New Coronavirus Disease (COVID-19): more questions than answers
Preliminary data available suggest that transmission of SARS-CoV-2 also occurs during the incubation period and possibly also from infected people who have not developed manifestations, but the frequency has not yet been definitively established11/03/2020
Fernando Martins & Terezinha Marta Castiñeiras
On December 31 2019, the World Health Organization (WHO) was notified of the occurrence of severe pneumonia cases of unknown etiology in the city of Wuhan (Hubei Province), China. The fact, immediately generated concern in the international medical-scientific community. In China, health authorities have taken emergency measures to contain the epidemic and have started epidemiological, microbiological and clinical investigations in order to quickly characterize the new disease and allow it to be controlled. On January 7 2020, Chinese scientists announced the isolation of a new coronavirus from a Wuhan patient that was initially called 2019-nCoV. In sequence, they developed a method of molecular biology for rapid confirmation of the diagnosis.
The epidemiological investigation of the first cases pointed to the visit to a wholesale seafood and wildlife market in Wuhan as a link, suggesting that the new coronavirus could have been initially transmitted to humans from an animal source. Inter-human transmission (person-to-person) was quickly proven and is responsible for the continued spread of the disease.
During the month of January, cases begun to be registered in other provinces of China and, although less frequently, also in other countries. On January 30 2020, WHO declared the respiratory disease epidemic to be a Public Health Emergency of International Interest. At the time, a total of 7,736 cases were confirmed, 83 of which were in different countries. On February 11 2020, the disease caused by the new coronavirus, was officially called by the WHO as Coronavirus Disease 19 (COVID-19, for short) and, in parallel, the virus was renamed to SARS-CoV-2.
Until March 8 2020 110,037 cases were registered in 109 countries (80,735 in mainland China) and 3,825 deaths (lethality of 3.5%). In Brazil, until the same date, there were 663 suspected cases, 632 discarded and 25 confirmed cases (including 1 asymptomatic).
Etiological agent of COVID-19
The causative agent of COVID-19 is a new coronavirus, SARS-CoV-2. Viruses of the coronaviridae family can cause infections in vertebrate animals. In humans, coronaviruses cause respiratory infections of varying severity, being one of the most common agents of the common cold (HCoV-229E, HCoV-NL63, HCoV-OC43 and HCoV-NKUI) and also recognized causes of severe pneumonia such as respiratory syndrome acute severe (SARS, for Severe Acute Respiratory Syndrome, described in 2002 and the Middle East Respiratory Syndrome (MERS, for Middle East Respiratory Syndrome, described in 2012), respectively caused by SARS-CoV and MERS-CoV.
Bats appear to be the primary source (reservoir) of several variants of coronavirus and are also likely to be for SARS-CoV-2, as suggested by phylogenetic studies in progress with the genome of the new coronavirus. However, it is likely that for humans to be infected, another animal host (still unknown for SARS-CoV-2) is involved, as demonstrated for SARS-CoV (civets) and for MERS-CoV (dromedaries).
Transmission modes of the SARS-CoV-2
Available information suggests that the primary mode of transmission of SARS-CoV-2 between humans is similar to that of influenza. That is, the transmission occurs from one person to another through droplets eliminated through coughing or sneezing. The transmission of SARS-CoV-2 by aerosols has not been established (nor discarded). It is accepted, for prudence, that the procedures that generate aerosols (orotracheal intubation, nebulization, airway aspiration, etc.) may involve some risk.
Transmission can also occur through contamination of the hands with respiratory secretions, through direct contact (handshake) or indirect (touching contaminated surfaces). The infection, however, does not occur through the skin. Transmission can occur when the susceptible individual puts the contaminated hands in contact with the oral, nasal or ocular mucosa.
The transmission of SARS-CoV-2 seems to occur more intensely after the onset of the disease and the available information suggests that the risk persists, on average, for seven days. The exact transmission period, however, has not yet been established for COVID-19. For flu, transmissibility begins 24 hours before the onset of manifestations and can occur up to four days afterwards. For measles, it starts four days before the exanthema appears (skin rash) and can occur up to four days later. Evidence points out that COVID-19, although easily transmissible like flu, is less transmissible than measles. It is estimated that each infected person can transmit SARS-CoV-2 to two to three other individuals, while in the case of measles virus transmission can occur for 12 to 18 susceptible people.
Preliminary data available, however, suggest that transmission of SARS-CoV-2 also occurs during the incubation period (from 2 to 14 days in general) of the disease (and possibly also from infected people who have not developed manifestations), but the frequency with which transmission by asymptomatic persons occurs has not yet been definitively established. However, there is clear evidence that the likely first case of local transmission in Europe (Germany) occurred from an infected and asymptomatic person.
The transmission that resulted in this first case in Germany would have occurred during business meetings (Munich, January 20 and 21, 2020) between a businessman and a Chinese executive from Shanghai. The businesswoman, asymptomatic during her stay in Germany, returned to China on January 22. She began to develop clinical manifestations during the flight and had her diagnosis of COVID-19 confirmed (PCR) on 26 January. On the 27th, the executive informed the Munich company about her illness. The businessman, previously healthy and with no travel history in the previous 14 days, fell ill on January 24 (fever of 39.1°C and productive cough). On the 27th, having improved, he returned to work and, due to the information received from the executive, he was referred for evaluation at the Infectious Diseases and Tropical Medicine Division in Munich. The diagnosis of COVID-19 was confirmed in an examination (PCR) of January 27 when the businessman was already asymptomatic. On January 28, three other employees of the company who presented clinical manifestations had their diagnosis confirmed (PCR). Of these patients, one had contact only with the executive and two only with the businessman.
A person exposed to the risk of infection (opportunity for infection), such as traveling to an area where sustained local transmission (community) is occurring, may or may not be infected with SARS-CoV-2. Once infected, it may or may not develop COVID-19 manifestations. In those who develop clinical manifestations, the incubation period is asymptomatic. In some people, there is no feeling of malaise, the manifestations can be very mild (mild dry cough, runny nose and absence of fever) and the cases evolve asymptomatic, without other problems. In others, the manifestations are more accentuated and the patients evolve with feeling of malaise, high fever, more exuberant cough (dry or productive), runny nose, sore throat and shortness of breath. Most of these patients evolve with a clinical picture ranging from mild to moderate. In a minority, however, evolution can result in severe or very severe conditions.
The report (16-24 February 2020) of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19), concerning 55,924 cases with confirmed diagnosis of COVID-19 in China, records that the disease was considered as clinically mild or moderate in 80.1%, severe in 13.8% and critical in 6.1%. Patients with mild or moderate clinical conditions do not require hospitalization, those with severe conditions should be admitted and those with critical conditions should be admitted to an intensive care unit.
Definition criteria and investigation flows, home isolation and care are extremely important and useful. However, caution is necessary, as there is no universal approach. The natural history of COVID-19 is still poorly characterized. The number of asymptomatic carriers is unknown and the exact period of transmissibility has not yet been established.
Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a de ive study. The Lancet 2020; S0140-6736(20)30211-7.
Hoehl, S, Berger A, Kortenbusch M, et al. Evidence of SARS-CoV-2 Infection in Returning Travelers from Wuhan, China. et al. N Engl J Med 2020; published online Feb 18. DOI:10.1056/NEJMc2001899.
Professor of Infectious and Parasitic Diseases and Travel Medicine, UFRJ Medical School.
Coordinator of Cives – Health Information Center for Travelers at UFRJ.
Terezinha Marta Castiñeiras
Professor of Infectious and Parasitic Diseases, UFRJ Medical School.
Head of the Department of Infectious and Parasitic Diseases, UFRJ Medical School.