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EBMG

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.
  • 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.
  • In the beginning of 2023, the predominant variant of SARS-CoV-2 is the Omicron variant (in over 99% of examined samples worldwide).
  • 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

Epidemiology

  • Common coronaviruses generally cause mild upper respiratory tract infections.
  • 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 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.
  • The pathogen of COVID-19 infection (SARS-CoV-2) resembles greatly that of the coronavirus epidemic in 2003.
  • 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 FFP2 and FFP3 masks, that must not have an outflow valve, 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-transmission.

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 considerably 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 there are less pulmonary symptoms. All types of clinical pictures are, however, possible also in the context of the Omicron variant.
  • In children and adolescents the disease is nearly always 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 common.
  • 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).
  • Mortality
    • Sporadic cases in patients below 50 years, about 0.2% in age group 50-59 years, about 3% in age group 60-69 years, about 4% in age group 70-74%, about 13% in age group 75-79, about 27% in patients over 80 years of age.
    • Significant differences in the aforementioned percentages may apply between countries, depending, for example, on treatment protocols, available health care resources and the epidemic situation.

Diagnosis

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, plasma creatinine (GFR Gfr Calculator), ALT, D dimer (> 1.5 mg/l predicts progression of the disease), 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.
  • Find out about and consult any national or regional advice and recommendations on thromboprophylaxis.
  • An increasing D dimer level predicts the development of acute respiratory distress syndrome (ARDS), multiple organ dysfunction and increased mortality.
  • 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).
  • Due to the increased coagulability of blood, the incidence of pulmonary embolism Pulmonary Embolism and deep vein thrombosis Deep Vein Thrombosis increases (in 18% of hospitalized patients and up to 30% of patients requiring intensive care). 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 prevents coagulation and alleviates inflammation. Thromboprophylaxis with LMWH is recommended to all patients in hospital care and in home care to patients with a clear risk of thrombosis, unless there are contraindications to it.
  • Thromboprophylaxis (with e.g. enoxaparin, dalteparin or tinzaparine) should be considered in patients with significantly increased risk of thrombosis, including the following patients if they are not already under anticoagulant therapy:
    • patients in hospital care
    • during pregnancy and postpartum (6 weeks after delivery)
      • consult a gynaecologist or an obstetrician concerning the need and choice of prophylactic medication
    • patients in home care with severe disease
      1. fever ≥ 38°C or dyspnoea or cough that significantly impairs general health AND
      2. mainly bed rest > 3 days AND
      3. significant risk of thrombosis, e.g. active cancer or cancer therapy, thrombophilia, earlier venous thrombosis or pulmonary embolism, recent major surgery, multiple injuries or spinal cord injury, OR several lesser risk factors (e.g. age ≥ 60, BMI > 30, smoking, diabetes, hormonal contraception, cardiovascular or autoimmune disease, immobilization, recent minor surgery, severe kidney disease, fatty liver)
    • Notice that these criteria are not inclusive and thromboprophylaxis may be warranted in other cases too, based on physician's assessment.
    • In cases with very high risk of thrombosis, based on individual assessment, consider also the need of a statin and aspirin, taking into account contraindications associated with other pharmacotherapy. Consult relevant specialists (e.g. a cardiologist), as necessary.
    • The decision regarding thromboprophylaxis is made on clinical grounds taking into account the patient's age, overall health and functional capacity as well as his/her bleeding risk. See also Prevention of Venous Thromboembolism.
  • 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
  • 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
      • in case of being hospitalized, inform staff about the increased tendency for thrombosis
  • Avoid, if possible, thrombogenic medications (weight loss drugs, calcium preparations; hypercalcaemia enhances blood coagulation) and avoid in kidney failure NSAIDs (both traditional ones and coxibs). Paracetamol may be used (unless there are contraindications).
  • 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, and their benefit in preventing venous thrombosis in not proven in medical (non-surgical) patients.

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

Other guidelines

COVID-19 testing

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.
  • In many poor countries the vaccination coverage is low even considering the first vaccination dose. This may prolong the pandemic and increase the risk of new variants developing.
  • The vaccines provide, at best, a protective effect exceeding 90% and the protection has been almost full against severe forms of the disease.
  • The efficacy of vaccines developed in China and Russia is, according to current knowledge, not equivalent to those developed in the western countries. This may pose a threat of further worsening of the pandemic in China, for example, following the lifting of restrictions there.
  • In the European Union, the mRNA vaccines developed by Pfizer and BioNTech as well as by Moderna, the adenovirus vaccines developed by AstraZeneca and Johnson & Johnson and the protein vaccine developed by Novavax have acquired marketing authorization.
  • Due to the risk of rare thromboembolic complications particularly in the younger age groups, the use of adenovirus vaccines has been restricted or discontinued in some countries.
    • Younger individuals vaccinated first with an adenovirus vaccine can be given the second dose using a mRNA vaccine.
  • mRNA vaccines, especially the Spikevax by Moderna, have been associated with myocarditis and pericarditis as rare adverse effects, occurring in most cases in young men http://www.ema.europa.eu/en/news/comirnaty-spikevax-possible-link-very-rare-cases-myocarditis-pericarditis. The cases have usually been mild. In some countries the Moderna vaccine is not given to young men (e.g. below 30 years of age).
  • In addition to the aforementioned vaccines - or instead of them - other vaccines may be in use in countries outside the EU.
  • According to the available evidence, vaccination by two different types of vaccines (adenovirus vaccine and mRNA vaccine) provides a very good protection http://www.nature.com/articles/d41586-021-01359-3.
  • See the European Vaccination Information Portal on COVID-19 vaccines fore more information http://vaccination-info.eu/en/covid-19/covid-19-vaccines.

Preparations

  • Check recommendations concerning the age of people to be vaccinated, vaccination intervals and other possible limitations of use from the web sites of relevant authorities and manufacturers.
  • Utilize also locally available drug database(s).
  • mRNA vaccine tozinameran BNT162b2, product name Comirnaty® , by Pfizer and BioNTech
  • mRNA vaccine mRNA-1273, product name Spikevax® , by Moderna
  • Adenovirus vaccine AZD1222, product name Vaxzevria® , by AstraZeneca
  • Adenovirus vaccine JNJ-78436735, product name JCovden® , by Janssen (Johnson & Johnson)
  • Laboratory-produced spike protein, product name Nuvaxovid® , by Novavax.

Long-standing symptoms ("long COVID")

Death investigation and certificate

References