HC extra: COVID-19

COVID-19 epidemiology

The start of a pandemic:

COVID-19 originates from Wuhan, in the province Hubei in China. Over 11 million people live there.

Numbers:

Important numbers to know are:

• Incidence: new number of cases/population
• Case fatality rate: number of deceased/total number infected
• R0reproductive number: average number of new cases infected by 1 infected person

In case of COVID-19, almost all numbers aren't correct:

• Only what is tested is known
  • What isn't tested, isn't known
  • Misclassification
• There is always delay
  • Reports are never up to date
  • Disease in specific subgroups can be underreported
• There are always aberrations
  • R0represents the average number, but not the real patterns of transmission

Transmission:

The transmission chain of COVID-19 consists of:

• Reservoir: bats
• Source: humans
• Host: humans

Transmission happens via different routes:

• Droplet-borne route: droplets cannot travel very far because they sink to the ground due to gravity
• Short-range airborne route: transmitted by aerosols
• Long-range airborne route: transmitted by aerosols
• Fornite route: via surface contact or contact between people

Clinical aspects

Clinical course:

From January to May 2020, there were 1,320,488 laboratory-confirmed COVID-19 cases, of which:

• 14% were hospitalized
• 2% were admitted to the intensive care unit
• 5% died

These percentages are only based on the confirmed COVID-19 cases → aren't realistic.

Symptoms of COVID-19 are:

• Cough (50%)
• Fever (43%)
• Myalgia (36%)
• Headache (34%)
• Dyspnea (29%)
• Sore throat (20%)
• Diarrhea (19%)
• Nausea/vomiting (12%)
• Loss of smell or taste, abdominal pain, rhinorrhea (10% each)

Complications of COVID-19 can be:

• Pulmonary embolism
• Acute respiratory distress syndrome
  • Possibly due to a cytokine-storm → hyper-inflammatory state

Diagnosis:

COVID-19 can be diagnosed with molecular techniques → the SARS-CoV2 viral load is highest in respiratory samples. For instance, in case of PCR, the sensitivity is the highest in lower airway samples.

COVID-19 diagnosis can also be done using serology. This is useful when the patient has had the virus for a while → antibodies can be detected around day 10.

Lastly, diagnosis of COVID-19 can be done using radiology. COVID-19 has a specific pattern on a CT-scan. A score is given to the images → a CO-RAD score of 4 or 5 indicates that there is a COVID-19 infection and a CO-RAD score of 1 or 2 indicates that an infection by this virus is unlikely.

Treatment:

There are 3 treatment options to treat COVID-19:

• Supportive care
• Anti-viral
  • Remdesivir
  • Convalescent plasma
• Anti-inflammatory
  • Corticosteroids
  • Dexamethasone
  • Anti-IL6 (tocilizumab)
  • Anti-IL1 (anakinra)
  • Bradykinine-inhibitor (Icatibant)
  • Anti-CD147 (meplazumab)
  • JAK-inhibitor (ruxolitinib)

Remdesivir is an anti-viral way to treat COVID-19. It was originally designed for the Hepatitis C virus, and later used for Ebola and Marburg. It is a ribonucleotide analogue inhibitor of viral RNA polymerase. It gives a faster clinical improvement but no difference in mortality. Usually it is prescribed 10 days after the symptoms start, so it may be more beneficial from an earlier start.

Corticosteroids dampen the inflammation, but potentially augment the viral replication. An example is dexamethasone, which is used in the recovery trial and shows light beneficial outcomes.

Autopsy

Autopsies provide disease insight, which is especially important when clinicians are faced with a new disease like COVID-19. Systematic analysis of the types of tissue injury can help to understand what is going on and may help to develop therapeutic regimes and guide clinical trials.

Pneumocytes:

There are 2 types of epithelial cells in the lung:

• Type I pneumocyte
  • Super thin but large cell
  • Involved in gas exchange
  • Unable to replicate
  • Susceptible to toxic/viral insults
• Type II pneumocyte
  • Involved in surfactant production
  • Able to replicate and differentiate into type I cells in case of damage

Normally, the alveolar walls in the lungs are very thin because the exchange between air and blood should be super smooth.

Pulmonary injury:

Pathologists systemically analyze COVID-19 related pulmonary injury in 3 ways:

• Epithelial damage
  • Due to direct viral injury
  • The virus enters the lung epithelia via ACE2 receptors
  • Pneumocytes are very prominent
    • The nucleus reacts and becomes big
    • The amount of cytoplasm grows
• Vascular injury
  • Etiology is under debate
  • Pulmonary embolisms
  • Micro-thrombotic injuries
• Chronic damage
  • Due to (anti-viral) immune response
    • The cytokine storm
  • The chronic state of inflammation causes collateral damage and remodeling of the normal archeology of the lung

Case:

In the lungs of the patient, a type of COVID-19 related injury can be identified:

• A combination of direct viral injury (epithelial) and chronic immune/inflammatory response related injury (fibrosis)
• No thrombosis
• COVID-19 PCR is still positive postmortem

However, there is evidence for non-COVID-19 related injury such as traces of a bacterial superinfection → clusters of neutrophils suggest a bacterial infection, possibly staphylococcus aureus.

Examination:

During autopsies, the weight of the organs is measured. In case of COVID-19, the weight of the lungs will be way to high due to the presence of infiltrate fluids. The virus can stay active in the pneumocytes for months after the patient has died → pathologists need to wear protective equipment while examining the tissue.

Fibrosis:

After 3 weeks of infection by COVID-19, tissue fibrosis can be developed. This is probably caused by the cytokine storm and hyper inflammatory state. This type of injury isn't reversible anymore, which is why the main goal of treatment is to prevent this fibrosis.

Prevention of transmission

COVID-19 is transmitted by inhaling droplets in the air exhaled by an infected individual. These droplets can also sink to the surface → infection is possible by touching these subjects.

Standard control measures:

Standard control measures can be taken to prevent transmission of COVID-19:

• Social distancing
• Sneezing and coughing in the elbow
• Washing and disinfecting hands

More measures:

More measures are taken to ensure prevention in the hospital:

1. Triage
   • All patients and visitors
   • Check on COVID complaints
   • (Out)patients: by SMS and at hospital gates
2. Separate suspected from non-suspected cases
   • In- and outpatients
   • COVID isolation wards
   • Special COVID outpatient clinic
   • Separate routes at emergency departments
3. Test and isolate suspected and proven COVID-cases
4. Contact tracing after unsuspected findings
5. Healthcare workers with complaints stay at home and are tested

Personal protective equipment:

There are several types of personal protective protective equipment (PPE):

• Protection by a mask
  • Surgical mask
  • FFP2 mask
• Protection of the eyes by safety glasses/goggles/facemask
• Gown with long sleeves
• Gloves

Source isolation:

There is a negative pressure in the patient room and lock compared to the corridor → no viruses will enter the corridor. All air in the lock is refreshed.

If there aren't enough isolation rooms, patients will be admitted in rooms with only a lock. Here, the pressure in the room and corridor are the same. If there aren't enough patient rooms, patients will go into cohortation. In this case, it is essential that all patients have the same disease.

Protective immunity:

The antibody response after illness depends on the severeness. The detection of antibodies to SARS-CoV2 does not directly indicate protective immunity. Correlates of protection for COVID have not yet been established.