COVID-19

Symptoms

Symptoms of Covid-19 include (selection):

  • Fever
  • Cough (irritating cough or with sputum)
  • Respiratory disorders, shortness of breath, shortness of breath.
  • Feeling sick, fatigue
  • Cold symptoms: runny nose, stuffy nose, sore throat.
  • Pain in the limbs, muscle and joint pain.
  • Gastrointestinal complaints: Diarrhea, nausea, vomiting, abdominal pain.
  • Nervous system: impairment of the sense of smell and taste, dizziness, headache.
  • Skin rash
  • Pneumonia (pneumonia), hemoptysis
  • Co-infections and superinfections, for example, with bacteria and fungi.
  • Severe course: Acute respiratory distress syndrome (ARDS), sepsis (blood poisoning), septic shock, organ failure, death.

The risk of a severe course and death increases with age and concomitant diseases. The mortality rate is higher than for seasonal influenza. Children, on the other hand, usually have a good prognosis. The disease was first reported in December 2019 in the Chinese megacity of Wuhan in Hubei province. The first cases were linked to a local fish and animal market that traded live animals such as poultry, bats, marmots and snakes. This market was closed by authorities on January 1, 2020. Wuhan and other Chinese cities were quarantined in January. Since then, the infectious disease has spread worldwide because there is no immunity to the new virus in the population. Millions of illnesses and deaths have been reported.

Causes

The cause of the respiratory disease Covid-19 is a viral infection with the enveloped and single-stranded RNA virus SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) of the coronavirus family. Like other coronaviruses, it is characterized by its large genome. The virus probably originated from wild animals in the Wuhan market and thus reached humans. Genetic analysis has shown that SARS-CoV-2 is closely related to the SARS (Severe Acute Respiratory Syndrome) virus that appeared in 2002 and belongs to the beta coronaviruses. Coronaviruses have been known since the 1960s and infect various animals besides humans, such as camels, cattle, cats, birds, and bats. The MERS virus (Middle East Respiratory Syndrome) also belongs to this family. Some cold viruses are also coronaviruses. Bats are the natural reservoir of SARS-CoV-2 and it is originally a bat virus. The intermediate hosts are thought to be pangolins, which are also used in traditional Chinese medicine.

Transmission

New coronavirus is transmitted primarily as a droplet infection and enters the body through the respiratory tract, eyes, nose, and mouth. Infection via aerosols is now considered possible. Infection via contaminated surfaces or objects cannot be ruled out. The virus can be detected on surfaces for up to 3 days. Even people without symptoms or with a mild illness can pass on the virus. The virus has been detected in stool in several studies. It is thought that it may also be transmitted fecal-orally as a smear infection, even from infected individuals without symptoms. It has been shown that SARS-CoV-2 can continue to be excreted in the stool even after respiratory symptoms have resolved. The viral receptor ACE2 is also found in the digestive tract. However, smear infections have rarely been observed. The incubation period is 1 to 14 days. Symptoms usually appear relatively quickly, within a few days. The basic reproduction number R0 indicates the average number of persons infected by an infected person in a population without immunity. It is at least 2 for the new coronavirus without measures, but much higher values are found in the literature. This leads to an exponential growth of infected individuals (2, 4, 8, 16, 32, 64, 128, 256, 512, 1024, …). The reproduction number can be reduced by measures such as social distancing.

Structure of the SARS-CoV-2 virus.

The components of SARS-CoV-2 include (selection): nucleic acids:

  • Single-stranded RNA with positive polarity: genome of the virus.

Enzymes:

  • RNA-dependent RNA polymerase (RdRp, also known as replicase): RNA amplification.
  • Proteases (3CLpro (= Mpro), PLpro): Release of the viral proteins
  • Helicase

Structural proteins:

  • Spike protein (S): binding to the host cell.
  • Envelope protein (E): component of the viral membrane, important in assembly and in the release of the virus from the host cell
  • Membrane protein (M): component of the viral membrane, important in morphology.
  • Nucleocapsid protein (N): Belongs to the RNA.

Replication cycle of SARS-CoV-2.

The spike protein binds to receptors on the host cell surface. This is angiotensin-converting enzyme 2 (ACE2). ACE2 is expressed in the lungs, the digestive tract, the heart and the kidneys, among other places. ACE2 – in contrast to ACE1 – is involved in the degradation of angiotensin II, which increases blood pressure and has proinflammatory effects. Spike protein binding inhibits the function of ACE2, which promotes the inflammatory response. ACE2 is further downregulated by viral infection. To enter (and leave) the host cell, the virus also requires the endogenous and membrane-bound protease TMPRSS2 (Transmembrane Protease Serine 2). This is therefore also discussed as a drug target. The virus is taken up into the host cell in endosomes. The RNA is released from them. It is needed on the one hand for the formation of the viral proteins and on the other hand for the synthesis of the new RNA. The newly formed viruses exit the cell by exocytosis.

Diagnosis

Diagnosis is made on the basis of patient history, clinical symptoms, physical examination, and laboratory methods. A method based on RT-PCR (reverse transcriptase polymerase chain reaction) was rapidly established for this purpose. Later, other tests were developed for serodiagnosis, i.e. for the detection of antigens or antibodies. These are much faster and easier to perform than RT-PCR (see below). See also Covid 19 antigen rapid tests. Warning symptoms include (Red Flags):

  • Difficulty breathing, shortness of breath
  • Blue lips or face
  • Pain and feeling of pressure in the area of the chest
  • Confusion

Oxygen saturation can be measured with a pulse oximeter.

Prevention

  • Wash hands frequently and during at least 20 seconds with soap and water.
  • As a second-line agent, alcohol-based hand sanitizers can be used, for example, ethanol 80%, see under glyceryl alcohol. An alternative is isopropanol. The WHO recommends 75% (V/V).
  • Do not touch the eyes, nose and mouth with unwashed hands.
  • Social distancing.
  • Avoiding close contact with other people. Keeping a distance.
  • Avoid shaking hands.
  • Clean and disinfect surfaces that may be contaminated.
  • Sick people should stay at home, avoid contact with other people and contact their health care provider or a hotline by phone.
  • Cough or sneeze into a paper handkerchief and dispose of it afterwards. Wash your hands. Or cough or sneeze into the crook of the arm.
  • Wear protective masks (eg hygiene masks, FFP2).

Medication prevention

Covid-19 vaccines are now available. The first agent to be approved was BNT162b2 on December 19. It will be followed by mRNA-1273 on January 12, 2021. They will make a significant contribution to preventing infection and controlling infectious disease. Examples:

  • BNT162b2 (BioNTech, Pfizer, Germany), approved in many countries.
  • MRNA-1273 (Moderna, USA), approved in many countries.
  • AZD1222 (Oxford University, AstraZeneca, England).
  • Sputnik V (Russia, initial launch date August 11, 2020).

See the article Covid-19 Vaccines Detailed Information The benefits of immune stimulants such as echinacea, zinc, cistus, vitamin C, and vitamin D have not yet been established for the prevention of covid-19. These agents are also used for prevention of the common cold, which can also be caused by coronaviruses.

Drug treatment

Mild illnesses can be treated at home in isolation like a cold or flu, for example, with antipyretic medicines such as acetaminophen and other pain relievers. Cough-irritant medicines and expectorants are used for coughs, and decongestant nasal sprays are used for colds.If the course is severe with complications, intensive medical care in a hospital is required, which includes oxygen ventilation and intravenous hydration.

Antiviral drugs

Various antiviral drugs (antiviralia) have been and are being studied in clinical trials and experimental therapies. The potential risks of the drug therapies must always be considered (contraindications, interactions, adverse effects)! Not all agents are equally suitable, and some are controversial: RNA polymerase inhibitors and nucleoside analogues:

  • Baloxavirmarboxil (Xofluza).
  • Favipiravir (Avigan, JPN)
  • Galidesivir (USA)
  • Remdesivir (Veklury)
  • Ribavirin (Copegus)

TMPRSS2 protease inhibitors:

Fusion inhibitors:

HIV protease inhibitor:

  • Lopinavir / Ritonavir (Kaletra)

Biologics:

  • Interferons
  • Monoclonal antibodies
  • Immunoglobulins from the blood of recovered patients.
  • Recombinant ACE2 (rhACE2): APN01

Other:

Immunomodulators

Immunosuppressants and immunomodulators inhibit the excessive and endogenous immune response, which is partly responsible for symptoms and complications (examples):

ACE inhibitors and sartans

Classical ACE inhibitors are not effective for preventing infection because they do not inhibit ACE2, which is required by the virus to enter the host cell. During viral infection, ACE2 is downregulated, which reduces its beneficial effects. Sartans are also not suitable because they bind to a different receptor. However, sartans abolish the proinflammatory effects of angiotensin II and thus could potentially make a positive contribution. Both ACE inhibitors and sartans may promote ACE2 expression and activity, potentially adversely affecting disease progression. At present, it is not clear whether a change in therapy is required. Patients should not discontinue the drugs themselves! Underlying diseases such as diabetes or cardiovascular disease may also increase the activity of ACE2, thereby increasing the risk for a severe course.

Ibuprofen

It has been suggested that the nonsteroidal anti-inflammatory drug ibuprofen may worsen the course of covid-19. This may also be through increased expression of ACE2 (see above). There is only one small study on this in rats (Qiao W. et al., 2015). The European Medicines Agency concludes that there is currently no scientific evidence that ibuprofen has a negative impact on the progression of covid-19. The WHO also no longer warns against the use of ibuprofen.

Immunity to Covid-19

Immunity to Covid-19 can be achieved with Covid-19 vaccines, on the one hand. On the other hand, individuals who have been infected with SARS-CoV-2 may be immune. Thus, they no longer develop symptoms upon contact with the virus. However, the detection of antibodies is not a guarantee of immunity. Possible immunity can be detected by two methods:

  • 1. previous medical diagnosis of infection, for example, with RT-PCR.
  • 2. detection of endogenous antibodies against SARS-CoV-2, e.g., by IgG or IgM detection in blood (serodiagnosis in the laboratory or with a rapid test).

For this purpose, rapid tests have also been developed, which can be performed within about 15 minutes. However, the reliability is controversial. Immune can also be someone who has come into contact with the virus and has not developed symptoms.People with immunity should still follow hygiene rules to avoid transmitting the virus from an infected person to a non-immune person.