Covid-19J12.1

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.

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).

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.

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

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).

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%).

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

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

Pneumonia of other genesis

Complications include:

- acute renal failure

- sepsis

- DVT or/and pulmonary artery embolism

- hypoxemic respiratory failure

- Guillain-Barré syndrome

- myocarditis

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

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

• Dexamethasone: On June 16, 2020, preliminary results of an open-label RCT of dexamethasone showed that it significantly reduced 28-day mortality, especially in critically ill COVID-19 patients who were mechanically ventilated. For patients not requiring oxygen, there was no evidence of benefit. 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 Randomized 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 only at randomization, 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, the 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: The interim results of the SOLIDARITY study, 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 to 2,708 controls (relative risk of death=0.95, 95% CI 0.81-1.11, p=0.50) (Pan H et al. 2020). The results of a double-blind RCT, ACTT-1, in 1,062 hospitalized COVID-19 patients showed that remdesivir was associated with a shorter median recovery time compared to placebo (10 vs. 15 days). The 14-day mortality rate 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 is of uncertain clinical significance. On June 25, 2020, the EMA's Committee for Medicinal Products for Human Use (CHMP) recommended that remdesivir be granted a conditional marketing authorization for the treatment of COVID-19 patients with pneumonia who require 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 study 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 terms of mortality, hospitalization or other outcomes. Two clinical trials examining the effect of HCQ at early onset (within 4-5 days of symptom onset) in non-hospitalized patients with mild symptoms showed no significant effect on symptom severity. An RCT on post-exposure prophylaxis involving 821 people 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 with lopinavir/ritonavir in 199 COVID-19 patients in China showed no statistically significant favorable effect on clinical course or mortality compared to standard treatment. The British RECOVERY study, in which 1,616 patients were randomized to lopinavir/ritonavir and compared with 3,424 patients randomized to standard treatment, also showed no benefit of lopinavir/ritonavir on survival, clinical outcome 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 US, tocilizumab was not effective in preventing intubation or death in moderately ill hospitalized patients with Covid-19. However, on November 19, 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 deaths and time spent in the ICU in critically ill patients with severe COVID-19 (Stone JH et al. 2020).
• Antibodies: Interim analyses of the Phase II study (BLAZE-1) of the human antibody Ly-CoV555 were published, which investigated 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 >65 age group. 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 of developing severe disease [26].
• Convalescent plasma therapy (plasma with antibodies from recovered COVID-19 patients): The administration of COVID-19 convalescent plasma (CCP) donated by individuals who have recovered from the disease is both a prophylactic and therapeutic option. Initial results from various non-RCTs suggested that transfusion of CCP containing a high titer of neutralizing antibodies 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 . Overall SARS-CoV-2 antibody titers tended to be higher in the convalescent plasma group on 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 already 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.

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

COVID-19 as an occupational disease(see also Newsletter: Covid-occupational-disease-that-is-a-doctor's-business): Number 3101 of the list of occupational diseases(BK 3101) covers persons who become infected with the SARS-CoV-2 coronavirus as a result of their work in the health service, in charity care or in a laboratory and therefore contract COVID-19. The same applies to groups of people who were particularly exposed to the risk of infection to a similar extent during their insured activity. Healthcare services include, for example, hospitals, doctors' surgeries, pharmacies, physiotherapy facilities, patient transportation, rescue services or nursing services. Whether an infection with the SARS-CoV-2 virus in the healthcare sector or in nursing can be an occupational disease depends largely on whether the person concerned had personal contact with patients or people requiring care. Simply working in a health service facility - for example in the administrative area - is not sufficient.

In addition to scientific and medical laboratories, other laboratories (e.g. for dental technology) with particular risks of infection are covered if those working there come into contact with sick people or handle substances that have been taken from sick people for examination purposes. When answering the question of whether individuals are similarly exposed to a risk of infection through their activities in other areas, it depends on the type of contact with infected persons. These must be intended to involve direct physical contact (e.g. hairdressing activities) or activities close to the face (e.g. cosmetic treatments).

COVID-19 infection as an occupational accident: If an infection with the corona virus leads to an illness, this can also be recognized as an occupational accident provided that the infection is attributable to the respective insured activity (employment, (high) school attendance, performance of certain honorary positions, assistance in the event of accidents, etc.) ("as a result"). in this context, intensive contact with an infectious person ("index person") must have demonstrably taken place. According to the Robert Koch Institute (RKI), this contact must have taken place between two days before the onset of the first symptoms in the index person and 10 days after the onset of symptoms, or even later in the case of severe or persistent symptoms. Without the onset of symptoms, the contact must have taken place between two days before the sample was taken for the positive laboratory test of the index person and 10 days afterwards.

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.

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