Symptoms of COVID-19

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Symptoms of COVID-19

Symptoms of COVID-19 are variable, ranging from mild symptoms to severe illness.[1][2] Common symptoms include headache, loss of smell and taste, nasal congestion and runny nose, cough, muscle pain, sore throat, fever, diarrhea, and breathing difficulties.[3] People with the same infection may have different symptoms, and their symptoms may change over time. Three common clusters of symptoms have been identified: one respiratory symptom cluster with cough, sputum, shortness of breath, and fever; a musculoskeletal symptom cluster with muscle and joint pain, headache, and fatigue; a cluster of digestive symptoms with abdominal pain, vomiting, and diarrhea.[3] In people without prior ear, nose, and throat disorders, loss of taste combined with loss of smell is associated with COVID-19 and is reported in as many as 88% of cases[4][5][6]

Of people who show symptoms, 81% develop only mild to moderate symptoms (up to mild pneumonia), while 14% develop severe symptoms (dyspnea, hypoxia, or more than 50% lung involvement on imaging) and 5% of patients suffer critical symptoms (respiratory failure, shock, or multiorgan dysfunction).[7] At least a third of the people who are infected with the virus do not develop noticeable symptoms at any point in time.[8][9] These asymptomatic carriers tend not to get tested and can spread the disease.[9][10][11][12] Other infected people will develop symptoms later, called "pre-symptomatic", or have very mild symptoms and can also spread the virus.[12]

As is common with infections, there is a delay between the moment a person first becomes infected and the appearance of the first symptoms. The median delay for COVID-19 is four to five days.[13] Most symptomatic people experience symptoms within two to seven days after exposure, and almost all will experience at least one symptom within 12 days.[13][14]

Most people recover from the acute phase of the disease. However, some people – over half of a cohort of home-isolated young patients[15][16] – continue to experience a range of effects, such as fatigue, for months after recovery, a condition called long COVID; long-term damage to organs has been observed. Multi-year studies are underway to further investigate the long-term effects of the disease.[17]

Overview

Symptoms of COVID-19

Some symptoms of COVID-19 can be relatively non-specific; the most common symptoms are fever, dry cough, and fatigue.[1][18] Among those who develop symptoms, approximately one in five may become more seriously ill and have difficulty in breathing. Emergency symptoms include difficulty in breathing, persistent chest pain or pressure, sudden confusion, difficulty walking, and bluish face or lips; immediate medical attention is advised if these symptoms are present.[1] Further development of the disease can lead to complications including pneumonia, acute respiratory distress syndrome, sepsis, septic shock, and kidney failure.

Some symptoms usually appear sooner than others. In August 2020, scientists at the University of Southern California reported the "likely" order of initial symptoms of the COVID-19 disease as a fever followed by a cough and muscle pain, and that nausea and vomiting usually appear before diarrhea.[19] This contrasts with the most common path for influenza where it is common to develop a cough first and fever later.[19] While health agency guidelines tend to recommend isolating for 14 days while watching for symptoms to develop,[20] there is limited evidence that symptoms may develop for some patients more than 14 days after initial exposure.[21]

Different Covid variants

The frequency of symptoms predominating for people suffering from different variants may differ from what was observed in the earlier phases of the pandemic. People infected with the Delta variant may mistake the symptoms for a bad cold and not realize they need to isolate. Common symptoms reported have been headaches, sore throat, a runny nose or a fever.[22][medical citation needed][23] In the United Kingdom, when the Delta variant accounted for 91 percent of new cases, one study found that the most reported symptoms were headache, sore throat, and runny nose.[24]

Systemic

Typical systemic symptoms include fatigue, and muscle and joint pains. Some people have a sore throat.[1][2][18]

Fever

Fever is one of the most common symptoms in COVID-19 patients. However, its absence at an initial screening does not rule out COVID-19. Fever in the first week of a COVID-19 infection is part of the body's natural immune response; however, if the infections develop into a cytokine storm the fever is counterproductive. As of September 2020, little research had focused on relating fever intensity to outcomes.[25]

A June 2020 systematic review reported a 75–81% prevalence of fever.[2] As of July 2020, the European Centre for Disease Prevention and Control (ECDC) reported a prevalence rate of ~45% for fever.[3]

Pain

A June 2020 systematic review reported a 27–35% prevalence of fatigue, 14–19% for muscle pain, 10–14% for sore throat.[2] As of July 2020, the ECDC reported a prevalence rate of ~63% for muscle weakness (asthenia), ~63% for muscle pain (myalgia), and ~53% for sore throat.[3]

Respiratory

Cough is another typical symptom of COVID-19, which could be either dry or a productive cough.[2]

Some symptoms, such as difficulty breathing, are more common in patients who need hospital care.[1] Shortness of breath tends to develop later in the illness. Persistent anosmia or hyposmia or ageusia or dysgeusia has been documented in 20% of cases for longer than 30 days.[4][5]

Respiratory complications may include pneumonia and acute respiratory distress syndrome (ARDS).[26][27][28][29]

As of July 2020, the ECDC reported a prevalence rate of ~68% for nasal obstruction, ~63% for cough, ~60% for rhinorrhoea.[3] A June 2020 systematic review reported a 54–61% prevalence of dry cough and 22–28% for productive cough.[2]

Cardiovascular

Cardiovascular complications may include heart failure, arrhythmias, heart inflammation, and blood clots.[30][31][32][33][34] They are common traits in severe COVID-19 patients.[35]

Hypertension seems to be the most prevalent risk factor for myocardial injury in COVID-19 disease. It was reported in 58% of individuals with cardiac injury in a recent meta-analysis.[36]

Several cases of acute myocarditis associated with COVID-19 have been described around the globe and are diagnosed in multiple ways. Taking into consideration serologyleukocytosis with neutrophilia and lymphopenia was found in many patients. Cardiac biomarkers troponin and N-terminal (NT)-prohormone BNP (NT-proBNP) were seen elevated. Similarly, the level of inflammation-related markers such as C-reactive protein (CRP), D-dimer, IL-6, procalcitonin was significantly increased, indicating an inflammatory process in the body. Electrocardiogram findings were variable and ranged from sinus tachycardia, ST-segment elevation, T-wave inversion and ST-depression.[37] In one case, viral particles were seen in the interstitial cell, and another case reported SARS-CoV-2 RT–PCR positivity in the cardiac tissue suggestive of direct viral injury to the myocardium.[38][39] Endomyocardial biopsy [EMB] remains the gold standard invasive technique in diagnosing myocarditis; however, due to the increased risk of infection, it is not done in COVID-19 patients.

The binding of the SARS-CoV-2 virus through ACE2 receptors present in heart tissue may be responsible for direct viral injury leading to myocarditis.[37]In a study done during the SARS outbreak, SARS virus RNA was ascertained in the autopsy of heart specimens in 35% of the patients who died due to SARS.[40] It was also observed that an already diseased heart has increased expression of ACE2 receptor contrasted to healthy individuals.[41] Hyperactive immune responses in COVID-19 Patients may lead to the initiation of the cytokine storm. This excess release of cytokines may lead to myocardial injury.[37]

Neurological

Patients with COVID-19 can present with neurological symptoms that can be broadly divided into central nervous system involvement, such as headache, dizziness, altered mental state, and disorientation, and peripheral nervous system involvement, such as anosmia and dysgeusia.[42] Some patients experience cognitive dysfunction called "COVID fog", or "COVID brain fog", involving memory loss, inattention, poor concentration or disorientation.[43][44] Other neurologic manifestations include seizures, strokes, encephalitis, and Guillain–Barré syndrome (which includes loss of motor functions).[45][46]

As of July 2020, the ECDC reported a prevalence rate of ~70% for headache.[3] A June 2020 systematic review reported a 10–16% prevalence of headache.[2]

Loss of smell

In some people, COVID-19 causes people to temporarily lose their sense of smell either partially or fully.[47][48]

This symptom, if it is present at all, often appears early in the illness.[47] Its onset is often reported to be sudden. Smell usually returns to normal within a month. However, for some patients it improves very slowly and is associated with odors being perceived as unpleasant or different than they originally did (parosmia), and for some people smell does not return for at least many months.[48] It is an unusual symptom for other respiratory diseases, so it is used for symptom-based screening.[47][48]

Loss of smell has several consequences. Loss of smell increases foodborne illness due to inability to detect spoiled food, and may increase fire hazards due to inability to detect smoke. It has also been linked to depression. If smell does not return, smell training is a potential option.[48]

It is sometimes the only symptom to be reported, implying that it has a neurological basis separate from nasal congestion. As of January 2021, it is believed that these symptoms are caused by infection of sustentacular cells that support and provide nutrients to sensory neurons in the nose, rather than infection of the neurons themselves. Sustentacular cells have many Angiotensin-converting enzyme 2 (ACE2) receptors on their surfaces, while olfactory sensory neurons do not. Loss of smell may also be the result of inflammation in the olfactory bulb.[48]

A June 2020 systematic review found a 29–54% prevalence of olfactory dysfunction for people with COVID-19,[47] while an August 2020 study using a smell-identification test reported that 96% of people with COVID-19 had some olfactory dysfunction, and 18% had total smell loss.[48] Another June 2020 systematic review reported a 4–55% prevalence of hyposmia.[2] As of July 2020, the ECDC reported a prevalence rate of ~70% for loss of smell.[3]

A disturbance in smell or taste is more commonly found in younger people, and perhaps because of this, it is correlated with a lower risk of medical complications.[47]

Loss of taste and chemesthesis

In some people, COVID-19 causes people to temporarily experience changes in how food tastes (dysgeusia or ageusia).[47][48] Changes to chemesthesis, which includes chemically triggered sensations such as spiciness, are also reported. As of January 2021, the mechanism for taste and chemesthesis symptoms were not well understood.[48]

A June 2020 systematic review found a 24–54% prevalence of gustatory dysfunction for people with COVID-19.[47] Another June 2020 systematic review reported a 1–8% prevalence of hypogeusia.[2] As of July 2020, the ECDC reported a prevalence rate of ~54% for gustatory dysfunction.[3]

Other neurological and psychiatric symptoms

Other neurological symptoms appear to be rare, but may affect half of patients who are hospitalized with severe COVID-19. Some reported symptoms include delirium, stroke, brain hemorrhage, memory loss, psychosis, peripheral nerve damage, anxiety, and post-traumatic stress disorder. Neurological symptoms in many cases are correlated with damage to the brain's blood supply or encephalitis, which can progress in some cases to acute disseminated encephalomyelitis. Strokes have been reported in younger people without conventional risk factors.[49]

As of September 2020, it was unclear whether these symptoms were due to direct infection of brain cells, or of overstimulation of the immune system.[49]

A June 2020 systematic review reported a 6–16% prevalence of vertigo or dizziness, 7–15% for confusion, and 0–2% for ataxia.[2]

Other

Itchy rash. Small erythematous spots are observed.
Itchy rash in COVID. 61-year-old woman. Small erythematous spots are observed.
Chilblain-like lesions in a patient with coronavirus infection.
Chilblain-like lesions in a patient with coronavirus infection.

Other symptoms are less common among people with COVID-19. Some people experience gastrointestinal symptoms such as loss of appetite, diarrhea, nausea or vomiting.[1][50] A June 2020 systematic review reported a 8–12% prevalence of diarrhea, and 3–10% for nausea.[2]

Less common symptoms include chills, coughing out blood, diarrhea, and rash.[18] The so-called "COVID toes" are pink to violaceous papules arising on the hands and feet. These chilblain-like lesions often occur only in younger patients and do not appear until late in the disease or during convalescence.[51] Certain genetic polymorphisms (in the TREX1 gene) have been linked to susceptibility towards developing COVID-toe.[52] A June 2020 systematic review reported a 0–1% prevalence of rash in COVID-19 patients.[2]

Approximately 20–30% of people who present with COVID-19 have elevated liver enzymes, reflecting liver injury.[53][54]

Complications include multi-organ failure, septic shock, and death.[26][27][28][29]

Stages of COVID-19 infection

There are three stages, according to the way COVID-19 infection can be tackled by pharmacological agents, in which the disease can be classified.[55] Stage I is the early infection phase during which the domination of upper respiratory tract symptoms is present. Stage II is the pulmonary phase in which the patient develops pneumonia with all its associated symptoms. Stage III is the hyperinflammation phase, the most severe phase, in which the patient develops acute respiratory distress syndrome (ADRS), sepsis and multi-organ failure.

Longer-term effects

Multisystem inflammatory syndrome in children

Following the infection, children may develop multisystem inflammatory syndrome, also called paediatric multisystem inflammatory syndrome. This has symptoms similar to Kawasaki disease, which can be fatal.[56][57][58]

Long COVID

Some early studies suggest that 10-20% of people with COVID-19 will experience symptoms lasting longer than a month.[59][60] A majority of those who were admitted to hospital with severe disease report long-term problems, including fatigue and shortness of breath.[61] About 5–10% of patients admitted to hospital progress to severe or critical disease, including pneumonia and acute respiratory failure.[62]

By a variety of mechanisms, the lungs are the organs most affected in COVID-19.[63] In people requiring hospital admission, up to 98% of CT scans performed show lung abnormalities after 28 days of illness even if they had clinically improved.[64]

People with advanced age, severe disease, prolonged ICU stays, or who smoke are more likely to have long-lasting effects, including pulmonary fibrosis.[65] Overall, approximately one-third of those investigated after four weeks will have findings of pulmonary fibrosis or reduced lung function as measured by DLCO, even in asymptomatic people, but with the suggestion of continuing improvement with the passing of more time.[63]

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