Covid-19

COVID-19 ('coronavirus disease 20'19) causes coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2, initially professionally referred to as 2019-nCoV''). Usually the disease manifests itself as an upper respiratory tract infection, in some patients develops pneumonia with a potentially serious, in some cases even fatal course. The infection may be associated with coagulopathy. Due to the global spread of the disease, who declared COVID-19 a pandemic on 11/03/2020.

Virology
The SARS-CoV-2 virus was first identified in China in early 2020 as the causative agent of an epidemic of pneumonia in the city of Wuhan. By sequencing epithelium from the respiratory tract of patients, it was possible to prove that the causative agent of the disease is the hitherto unknown β-coronavirus from the subgenus sarbecovirus subfamily Orthocoronaviridae. It is the seventh representative of the family coronaviruses, which causes human diseases. . Sekvence SARS-CoV-2 se ze 70 % shoduje s genetickou informací viru SARS-CoV. The first cases of this coronavirus at the end of 2019 were linked to a visit to a seafood and live animal market in the city of Wuhan. The probable source is a bat, e.g. Rhinolopus affinis, sinicus or ferrumequinum. Some authors believe that transmission to humans may have occurred directly, as excrement and dried parts of bat bodies are used in Chinese folk medicine. However, the virus isolated from bats differs from viruses that are transmitted interhumanly in several amino acids crucial for binding to human cells. It is therefore more likely that the transmission to humans occurred through intermediate hosts, which could be, for example, some snakes, turtles or minks. Especially discussed are pangolins, whose meat is consumed in China and whose body parts are also used in folk medicine. The sequence RNA isolated from pangolin coronaviruses differed more from SARS-CoV-2 than from bats coronaviruses, but it was identical in the domain responsible for binding to human cells. . Uvažuje se proto, že SARS-CoV-2 vznikl rekombinací velmi podobného netopýřího koronaviru s koronavirem luskounů.

náhled | Model virionu koronaviru SARS-CoV-2. Na stavbě se podílejí čtyři strukturní bílkoviny. Šedě je znázorněná obálka, kterou tvoří fosfolipidová dvojvrstva. Pod ní je nukleokapsidový protein N s navázanou ribonukleovou kyselinou viru. Do obálky virionu jsou zavzaty proteiny S, E a M. Červeně znázorněný peplomerový glykoprotein S (spike) je odpovědný za vazbu na hostitelskou buňku. Dále jsou vyznačeny proteiny E (envelope) a M (membránový protein).

Pro vstup viru SARS-CoV-2 do hostitelské buňky je klíčový jeden z glykoproteinů virionového obalu („korony“), S-protein (spike-protein). Ten se váže na angiotenzin konvertující enzym 2 (ACE2) exprimovaný na povrchu vnímavých buněk a využívá jej jako receptor. Analysis of the spike protein coronavirus identified two variants, caused by the substitution of glycineu (G) for aspartate (D) at position 614. The G614 variant was associated with higher viral loads in vitro and may therefore indicate higher infectivity. The effect on the course of the disease and the risk of hospitalization has not been proven.

Incubation period and transfer
The average incubation period is given as 4–5 days, with the range of the incubation period usually being 2–14 days. . Transfer path data is not yet complete. The basic mode of transmission is direct interpersonal contact, it is assumed that it occurs mainly by droplet infection. Droplets usually do not spread further than 2 meters and do not remain in the air. The risk of direct transmission through the air is also discussed, especially in aerosol-producing procedures, but its significance is debatable and the impact on the spread of the pandemic rather questionable. The possibilities of transmission over longer distances are likely to increase in enclosed, unventilated areas (restaurants, bus,...). .

Viral RNA has also been demonstrated in the blood, faeces and urine of patients, although these routes of transmission are probably not very epidemiologically significant. The epidemiological significance of transmission by touching contaminated areas and subsequent contact with eyes, mouth or nose is still unclear, but extensive contamination of areas near patients with viral particles that can be a source of infection has been repeatedly described. The risk of infection from surfaces is higher in the case of massive contamination, for example, in the house of a infected person.

Risk of infection depends on the course of the disease – an infected patient with a mild course of the disease usually becomes infectious approximately 2.5 days before the onset of symptoms, the highest risk is around the onset of symptoms and gradually decreases approximately by the 7th–10th day after the onset of symptoms. The risk of transmission after day 10 is small in immunocompetent patients with a mild course of the disease. Při závažném či kritickém průběhu onemocnění (dušnost, pneumonie) je obvykle pacient infekční ne déle než 20 dní. PCR pozitivita však může přetrvávat výrazně déle i při neinfekčnosti vzhledem k přítomnosti neviabilních virových částic na sliznicích. Medián doby do negavního výsledku PCR testů ze sliznic je 18,4 dne, avšak pozitivita PCR detekce virové RNA může přetrvávat až po 3 měsíce.

The degree of risk of transmission of infection also depends on the time of contact, the protective equipment used and epidemiological measures, or the amount of viral particles in the secretion of the upper respiratory tract. The most common secondary transmission has been described between members of the same household or in healthcare facilities where personal protective equipment was not used. Infection is also possible from asymptomatic carriers of the virus, who are likely to be infectious for a similar length of time as symptomatic patients, but the importance of this type of transmission for the spread of the epidemic is still unknown.

Animal infections have been described in a case-by-case manner, but there is no evidence that transmission from animals to humans is present in a significant percentage. It is assumed only at the beginning of the epidemic, the further meaning is not confirmed.

Basic reproductive constant R 0 je kolem 3.

Clinical course
The clinical course of the disease can be diverse, the manifestations range from asymptomatic or very mild to a critical course ending in the death of the patient.

The frequency of asymptomatic infections is questionable. Some studies estimate their incidence to be around 40%, but for now there are no analyses with a long enough follow-up to assess whether the symptoms did not manifest themselves later. Thus, the number of purely asymptomatic cases is probably lower.

According to the current concept, no symptom is downright pathognomonic and diagnosis solely on the basis of clinical signs can be difficult.

Symptoms of ongoing COVID-19 may include :
 * fever – the estimated incidence and height of which fluctuates significantly between studies (often only subfebrile is reported),
 * fatigue,
 * dry cough,
 * muscle pain, headache,
 * sore throat,
 * nausea, vomiting, diarrhea,
 * loss or disturbance of smell or taste – various studies report the incidence of these disorders in the range of 5–98%, but appears to be more common in the early stages of the disease than in other respiratory tract diseases,
 * shortness of breath – occurs in approximately one third of patients, typical is its onset approximately 5 days after the onset of the disease,
 * stuffy nose or runny nose.

Complications
In the course of the disease, even with an initially mild course, a spectrum of complications may develop. Originally mild pneumonia can progress, as mentioned in the previous chapter, to a more severe state with shortness of breath approximately 5 days after the onset of symptoms. Other complications include :
 *  'respiratory insufficiency'  to image failure  'ARDS' ;
 *  'cardiac and cardiovascular complications' , including arrhythmias, acute coronary syndrome or shock;
 *  'thromboembolic complications' , such as CMP or pulmonary embolism, may occur in younger patients without risk factors for complicated disease;
 * dysregulation inflammatory responses;
 * secondary infections.

Risk factors for the course of the disease, prognosis
More than 80% of symptomatic COVID-19 cases have a mild course. Approximately 15% of patients develop clinically severe pneumonia with dyspneas, hypoxia, and extensive bilateral infiltrates on radiographs 24 to 48 hours after onset. About 5% of patients require intensive care for respiratory distress, shock, or multiorgan failure. A critical to fatal course of the disease can occur even in young, otherwise healthy persons, but is usually associated with one or more of the following risk factors.

Mortality in clinically manifested disease is estimated at 2.3%, with no deaths reported in patients with mild initial symptoms. According to the WHO-China fact-finding mission, the mortality rate in China ranged from 0.7% to 4%, depending on location.

Deaths most commonly occur in patients with significant comorbidities (cardiovascular disease, lung disease, diabetes mellitus, cancer or high blood pressure). Higher mortality is associated with higher age, with 80% of deaths due to COVID-19 occurring at age ≥ 65 years according to Chinese data. The mortality rate under 19 years is 0.1% and 14.8% over 80 years.

Recovery occurs after approximately two weeks in patients with a mild course, in 3-6 weeks in a severe course.

Some patients who have had COVID-19 have one or more symptoms that persist after the acute phase of the disease (long COVID, long-haul COVID, chronic post-COVID syndrome). The most common symptoms are fatigue, shortness of breath, chest pain, cough or cognitive impairment. Preliminary data suggest that full recovery occurs after about three additional weeks if the course of COVID-19 has been mild. In the case of a moderate or severe course, symptoms persist for more than two months after hospital discharge.

There are increasing data that some patients have long-term respiratory or cardiac damage.

Treatment
The treatment strategy depends on the severity of the manifestations. In mild cases, the patient can be left in home isolation, where the basis is prevention of further spread of the virus e.g. by wearing a mask when close to another person or by frequently disinfecting surfaces. Such a patient should be regularly monitored for symptoms to worsen and there is no need for hospitalization. Home isolation is terminated according to valid hygiene regulations, always in sufficient time after the symptoms subside (reduction of fever without the use of antipyretics and improvement of respiratory symptoms). (see rules of isolation according to valid regulations of the Ministry of Health of the Czech Republic)

Therapy of complicated cases require treatment during hospitalization, often with varying degrees of [oxygen therapy|oxygen therapy] from a simple half mask with a reservoir, through high-flow oxygen therapy to artificial lung ventilation when developing [Acute respiratory distress syndrome|syndrome acute respiratory distress]] (ARDS). In carefully indicated cases with refractory hypoxia, extracorporal membrane oxygenation (ECMO) may be indicated. ===Pharmacotherapy=== * Corticosteroids – dexamethasone is most commonly used ** indication: Patients with severe disease whose treatment requires oxygen therapy or ventilation support are recommended to receive . Administration of dexamethasone leads to a reduction in mortality, especially in the group of patients requiring mechanical ventilation or ECMO.

'NSAIDs (non-steroidal anti-inflammatory drugs) are the mainstay of fever therapy in COVID-19 and should be dosed according to current recommendations. Single case reports of deterioration after NSAID use in younger patients have been published, but other observational studies have not confirmed an association between NSAID use and disease severity. According to current recommendations, NSAIDs should be used according to the usual clinical indications.

Due to the risk of thromboembolic complications, antithrombotic prophylaxis should be administered according to recommendations depending on the severity of the condition and the patient's history.
 * "anticoagulation"


 * Nebulization'

Drugs under investigation
A list of ongoing trials for COVID-19 therapy can be viewed on this WHO website.

Drugs under investigation include :

Thus, there is not enough data for the use of ivermectin in COVID-19, and further studies are ongoing.
 * 'Remdesivir' - a nucleotide analogue with proven in vitro efficacy against SARS-CoV-2 confirmed in animal models. It is used for moderate and severe disease, and its efficacy in previous studies shows benefit when used in patients with severe disease with low need for oxygen supplementation. In the general population, available data suggest that it does not reduce mortality, but new research is being analysed.
 * Convalescent plasma - data on the provision of passive immunization by plasma administration to cured patients are still insufficient. The effect is mainly expected in patients in the early phase of the disease (before sufficient self-titre of antibodies is formed), in patients with immunosuppressive conditions or when plasma with high titres of neutralising antibodies is used.
 * Tocilizumab', an IL-6 monoclonal antibody, is being evaluated for efficacy in the treatment of severe forms of COVID-19 with IL-6 elevation in systemic inflammation.
 * Favipavir' - an RNA polymerase inhibitor that preliminary data suggest may accelerate viral clearance.
 *  – antiparasitic, which also has antiviral effects. An in vitro effect on SARS-CoV-2 has been demonstrated, but its concentration was much higher than the safe doses of this substance. . In one retrospective study, ivermectin was associated with lower mortality in COVID-19 patients, but more patients treated with ivermectin required corticosteroids. . In a recently published double-blind intervention study of less than 500 subjects, administration of 300 μg of ivermectin per kilogram body weight for 5 days compared to placebo had no significant effect either on recovery time or on the number of deaths.
 * No Chloroquine/hydroxychloroquine - these antimalarials have been shown to inhibit SARS-CoV-2 in vitro. Despite initially promising study results, treatment is no longer recommended either alone or in combination with azithromycin. No sufficient benefit has been demonstrated and all these drugs are not recommended because of their side effects.
 * No Lopinavir-ritonavir - this drug has also not been shown to be effective.
 * Many other agents are being tested in clinical trials without widespread use. An example is Famotidine, a histamine receptor antagonist used for the treatment of gastric ulcer disease.