Disease & Contagion
Pathogen
The new human coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV-2), belongs to the species of Severe Acute Respiratory Syndrome related Coronavirus, genus beta-coronavirus, subgenus Sarbecoviruses, lineage B (Zhou 2019) . Coronaviruses cause respiratory infections, sometimes with an enteral component, in humans and animals. This group also includes SARS-CoV, which caused outbreaks in 2003 in various regions of the world.

Pathogenesis
The new coronavirus (SARS-CoV-2) is genetically most closely related to the SARS coronavirus. Like SARS, it uses the ACE2 receptor. This occurs, among other things, on the alveolar epithelium, which is seen as the explanation for the predilection of SARS for replication in the low airways (Haagmans 2020 ).

Incubation period
2-14 days (average 5-6 days).

Disease symptoms
Varying, from mild nonspecific respiratory complaints: colds; sore throat (14%); (dry) cough ( 68%); fatigue (38%); sputum production (33%); muscle and joint pains (15%) ; headache (14%) and increase, to more serious syndromes with fever (> 38 degrees Celsius, 88%); shortness of breath (19%) and pneumonia , up to acute respiratory stress syndrome and septic shock. Also reported (in a smaller proportion of patients): diarrhea (4%) ; nausea and vomiting (5%). About 80% of the reported cases have mild to moderate complaints, 13.8% had serious complaints and 6.1% had very serious complaints.

The patients with complications are divided into ‘severe pneumonia’ if they are in need of oxygen (about 65% of the cases), ‘critical’ if they need ventilation (about 20%), or ‘fatal’ (about 15% of the patients with pneumonia).

China reported a case fatality rate of 2.3% in March 2020. Both the severity, course and case fatality rate depend on underlying conditions and increase in the elderly above 70 years.

(Guan 2020, Huang 2020, Wang 2020, Haagmans 2020, ECDC 2020a)

Pregnancy
Disease symptoms in pregnancy
There are no indications that a COVID-19 infection is different in a healthy pregnant woman than in a non-pregnant woman. But like some other viral respiratory infections, complications such as pneumonia and fever in a pregnant woman can be serious. This is especially true for the third trimester (> 28 weeks) of pregnancy, due to the mechanical limitation of the growing abdomen resulting in a reduction in lung capacity. This therefore applies not only to COVID-19 infections but also to other respiratory infections.

Natural immunity
Follows.

Pregnancy
Natural immunity in pregnancy
Unknown.

Reservoir
Not applicable. It is assumed that a zoonotic source (bats and / or pangolins) ( Wang 2020).

Contamination path
The disease is transmitted from person to person.

Straight away
Drip infection: transmission via large drops from coughing and sneezing within a distance of 1.5 meters. Via aerosols during aerosol-forming procedures (tracheal intubation, non-invasive ventilation, tracheostomy, cardiopulmonary resuscitation, manual manual ventilation prior to intubation, bronchoscopy, tracheostomy procedures, suctioning) ( WHO 2020a).

Aerogenic
There is no evidence that the virus spreads aerogenically (via airborne particles), except through aerosols during aerosol-forming procedures (tracheal intubation, non-invasive ventilation, tracheostomy, cardiopulmonary resuscitation, manual manual ventilation prior to intubation, bronchoscopy, operations on the tracheostomy, suction) ( WHO 2020a).

Perinatal transmission
There is no evidence of perinatal transmission.

Lactation
As with other viral respiratory infections, transmission of the virus through breastfeeding is unlikely to play a role. Good hand and cough hygiene while breastfeeding is important. If the mother coughs a lot, you can choose to have expressed milk given by another parent / caregiver.

Contagious period
Exact data about the contagious period is missing. In any case, a patient is contagious during the symptomatic phase ( Huang 2020 ). Both patients with mild and severe complaints can excrete virus (Zhang 2020). The virus can also be detected by PCR in the patient’s faeces ( WHO 2020b, ECDC 2020b). After the symptoms have disappeared, the virus can still be detected by PCR in both the throat (7-14 days) and faeces (4-5 weeks). Virus has also been detected in the throat by PCR 1-2 days before symptoms appear (Tong 2020). In some asymptomatic individuals, the virus can be detected in the throat by PCR without becoming ill themselves later (Bai 2020, Hoehl 2020, Pan 2020, Zou 2020).

It is unclear whether the detection of virus in asymptomatic persons is related to infectivity. Based on the current literature, it is mainly symptomatic persons who contribute to the spread and the contribution of the asymptomatic persons to the spread seems to be limited (Ghinai 2020). Only one asymptomatic person with a virus detected in the throat by PCR was able to actually breed the virus ( Hoehl 2020). Also, there are currently no indications that faeco-oral transmission contributes to the spread.

Contagiousness
Exact data on the infectiousness are missing. The sicker someone is, the more virus the person can spread. Outside the body, the virus can only survive for a short time. How long that is exactly is still unknown. This can vary from a few hours to a few days. This depends on, for example, the type of surface, the temperature and the humidity. There is no evidence that people have been infected by this ( ECDC 2020b). Until now it has not been possible to establish that contaminated surfaces play a role in the spread (Moriarty 2020).

Pregnancy
Perinatal transmission
To date, no intrauterine transmission or an increased risk of miscarriage or birth defect from infection with the new coronavirus has been described. Perinatal transmission has been described (Liu 2020, Mullens 2020).

Upwards
Diagnostics
Direct diagnostics
Detection of the virus can be done with (real-time) reverse transcription (RT) -PCR for detection of viral RNA . Obviously, for optimal detection of the virus, regardless of the technique, the sample collection – nasopharynx (nose) some and oropharynx (throat) some – should be done correctly. SARS-CoV-2 is more detectable in nasopharynx smears than in oropharynx smears in patients with COVID-19. It remains important to decrease both, as there are patients who are positive only in one of the two locations. Therefore, for SARS-CoV-2 diagnostics, always send in a nasopharynx watts, in addition to an oropharynx watts and, if possible, a sputum sample or bronchoalveolar lavage fluid (Yang 2020).

To save material, it is possible to sample both nose and throat with one stick, send two sticks in one tube with shipping medium, or test materials pooled. For explanation, see the appendix Additional diagnostic information .

The PCR assays used for SARS-CoV-2 to date target two targets: the E gene and the RdRP gene. With the experience gained so far, testing for the E gene can only be considered. The amplification curve should be well assessed (especially at a Ct> 30). If the curve is abnormal, unreliable or difficult to interpret, or if there is an epidemiologically unexpected positive, for example the first case on one of the Caribbean islands, confirmation is necessary. Depending on the sensitivity of the local implementation, this can be done with the RdRP PCR , by retesting the same sample, or by resampling the patient. Also, false positive signals from primers and probe that may be contaminated with synthetic E gene run control should still be monitored. A comprehensive entry check therefore remains crucial (Corman 2020).

Collection technique and protective measures
For collection technique, see the appendix Collection technique specific viral diagnostics .

For hygiene measures during acceptance, see Generic scenario , appendix 8: ‘Hygiene measures’, section ‘Protection during sampling’ (page 2).

Executive laboratories
In addition to Erasmus MC and RIVM-IDS, there are 13 regional upscaling laboratories where diagnostics can be performed to SARS-CoV-2 . In addition, since the beginning of March, other medical microbiological laboratories have started or are implementing diagnostics to SARS-CoV-2. An urgent request is being made to all GGDs to send the samples to the upscaling laboratory in their OWN region.

For an overview of the relevant laboratories and for additional information about accessibility, transport, laboratory safety and sampling materials, see the Appendix Additional diagnostics information .

Indirect diagnostics
Serology is not (yet) available, but research is being conducted into the usefulness of serological tests. If patient’s serum is available, the applicant is requested to send it along with the other samples. If a serological test is not yet available, this does not directly contribute to diagnostics for the acute phase, but to subsequent imaging of the COVID-19. Serum samples can be sent to RIVM-IDS and / or Erasmus MC .

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