We review aspects of the antibody response to SARS-CoV-2, the causative agent of the COVID-19 pandemic. The topics we cover are relevant to immunotherapy with plasma from recovered patients, monoclonal antibodies against the viral S-protein, and soluble forms of the receptor for the virus, angiotensin converting enzyme 2. The development of vaccines against SARS-CoV-2, an essential public health tool, will also be informed by an understanding of the antibody response in infected patients. Although virus-neutralizing antibodies are likely to protect, antibodies could potentially trigger immunopathogenic events in SARS-CoV-2-infected patients or enhance infection. An awareness of these possibilities may benefit clinicians and the developers of antibody-based therapies and vaccines.
Remdesivir is a nucleotide prodrug with in vitro and in vivo efficacy against coronaviruses. Here, we tested the efficacy of remdesivir treatment in a rhesus macaque model of SARS-CoV-2 infection.
To evaluate the effect of remdesivir treatment on SARS-CoV-2 disease outcome, we used the recently established rhesus macaque model of SARS-CoV-2 infection that results in transient lower respiratory tract disease. Two groups of six rhesus macaques were infected with SARS-CoV-2 and treated with intravenous remdesivir or an equal volume of vehicle solution once daily. Clinical, virological and histological parameters were assessed regularly during the study and at necropsy to determine treatment efficacy.
In contrast to vehicle-treated animals, animals treated with remdesivir did not show signs of respiratory disease and had reduced pulmonary infiltrates on radiographs. Virus titers in bronchoalveolar lavages were significantly reduced as early as 12hrs after the first treatment was administered. At necropsy on day 7 after inoculation, lung viral loads of remdesivir-treated animals were significantly lower and there was a clear reduction in damage to the lung tissue.
Therapeutic remdesivir treatment initiated early during infection has a clear clinical benefit in SARS-CoV-2-infected rhesus macaques. These data support early remdesivir treatment initiation in COVID-19 patients to prevent progression to severe pneumonia.
Editor’s note: ‘preprints’ are released prior to publication, and in many cases, prior to peer review.
Motivated by the rapid spread of COVID-19 in Mainland China, we use a global metapopulation disease transmission model to project the impact of travel limitations on the national and international spread of the epidemic. The model is calibrated based on internationally reported cases.
The model shows that at the start of the travel ban from Wuhan on 23 January 2020, most Chinese cities had already received many infected travelers. The travel quarantine of Wuhan delayed the overall epidemic progression by only 3 to 5 days in Mainland China, but has a more marked effect at the international scale, where case importations were reduced by nearly 80% until mid February. Modeling results also indicate that sustained 90% travel restrictions to and from Mainland China only modestly affect the epidemic trajectory unless combined with a 50% or higher reduction of transmission in the community.
The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets.
Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.
To estimate the serial interval of novel coronavirus (COVID-19) from information on 28 infector-infectee pairs, we collected dates of illness onset for primary cases (infectors) and secondary cases (infectees) from published research articles and case investigation reports. We estimated the median serial interval at 4.0 days (95% credible interval [CrI]: 3.1, 4.9). Limiting our data to only the most certain pairs, the median serial interval was estimated at 4.6 days (95% CrI: 3.5, 5.9).
The serial interval of COVID-19 is close to or shorter than its median incubation period. This suggests that a substantial proportion of secondary transmission may occur prior to illness onset.
EDITOR’S NOTE: The serial interval, in a communicable disease, refers to the time between successive cases in a chain of transmission.
SOURCE: International Journal of Infectious Diseases
This study aimed to assess the affective and cognitive risk perceptions in the general population of Middle East respiratory syndrome (MERS) during the 2015 MERS coronavirus (MERS-CoV) outbreak in South Korea and the influencing factors. Overall 4010 respondents (aged 19 years and over) from the general population during the MERS-CoV epidemic were included. The main outcome measures were (1) affective risk perception, (2) cognitive risk perception, and (3) trust in the government. Multivariate logistic regression models were used to identify factors (demographic, socioeconomic, area and political orientation) associated with risk perceptions.
Both affective and cognitive risk perceptions decreased as the MERS-CoV epidemic progressed. Proportions of affective risk perception were higher in all surveys and slowly decreased compared with cognitive risk perception over time. Females and lower self-reported household economic status respondents were more likely to perceive the affective risk. The older the adults, the higher the affective risk perception, but the lower the cognitive risk perception compared with younger adults. The respondents who had low trust in the government had higher affective and cognitive risk perceptions.
This study suggests that even if cognitive risk perception is dissolved, affective risk perception can continue during MERS-CoV epidemic. Risk perception associating factors (ie, gender, age and self-reported household economic status) appear to be noticeably different between affective and cognitive dimensions. It also indicates that trust in the government influences affective risk perception and cognitive risk perception.
SOURCE: BMJ Open
EDITOR’S NOTE: see ‘Risk as Feelings‘, which introduces the concept that emotions or mood often have a greater effect than rational thought does on the perception of risk.
With the outbreak of unknown pneumonia in Wuhan, China, in December 2019, a new coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), aroused the attention of the entire world. The current outbreak of infections with SARS-CoV-2 is termed Coronavirus Disease 2019 (COVID-19). The World Health Organization declared COVID-19 in China as a Public Health Emergency of International Concern. Two other coronavirus infections—SARS in 2002-2003 and Middle East Respiratory Syndrome (MERS) in 2012—both caused severe respiratory syndrome in humans. All 3 of these emerging infectious diseases leading to a global spread are caused by β-coronaviruses.
Although coronaviruses usually infect the upper or lower respiratory tract, viral shedding in plasma or serum is common. Therefore, there is still a theoretical risk of transmission of coronaviruses through the transfusion of labile blood products. Because more and more asymptomatic infections are being found among COVID-19 cases, considerations of blood safety and coronaviruses have arisen especially in endemic areas. In this review, we detail current evidence and understanding of the transmission of SARS-CoV, MERS–CoV, and SARS-CoV-2 through blood products as of February 10, 2020, and also discuss pathogen inactivation methods on coronaviruses.
SOURCE: Transfusion Medicine Reviews
Since its 2012 emergence, 2260 cases and 803 deaths due to Middle East respiratory syndrome coronavirus (MERS-CoV) have been reported to the World Health Organization. Most cases were due to transmission in healthcare settings, sometimes causing large outbreaks.
We analyzed epidemiologic and clinical data of laboratory-confirmed MERS-CoV cases from eleven healthcare-associated outbreaks in the Kingdom of Saudi Arabia and the Republic of Korea between 2015–2017. We quantified key epidemiological differences between outbreaks.
Twenty-five percent (n = 105/422) of MERS cases who acquired infection in a hospital setting were healthcare personnel. In multivariate analyses, age ≥65 (OR 4.8, 95%CI: 2.6–8.7) and the presence of underlying comorbidities (OR: 2.7, 95% CI: 1.3–5.7) were associated with increased mortality whereas working as healthcare personnel was protective (OR 0.07, 95% CI: 0.01–0.34).
At the start of these outbreaks, the reproduction number ranged from 1.0 to 5.7; it dropped below 1 within 2 to 6 weeks.
SOURCE: Scientific Reports
Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes a spectrum of respiratory illness, from asymptomatic to mild to fatal. MERS-CoV is transmitted sporadically from dromedary camels to humans and occasionally through human-to-human contact. Current epidemiologic evidence supports a major role in transmission for direct contact with live camels or humans with symptomatic MERS, but little evidence suggests the possibility of transmission from camel products or asymptomatic MERS cases. Because a proportion of case-patients do not report direct contact with camels or with persons who have symptomatic MERS, further research is needed to conclusively determine additional mechanisms of transmission, to inform public health practice, and to refine current precautionary recommendations.
SOURCE: Emerging Infectious Diseases
The three-month-old patient, in Xiaogan, Hubei, was hospitalized for 4 hours with fever, and the peripheral white blood cells were not high. A chest X-ray film showed a slightly thickened right lung texture, which seemed to be a little patchy. The (2019-nCoV) nucleic acid test was positive, and the 2019-nCoV infection diagnosis was established, which is consistent with the ordinary type. He was discharged after 15 days of active treatment. The child’s respiratory symptoms appeared later in the course and were milder.
The parents of the child tested positive for 2019-nCoV 7 days after the onset of the disease, suggesting that intra-family transmission is an important transmission route for 2019-nCoV infection. Although the patient’s throat swabs turned negative for 3 consecutive times, 2019-nCoV nucleic acid was still detected in the sputum and feces over the same period. The mother of the child had no fever and respiratory symptoms, but chest CT revealed exudative lesions in the left and right upper lungs, suggesting that pulmonary lesions can be seen in asymptomatic 2019-nCoV infection.
SOURCE: Chin J Pediatr