 confirmed cases of COVID-19 outside Wuhan, China, found the mean incubation period to be 5.1 days and that 97.5% of individuals who developed symptoms did so within 11.5 days of infection. [14]

The following symptoms may indicate COVID-19 [16] :

  • 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 have included the following:

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

Cheung and colleagues [134] conducted a systematic review and meta-analysis to evaluate the occurrence of gastrointestinal (GI) symptoms (anorexia, nausea, vomiting, diarrhea, abdominal pain or discomfort) in patients with COVID-19. They found that 17.6% of patients with COVID-19 had GI symptoms. Stool tested positive for SARS-CoV-2 RNA in 48.1%, including stool collected after respiratory samples tested negative for viral RNA.

Wu and McGoogan [15]  reported that, among 72,314 COVID-19 cases reported to the Chinese Center for disease Control and Prevention (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.

In an initial report of 41 patients infected in Wuhan, China, Huang and colleagues [80] reported that most common clinic finding was fever (98%), followed by cough (76%) and myalgia/fatigue (44%). Headache, sputum production, and diarrhea were less common. The clinical course was characterized by the development of dyspnea in 55% of patients and lymphopenia in 66%. All patients with pneumonia had abnormal lung imaging findings. Acute respiratory distress syndrome (ARDS) developed in 29% of patients, and ground-glass opacities are common on CT scans. [53]

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. [135]

Risk factors for severe COVID-19, regardless of age, include the following [15, 43, 123, 136, 137] :

  • Chronic kidney disease
  • COPD
  • Immunocompromised state due to solid organ transplant
  • Obesity (BMI ≥30)
  • Serious heart conditions (eg, heart failure, coronary artery disease, cardiomyopathies)
  • Sickle cell disease
  • Type 1 diabetes mellitus
  • Type 2 diabetes mellitus

The following are underlying conditions that may represent an increased risk of severe COVID-19:

  • Asthma (moderate to severe)
  • Cerebrovascular disease
  • Cystic fibrosis
  • Immunocompromised state due to blood or bone marrow transplant, immunodeficiencies, HIV infection, corticosteroid use (or other medications that weaken the immune system)
  • Neurologic conditions (eg, dementia)
  • Liver disease
  • Pregnancy
  • Pulmonary fibrosis
  • Smoking
  • Thalassemia

Williamson and colleagues, [138] 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.

A multicenter observational cohort study conducted in Europe found frailty to be a greater predictor of mortality than age or comorbidities. [139]

Type A blood has been suggested as a potential factor that predisposes to severe COVID-19, specifically in terms of increasing the risk of respiratory failure. Blood type O appears to confer a protective effect. [140, 141]

Patients with suspected COVID-19 should be reported immediately to infection-control personnel at their healthcare facility and the local or state health department. Current CDC guidance calls for the patient to be cared for with airborne and contact precautions (including eye shield) in place. [19] 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. [135]

Early in the outbreak, one patient with COVID-19 (a 61-year-old man with an underlying abdominal tumor and cirrhosis) was admitted with severe pneumonia and respiratory failure. Complications of infection included severe pneumonia, septic shock, acute respiratory distress syndrome (ARDS), and multiorgan failure, resulting in death. [33]

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. [17] 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. [18] In a European study of 72 patients with PCR results positive for COVID-19, 53 patients (74%) reported reduced olfaction, while 50 patients (69%) reported a reduced sense of taste. Forty-nine patients (68%) reported both symptoms. [142]

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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. [19]

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. [80, 143, 144, 145]

Huang and colleagues [138] 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. [80]

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Complications

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

Acute respiratory distress syndrome

ARDS is a major complication in severe cases of COVID-19, affecting 20-41% of hospitalized patients. [145, 146] Wu and colleagues [146] reported that, among 200 patients with COVID-19 who were hospitalized, older age, neutrophilia, and elevated lactate dehydrogenase and D-dimer levels increased the risks of ARDS and death.

Cardiac concerns

Increasing data have shown a significant burden of cardiac injury in COVID-19. Up to 20% of patients in a cohort in China demonstrated cardiac injury, often associated with more severe disease. They were more likely to be older, to have ARDS, and to experience higher mortality rates. [147]

Clerkin and colleagues [148] and Driggin and colleagues [149] published excellent reviews delineating the current understanding and future investigation needs. Multiple case series have noted an increased burden of cardiovascular disease (4-14%) and cardiovascular comorbidities in patients with COVID-19, often associated with increased morbidity and mortality. The risk for cardiac injury, evidenced by increased troponin levels, was up to 22% in ICU patients. Interestingly, up to 12% of patients without known cardiovascular disease had elevated troponin levels or experienced cardiac arrest during hospitalization for COVID-19. The pathophysiology of injury is under investigation, but some presentations seem related to cytokine storm.

Arentz and colleagues, [150] in a study of 21 patients with severe COVID-19 admitted to the ICU in Washington State, reported that 33% had cardiomyopathy.

A study of 100 randomly selected patients in Germany showed 78% had abnormal MRI findings a median of 71 days after testing positive for SARS-CoV-2. Of these, 60% showed cardiac inflammation that was independent of preexisting conditions, severity and overall course of the acute illness. Approximately 20% reported atypical chest pain or palpitations at the time of MRI. Over one-third complained of ongoing shortness of breath. [151] Data continue to emerge regarding cardiovascular complications and ongoing research is warranted.

Acute kidney injury

In a study of 5,449 patients hospitalized with severe COVID-19 in New York, 1,993 (36.6%) developed acute kidney injury, 14.3% of whom required dialysis. The need for dialysis was associated with severe disease and respiratory failure. [152]

Thyrotoxicosis

Preliminary data analysis of patients with COVID-19 who required high intensity care in Milan, Italy showed individuals commonly had low or suppressed serum thyroid stimulating hormone, with and without elevated free thyroxine concentrations. Subacute thyroiditis has been described with other viral infections. [153, 154]  

Neurologic manifestations

Neurologic symptoms (eg, encephalitis, headache, altered mentality, anosmia) have been described in patients during and following infection with SARS-CoV-2 infection. [155, 156]  Additionally, myasthenia gravis has been described following infections, manifested by development of antibodies to acetylcholine receptors. Restivo and colleagues [157] describe 3 cases of myasthenia gravis with symptoms appearing 5-7 days after onset of fever due to ARS-CoV-2 infection. 

Thrombosis

Venous and arterial thromboses have increasingly been seen in patients with COVID-19 infection. Malas and colleagues [158] performed a systematic review and meta-analysis of studies evaluating thromboembolism in COVID-19. They included 42 studies enrolling 8271 patients finding and overall rate of venous thromboembolism of 21% with an increased incidence in ICU patients of 31%. The arterial thromboembolism rate was 2% and 5% in the ICU. The pooled mortality rate among all patients with thrombosis was 23% vs 13% among patients without. The pooled odds of mortality were 74% higher among patients who developed thromboembolism compared to those who did not (odds ratio, 1.74; P = 0.04).

Clinical trials are underway to assess treatment and prophylaxis for thrombosis in outpatients, hospitalized patients, and convalescent patients. The American College of Chest Physicians has issued guidelines

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Clinical Progression

A retrospective, single-center study from Shanghai evaluated clinical progression of COVID-19 in 249 patients. The interval from symptom onset to hospitalization averaged 4 days (range, 2-7 days) among symptomatic patients. The vast majority (94.3%) of patients developed fever. Hospitalization lasted an average of 16 days (range, 12-20 days) before discharge.

The estimated median duration of fever in all febrile patients was 10 days after symptom onset.

In 163 patients (65.7%), radiological abnormalities (compared with baseline) occurred on day 7 following symptom onset, 154 (94.5%) of whom improved radiologically by day 14.

The median duration to negative results on RT-PCT using upper respiratory tract samples was 11 days. Viral clearance was more likely to be delayed in ICU patients. 

The authors concluded that most cases of COVID-19 are mild. Early viral replication control and host-directed therapy applied at later stages were essential to improving outcomes. [159]

In collaboration with the National Health Commission of China, Liang and colleagues [160] developed clinical scoring at hospital admission to predict progression to critical illness (online risk calculator free for public use). The clinical scoring system was validated with data from a nationwide cohort (n = 1590) in China.

In Germany, postmortem examination of ten patients with COVID-19 revealed extensive lung pathology over time with both acute and organizing components. Nonspecific and seemingly mild liver and cardiac inflammation was also found, but no CNS involvement. [161] A separate autopsy study of 7 lungs described widespread thrombosis and microangiopathy with evidence of severe endothelial injury. Compared with findings in patients who died of ARDS due to influenza A (H1N1), the lungs from patients with COVID-19 had significantly more microthrombi. [162]  

Long COVID Syndrome

As the COVID-19 pandemic has matured, more patients have reported long-term, post infection sequelae. The majority of patients recover fully but those that do not have reported adverse symptoms such as fatigue, dyspnea, cough, 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. [163]  

The US National Institutes of Health includes discussion of persistent symptoms or organ dysfunction after acute COVID-19 within guidelines that discuss the clinical spectrum of the disease. [164]  

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. [165]  

An international web-based survey of respondents (n = 3,762) with suspected and confirmed COVID-19 from 56 countries tallied prevalence of 205 symptoms in 10 organ systems, with 66 symptoms traced over 7 months. The most frequent symptoms reported after 6 months were fatigue (77.7%), postexertional malaise (72.2%), and cognitive dysfunction (55.4%). [166]  

A long-term follow-up study of adults with non-critical COVID-19 at 30 and 60 days post infection revealed ongoing symptoms in two-thirds of patients. The most common symptoms included anosmia/ageusia in 28% (40/150) at day 30 and 23% (29/130) at day 60; dyspnea in 36.7% (55/150) patients at day 30 and 30% (39/130) at day 60; and fatigue/weakness in 49.3% (74/150) at day 30 and 40% (52/130) at day 60. Persistent symptoms at day 60 were significantly associated with age 40 to 60 years old, hospital admission, and abnormal auscultation at symptom onset. [167]  

A follow-up study of COVID-19 consequences in 1,733 patients discharged from the hospital in Wuhan, China after 6 months reported fatigue or muscle weakness (63%), sleep difficulties (26%), and anxiety or depression (23%) were the most common symptoms. Lung function, as measured by CT showing interstitial change and 6-minute walking distance, was less than the lower limit of normal for 22-56% across different severity scales. [168]

A study of 55 patients from China looked at long-term pulmonary follow-up 3 months after discharge from a symptomatic COVID-19 illness. Patients’ mean age was 47 years, 42% were female, and 85% had moderate disease. Only 9 patients (16.4%) had underlying comorbidities including hypertension, diabetes mellitus, and cardiovascular diseases, but none had preexisting pulmonary disease. None of the patients required mechanical ventilation. At 3 months, 71% still had abnormal chest CT scans, most commonly showing interstitial thickening. Spirometry was also checked in all patients. Lung function abnormalities were detected in 25.5%. Anomalies were noted in total lung capacity of 4 patients (7.3%), FEV1 of 6 patients (11%), FVC of 6 patients (11%), DLCO of 9 patients (16%), and small airway function in 7 patients (12%) despite most patients having no respiratory complaints. [169]  

These data are consistent with the findings of a study of 124 patients recovered from COVID-19 after 6 weeks in the Netherlands. The mean age was 59±14 years and 60% were male; 27 with mild, 51 with moderate, 26 with severe, and 20 with critical disease. Nearly all patients (99%) had improved imaging, but residual parenchymal abnormalities remained in 91% and correlated with reduced lung diffusion capacity in 42%. Twenty-two percent had low exercise capacity, 19% low fat-free mass index, and problems in mental and/or cognitive function were found in 36% of the patients. [170]  

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. [171]

Reinfection

Clinicians, infectious disease specialists, and public health experts are examining the potential for patient reinfection with the SARS CoV-2 virus. [172]

Cases of reinfection with SARS CoV-2 have emerged worldwide. [173]  Several cases have shown differing viral genomes tested in the patient, which suggests reinfection rather than prolonged viral shedding.  

A case report showed a 42-year-old male who was infected with SARS CoV-2 on March 21, 2020 following a workplace exposure. The patient had resolution of symptoms after 10 days with continued good health for 51 days. On May 24, 2020, the patient presented with symptoms suggestive of COVID-19 following a new household exposure. Upon testing via SARS-CoV-2 RT-PCR, the patient had confirmed positive COVID-19 with several potential genetic variations that differed from the SARS-CoV-2 strain sequenced from the patient in March. [174]  

In another case, a 33-year-old male in Hong Kong had contracted COVID-19 in March 2020, which was confirmed via saliva SARS-CoV-2 RT-PCR. The patient had resolution of symptoms along with two negative SARS-CoV-2 RT-PCR results by April 14, 2020. The patient experienced a second episode of COVID-19 in August 2020 following a trip to Spain. Although asymptomatic, the patient was tested upon returning to Hong Kong and tested positive via SARS-CoV-2 RT-PCR. Genomic sequencing was performed on both RT-PCR specimens collected in March and August. The genomic analysis showed the two strains of SARS-CoV-2 (from March and August) belonged to different viral lineages, which suggests that the strain from the first episode differed from the strain in the second episode. [175]  

The Collaborative Study COVID Recurrences (COCOREC) group in France reported 11 virologically-confirmed cases of patients with a second clinically- and virologically confirmed acute COVID-19 episodes between April 6, 2020 and May 14, 2020. Although, the letter does not describe confirmation with viral genomic sequencing to understand if the cases were a relapse of the initial infection or a new infection. [176]  

Two cases of reinfection have emerged in the United States, a 25-year-old man from Nevada and a 42-year-old man in Virginia. These cases were confirmed by gene testing that showed different strains of the SARS-CoV-2 virus during the 2 infection episodes  in each patient. In these cases, the patients experienced more severe symptoms during their second infections. It is unclear if the symptom severity experienced the second time were related to the virus or the how the patients’ immune systems reacted. Vaccine development may need to take into account circulating viral strains. [173, 177]  

These case reports give insight to the possibility of reinfection. Further research to determine the prevalence of COVID-19 reinfections is needed, including the frequency at which they occur and longevity of COVID-19 immunity. 

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