Clinical characteristics of COVID-19

This section is aimed at assisting public health professionals and is based on an ongoing rapid review of the latest evidence.

Detailed epidemiological information on laboratory-confirmed cases reported to The European Surveillance System (TESSy) are published in the ECDC weekly COVID-19 country report and the weekly COVID-19 surveillance report.

Symptoms and signs

(Latest update 17 February 2022)

Systematic reviews indicate that up to 40% of COVID-19 cases are asymptomatic [1]. The most commonly reported symptoms are cough (63-83%), fever (43-45%), fatigue (63%), myalgia (36-63%) and headache (34-70%) [2,3]. The most commonly reported symptoms are cough (63-83%), fever (43-45%), fatigue (63%), myalgia (36-63%) and headache (34-70%) headache (70.3%), loss of smell (70.2%), nasal obstruction (67.8%), cough (63.2%), asthenia (63.3%), myalgia (62.5%), rhinorrhoea (60.1%), gustatory dysfunction (54.2%), and sore throat (52.9%) and fever (45.4%) [2,3]. Olfactory and gustatory dysfunction have been identified as common symptoms, with a 52.7% pooled prevalence across 10 studies [4]. Similarly, altered taste sensation was found among 49.8% of COVID-19 patients in a pooled analysis of five studies [5].

Among 81 cases infected with the Omicron variant of concern (VOC) in Norway in November-December 2021, the most common symptoms were cough (83%), runny/stuffy nose (78%), fatigue/lethargy (74%), sore throat (72%), headache (68%) and fever (54%) [6]. A community-based study in the United Kingdom comparing symptoms in PCR-positive COVID-19 cases between October-November 2021 (Delta period) and December 2021-January 2022 (Omicron period) reported that cases likely infected with the Omicron VOC had increased odds of reporting sore throat, fever, and cough compared to the cases likely infected with the Delta VOC. The cases had similar odds of reporting headache, fatigue, nausea or vomiting, and diarrhoea. Cases infected during the Omicron period reported significantly less loss of taste and loss of smell [7,8].

The most commonly reported symptoms in children are fever and cough [9-11]. Other symptoms include gastrointestinal symptoms, sore throat/pharyngitis, shortness of breath, myalgia, rhinorrhoea/nasal congestion, and headache, with varying prevalence among different studies [9-12].

Severity

(Latest update 17 February 2022)

Most cases of COVID-19 are mild or moderate and do not require hospitalisation or advanced medical care. The most common manifestation of severe COVID-19 is pneumonia with fever, cough, dyspnoea and pulmonary infiltrates [13]. Pneumonia can be complicated by respiratory failure requiring oxygen supplementation and mechanical ventilation (3% of cases) [14]. Other severe complications include thromboembolism (such as pulmonary embolism and stroke), circulatory shock, myocardial damage, arrhythmias, and encephalopathy [14-16]. Severe illness usually develops approximately one week after the onset of symptoms.

The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) reported on outcomes of an international cohort of more than 400 000 hospitalised patients with COVID-19 from January 2020 to May 2021. The most common symptoms on presentation were fever, cough and shortness of breath, although older age groups (80 years and above) presented more frequently with altered consciousness. The most commonly abnormal laboratory finding in hospitalised COVID-19 patients was lymphocytopenia (0.9 × 109; IQR 0.6-1.3 × 109 cells/Lt). Comorbidities varied by age group, but the most common included hypertension, diabetes, and cardiac disease. In this case series, 16.3% of patients were admitted to an intensive care unit (ICU), but patients aged 80 years and above were less likely so. Use of mechanical ventilation increased with age until about 60 years. The hazard ratio for death increased by 50% for each decade of age [(Hazard Ratio (HR)) 1.49 (95% CI: 1.48, 1.50) per 10 years higher age]. Tuberculosis and HIV significantly increased the risk of death by 86% and 87%, respectively [17].

Overall, 6% of COVID-19 cases diagnosed from August 2020 to December 2021 and reported by European Union and European Economic Area (EU/EEA) countries to The European Surveillance System (TESSy) were hospitalised. This varied by age, with hospitalisation rates of 1.2% in cases under 30 years, 3.6% in those 30-59 years, 11.4% in 60-69 years, 23.2% in 70-79 years and 33.9% in those 80 years and older. Overall, 0.6% of all reported COVID-19 cases, and 14.2% of hospitalised cases, were reported as severe, requiring ICU admission and/or oxygen supportive therapy. A strong age gradient is also observed for severe hospitalisation, with higher rates in older age groups. Overall, the crude case fatality rate among COVID-19 cases reported to TESSy since August 2020 is 1.5%, with very low rates (0.01%) in cases under 30 years, 0.2% in those 30-59 years, 2.0% in those 60-69 years, 7.0% in those 70-79 years and 18.9% in those 80 years and older.

Among Omicron VOC cases with known outcomes reported into TESSy as of 19 January 2022, 884 (1.14%) were hospitalised, 120 (0.16%) required ICU admission/respiratory support, and 48 (0.06%) died [18]. The pattern of higher rates of hospitalisation, ICU admission, and death with increased age is also apparent for Omicron VOC cases, as it was for cases due to the Delta VOC, other previous VOCs, and the original strain of SARS-CoV-2.

Preliminary analysis of case-based data submitted by 15 EU/EEA countries to TESSy between week 46 2021 and week 2 2022 compared the overall adjusted odds ratio (aOR) of hospital admission for infection with the Omicron VOC compared to infection with the Delta VOC among symptomatic cases. Logistic regression models adjusted for age group, sex, preconditions, reporting country, reporting week, and vaccination status showed that infection with the Omicron VOC was less likely to be reported with admission to hospital compared to infection with the Delta VOC (aOR 0.41; 95% CI: 0.37-0.46).

Similarly, evidence from a variety of settings suggests that infections with the Omicron VOC have a less severe clinical presentation than those due to the Delta VOC. A low hospital admission rate (0.3%) and case fatality rate (<0.1%) for Omicron VOC cases have been observed in Canada [19]. In Texas (US), California (US), and Denmark, a shorter median length of hospital stay and/or significantly reduced need for respiratory support have been reported for infection with the Omicron VOC [20-22].

The observed lower severity of the Omicron VOC can be attributed at least partially to the protective effect of vaccination, time since vaccination, and/or previous infection, and does not necessarily reflect the inherent severity of the Omicron VOC. Therefore, the comparative intrinsic capacity of the Omicron VOC to cause severe infection may be underestimated due to the large numbers of vaccinated or previously infected people that had accumulated prior to its emergence, which was not the case in the beginning of preceding waves.

The burden of COVID-19 in children indicates that case notification and hospital admission rates among children rise as transmission increases, but that most children with symptomatic COVID-19 have a very low risk of hospitalisation or death. For every 10 000 symptomatic paediatric cases reported in TESSy, approximately 117 were hospitalised and eight required ICU admission or respiratory support [23].

A severe complication of COVID-19 in children is an inflammatory multisystem syndrome, initially identified by physicians in the United Kingdom (UK) in April 2020. The Royal College of Paediatrics and Child Health defined it as paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS), while the World Health Organization (WHO) and the US CDC refer to it as Multisystem inflammatory syndrome in children (MIS-C) [24,25]. There is currently no specific test available to diagnose this syndrome, so diagnosis is based on clinical signs and symptoms, as well as evidence of a previous SARS-CoV-2 infection or exposure. Children who develop PIMS-TS/MIS-c are generally previously healthy, and the primary infection with SARS-CoV-2 is usually mild or asymptomatic [26].

PIMS-TS/MIS-C is rare and shares common clinical features with other paediatric inflammatory syndromes such as Kawasaki disease, toxic shock syndrome, and macrophage activation syndrome. Children with PIMS-TS/MIS-C often present four to six weeks after infection, with a wide clinical spectrum including Kawasaki disease-like symptoms, life-threatening shock, and milder forms of illness such as persistent fever, inflammation, and gastrointestinal manifestations [26]. The median age of children diagnosed with PIMS-TS/MIS is eight years [26]. Early recognition and prompt treatment of PIMS-TS/MIS-C cases is essential.

Post COVID-19 condition

Patients with COVID-19 often report persisting symptoms or develop new symptoms after the acute infection is over [27]. Post-COVID-19 condition, also referred to as ‘long COVID’, has manifestations from multiple organ systems and its pathophysiology remains unclear and is most likely multifactorial. Increasing age, female sex, and hospitalisation for acute COVID-19 are linked to a higher prevalence of prolonged symptoms [28]. The estimates of prevalence of prolonged symptoms vary widely depending on the time of follow up and the applied definition, and range from 2.3% [28] to 80% [29]. The UK Office of National Statistics estimates that between 7% and 18% of people who have had COVID-19 develop some symptoms of post COVID-19 condition persisting for at least five weeks [30] leading to an estimated 1.3 million people in the UK (1 in 50) experiencing self-reported post-COVID condition [31].

Persistence of symptoms or the development of new symptoms for at least two months within three months from the onset of COVID-19 is defined as ‘post-acute COVID-19’ [32]. The spectrum of presentation, pathophysiology, clinical course, diagnosis, and management of these conditions is under investigation.

Symptoms from the respiratory tract include shortness of breath, cough, and sore throat. Decreased diffusing capacity and abnormalities in lung imaging are commonly observed. Cardiovascular presentations include chest pain and arrhythmias, such as atrial fibrillation presenting as palpitations or tachycardia, as well as heart failure and thromboembolic events [16]. Neuropsychiatric conditions are common. Chronic fatigue, headaches and loss of smell are the most common symptoms of post-acute COVID-19, but cognitive symptoms, such as difficulty concentrating, sleep disturbances and depression are commonly reported [28]. Manifestations from other organ systems, such as endocrine, gastrointestinal, renal, and skin, are reported less frequently. Increasing age, female sex and hospitalisation for acute COVID-19 are linked to a higher prevalence of prolonged symptoms [28]. The prevalence of post-acute COVID-19 decreases over time since the acute presentation [28] but it is not yet possible to determine how long the symptoms may persist.

Prolonged symptoms are common in hospitalised patients with severe COVID-19 after discharge [33]. Among COVID-19 patients discharged from hospital, decreased quality of life was observed in 44% of patients and 10-30% of patients required rehospitalisation over the months following discharge [34,35]. However, prolonged symptoms can also be reported after mild COVID-19 [36], but the extent of the burden on the healthcare system of prolonged symptoms after mild COVID-19 is uncertain.

There is currently no consensus on the possible effects of being vaccinated on post-COVID-19 condition. A study of breakthrough infections suggested that people who have completed the primary vaccination series who developed a breakthrough SARS-CoV-2 infection were 49% less likely than unvaccinated people to report symptoms persisting at least four weeks after infection [37]. A pre-print article from Israel from January 2022 also confirmed that people who had completed the primary vaccination series were not more likely to report long-term symptoms than people who did not report SARS-CoV-2 infection and were less likely to report long-term symptoms than unvaccinated people or those who had not completed the primary vaccination series [38]. However, a retrospective cohort study of electronic health records in the US comparing COVID-19 outcomes between vaccinated and unvaccinated people could not identify any effect of vaccination on post-COVID-19 condition [39].

The presence of post COVID-19 condition has been also reported in cohorts of children from several countries [40]. A large nationwide study in Denmark showed that post-acute COVID-19 in children is rare. Children with SARS-CoV-2 infection aged 6-17 years reported prolonged symptoms more frequently than a control group (percent difference 0.8%), and most symptoms resolved within 1-5 months. The most common prolonged symptoms among school-children with a history of SARS-CoV-2 infection in this study were loss of smell (relative difference, RD, 12%), loss of taste (RD 10%), fatigue (RD 5%), respiratory problems (RD 3%), dizziness (RD 2%), muscle weakness (RD 2%), and chest pain (RD 1%) [41]. Similarly, in Finland repeated surveys on the state health register and in hospitals failed to discover increased numbers of post-COVID-19 condition cases in children in the country. There is no registry-based evidence on excess healthcare use after laboratory-confirmed COVID-19 in children younger than 16 years [42].

 

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