Covid-19 J12.1

Author: Prof. Dr. med. Peter Altmeyer

Co-Autor: Dr. med. Jeton Luzha

All authors of this article

Last updated on: 04.05.2021

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Synonym(s)

Coronavirus infection; New severe acute respiratory syndrome

History
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In December 2019, China reported the first cases of the 2019 coronavirus disease (COVID-19). This disease, caused by severe acute respiratory syndrome - coronavirus 2 (SARS-CoV-2), has become a pandemic. To date, it has resulted in approximately 10 million confirmed cases (and rising) and caused nearly 500,000 associated deaths worldwide. The COVID-19 pandemic is undoubtedly the most serious health and socio-economic crisis of our time.

Definition
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New "Severe acute respiratory syndrome" caused by the new corona virus type "SARS-CoV-2", known as COVID-19. The incubation period is up to 14 days (data of the RKI and WHO; Jiang X et al. 2020). In this respect it does not differ significantly from SARS and MERS-CoV (see below coronavirus infections).

Etiopathogenesis
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SARS-CoV-2 is transmissible from person to person. The main route of transmission is droplet infection. This can occur directly from person to person via the mucous membranes or indirectly via hands with subsequent contact of the mucous membranes of the mouth or nose and the conjunctiva of the eyes. Cases are now known in which infection occurred via persons who showed only mild or unspecific signs of illness. The novel coronaviruses have also been found in stool samples from some affected individuals. Whether SARS-CoV-2 can also be spread fecal-orally has not yet been conclusively determined.

The spike protein is considered the virus's sharpest weapon and equally the coronavirus's weak point. The virus uses its surface protein to dock onto the ACE2 receptors of human cells and thus penetrate the cell membrane. However, it is now known that specific antibodies can prevent the spike protein from binding by attaching themselves. New vaccines such as the RNA-based Covid-19 pandemic vaccine BNT162-01 (approved in Germany and the European Union as well as in the USA since 21 December 2020), developed by the companies BioNTech and Pfizer, precisely target this viral protein.

Manifestation
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w:m=1:1; at the beginning of the pandemic rare in children; in the meantime all age groups are affected.

Clinical features
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The course of the disease with coronavirus depends on the age of the patient and his other diseases. The most frequent symptoms are:

  • Onset like flu-like infection with fever (91.7%).
  • Dry cough (75,0%)
  • Slight shortness of breath
  • Fatigue (75.0%)

Less common symptoms:

  • Limb pain
  • Sore throat
  • gastrointestinal symptoms (39.6%), diarrhea symptoms
  • conjunctivitis
  • headache
  • loss of sense of taste or smell
  • Skin les ions (1-10%): exanthematous and vasculitic skin lesions (frostbitten chilblain lupus = "COVID toes", urticarial, vesicular (varicelliform), maculo-papular (morbilliform), painful; pillow-like; livid frostbitten lesions(chilblain) on fingers or toes (so-called COVID toes).

Severe symptoms:

  • Difficulty breathing or shortness of breath
  • Chest pain or pressure
  • Loss of speech or mobility

Comorbidities included Hypertension (30.0%) and Diabetes mellitus (12.1%) in a collective of 140 patients. Furthermore: drug hypersensitivities (11.4%) (Zhang JJ et al 2020).

People who have only mild symptoms and do not otherwise suffer from other illnesses should take home rest.On average, 5-6 days pass from the time a person is infected with the virus until symptoms appear. However, it can take up to 14 days.
More severe courses with pneumonia and respiratory distress syndrome, possibly kidney failure, have been observed mainly in older persons with previous illnesses. In general, the course is milder in younger, previously healthy persons.

Children and adolescents(multisystemic inflammatory syndrome associated with COVID-19): Worldwide, COVID-19 infection caused by coronavirus 2 (SARS-CoV-2) takes a milder clinical course in children compared to adults. However, European and US pediatricians observed cases (>200) of myocarditis sharing some clinical features with toxin shock syndrome, Kawasaki syndrome (pseudo-Kawasaki syndrome ), and macrophage activation syndrome in otherwise healthy patients (Berardicurti O et al 2020). The spectrum of severity ranged from standard hospitalization to treatment in pediatric intensive care units (Ebina-Shibuya R et al. 2020).

Imaging
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Bilateral frosted glass infiltrates (areas with slightly elevated lung density in which the vessels and bronchial tubes can still be delimited) or spotty opacities (89.6%).

Laboratory
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lymphopenia (75.4%); eosinopenia (52.9%). D-dimer ↑, C-reactive protein ↑, Procalcitonin↑.

Diagnosis
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travel history+clinical+imaging+pathogen detection (PCR), rapid tests

Differential diagnosis
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Pneumonia of other genesis

Therapy
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Potential treatments should be carefully evaluated in randomized controlled trials (RCTs). Several large-scale, multicentre trials are underway that use appropriately robust methodology to evaluate potential therapeutics, including the WHO Solidarity Trial, several United States (US) National Institutes of Health studies, and international and national studies in Europe.

Several drugs have been or are still being studied in clinical trials to evaluate their safety and efficacy as potential treatments for COVID-19, including corticosteroids, the antiviral nucleotide analogue remdesivir, systemic interferons and in particular interferon β-1a, monoclonal antibodies against components of the immune system such as interleukin-6 (IL-6) and IL-4, other immunomodulators, and antibodies against components of SARS-CoV-2.

  • Dexamethasone: On June 16, 2020, preliminary results from an open-label RCT of dexamethasone showed that it significantly reduced 28-day mortality, particularly in critically ill COVID-19 patients receiving mechanical ventilation. There was no evidence of benefit for patients not requiring oxygen. Based on these results, the US National Institutes of Health (NIH) recommends the administration of dexamethasone for COVID-19 patients who are either mechanically ventilated or require supplemental oxygen. On July 17, 2020, the Randomised Evaluation of COVid-19 thERapY (RECOVERY) group published results from 2 100 patients concluding that the use of dexamethasone resulted in lower 28-day mortality in those who received either invasive mechanical ventilation or oxygen alone at randomisation, but not in those who did not receive respiratory support. On September 2, 2020, based on a systematic review and meta-analysis of the results of eight RCTs, WHO published a strong recommendation for the use of systemic corticosteroids in severely ill patients with COVID-19 and a conditional recommendation not to use systemic corticosteroids in patients with non-severe COVID-19 (7th Group WHOREAfC-TW et al. (2020).
  • Remdesivir: Interim results from the SOLIDARITY trial, an RCT comparing four agents with control treatment from 405 hospitals in 30 countries, showed that remdesivir had no effect on mortality in 2 743 patients compared with 2 708 controls (relative risk of death=0.95, 95% CI 0.81-1.11, p=0.50) (Pan H et al. 2020). Results from a double-blind RCT, ACTT-1, in 1 062 hospitalised COVID-19 patients showed that remdesivir was associated with a shorter median recovery time compared with placebo (10 vs 15 days). The 14-day mortality was 6.7% in the group of patients receiving remdesivir and 11.9% in the placebo group, but the difference was not statistically significant. The authors concluded that the finding was of uncertain clinical significance. On 25 June 2020, the Committee for Medicinal Products for Human Use (CHMP) of the EMA recommended that remdesivir be granted a conditional marketing authorisation for the treatment of COVID-19 patients with pneumonia requiring supplemental oxygen (European Medicines Agency 2020).
  • The US Food and Drug Administration (FDA) has warned against the use of remdesivir in combination with hydroxychloroquine.
  • Hydroxychloroquine: RCTs such as the WHO SOLIDARITY trial and RECOVERY found no evidence of significant benefit of HCQ for the treatment of COVID-19 and discontinued their HCQ arm. The results of the RECOVERY RCT, which compared 1 542 patients randomized to HCQ with 3 132 patients receiving usual care, found no difference between the two groups in mortality, hospitalization, or other outcomes. Two clinical trials examining the effect of HCQ at early onset (within 4-5 days of symptom onset) in nonhospitalized patients with mild symptoms showed no significant effect on symptom severity. A post-exposure prophylaxis RCT involving 821 individuals with domestic or occupational exposure to confirmed COVID-19 cases showed no statistically significant difference in the incidence of COVID-19 compatible disease between the group receiving HCQ and the group receiving placebo (RECOVERY Collaborative Group et al. 2020).
  • Lopinavir/ritonavir: An RCT of lopinavir/ritonavir in 199 COVID-19 patients in China showed no statistically significant beneficial effect on clinical course or mortality compared with standard treatment. Similarly, the UK RECOVERY trial, which randomized 1 616 patients to lopinavir/ritonavir and compared them with 3 424 patients randomized to usual care, showed no benefit of lopinavir/ritonavir on survival, clinical course, or length of hospital stay (World Health Organization WHO, 2021).
  • Tocilizumab: In the BACC Bay Tocilizumab Trial, a randomized, double-blind, placebo-controlled study of 243 patients with covid-19 in the U.S., tocilizumab was not effective in preventing intubation or death in moderately ill hospitalized patients with covid-19. On 19. November, however, the investigators of another RCT, the REMAP-CAP trial, announced in a press release that an early analysis of the data showed that tocilizumab treatment was effective in reducing death and time spent in the ICU in critically ill patients with severely COVID-19 (Stone JH et al 2020).
  • Antibodies: Interim analyses of the phase II trial (BLAZE-1) of the human antibody Ly-CoV555 were published, evaluating the efficacy of LY-CoV555 in the outpatient treatment of mild or moderate covid-19 (Chen P et al 2020). The results showed reduced hospitalization especially in the age group >65 years. The US Food and Drug Administration (FDA) has approved casirivimab plus imdevimab as a monoclonal antibody combination therapy for patients with mild to moderate COVID-19 who are at high risk for developing severe disease [26].
  • Convalescent plasma therapy (plasma containing antibodies from recovered COVID-19 patients): Administration of COVID-19 convalescent plasma (CCP) donated by individuals who have recovered from the disease is both a prophylactic and therapeutic option. Early results from several non-RCTs suggested that transfusion of CCP containing a high titer of neutralizing antibody could effectively reduce mortality in hospitalized patients (Joyner M et al 2020, Liu STH et al 2020). However, in an RCT involving 333 hospitalized patients with COVID-19, no difference in mortality or other clinical outcomes was observed between the convalescent plasma and placebo groups at day 30. Overall mortality was 10.96% in the convalescent plasma group and 11.43% in the placebo group . Total SARS-CoV-2 antibody titers tended to be higher in the convalescent plasma group at day 2 after the intervention. Adverse events and serious adverse events were similar in both groups (Simonovich VA et al 2020).

Several vaccines are available and in use in China, the USSR, Europe, and the USA. The vaccine BNT162b2 (BioNTech/Pfizer), approved in the European Union and the USA, is a lipid nanoparticle-formulated, nucleoside-modified RNA vaccine encoding a prefusion-stabilized, membrane-anchored, full-length SARS-CoV-2 spike protein.

Prophylaxis
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Since coronaviruses are transmitted by droplet or smear infection, the Robert Koch Institute recommends the following measures against infection with the coronavirus:

  • good hand hygiene
  • cough and sneeze etiquette
  • distance to infected persons and possible infected persons (approx. 1.5 - 2 meters)

However, in view of the current wave of influenza, these measures are not only valid as prevention against the coronavirus, but also to avoid influenza.

Vaccination of the population against Covid 19

Practical tips
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It can be assumed that the precursor of SARS-CoV-19 originates from wild animals. It is currently assumed that the first patients became infected in early December 2019 at the Huanan Seafood Market in Wuhan (11 million inhabitants), which was closed on 1.1.2020.

Persons who have stayed in a risk area designated by the Robert Koch Institute should - regardless of symptoms - avoid unnecessary contact and stay at home if possible. If acute respiratory symptoms occur, they should observe the coughing and sneezing label, as well as good hand hygiene and, after making an appointment in advance by telephone with reference to the trip, consult a doctor.

Literature
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  2. Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al. Remdesivir for the Treatment of Covid-19 - Final Report. The New England journal of medicine. 2020.
  3. Chen P et al. (2020) SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19. new England journal of medicine. 2020.
  4. Colson P et al. (2020) Chloroquine for the 2019 novel coronavirus SARS-CoV-2. Int J Antimicrob Agents doi:10.1016/j.ijantimicag.2020.105923.
  5. Ebina-Shibuya R et al (2020) Multisystem inflammatory syndrome in children (MIS-C) with COVID-19: insights from simultaneous familial Kawasaki Disease cases. Int J Infect Dis 97:371-373.
  6. European Medicines Agency (2020). First COVID-19 treatment recommended for EU authorisation [Internet]. Amsterdam: EMA; Retrieved from: https://www.ema.europa.eu/en/news/first-covid-19-treatment-recommended-eu-authorisation.
  7. Group WHOREAfC-TW et al. (2020) Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis. JAMA. 2020.
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Last updated on: 04.05.2021