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 Joint ECDC-WHO Regional Office for Europe Weekly COVID-19 Surveillance Bulletin.

Symptoms and signs

(Last update 15 August 2022)

Symptoms of SARS-CoV-2 infections may vary, both in frequency and severity, according to the SARS-CoV-2 variant. Systematic reviews indicate that up to 40% of COVID-19 cases are asymptomatic [1-3]. The most commonly reported symptoms prior to Omicron were a cough (63-83%), fever (43-45%), fatigue (63%), myalgia (36-63%) and headache (34-70%), loss of smell (70.2%), nasal obstruction (67.8%), cough (63.2%), asthenia (63.3%), rhinorrhoea (60.1%), and sore throat (52.9%) [4,5]. Olfactory and gustatory dysfunction were identified as common symptoms, with 49.8%-52.7% pooled prevalence across 15 studies [6,7].

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%) [8]. A community-based study in the United Kingdom comparing symptoms in PCR-positive COVID-19 cases between October-November 2021 (Delta predominant) and December 2021-January 2022 (Omicron predominant) reported that cases likely infected with the Omicron VOC had increased likelihood of reporting sore throat, fever, and cough but had similar likelihoods of reporting headache, fatigue, nausea or vomiting and diarrhoea compared to the cases likely infected with the Delta VOC. Cases infected during the Omicron period reported significantly less loss of taste and loss of smell [3,9,10].

The most 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 [11-14].

Individuals who received a full course of vaccination may still experience flu-like symptoms including fever, chills, cough, headache, myalgia and sore throat but these cases are typically less likely to require hospitalisation [1,15,16].

Severity

(Last update 15 August 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 [1]. Pneumonia can be complicated by respiratory failure requiring oxygen supplementation and mechanical ventilation (3% of cases) [17]. Other severe complications include thromboembolism (such as pulmonary embolism and stroke), circulatory shock, myocardial damage, arrhythmias, and encephalopathy [17-19]. 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). Co-morbidities 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 to be 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 [20].

The ECDC COVID-19 country report provides a concise overview of the current epidemiological situation of the COVID-19 pandemic by country. The joint ECDC-WHO Regional Office for Europe Weekly COVID-19 Surveillance Bulletin gives a detailed overview of the hospitalised cases by country, as well as ICU occupancy.

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 [1]. A low hospital admission rate (0.3%) and case fatality rate (<0.1%) for Omicron VOC cases have been observed in Canada [21]. In Texas (US), California (US), and Denmark, a shorter median length of hospital stays and/or significantly reduced need for respiratory support have been reported for infection with the Omicron VOC [1,22-24].

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. Recent studies have demonstrated that infection with Omicron was associated with less severe illness than that caused by Delta, and that vaccination appeared to be independently associated with lower in-hospital severity [25].

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 [26].

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 this condition 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) [27,28]. 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 generally have no known underlying conditions, and the primary infection with SARS-CoV-2 is usually mild or asymptomatic [29].

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 [29]. The median age of children diagnosed with PIMS-TS/MIS is eight years [29]. Early recognition and prompt treatment of PIMS-TS/MIS-C cases is essential.

Post COVID-19 condition

In October 2021, the World Health Organization (WHO) proposed a clinical definition and a name ‘post-COVID-19 condition’ to unify various existing definitions [30]. Previously, the occurrence of long-term ailments of COVID-19 was commonly defined as new or persistent symptoms four or more weeks from infection with SARS-CoV-2. Current definition states ‘the condition that occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually three months from the onset of COVID-19, with symptoms that last for at least two months and cannot be explained by an alternative diagnosis’ [31]. Post-COVID-19 condition has manifestations from multiple organ systems and its pathophysiology remains unclear and is most likely multifactorial. Patients with co-morbidities, obese individuals, smokers, those who are older (>50 years and, particularly, those >85 years), women and hospitalised patients are more likely to report prolonged symptoms [32]. 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% [32] to 80% [33]. The reported prevalence of post-COVID-19 condition has varied across and within many countries: UK 1.6–71%, [34], Germany 35–77% [35], China 49–76% [36], India 22% [37], Italy 5–51% [38], USA 16–53% [39] and Norway 61% [40].

A comprehensive meta-analysis including 31 studies, estimated that the pooled global prevalence of post-COVID-19 condition was 0.43% (95% CI, .39–.46) [41]. However, it has to be noted that the global prevalence of post-COVID-19 condition may change over time due to immune/vaccination status or emergence of new VOCs. Additionally, the meta-analysis showed that female sex and pre-existing asthma correspond with higher proportions of post-COVID-19 condition development [41]. Post-COVID-19 condition is a large collection of conditions, with unclear aetiology [42]. Symptoms are often episodic and multisystem, including respiratory, cardiovascular, gastrointestinal, neurological, cognitive, musculoskeletal, as well as mental health symptoms. 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 [19]. 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.

In a community-based cohort study in the UK, a first vaccine dose was associated with an initial 12.8% decrease in the odds for developing post-COVID-19 condition, whereas a second vaccine dose was associated with an initial 8.8% decrease in the odds for post-COVID-19 condition [43]. 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 [44]. Vaccination was associated with an initial 14.9% decrease in the odds of post-COVID-19 condition after a first dose of an adenovirus vector vaccine, and an 8.9% decrease after a first dose of a mRNA vaccine. Decreases in the odds after a second vaccine dose were numerically similar between vaccine types, at 8.7% for an adenovirus vector vaccine and 8.9% for a mRNA vaccine [43].

Post COVID-19 condition has been also reported in cohorts of children from several countries [45]. A 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%, p=0.02), and most symptoms resolved within one to five 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%) [46]. 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 [47].

References