Covid-19 and other Coronavirus Infections

Essentials

• Seasonal coronaviruses that commonly infect humans usually cause a mild respiratory infection. Infections occur particularly during the autumn and winter.
• Coronaviruses are transmitted through droplets, airborne route (aerosols), direct contact and from surfaces.
• Novel coronaviruses may cause also severe, lethal infections. Local epidemics with considerable mortality rate include SARS and MERS.
• In the beginning of 2024, the predominant variant of SARS-CoV-2 is the Omicron variant.
• In healthy adults, COVID-19 is usually a respiratory infection that does not threaten patient's life and its severity varies from asymptomatic or mild to a moderately severe disease with high fever.
• The infection may be severe and even fatal, especially in the elderly and in people with some underlying condition, particularly if they lack immunity from vaccination or earlier infection, and occasionally also in previously healthy people.
• Vaccinations are effective in preventing severe disease forms, but their effect on preventing the virus from spreading is modest.
• There are also drugs available for the treatment of severe forms of COVID-19 infection.

Sources of current information on COVID-19

• Current information on COVID-19 infection is available from the following sources:
  • WHO epidemiological and operational updates (world) http://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports
  • ECDC European Respiratory Virus Surveillance Summary (ERVISS) http://www.ecdc.europa.eu/en/publications-data/european-respiratory-virus-surveillance-summary-erviss
  • CDC COVID-19 Data and Surveillance http://www.cdc.gov/coronavirus/2019-ncov/cases-updates/index.html
  • Visualizations: WHO (world) http://who.sprinklr.com/, WHO (Europe) http://who.maps.arcgis.com/apps/opsdashboard/index.html#/ead3c6475654481ca51c248d52ab9c61 and the Johns Hopkins University (world) http://www.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6
  • COVID-19 variants
    • Variants Surveillance (CDC, USA http://www.cdc.gov/coronavirus/2019-ncov/variants/index.html)
    • Variants of concern in http://www.ecdc.europa.eu/en/covid-19/situation-updates and Virus Characterisation in http://erviss.org/ (ECDC, Europe)
• Consult locally relevant official sources especially for epidemiological data and criteria for selecting patients that should be tested for and vaccinated against the infection.
• The ECDC has published guidance on prevention and control measures in primary care, including general practitioner practices, dental clinics and pharmacy settings http://www.ecdc.europa.eu/en/publications-data/covid-19-infection-prevention-and-control-primary-care, and more generally in healthcare settingshttp://www.ecdc.europa.eu/en/news-events/healthcare-facilities-should-maintain-and-strengthen-infection-prevention-and-control http://www.ecdc.europa.eu/en/publications-data/considerations-infection-prevention-and-control-practices-relation-respiratory http://www.ecdc.europa.eu/en/publications-data/infection-prevention-and-control-and-preparedness-covid-19-healthcare-settings. For WHO publications on prevention and control, see http://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance-publications?publicationtypes=d198f134-5eed-400d-922e-1ac06462e676.
• See also guidance on preventing and managing COVID-19 in long-term services by the ECDC http://www.ecdc.europa.eu/en/all-topics-z/coronavirus/threats-and-outbreaks/covid-19/prevention-and-control/LTCF.
• See also the main COVID-19 sections on the websites of WHO, ECDC, CDC listed in references below.

Epidemiology

• Common coronaviruses generally cause mild upper respiratory tract infections.
• The SARS (Severe Acute Respiratory Syndrome) epidemic that originated in China in 2003 infected about 8 000 individuals, of whom about one in ten died.
• A new previously unknown SARS-like coronavirus known as MERS (Middle East Respiratory Syndrome Coronavirus, MERS-CoV) was identified in September 2012.
• COVID-19 infection, caused by the SARS-CoV-2 virus, emerged in Wuhan, China at the end of year 2019 and gave rise to a global pandemic.
• The pathogen of COVID-19 infection (SARS-CoV-2) resembles greatly that of the coronavirus epidemic in 2003.
• Coronaviruses are transmitted through droplets, direct contact as well as aerosols http://www.cdc.gov/coronavirus/2019-ncov/science/science-briefs/sars-cov-2-transmission.html. The period of infectiousness usually begins 1-2 days prior to symptom onset and lasts 5-7 days after symptom onset. In immunosuppressed patients, virus excretion may last longer.
• The disease caused by the Omicron variant is often milder than disease caused by earlier variants, but this is partly due to immunity acquired through vaccinations and earlier infection.
• The Omicron variant is more capable than the earlier variants of evading immunity acquired from vaccinations and earlier disease.
• Views vary concerning the protective effect of face masks. Fabric masks do not protect their user very well and they are not considered as adequate protection in all countries and situations. Surgical masks are somewhat better, and valveless FFP2 and FFP3 masks are the best. Recommendations concerning use of masks vary across countries. See also guidance from the ECDC http://www.ecdc.europa.eu/en/publications-data/using-face-masks-community-reducing-covid-19-transmissionhttp://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2023.28.32.2200718.

Clinical presentation

• None of the symptoms are specific. The disease may even be asymptomatic or produce no fever and resemble a mild respiratory tract infection.
• Incubation time is 2-14 days, typically 4-5 days. Symptoms of the Omicron variant usually appear about 3 days after acquiring the infection.
• The symptomatic form of the disease often starts with sudden high fever (> 38.5 °C) and cough.
• Further symptoms that have been observed include gastrointestinal symptoms (nausea, diarrhoea), myalgia, headache, dizziness/vertigo, sore throat, and, more rarely, loss off the sense of smell or taste, as well as vasculitis-like eczema resembling perniones (chilblains).
• The risk of thromboembolic complications is higher than in the usual respiratory infections.
• When assessing patients' symptoms, especially remotely (over the phone or online, for example), keep in mind that the stress caused by an acute infection may exacerbate possible underlying primary diseases. The symptoms may be caused by exacerbated coronary artery disease or diabetes, for example.
• The clinical picture varies significantly according to the age group of patients. Severe clinical picture is more common in elderly patients (> 70 years), who often have some primary diseases. A disease with severe symptoms is, however, possible also in younger, otherwise healthy individuals.
• Compared with the earlier virus variants, the symptoms caused by the Omicron variant are more focused in the upper respiratory tract and pulmonary symptoms occur less frequently. All types of clinical pictures are, however, possible also in the context of the Omicron variant.
• In children and adolescents the disease is in most cases mild.
  • However, a hyperinflammatory syndrome (Multisystem Inflammatory Syndrome in Children, MIS-C) has been described in paediatric and adolescent patients Multisystem Inflammatory Syndrome in Children (Mis-C) with Covid-19 Infection. The symptom picture includes fever, laboratory findings suggesting inflammation, and a severe disease of one or more organ system(s), requiring hospital care. A severe cardiac failure and circulatory insufficiency requiring intesive care develops in up to half of these patients 18.
• Mild or moderate clinical picture, patient in home care
  • Typical symptoms include cough, fever and respiratory difficulties.
  • The disease may be non-febrile and resemble a common cold, or it may be completely asymptomatic. The prevalence of an asymptomatic infection is not known.
• Disease requiring hospital care
  • The worsening of symptoms often takes place at about 5 days after symptom onset.
  • The patients have dyspnoea and high fever.
  • A chest x-ray will show bilateral diffuse infiltrates typical for viral pneumonia (not a lobar pneumonia). In a hospital setting, the lungs are often investigated by performing a pulmonary CT scan.
  • Thromboembolic complications are possible.
• Disease requiring intensive care
  • The disease may develop into acute respiratory distress syndrome (ARDS).
  • Multiple organ damage may develop, including e.g. renal failure.
  • Cardiac symptoms may occur (arrhythmias, myocarditis).

Diagnosis

• WHO has issued guidance on emergency use of ICD codes, see http://www.who.int/classifications/classification-of-diseases/emergency-use-icd-codes-for-covid-19-disease-outbreak and national guidance.
• Acute infection
  • As in any other respiratory infection, the need to contact health care depends on the severity of the patient's symptoms.
  • Isolation practices are the same as in other respiratory infections. Routine precision diagnostic testing for coronavirus is not needed.
  • Some countries utilize online questionnaires to assess the need for health services, including COVID-19 testing. Find out about local availability of such services.
  • An acute COVID-19 infection can be diagnosed with a PCR or antigen test of a sample usually taken from the nasopharynx, if there is a reason for specific diagnosis of an infection.
    • Sources of error include, among others, deficient specimen collection technique and the virus not occurring in the area where the sample is taken from.
    • The PCR test result takes about 12-24 hours to be ready, but there are also rapid tests available.
    • Viral RNA may already be detectable by a PCR test some days before the onset of symptoms, but during that time the rate of false negative results is, however, considerable..
    • Some tests are able to detect the most common influenza viruses, RS virus and SARS-2 coronavirus, for example.
    • Overall, viral antigen tests are less sensitive than nucleic acid detection tests. The advantage of antigen tests compared with PCR tests include their speed and ease-of-use, as well as lower unit price.
  • The primary target groups of coronavirus testing in health care are
    • all patients with severe symptoms
    • symptomatic patients belonging to risk groups
    • pregnant women
    • social and health care staff members.
  • The accuracy of antigen tests for home use is clearly inferior to that of PCR tests performed in a laboratory. The sensitivity of various antigen tests in detecing an infection varies considerably. In home testing, it is essential to take the sample according to the test instructions. False negative results are more common than false positive ones.
• See also locally available instructions on when and whom to test for COVID-19 and when and whom to consult.
• Determination of antibodies
  • Antibodies against coronavirus usually begin to develop during the 2^nd week of being ill, and IgM/IgG seroconversion has taken place in almost all patients (in more than 90%) by the 3^rd or 4^th week of being ill.
  • Determining antibodies to detect an earlier COVID-19 infection or the presence of immunity is not recommended.

Treatment

Home care

• The principles in the treatment of a patient in home care with rather mild symptoms do not differ from those applied in a regular respiratory infection.
• The focus of care is on non-pharmacological treatment, such as rest, adequate nutrition and intake of fluids.
• Pain-reducing and antipyretic medication (paracetamol, NSAIDs) may be used, as required.
• Severe nausea may be treated with metoclopramide or prochlorperazine, see article on Nausea and vomiting Nausea and Vomiting.
• In home care, thromboprophylaxis is considered individually in patients known to have an increased risk of thrombosis. Blood clotting tests are not performed routinely in patients whose condition allows home care.
• If the symptoms of a patient with COVID-19 infection become more severe or prolonged, laboratory tests (basic blood count with platelet count, platelet count, D dimer, prothrombin time or INR, and CRP, for example) and/or imaging studies are performed based on clinical consideration, unless the patient is referred directly to a hospital for assessment. Remember that the clinical state of a patient with COVID-19 may deteriorate and become critical within hours, and hence the threshold for referring a patient to hospital should be kept at a sufficiently low level.
• Symptoms that warrant hospital care to be considered include, among others, high fever and fatigue, dyspnoea, and deterioration of general condition.

Thromboprophylaxis

• An acute COVID-19 infection is associated with increased activation of the blood coagulation system.
• An increase in the D dimer level to 3-4-fold of the normal (< 0.5 mg/l) level is an indication for hospital care in patients with prolonged COVID-19 infection and bed rest (> 4 days).
  • This applies especially in patients belonging to risk groups for COVID-19 and venous thrombosis, and who generally are the same patients.
• An increasing D dimer level predicts the development of acute respiratory distress syndrome (ARDS), multiple organ dysfunction and increased mortality.
• Due to the increased coagulability of blood, the incidence of pulmonary embolism Pulmonary Embolism and deep vein thrombosis Deep Vein Thrombosis increases.
• Pneumonia or oxygenation disturbances caused by COVID-19 infection may mask the symptoms of pulmonary embolism.
• Also, arterial occlusions and organ damage caused by occlusions in small vessels may occur (e.g. heart and kidney failure).
• Heparin therapy, started as early as possible, prevents coagulation and alleviates inflammation in patients with severe clinical picture (e.g. high concentrations of CRP, fibrinogen and D dimer).
• Thromboprophylaxis with LMWH is recommended, unless there are contraindications to it, to a) all patients in hospital care, b) in home care to patients with a high risk of thrombosis, and c) pregnant women in certain cases,
  • An individual assessment concerning the need of thromboprophylaxis should be made based on the severity of the disease, patient-specific thrombosis risk factors, and the patient's bleeding risk.
  • Find out about and consult any national or regional advice and recommendations on thromboprophylaxis.
• In the acute phase of COVID-19 infection, direct anticoagulants (DOACs; dabigatran, apixaban, edoxaban, rivaroxaban) are not recommended for the prophylaxis or treatment of thromboembolism, since the best available evidence applies to heparin.
  • Through their action on tissue level, DOACs may unexpectedly trigger alveolar haemorrhage, for example.
• Consult a specialist concerning thromboprofylaxis (at least) in the following cases:
  • Pregnant women (throughout the whole pregnancy), section, puerperium (6 weeks); gynaecologist or obstetrician
  • Paediatric patients (< 16 years of age); paediatrician, as necessary
  • Recently (< 3 months) placed coronary stent or acute myocardial infarction; cardiologist
  • Patients with very high risk of thrombosis, such as in patients with antiphospholipid antibody syndrome or several types of thrombophilia
• Inform at-risk patients in home care on
  • the susceptibility to thrombosis in the following situations
    • dehydration (fever over 38 °C, diarrhoea, vomiting etc.)
    • weakened overall condition
    • immobility (over 3 days)
  • recognizing the symptoms of thrombosis
    • for example: pain in the lower extremity, chest pain, reduced performance level, dyspnoea, haemoptysis/cough, increased pulse rate, abdominal pain and headache
  • how to decrease the risk of thrombosis
    • repeatedly stretch legs (get up), change position and move legs (also patients in bed rest!)
    • avoid hypnotics
    • drink adequately (2-2.5 litres/day)
    • use medical stockings, support stockings/bandages or flight socks (this is especially important if anticoagulation therapies cannot be used due to bleeding risk)
    • stop smoking and take care of oral and dental hygiene
    • use according to instructions any home medications for anticoagulation, blood pressure, diabetes and dyslipidemia, and monitor blood pressure and blood sugar if the patient has the meters at home.
    • in case of being hospitalized, inform staff about the increased tendency for thrombosis
• Avoid, if possible, potentially thrombogenic medications (calcium preparations; hypercalcaemia enhances blood coagulation) and in kidney failure NSAIDs (both traditional ones and coxibs). Paracetamol is the first-line drug against fever and pain.
• With the emergence of new virus variants and with wider vaccination coverage, the incidence of severe COVID-19 disease and its infectivity have significantly reduced. Also the risk of thrombosis has decreased.
• Long-lasting COVID-symptoms may be associated with small vessel thromboinflammation. Some of these patients with established coagulation disorder may benefit from LMWH therapy.

Respiratory insufficiency

• Patients with more severe symptoms, requiring hospital care, often need, for example, supplemental oxygen and other supportive treatments, for instance antimicrobial pharmacotherapy for a potential secondary bacterial pneumonia. Risk of thrombosis is increased and usually a prophylactic LMWH therapy is started, see above.
• In severe respiratory insufficiency, ventilator therapy, treatment of septic shock.
• See also Respiratory Failure and local guidance.

Pharmacotherapy

• The actual coronavirus drugs are more effective the sooner they are started after the onset of symptoms.
• If the patient already receives respirator treatment, starting antiviral drugs has usually not been beneficial.
• The following drugs have marketing authorization in the EU (May 2024) for the treatment of COVID-19 in patients who do not need supplemental oxygen and who are at increased risk of the disease becoming severe
  • Nirmatrelvir-ritonavir (antiviral drugs) combination preparation, (tablet)
    • 300 mg nirmatrelvir (two 150 mg tablets) and 100 mg ritonavir (one 100 mg tablet) orally every 12 hours for 5 days.
  • Remdesivir, administered by intravenous infusion; most recommended duration of treatment is 3 days in outpatients and 5 days in hospitalized patients.
  • Monoclonal antibody infusions
    • Sotrovimab
    • Regdanvimab
    • Casirivimab-imdevimab
    • Tixagevimab-cilgavimab, indications include also post-exposure prophylaxis
    • Tocilizumaband anakinra, biological drugs; official indication for the treatment of rheumatoid arthritis.
• The following are available for the treatment of severe COVID-19 infection
  • Dexamethasone 6 mg/day for 10 days
  • Remdesivir
  • Tocilizumab and anakinra
• See also COVID-19 treatments by EMA http://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/coronavirus-disease-covid-19/treatments-vaccines/covid-19-treatments (Europe) and FDA http://www.fda.gov/drugs/emergency-preparedness-drugs/coronavirus-covid-19-drugs (USA).

Other guidelines

• Patient management guidance by the WHO, see http://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/patient-management and the documents Therapeutics and COVID-19: living guideline http://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2023.2 and Clinical management of COVID-19: Living guideline http://www.who.int/publications/i/item/WHO-2019-nCoV-Clinical-2022.2.
• Patient management guidance by the CDC, see http://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/outpatient-treatment-overview.html.
• Treatment guidelines by the NIH, see http://www.covid19treatmentguidelines.nih.gov/ (available until 16 Aug 2024).
• Appropriate protection when dealing with a person with COVID-19, see guidance from ECDC http://www.ecdc.europa.eu/en/publications-data/infection-prevention-and-control-and-preparedness-covid-19-healthcare-settings, WHO http://www.who.int/teams/health-product-policy-and-standards/assistive-and-medical-technology/medical-devices/ppe/ppe-covid and an update concerning the Omicron variant http://www.who.int/publications/i/item/WHO-2019-nCoV-IPC_Masks-Health_Workers-Omicron_variant-2021.1.
• Guidance on quarantine, close contacts and isolation by the ECDC, see http://www.ecdc.europa.eu/en/covid-19/prevention-and-control/quarantine-and-isolation http://www.ecdc.europa.eu/en/publications-data/covid-19-guidance-discharge-and-ending-isolation.

Vaccine and vaccination

• Recommendations concerning vaccination depend on person's age, underlying illnesses as well as earlier vaccinations and COVID-19 infections. Find out about local recommendations.
• The vaccines provide, at best, a protective effect exceeding 90% and the protection has been almost full against severe forms of the disease.

Long-standing symptoms ("long COVID")

• After a COVID-19 infection, some patients will develop long-lasting postinfectious symptoms, such as fatigue, headache, attention disorder, hair loss, dyspnoea, other respitatory symptoms, cardiac symptoms and joint pains.
• See separate article on Long-term symptoms of coronavirus infection (COVID-19) Long-Term Symptoms of Coronavirus Infection (Covid-19).
• Find out about the local organization of care for those with long-term symptoms following a COVID-19 infection.
• See also information on post-COVID conditions by the CDC http://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/post-covid-conditions.html.

Death investigation and certificate

• In the case of death caused by COVID-19, consult local policies and instructions concerning medicolegal requirements and practices.
• For international guidelines for certification and classification (coding) of COVID-19 as cause of death, see http://www.who.int/classifications/classification-of-diseases/emergency-use-icd-codes-for-covid-19-disease-outbreak.