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A key unsolved question in the current coronavirus disease 2019 (COVID-19) pandemic is the duration of acquired immunity. Insights from infections with the four seasonal human coronaviruses might reveal common characteristics applicable to all human coronaviruses. We monitored healthy individuals for more than 35 years and determined that reinfection with the same seasonal coronavirus occurred frequently at 12 months after infection. The durability of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. Lessons from seasonal coronavirus infections in humans show that reinfections can occur within 12 months of initial infection, coupled with changes in levels of virus-specific antibodies.

A lockdown of people has been used as an efficient public health measure to fight against the exponential spread of the coronavirus disease (Covid-19) and allows the health system to manage the number of patients. The aim of this study (clinicaltrials.gov NCT00430818) was to evaluate the impact of both perceived stress aroused by Covid-19 and of emotions triggered by the lockdown situation on the individual experience of time. A large sample of the French population responded to a survey on their experience of the passage of time during the lockdown compared to before the lockdown. The perceived stress resulting from Covid-19 and stress at work and home were also assessed, as were the emotions felt. The results showed that people have experienced a slowing down of time during the lockdown. This time experience was not explained by the levels of perceived stress or anxiety, although these were considerable, but rather by the increase in boredom and sadness felt in the lockdown situation. The increased anger and fear of death only explained a small part of variance in the time judgment. The conscious experience of time therefore reflected the psychological difficulties experienced during lockdown and was not related to their perceived level of stress or anxiety.

A new coronavirus, called SARS-CoV-2, was identified in Wuhan, China, in December 2019. The SARS-CoV-2 spread very rapidly, causing a global pandemic, Coronavirus Disease 2019 (COVID-19). Older adults have higher peak of viral load and, especially those with comorbidities, had higher COVID-19-related fatality rates than younger adults. In this Perspective paper, we summarize current knowledge about SARS-CoV-2 and aging, in order to understand why older people are more affected by COVID-19. We discuss about the possibility that the so-called “immunosenescence” and “inflammaging” processes, already present in a fraction of frail older adults, could allow the immune escape of SARS-CoV-2 leading to COVID-19 serious complications. Finally, we propose to use geroscience approaches to the field of COVID-19.

Little research on coronaviruses has been conducted on wild animals in Africa. Here, we screened a wide range of wild animals collected in six provinces and five caves of Gabon between 2009 and 2015. We collected a total of 1867 animal samples (cave-dwelling bats, rodents, non-human primates and other wild animals). We explored the diversity of CoVs and determined the factors driving the infection of CoVs in wild animals. Based on a nested reverse transcription-polymerase chain reaction, only bats, belonging to the Hipposideros gigas (4/156), Hipposideros cf. ruber (13/262) and Miniopterus inflatus (1/249) species, were found infected with CoVs. We identified alphacoronaviruses in H. gigas and H . cf . ruber and betacoronaviruses in H. gigas . All Alphacoronavirus sequences grouped with Human coronavirus 229E (HCoV-229E). Ecological analyses revealed that CoV infection was significantly found in July and October in H. gigas and in October and November in H . cf ruber . The prevalence in the Faucon cave was significantly higher. Our findings suggest that insectivorous bats harbor potentially zoonotic CoVs; highlight a probable seasonality of the infection in cave-dwelling bats from the North-East of Gabon and pointed to an association between the disturbance of the bats’ habitat by human activities and CoV infection.

Background The mucus layer provides the first defense that keeps the epithelium free from microorganisms. However, the effect of the small intestinal mucus layer on pathogen invasion is still poorly understood, especially for swine enteric coronavirus. To better understand virus‒mucus layer‒intestinal epithelium interactions, here, we developed a porcine intestinal organoid mucus‒monolayer model under air‒liquid interface (ALI) conditions. Results We successfully established a differentiated intestinal organoid monolayer model comprising various differentiated epithelial cell types and a mucus layer under ALI conditions. Mass spectrometry analysis revealed that the mucus derived from the ALI monolayer shared a similar composition to that of the native small intestinal mucus. Importantly, our results demonstrated that the ALI monolayer exhibited lower infectivity of both TGEV and PEDV than did the submerged monolayer. To further confirm the impact of ALI mucus on coronavirus infection, mucus was collected from the ALI monolayer culture system and incubated with the viruses. These results indicated that ALI mucus treatment effectively reduced the infectivity of TGEV and PEDV. Additionally, Mucin 2 (Muc2), a major component of native small intestinal mucus, was found to be abundant in the mucus derived from the ALI monolayer, as determined by mass spectrometry analysis. Our study confirmed the potent antiviral activity of Muc2 against TGEV and PEDV infection. Considering the sialylation of Muc2 and the known sialic acid-binding activity of coronavirus, further investigations revealed that the sialic acid residues of Muc2 play a potential role in inhibiting coronavirus infection. Conclusions We established the porcine intestinal organoid mucus monolayer as a novel and valuable model for confirming the pivotal role of the small intestinal mucus layer in combating pathogen invasion. In addition, our findings highlight the significance of sialic acid modification of Muc2 in blocking coronavirus infections. This discovery opens promising avenues for the development of tailor-made drugs aimed at preventing porcine enteric coronavirus invasion.

A novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) recently emerged and is rapidly spreading in humans, causing COVID-19 1 , 2 . A key to tackling this pandemic is to understand the receptor recognition mechanism of the virus, which regulates its infectivity, pathogenesis and host range. SARS-CoV-2 and SARS-CoV recognize the same receptor—angiotensin-converting enzyme 2 (ACE2)—in humans 3 , 4 . Here we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 (engineered to facilitate crystallization) in complex with ACE2. In comparison with the SARS-CoV RBD, an ACE2-binding ridge in SARS-CoV-2 RBD has a more compact conformation; moreover, several residue changes in the SARS-CoV-2 RBD stabilize two virus-binding hotspots at the RBD–ACE2 interface. These structural features of SARS-CoV-2 RBD increase its ACE2-binding affinity. Additionally, we show that RaTG13, a bat coronavirus that is closely related to SARS-CoV-2, also uses human ACE2 as its receptor. The differences among SARS-CoV-2, SARS-CoV and RaTG13 in ACE2 recognition shed light on the potential animal-to-human transmission of SARS-CoV-2. This study provides guidance for intervention strategies that target receptor recognition by SARS-CoV-2. The crystal structure of the receptor-binding domain of the SARS-CoV-2 spike in complex with human ACE2, compared with the receptor-binding domain of SARS-CoV, sheds light on the structural features that increase its binding affinity to ACE2.

The current outbreak of coronavirus disease-2019 (COVID-19) poses unprecedented challenges to global health 1 . The new coronavirus responsible for this outbreak—severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—shares high sequence identity to SARS-CoV and a bat coronavirus, RaTG13 2 . Although bats may be the reservoir host for a variety of coronaviruses 3 , 4 , it remains unknown whether SARS-CoV-2 has additional host species. Here we show that a coronavirus, which we name pangolin-CoV, isolated from a Malayan pangolin has 100%, 98.6%, 97.8% and 90.7% amino acid identity with SARS-CoV-2 in the E, M, N and S proteins, respectively. In particular, the receptor-binding domain of the S protein of pangolin-CoV is almost identical to that of SARS-CoV-2, with one difference in a noncritical amino acid. Our comparative genomic analysis suggests that SARS-CoV-2 may have originated in the recombination of a virus similar to pangolin-CoV with one similar to RaTG13. Pangolin-CoV was detected in 17 out of the 25 Malayan pangolins that we analysed. Infected pangolins showed clinical signs and histological changes, and circulating antibodies against pangolin-CoV reacted with the S protein of SARS-CoV-2. The isolation of a coronavirus from pangolins that is closely related to SARS-CoV-2 suggests that these animals have the potential to act as an intermediate host of SARS-CoV-2. This newly identified coronavirus from pangolins—the most-trafficked mammal in the illegal wildlife trade—could represent a future threat to public health if wildlife trade is not effectively controlled. A newly identified coronavirus found in Malayan pangolins shares considerable sequence identity with SARS-CoV-2, which suggests that the latter may have originated from a recombination event involving SARS-related coronaviruses from bats and pangolins.

Key Points Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are zoonotic pathogens that can cause severe respiratory disease in humans. Although disease progression is fairly similar for SARS and MERS, the case fatality rate of MERS is much higher than that of SARS. Comorbidities have an important role in SARS and MERS. Several risk factors are associated with progression to acute respiratory distress syndrome (ARDS) in SARS and MERS cases, especially advanced age and male sex. For MERS, additional risk factors that are associated with severe disease include chronic conditions such as diabetes mellitus, hypertension, cancer, renal and lung disease, and co-infections. Although the ancestors of SARS-CoV and MERS-CoV probably circulate in bats, zoonotic transmission of SARS-CoV required an incidental amplifying host. Dromedary camels are the MERS-CoV reservoir from which zoonotic transmission occurs; serological evidence indicates that MERS-CoV-like viruses have been circulating in dromedary camels for at least three decades. Human-to-human transmission of SARS-CoV and MERS-CoV occurs mainly in health care settings. Patients do not shed large amounts of virus until well after the onset of symptoms, when patients are most probably already seeking medical care. Analysis of hospital surfaces after the treatment of patients with MERS showed the ubiquitous presence of infectious virus. Our understanding of the pathogenesis of SARS-CoV and MERS-CoV is still incomplete, but the combination of viral replication in the lower respiratory tract and an aberrant immune response is thought to have a crucial role in the severity of both syndromes. The severity of the diseases that are caused by emerging coronaviruses highlights the need to develop effective therapeutic measures against these viruses. Although several treatments for SARS and MERS (based on inhibition of viral replication with drugs or neutralizing antibodies, or on dampening the host response) have been identified in animal models and in vitro studies, efficacy data from human clinical trials are urgently required. Insights into coronavirus emergence, replication and pathogenesis gained from the SARS and MERS outbreaks have guided the development of preventive and therapeutic measures. In this Review, Munster and colleagues highlight recent achievements and areas that need to be addressed to combat novel coronaviruses. The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 marked the second introduction of a highly pathogenic coronavirus into the human population in the twenty-first century. The continuing introductions of MERS-CoV from dromedary camels, the subsequent travel-related viral spread, the unprecedented nosocomial outbreaks and the high case-fatality rates highlight the need for prophylactic and therapeutic measures. Scientific advancements since the 2002–2003 severe acute respiratory syndrome coronavirus (SARS-CoV) pandemic allowed for rapid progress in our understanding of the epidemiology and pathogenesis of MERS-CoV and the development of therapeutics. In this Review, we detail our present understanding of the transmission and pathogenesis of SARS-CoV and MERS-CoV, and discuss the current state of development of measures to combat emerging coronaviruses.

Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 2019 1 , 2 . Initial outbreaks in China involved 13.8% of cases with severe courses, and 6.1% of cases with critical courses 3 . This severe presentation may result from the virus using a virus receptor that is expressed predominantly in the lung 2 , 4 ; the same receptor tropism is thought to have determined the pathogenicity—but also aided in the control—of severe acute respiratory syndrome (SARS) in 2003 5 . However, there are reports of cases of COVID-19 in which the patient shows mild upper respiratory tract symptoms, which suggests the potential for pre- or oligosymptomatic transmission 6 – 8 . There is an urgent need for information on virus replication, immunity and infectivity in specific sites of the body. Here we report a detailed virological analysis of nine cases of COVID-19 that provides proof of active virus replication in tissues of the upper respiratory tract. Pharyngeal virus shedding was very high during the first week of symptoms, with a peak at 7.11 × 10 8  RNA copies per throat swab on day 4. Infectious virus was readily isolated from samples derived from the throat or lung, but not from stool samples—in spite of high concentrations of virus RNA. Blood and urine samples never yielded virus. Active replication in the throat was confirmed by the presence of viral replicative RNA intermediates in the throat samples. We consistently detected sequence-distinct virus populations in throat and lung samples from one patient, proving independent replication. The shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (and by day 14 in all patients), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild illness of the upper respiratory tract. The confirmation of active virus replication in the upper respiratory tract has implications for the containment of COVID-19. Detailed virological analysis of nine cases of coronavirus disease 2019 (COVID-19) provides proof of active replication of the SARS-CoV-2 virus in tissues of the upper respiratory tract.

Scientists are piecing together how SARS-CoV-2 operates, where it came from and what it might do next — but pressing questions remain about the source of COVID-19. Scientists are piecing together how SARS-CoV-2 operates, where it came from and what it might do next — but pressing questions remain about the source of COVID-19.