As the outbreak continues, we learn more about this coronavirus, the disease it causes, and how it spreads. On this page, we provide summaries of the latest articles from peer-reviewed journals (including perspectives and correspondences) that highlight new findings.

The Latest

CLINICAL CHARACTERISTICS AND INTRAUTERINE VERTICAL TRANSMISSION POTENTIAL OF COVID-19 INFECTION IN NINE PREGNANT WOMEN: A RETROSPECTIVE REVIEW OF MEDICAL RECORDS

The Lancet | Chen et al. | Feb 12, 2020
This study aimed to determine the clinical characteristics of COVID-19 during pregnancy and the potential for the virus to transmit from mother to fetus. Researchers reviewed medical charts of 9 pregnant women who tested positive for COVID-19.

None of the patients developed severe pneumonia, indicating that all infections were relatively mild. Seven of nine patients presented with a fever, four presented with a cough, three had muscle pain, two had a sore throat, and two were fatigued, all similar to the symptoms seen in non-pregnant patients.

Various measures were taken to determine if the children had been infected, including testing the amniotic fluid, cord blood, throat swabs, and breast milk samples. All samples tested negative for the virus. The pregnant women in this study did not present differently than non-pregnant patients with COVID-19. Additionally, there was no evidence of intrauterine transmission of the infection from mother to child.

This study did utilize a small sample of only nine patients, all of whom were in their third trimester of pregnancy, therefore limiting the extent to which these findings can be generalized to a broader population. This study doesn’t tell us that intrauterine transmission is impossible, only that it seems unlikely based on this evidence. It also does not tell us how COVID-19 infection might present in patients at a different stage of pregnancy.

Clinical Characteristics of 138 Hospitalized Patients With Novel Coronavirus-Infected Pneumonia in Wuhan, China

JAMA | Wang et al. | Feb 7, 2020
With numerous articles focusing on clinical characteristics, this research effort attempted to compare severe cases of novel coronavirus infection with non-severe cases in a larger group of patients than has been examined previously.

Study size: 138 patients with confirmed novel coronavirus infection. Average age: 56 years; 54.3% were men. Most common symptoms: fever, fatigue, and dry cough. Chest scans revealed: lungs of all patients showed “bilateral patchy shadows” or “ground glass opacities,” indicative of novel coronavirus-infected pneumonia. The death rate was 4.3%. 34% were discharged. Thirty-six (26.1%) of the patients required transfer to the intensive care unit (ICU). Reasons included: facute respiratory distress syndrome (61%), arrhythmia (44%), and shock (31%).

Compared to those not treated in the ICU, patients treated in the ICU tended to be older (61 vs. 55 years), were more likely to have underlying health conditions, such as diabetes or high blood pressure (72% vs. 37%), and were more likely to have difficulty breathing (64% vs. 20%).

The authors noted that 40 health professionals and 17 hospital patients were infected and included in this cohort, indicating that hospital-associated transmission of the virus was likely, but this could not be proven.

This study suggests that older age and the presence of underlying health conditions may put people at increased risk of more severe negative health outcomes from novel coronavirus infection. Many of the patients were still hospitalized when this paper was written, making it impossible to determine the ultimate outcomes of many of the patients. Many treatment efforts, including antibacterial agents, have been shown to be ineffective against the virus.

 

Other Key Articles (in chronological order)

CLINICAL CHARACTERISTICS OF 138 HOSPITALIZED PATIENTS WITH NOVEL CORONAVIRUS-INFECTED PNEUMONIA IN WUHAN, CHINA

JAMA | Wang et al.| Feb 7, 2020
With numerous articles focusing on clinical characteristics, this research effort attempted to compare severe cases of novel coronavirus infection with non-severe cases in a larger group of patients than had been examined previously.

138 patients with confirmed novel coronavirus infection were included in the study. Average age was 56 years, 54.3% were men. The most common symptoms among patients were: fever, fatigue, dry cough. Chest scans revealed that the lungs of all patients showed “bilateral patchy shadows” or “ground glass opacities,” indicative of novel coronavirus-infected pneumonia. The death rate for this cohort of patients was 4.3%.
34% were discharged.

Thirty-six (26.1%) of the patients required transfer to the intensive care unit (ICU). Reasons included acute respiratory distress syndrome (61%), arrhythmia (44%), and shock (31%).

Compared to those not treated in the ICU, patients who were treated in the ICU tended to be older (61 vs. 55 years), were more likely to have underlying health conditions, such as diabetes or high blood pressure (72% vs. 37%), and were more likely to have difficulty breathing (64% vs. 20%).

The authors noted that 40 health professionals and 17 hospital patients were infected and included in this cohort, indicating that hospital-associated transmission of the virus was likely, but this could not be proven.

This study suggests that older age and the presence of underlying health conditions may put people at increased risk of more severe negative health outcomes from novel coronavirus infection. Many of the patients were still hospitalized when this paper was written, making it impossible to determine the ultimate outcomes of many of the patients. Many treatment efforts, including antibacterial agents, have been shown to be ineffective against the virus.

 

THE NOVEL CORONAVIRUS: ASSESSING THE AMERICAN RESPONSE

Health Affairs (Blog), Ashish Jha, Jan 31, 2020
Ashish Jha breaks down the coronavirus outbreak thus far. Offering insight into what we know about it, what is needed for the effective domestic control of the outbreak within the U.S. and how our approach to global health security can be improved. Jha also highlights how exceptional the scientific response to this outbreak has been and what we can do to be more prepared in the future.

First Case of Novel 2019 Coronavirus in the United States

NEJM, Holhue et. al, Jan 31, 2020.
This article, by the Washington State 2019-nCoV Case Investigation Team*, documents clinical history of the first case in the U.S., which began in Snohomish County, Washington when a 35-year-old man who had just traveled back from Wuhan, China presented to an urgent care clinic, and was hospitalized after he tested positive for 2019-nCoV. After developing pneumonia on hospital day 5 (illness day 9), he remained hospitalized as of January 30th (day 8), with the only remaining symptom being his cough.

 

Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study 
The Lancet, Wu et. al, Jan. 30, 2020.

A group of researchers from the University of Hong Kong used data from December 31st, 2019 to January 28th, 2020 on the number of novel coronavirus (2019-nCoV) infections to be exported internationally from Wuhan to estimate the extent of the outbreak within Wuhan from December 1st, 2019 to January 25th, 2020. Additionally, using this data in combination with various sources pertaining to travel patterns and human mobility, the estimated extent of viral spread was forecasted.

The researchers calculated the R0 (pronounced R-nought) value of the virus to be 2.68. (For more information on what this value means and the difficulty of interpreting it see our blog explaining R-nought, and Ed Yong’s article in The Atlantic.) They also estimated that, as of January 25th, 2020, there were 75,815 infected individuals in greater Wuhan and that the average doubling time of the epidemic was 6.4 days.

The authors also estimated that five major Chinese cities, which together account for 53% of all outbound international air travel from China, had imported a total of 863 infections from Wuhan. The cities (with estimated number of imported infections) were Chongqing (461), Beijing (113), Shanghai (98), Guangzhou (111), and Shenzhen (80). Given the size of these cities and the amount of travel to and from them, increased spread of 2019-nCoV in these metropolitan areas would likely contribute to the increased spread of the virus both within and beyond China.

While these numbers provide invaluable insight for decision-makers, they can also easily raise alarm. It is important to remember that these are estimates, and we don’t know the true extent of the outbreak. The estimates help local, state, and national governments and public health authorities make informed decisions about how to best handle the spread of 2019-nCoV.

Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany
NEJM. Rothe et al. Jan 30, 2020.

The key finding of this paper was that 2019-nCoV appeared to be transmissible prior to the development of symptoms, a trait that neither SARS nor MERS (both in the same family of virus as 2019-nCoV) share. However, this assumption seems to have been based on second hand information, and has since been called into question by a leading Public Health Institute in Germany after investigating further. Details on this latest development can be found in this Feb. 3 Science Magazine story by Kai Kupferschmidt.  

 

Transmission Dynamics

Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia NEJM | Li et al. | Jan 29, 2020.

In an effort to elucidate the epidemiologic characteristics of the novel coronavirus (2019-nCoV), researchers in China analyzed data on the first 425 confirmed cases of the virus in Wuhan. Patient characteristics were examined broken down by three time periods: 1) those with illness onset prior to January 1st, 2020 (the day the Huanan Seafood Market was closed), 2) those with illness onset between January 1st and January 11th (when RT-PCR reagents were provided to Wuhan), and 3) those with illness onset after January 12th.

The median age of all patients was 59 years and 56% were male. Those in group 1 tended to be younger (56 vs. 60 and 61-years-old for groups 2 and 3 respectively) and a greater proportion of them were male (66% vs 59% and 48% respectively). There were no confirmed cases in patients under the age of 15. There have been healthcare workers who have become infected, but the proportion of these infections is lower than it was during either the SARS or MERS outbreaks.

Perhaps most interestingly, they found that the proportion of patients who were exposed to the Huanan Seafood Market decreased over time (group 1 vs. groups 2 and 3), from 55% of patients in group 1, to 10% and 6% of patients in groups 2 and 3. Additionally, the proportion of patients having no exposure to a wet market or another person with respiratory symptoms increased over time, with 26% of patients in group 1 to 72% and 73% of patients in groups 2 and 3.

The average incubation time (time from illness onset to symptom development) was estimated using data from only 10 of the 425 cases and was found to be 5.2 days. There was variability though, with some cases having incubation times of 12 days or even longer. The researchers also calculated the duration over which the number of cases has doubled to be every 7.4 days.

 

Evidence for Human to Human (H2H) Transmission

Importation and Human-to-Human Transmission of a Novel Coronavirus in Vietnam
NEJM | Phan et al. | Jan 28th, 2020.

A 65-year-old man was hospitalized on January 22nd, 2020 in Ho Chi Minh City, Vietnam with a fever and fatigue that reportedly began five days prior on January 17th. On January 13th, he and his wife had flown to Hanoi from Wuhan, China, the location from which the outbreaks of novel coronavirus have been spreading. The man reported no exposure to a wet market like the Huanan Seafood Market while in China, but he and his wife spent three days together with their otherwise healthy 27-year-old son in Nha Trang, Vietnam starting on January 17th. The three of them shared a bedroom for those three days. The son had not traveled to a region known to have coronavirus and had no prior contact with someone who had. As of January 20th, the son developed a dry cough and fever, and later tested positive for 2019-nCoV. This family cluster of the infection provides clear evidence of human-to-human transmission, but also indicates that the incubation period for the virus may be as little as three days.

 

The Virus

A Novel Coronavirus from Patients with Pneumonia in China
NEJM | Zhu et al. | Jan 24t, 2020

In Wuhan China, three patients were hospitalized for pneumonia in December of 2019. Bronchoalveolar lavage was performed on the patients so that they could use the epithelial cells from the lungs of the patients to isolate and grow the virus in the lab. The genome of the virus was sequenced, and it was determined to be a novel coronavirus, one in the same family as severe acute respiratory syndrome (SARS) and Middle-East respiratory syndrome (MERS). The virus was found to have 80% similarity to a coronavirus found in bats, but this does not definitively mean the virus originated in bats. Importantly, they were able to develop an assay that allows for the rapid testing of people for this novel coronavirus.

 

Who Was First Infected

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China
The Lancet | Huang et al. | Jan 24, 2020

In response to the cluster of pneumonia patients in Wuhan, China, the clinical characteristics of 41 patients were reported. The 41 patients, all of whom tested positive for the novel coronavirus (2019-nCoV), presented with symptoms resembling severe pneumonia, their average age was 49, and they were mostly (73%) men. Two-thirds of the patients had direct exposure to the Huanan Seafood Market, and 13 (32%) required ICU care. The first fatal case was a man who had continuous exposure to the Huanan seafood market. Prior to hospitalization, he had a fever for seven days, a cough, and difficulty breathing. His wife, who was hospitalized for pneumonia symptoms five days after the onset of his illness, had no direct exposure to the market.

The most common symptoms at the onset of the illness were fever (98%), cough (76%), and fatigue (44%). Chest CT scans showed abnormalities in both lungs of all patients. Over half of the patients also presented with difficulty breathing, but that typically occurred later (eight days after illness onset). These symptoms are similar to SARS and MERS with two main exceptions – a lack of upper respiratory symptoms, such as sneezing and sore throat, and a lack of intestinal symptoms, such as diarrhea. The majority (68%) of the 41 patients were discharged as of January 22nd, 2020, but the infection resulted in the death of six (15%) of the patients.

It is important to note that, while the Huanan seafood market has been implicated to be the common exposure in all the cases, 13 of the 41 patients in this study had no link to the market. In an interview with Science Magazine, Dan Lucey, an infectious disease specialist from Georgetown University, offers evidence that the first case likely occurred in November 2019 and that the virus likely traveled into the Huanan Seafood Market before spreading from it.

 

Coronaviruses in Context

Another Decade, Another Coronavirus
NEJM | Perlman, S. | Jan 24, 2020.

We have only recently stepped into a new decade, and for the third time in three decades, we are dealing with a coronavirus outbreak. Similar to SARS and MERS, both of which are in the same family of virus, this novel coronavirus (2019-nCoV) was identified and characterized in the lab. Its genome has been sequenced, showing it to be 75-80% identical to SARS-CoV. These are critical first steps that have led to the development of assays for rapid detection of the virus in humans, but also provide foundational information necessary for the development of antiviral therapies and vaccines. While we are only in the beginning of the development of such treatments and none are available at this time, they will likely be critical in ultimately mitigating the spread of 2019-nCoV.

Uncertainty often elicits fear and anxiety, and in fact, fear was a major contributor to the economic and social consequences of the SARS epidemic in the early 2000s. In 2020, we are far better equipped to manage such outbreaks, but nonetheless fear has and will continue to play a role as we navigate through current situation. We should be hopeful that our experience in containing similar coronavirus outbreaks will lead to our success in reducing the transmission of this novel coronavirus.