No 7/8 - 2020

Pneumonia outbreak with novel coronavirus (COVID-19) - update

Seven weeks have passed since the World Health Organization (WHO) on 5 January 2020 for the first time announced an outbreak of pneumonia of unknown cause in Wuhan in the Hubei Province of Eastern China.

The outbreak was linked to a fish market where other non-domesticated animals were also sold. Already on 7 January, it was announced that the cause of the outbreak was a novel type of coronavirus that was very similar to the coronaviruses found in bats, but also similar to SARS coronavirus. This facilitated the development of a specific PCR analysis very early in the course of the outbreak that can detect the virus. Presumably, the virus was introduced in humans from animals, and was then transmitted from human to human.

The WHO summoned its emergency committee for the first time on 23 January; and by 30 January, the committee assessed that the spread of the new corona virus constitutes a public health emergency of international concern (PHEIC). The WHO has now coined the new coronavirus SARS-COV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) and the condition COVID-19 (Coronavirus Disease 2019).

It became clear that the virus was capable of human-to-human transmission, and now - about one and a half month after the outbreak was acknowledged – more than 75,000 cases and 2,000 deaths have been recorded worldwide. Even so, 98.8% of all cases have so far been detected in China (74,279/75,197), and only six deaths have been recorded outside of China.

In China, the Hubei Province remains the epidemic’s epi-centre (61,682 cases, corresponding to 83% of all Chinese cases), but cases have been detected in all 31 Chinese regions.

Changed registration in China triggered considerable increase

On 13 February, China changed the manner in which cases are recorded in the Hubei Province to also comprise suspected cases with image-diagnostic signs of pneumonia. This caused the number of recorded cases to increase by 13,332 clinical cases and a total of 245 deaths in a single day. However, these clinical cases and associated deaths were distributed on a longer period and were therefore not a sign that the epidemic was expanding rapidly.

Declining trend in China and no signs of uncontrolled spreading of infection in other parts of the world

Overall, the daily reported number of new cases in China has followed a slightly decreasing trend since 6 February, and there are no signs of substantial transmission of the infection in other countries than China. Even so, limited chains of infection have been recorded in Singapore, Japan and Vietnam.

On 17 February, the Chinese Center for Disease Control and Prevention (CCDC) published its first detailed epidemiological analysis of the Chinese outbreak. The report is based on 72,314 cases recorded in the national monitoring system from the outbreak started on 8 December 2019 to 11 February 2020. Among the recorded cases, 61.8% are laboratory-confirmed, 22.4% are suspected cases based on symptoms and exposure, and 14.6% are clinical cases (from the Hubei Province only). Furthermore, SARS-CoV-2 was detected in 889 (1.2%) symptom-free individuals.

The majority (78%) of the recorded cases belonged to the 30-69-year age group, and more than four out of five (81%) cases have experienced a mild disease course, whereas less than 5% have been critically ill. Among all recorded cases, 64% are men, but the male share of the laboratory-confirmed cases is 51.4%. The majority of patients (86%) are believed to have become infected in Wuhan or in relation hereto.

Overall, the mortality among recorded cases is 2.3%, but the rate is higher in the Hubei Province (2.9%) than among the cases recorded in the rest of China (0.4%).

Underlying chronic diseases are associated with a higher mortality; such diseases include cardiovascular disease (10.5% mortality), diabetes (7.3% mortality), chronic respiratory disease (6.3% mortality) and cancer (5.6% mortality). Additionally, mortality correlates with increasing age. No deaths were recorded among 416 infected children below ten years of age. In the 10-39-year age group, mortality is 0.2%. In the 40-59-year age group, recorded mortality falls in the 0.4-1.3% range, whereas it increases to 3.6-8% among 60-79-year-olds and mortality peaks at 14.8% among persons aged 80 years or more.

Finally, the report shows that with respect to onset of symptoms among confirmed cases, the epidemic peaked in China in the period from 23 to 27 January.

Outside of China, a total of 918 cases have currently been detected in 26 countries. More than half of these are the 542 cases onboard the cruise ship Diamond Princess, docked by the Japanese city of Yokohama. In the EU and Great Britain, a total of 45 cases and one death have currently been detected. Limited further transmission has been detected within delimited chains of infection in England, France and Germany, but there are no signs of ongoing spreading of the infection. No cases have been detected in Denmark.

Cautious optimism is therefore warranted with respect to the current Chinese containment strategy. Even so, the risk remains that the virus may spread to more countries with weak healthcare systems and insufficient resources to conduct comprehensive infection tracing and implement quarantine measures targeting healthy contacts to infected people.

The evolution of the epidemic may be followed on the ECDC’s and the WHO’s interactive websites. You will also find regular outbreak updates at the SSI website, including the case definition for suspicion of the condition and thereby indication for referral and sampling.

Development of specific treatment and of a vaccine

No internationally approved treatment exists for infection with SARS-CoV-2. Ongoing Chinese trials exploring the effect of the protease inhibitor Kaletra (lopinavir/ritonavir) are concluding, and the preliminary results are expected shortly. Kaletra, which is approved for HIV treatment, also forms part of an ongoing trial on the treatment of MERS cases in Saudi Arabia.

Remdesivir, a RNA polymerase inhibitor is assessed as the most promising candidate, as it has been shown to have a broad antiviral effect on many different types of coronavirus, including SARS and MERS, based on laboratory studies and monkey and mouse models. Broad experience exists with its use in humans, as remdesivir was part of an Ebola treatment trial in the Democratic Republic of the Congo. Remdesivir trials in China are expected to start by February 2020.

No approved vaccines exist. Work is underway to develop several types of experimental vaccines, including so-called DNA, RNA and subunit vaccines targeting SARS-CoV-2, which will possibly start being used in trials in the course of some months. Initially, the vaccines need to be tested on animals and then on a small group of humans to explore their effect and establish any side effects.

Another year will probably pass before the vaccines are tested in larger groups of people.

What we do not know yet

It remains unknown from which animal SARS-CoV-2 originated. Furthermore, it is also unknown if an intermediary host, i.e., another animal species, was infected before the virus adapted so that it could be transmitted to humans. Retrospectively, cases of COVID-2019 were detected in Wuhan in December 2019 who had no previous contact with the fish market. This may mean that the virus was already spreading from human to human in that period. It may also mean that the spread via the fish market was not due to animal-to-human transmission, but was instead caused by human-to-human transmission.

Despite the new national report referred to above, it remains unclear to exactly which extent unrecognized mild cases of the COVID-19 are occurring in China. Based on the detection of asymptomatic and mild cases both within China and in other countries, it is likely that the real number of cases is far higher than the official figures suggest. This is underpinned by mathematical modelling studies, which have estimated the number of disease cases to be 10-20 fold higher than the official estimates. If this is confirmed, the recorded overall mortality, which has settled at approx. 2.3%, will decline correspondingly. On the other hand, there are also indications that the serious COVID-19 cases may remain ill for many weeks before they succumb to the infection. This may mean that the mortality would instead increase.

The infectious period for COVID-19 has also not yet been fully established. The virus was found in the upper airways of people with mild symptoms, and examples were seen of infection prior to symptom onset, but the possible effect of transmission from asymptomatic or mild cases on the spread of the virus remains unknown.

Several findings indicate that it may be possible to contain the virus, also because spring and summer are coming to the Northern Hemisphere, which normally reduces the risk of viral transmission.

As COVID-19 seems to be very infectious and everyone is presumably susceptible to the disease, it may have pandemic potential. Even so, there are several indications that COVID-19 will run a mild course in most people, but that elderly and chronically ill people may be at risk of running a more serious disease course. COVID-19 may, in this respect, be more similar to other airway viruses, like e.g., influenza than to SARS and MERS.

(P.H. Andersen, P. Valentiner-Branth, T.G. Krause, Department of Infectious Disease Epidemiology and Prevention, K. Mølbak, Infection Preparedness)