Journal: Nature medicine
We identified seasonal human coronaviruses, influenza viruses and rhinoviruses in exhaled breath and coughs of children and adults with acute respiratory illness. Surgical face masks significantly reduced detection of influenza virus RNA in respiratory droplets and coronavirus RNA in aerosols, with a trend toward reduced detection of coronavirus RNA in respiratory droplets. Our results indicate that surgical face masks could prevent transmission of human coronaviruses and influenza viruses from symptomatic individuals.
We report temporal patterns of viral shedding in 94 patients with laboratory-confirmed COVID-19 and modeled COVID-19 infectiousness profiles from a separate sample of 77 infector-infectee transmission pairs. We observed the highest viral load in throat swabs at the time of symptom onset, and inferred that infectiousness peaked on or before symptom onset. We estimated that 44% (95% confidence interval, 25-69%) of secondary cases were infected during the index cases' presymptomatic stage, in settings with substantial household clustering, active case finding and quarantine outside the home. Disease control measures should be adjusted to account for probable substantial presymptomatic transmission.
The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS)-CoV underscores the threat of cross-species transmission events leading to outbreaks in humans. Here we examine the disease potential of a SARS-like virus, SHC014-CoV, which is currently circulating in Chinese horseshoe bat populations. Using the SARS-CoV reverse genetics system, we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone. The results indicate that group 2b viruses encoding the SHC014 spike in a wild-type backbone can efficiently use multiple orthologs of the SARS receptor human angiotensin converting enzyme II (ACE2), replicate efficiently in primary human airway cells and achieve in vitro titers equivalent to epidemic strains of SARS-CoV. Additionally, in vivo experiments demonstrate replication of the chimeric virus in mouse lung with notable pathogenesis. Evaluation of available SARS-based immune-therapeutic and prophylactic modalities revealed poor efficacy; both monoclonal antibody and vaccine approaches failed to neutralize and protect from infection with CoVs using the novel spike protein. On the basis of these findings, we synthetically re-derived an infectious full-length SHC014 recombinant virus and demonstrate robust viral replication both in vitro and in vivo. Our work suggests a potential risk of SARS-CoV re-emergence from viruses currently circulating in bat populations.
Several coronavirus disease 2019 (COVID-19) vaccines are currently in human trials. In June 2020, we surveyed 13,426 people in 19 countries to determine potential acceptance rates and factors influencing acceptance of a COVID-19 vaccine. Of these, 71.5% of participants reported that they would be very or somewhat likely to take a COVID-19 vaccine, and 61.4% reported that they would accept their employer’s recommendation to do so. Differences in acceptance rates ranged from almost 90% (in China) to less than 55% (in Russia). Respondents reporting higher levels of trust in information from government sources were more likely to accept a vaccine and take their employer’s advice to do so.
The clinical features and immune responses of asymptomatic individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been well described. We studied 37 asymptomatic individuals in the Wanzhou District who were diagnosed with RT-PCR-confirmed SARS-CoV-2 infections but without any relevant clinical symptoms in the preceding 14 d and during hospitalization. Asymptomatic individuals were admitted to the government-designated Wanzhou People’s Hospital for centralized isolation in accordance with policy1. The median duration of viral shedding in the asymptomatic group was 19 d (interquartile range (IQR), 15-26 d). The asymptomatic group had a significantly longer duration of viral shedding than the symptomatic group (log-rank P = 0.028). The virus-specific IgG levels in the asymptomatic group (median S/CO, 3.4; IQR, 1.6-10.7) were significantly lower (P = 0.005) relative to the symptomatic group (median S/CO, 20.5; IQR, 5.8-38.2) in the acute phase. Of asymptomatic individuals, 93.3% (28/30) and 81.1% (30/37) had reduction in IgG and neutralizing antibody levels, respectively, during the early convalescent phase, as compared to 96.8% (30/31) and 62.2% (23/37) of symptomatic patients. Forty percent of asymptomatic individuals became seronegative and 12.9% of the symptomatic group became negative for IgG in the early convalescent phase. In addition, asymptomatic individuals exhibited lower levels of 18 pro- and anti-inflammatory cytokines. These data suggest that asymptomatic individuals had a weaker immune response to SARS-CoV-2 infection. The reduction in IgG and neutralizing antibody levels in the early convalescent phase might have implications for immunity strategy and serological surveys.
Temperatures that deviate from the long-term local norm affect human health, and are projected to become more frequent as the global climate changes1. There are limited data on how such anomalies affect deaths from injuries. In the present study, we used data on mortality and temperature over 38 years (1980-2017) in the contiguous USA and formulated a Bayesian spatio-temporal model to quantify how anomalous temperatures, defined as deviations of monthly temperature from the local average monthly temperature over the entire analysis period, affect deaths from unintentional (transport, falls and drownings) and intentional (assault and suicide) injuries, by age group and sex. We found that a 1.5 °C anomalously warm year, as envisioned under the Paris Climate Agreement2, would be associated with an estimated 1,601 (95% credible interval 1,430-1,776) additional injury deaths. Of these additional deaths, 84% would occur in males, mostly in adolescence to middle age. These would comprise increases in deaths from drownings, transport, assault and suicide, offset partly by a decline in deaths from falls in older ages. The findings demonstrate the need for targeted interventions against injuries during periods of anomalously warm temperatures, especially as these episodes are likely to increase with global climate change.
In Italy, 128,948 confirmed cases and 15,887 deaths of people who tested positive for SARS-CoV-2 were registered as of 5 April 2020. Ending the global SARS-CoV-2 pandemic requires implementation of multiple population-wide strategies, including social distancing, testing and contact tracing. We propose a new model that predicts the course of the epidemic to help plan an effective control strategy. The model considers eight stages of infection: susceptible (S), infected (I), diagnosed (D), ailing (A), recognized ®, threatened (T), healed (H) and extinct (E), collectively termed SIDARTHE. Our SIDARTHE model discriminates between infected individuals depending on whether they have been diagnosed and on the severity of their symptoms. The distinction between diagnosed and non-diagnosed individuals is important because the former are typically isolated and hence less likely to spread the infection. This delineation also helps to explain misperceptions of the case fatality rate and of the epidemic spread. We compare simulation results with real data on the COVID-19 epidemic in Italy, and we model possible scenarios of implementation of countermeasures. Our results demonstrate that restrictive social-distancing measures will need to be combined with widespread testing and contact tracing to end the ongoing COVID-19 pandemic.
We use COVID-19 case and mortality data from 1 February 2020 to 21 September 2020 and a deterministic SEIR (susceptible, exposed, infectious and recovered) compartmental framework to model possible trajectories of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the effects of non-pharmaceutical interventions in the United States at the state level from 22 September 2020 through 28 February 2021. Using this SEIR model, and projections of critical driving covariates (pneumonia seasonality, mobility, testing rates and mask use per capita), we assessed scenarios of social distancing mandates and levels of mask use. Projections of current non-pharmaceutical intervention strategies by state-with social distancing mandates reinstated when a threshold of 8 deaths per million population is exceeded (reference scenario)-suggest that, cumulatively, 511,373 (469,578-578,347) lives could be lost to COVID-19 across the United States by 28 February 2021. We find that achieving universal mask use (95% mask use in public) could be sufficient to ameliorate the worst effects of epidemic resurgences in many states. Universal mask use could save an additional 129,574 (85,284-170,867) lives from September 22, 2020 through the end of February 2021, or an additional 95,814 (60,731-133,077) lives assuming a lesser adoption of mask wearing (85%), when compared to the reference scenario.
Although COVID-19 is most well known for causing substantial respiratory pathology, it can also result in several extrapulmonary manifestations. These conditions include thrombotic complications, myocardial dysfunction and arrhythmia, acute coronary syndromes, acute kidney injury, gastrointestinal symptoms, hepatocellular injury, hyperglycemia and ketosis, neurologic illnesses, ocular symptoms, and dermatologic complications. Given that ACE2, the entry receptor for the causative coronavirus SARS-CoV-2, is expressed in multiple extrapulmonary tissues, direct viral tissue damage is a plausible mechanism of injury. In addition, endothelial damage and thromboinflammation, dysregulation of immune responses, and maladaptation of ACE2-related pathways might all contribute to these extrapulmonary manifestations of COVID-19. Here we review the extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.
The COVID-19 pandemic has shown a markedly low proportion of cases among children1-4. Age disparities in observed cases could be explained by children having lower susceptibility to infection, lower propensity to show clinical symptoms or both. We evaluate these possibilities by fitting an age-structured mathematical model to epidemic data from China, Italy, Japan, Singapore, Canada and South Korea. We estimate that susceptibility to infection in individuals under 20 years of age is approximately half that of adults aged over 20 years, and that clinical symptoms manifest in 21% (95% credible interval: 12-31%) of infections in 10- to 19-year-olds, rising to 69% (57-82%) of infections in people aged over 70 years. Accordingly, we find that interventions aimed at children might have a relatively small impact on reducing SARS-CoV-2 transmission, particularly if the transmissibility of subclinical infections is low. Our age-specific clinical fraction and susceptibility estimates have implications for the expected global burden of COVID-19, as a result of demographic differences across settings. In countries with younger population structures-such as many low-income countries-the expected per capita incidence of clinical cases would be lower than in countries with older population structures, although it is likely that comorbidities in low-income countries will also influence disease severity. Without effective control measures, regions with relatively older populations could see disproportionally more cases of COVID-19, particularly in the later stages of an unmitigated epidemic.