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Conditionals in Mandarin can be expressed by conjunctive sentences with no overt conditional connective (Type 1: P, Q) or with a conditional connective (CC) in the antecedent (Type 2: CC P, Q) and/or a conditional particle (CP) in the consequent (Type 3: (CC) P, CP Q). In this paper, we focus on jiu-conditionals (Type 3) without CCs. We assume that jiu in Mandarin is ambiguous between jiu 1 (unstressed, nonexclusive, left associating) and jiu 2 (stressed, exclusive, right associating), and that jiu-conditionals involve jiu 1 without exclusive force. We argue against a conditional conjunction analysis of jiu-conditionals and for a scalar analysis of jiu in conditionals as well as in temporal or spatial use. Furthermore, we present what we believe is the first uniform pragmatic account of Mandarin conditional constructions across Types 1–3: it is the subjective (non)veridicality property of the first clause P that determines the reading of the sentence P, Q. If P is entailed or presupposed, we get a conjunctive reading; if P is not entailed or presupposed, that is, if it is nonveridical, we get a conditional reading. Devices triggering the conditional reading include CCs or negative polarity items in the antecedent, as well as the broader discourse context or world knowledge.

Antilocality effects provide strong evidence for expectation-based sentence parsing models. Previous discussion of the antilocality effect, however, largely focused on the argument-verb dependencies in verb-final constructions, for which a memory retrieval-based account has been argued to be equally adequate. To test whether the principles of expectation/memory-based accounts hold for a wider range of dependencies, we report on two self-paced reading experiments that compared two different determiners in German: the morphologically complex determiner

The concept of bias is familiar to linguists primarily from the literature on questions. Following the work of Giannakidou and Mari (Truth and Veridicality in Grammar and Thought: Modality, Mood, and Propositional Attitudes, University of Chicago Press, Chicago, 2021), we assume “nonveridical equilibrium” (implying that p and ¬p as equal possibilities) to be the default for epistemic modals, questions and conditionals. The equilibrium of conditionals, as that of questions, can be manipulated to produce bias (i.e., reduced or higher speaker commitment). In this paper, we focus on three kinds of modal elements in German that create bias in conditionals and questions: the adverb wirklich ‘really’, the modal verb sollte ‘should’, and conditional connectives such as falls ‘if/in case’. We conducted two experiments collecting participants’ inference about speaker commitment in different manipulations, Experiment 1 on sollte/wirklich in ob-questions and wenn-conditionals, and Experiment 2 on sollte/wirklich in wenn/falls/V1-conditionals. Our findings are that both ob-questions and falls-conditionals express reduced speaker commitment about the modified (antecedent) proposition in comparison to wenn-conditionals, which did not differ from V1-conditionals. In addition, sollte/wirklich in the antecedent of conditionals both create negative bias about the antecedent proposition. Our studies are among the first that deal with bias in conditionals (in comparison to questions) and contribute to furthering our understanding of bias.

Negation is a universal component of human language; polarity sensitivity (i.e., lexical distributional constraints in relation to negation) is arguably so while being pervasive across languages. Negation has long been a field of inquiry in psychological theories and experiments of reasoning, which inspired many follow-up studies of negation and negation-related phenomena in psycholinguistics. In generative theoretical linguistics, negation and polarity sensitivity have been extensively studied, as the related phenomena are situated at the interfaces of syntax, semantics and pragmatics, and are thus extremely revealing about the architecture of grammar. With the now long tradition of research on negation and polarity in psychology and psycholinguistics, and the emerging field of experimental semantics and pragmatics, a multitude of interests and experimental paradigms have emerged which call for re-evaluations and further development and integration. This special issue contains a collection of 16 research articles on the processing of negation and negation-related phenomena including polarity items, questions, conditionals, and irony, using a combination of behavioral (e.g., rating, reading, eye-tracking and sentence completion) and neuroimaging techniques (e.g., EEG). They showcase the processing of negation and polarity with or without context, in various languages and across different populations (adults, typically developing and ADHD children). The integration of multiple theoretical and empirical perspectives in this collection provides new insights, methodological advances and directions for future research. Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659 Humboldt-Universität zu Berlin (1034)

Existing work on the acquisition of polarity-sensitive expressions (PSIs) suggests that children show an early sensitivity to the restricted distribution of negative polarity items (NPIs), but may be delayed in the acquisition of positive polarity items (PPIs). However, past studies primarily targeted PSIs that are highly frequent in children’s language input. In this paper, we report an experimental investigation on children’s comprehension of two NPIs and two PPIs in German. Based on corpus data indicating that the four tested PSIs are present in child-directed speech but rare in young children’s utterances, we conducted an auditory rating task with adults and 11- to 12-year-old children. The results demonstrate that, even at 11–12 years of age, children do not yet show a completely target-like comprehension of the investigated PSIs. While they are adult-like in their responses to one of the tested NPIs, their responses did not demonstrate a categorical distinction between licensed and unlicensed PSI uses for the other tested expressions. The effect was led by a higher acceptance of sentences containing unlicensed PSIs, indicating a lack of awareness for their distributional restrictions. The results of our study pose new questions for the developmental time scale of the acquisition of polarity items. Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659 Universität Osnabrück (3158)

Domestic cats, an important companion animal, can be infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This has aroused concern regarding the ability of domestic cats to spread the virus that causes coronavirus disease 2019. We systematically demonstrated the pathogenesis and transmissibility of SARS-CoV-2 in cats. Serial passaging of the virus between cats dramatically attenuated the viral transmissibility, likely owing to variations of the amino acids in the receptor-binding domain sites of angiotensin-converting enzyme 2 between humans and cats. These findings provide insight into the transmissibility of SARS-CoV-2 in cats and information for protecting the health of humans and cats.

Coronavirus disease 2019 (COVID-19), which is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. It is unclear whether convalescing patients have a risk of reinfection. We generated a rhesus macaque model of SARS-CoV-2 infection that was characterized by interstitial pneumonia and systemic viral dissemination mainly in the respiratory and gastrointestinal tracts. Rhesus macaques reinfected with the identical SARS-CoV-2 strain during the early recovery phase of the initial SARS-CoV-2 infection did not show detectable viral dissemination, clinical manifestations of viral disease, or histopathological changes. Comparing the humoral and cellular immunity between primary infection and rechallenge revealed notably enhanced neutralizing antibody and immune responses. Our results suggest that primary SARS-CoV-2 exposure protects against subsequent reinfection in rhesus macaques.

In the literature on relative clauses (e. g. Alexiadou et al.2000: 4), it is occasionally observed that the German complex definite determiner d-jenige (roughly ‘the one’) must share company with a restrictive relative clause, in contrast to bare determiners der/die/das (Roehrs2006: 213–215; Gunkel2006; Gunkel2007). Previous works such as Sternefeld (2008: 378–379) and Blümel (2011) treat the relative clause as a complement of D to account for its mandatory occurrence. While such syntactic analyses have intuitive appeal, they pose problems for a compositional semantic analysis. The goal of this paper is twofold. First, we report on two rating studies providing empirical evidence for the obligatoriness of relative clauses in German DPs introduced by the complex determiner d-jenige. Secondly, following Simonenko (2014, 2015), we provide an analysis of the phenomenon at the syntax-semantics interface that captures familiar (Blümel2011) as well as novel related observations. Particularly, the analysis accounts for the facts that postnominal modifiers can figure in d-jenige-DPs and that the element can have anaphoric demonstrative pronominal uses.

Myocardial infarction arises from an excessive or prolonged inflammatory response, leading to ventricular remodeling or impaired cardiac function. Macrophages exhibit different polarization types associated with inflammation both at steady state and after myocardial infarction. Exosomal miR-146a-5p has been identified as an important molecule in the cardiovascular field in recent years. However, the effect of cardiomyocyte-derived exosomal miR-146a-5p on macrophages has not yet been elucidated. Initially, we found that exosomes with low expression of miR-146a-5p derived from myocardial infarction tissues modulated macrophage polarization. To determine whether cardiomyocyte-derived exosomal miR-146a-5p mediated macrophage polarization, we treated macrophages with exosomes rich in miR-146a-5p collected from neonatal mouse cardiomyocytes. The effects of exosomal miR-146a-5p on macrophage polarization were measured using RT-qPCR, transwell assays, and western blotting. The results showed that the increased expression of miR-146a-5p promoted M1 macrophage polarization, inhibited M2 macrophage polarization, and increased the expression of VEGFA. However, the decreased expression of exosomalmiR-146a-5p showed the opposite trends. Interestingly, in contrast to treatment with the solitary miR-146a-5p mimic, exosomal miR-146a-5p derived from neonatal mouse cardiomyocytes reduced TNFα and iNOS expression. In addition, when macrophages were activated by the miR-146a-5p mimic or exosomal miR-146a-5p, the expression of TNF receptor-associated factor 6 (TRAF6), a target gene of miR-146a-5p, was reduced significantly. Taken together, these findings indicate that exosomal miR-146a-5p derived from cardiomyocytes could stimulate M1 macrophage polarization to induce an inflammatory reaction, while targeting TRAF6, exerting an anti-inflammatory effect. Exosomal miR-146a-5p plays important roles in macrophages, illuminating a novel potential therapeutic target in myocardial infarction.

Comprehending conditional statements is fundamental for hypothetical reasoning about situations. However, the online comprehension of conditional statements containing different conditional connectives is still debated. We report two self-paced reading experiments on German conditionals presenting the conditional connectives wenn (‘if’) and nur wenn (‘only if’) in identical discourse contexts. In Experiment 1, participants read a conditional sentence followed by the confirmed antecedent p and the confirmed or negated consequent q. The final, critical sentence was presented word by word and contained a positive or negative quantifier (ein/kein ‘one/no’). Reading times of the two quantifiers did not differ between the two conditional connectives. In Experiment 2, presenting a negated antecedent, reading times for the critical positive quantifier (ein) did not differ between conditional connectives, while reading times for the negative quantifier (kein) were shorter for nur wenn than for wenn. The results show that comprehenders form distinct predictions about discourse continuations due to differences in the lexical semantics of the tested conditional connectives, shedding light on the role of conditional connectives in the online interpretation of conditionals in general.

In natural language conversations, speakers often communicate ‘if and only if’ when they say ‘if’. The reasons why in some circumstances, yet not all, conditionals receive a biconditional interpretation remain under investigation. Von Fintel (2001) proposed an account where the interpretation of a conditional (“if p, then q”) is predicted to depend on the focus of the conversation which may either lie on the conditions that make the consequent, q, true or on the consequences following when the antecedent, p, is true. To test this account, we present two novel behavioral experiments with non-text based stimuli that take advantage of participants’ intuitive understanding of physics. We find some supporting evidence for the tested account that is not conclusive but suggests that other aspects, like the nature of potential alternative causes for the consequent to become true (e.g., with or w/o the influence of an external variable), also play a role for the interpretation of the conditional.

In this paper, the meaning and processing of the German conditional connectives (CCs) such as wenn ‘if’ and nur wenn ‘only if’ are investigated. In Experiment 1, participants read short scenarios containing a conditional sentence (i.e., If P, Q.) with wenn/nur wenn ‘if/only if’ and a confirmed or negated antecedent (i.e., P/not-P), and subsequently completed the final sentence about Q (with or without negation). In Experiment 2, participants rated the truth or falsity of the consequent Q after reading a conditional sentence with wenn or nur wenn and a confirmed or negated antecedent (i.e., If P, Q. P/not-P. // Therefore, Q?). Both experiments showed that neither wenn nor nur wenn were interpreted as biconditional CCs. Modus Ponens (If P, Q. P. // Therefore, Q) was validated for wenn, whereas it was not validated in the case of nur wenn. While Denial of the Antecedent (If P, Q. not-P. // Therefore, not-Q.) was validated in the case of nur wenn, it was not validated for wenn. The same method was used to test wenn vs. unter der Bedingung, dass ‘on condition that’ in Experiment 3, and wenn vs. vorausgesetzt, dass ‘provided that’ in Experiment 4. Experiment 5, using Affirmation of the Consequent (If P, Q. Q. // Therefore, P.) to test wenn vs. nur wenn replicated the results of Experiment 2. Taken together, the results show that in German, unter der Bedingung, dass is the most likely candidate of biconditional CCs whereas all others are not biconditional. The findings, in particular of nur wenn not being semantically biconditional, are discussed based on available formal analyses of conditionals.

This study was designed to investigate the sensitivity of SARS‐CoV‐2 to different temperatures, to provide basic data and a scientific basis for the control of COVID‐19 epidemic. The virus was dispersed in 1 mL basal DMEM medium at a final concentration of 103.2 TCID50/mL and then incubated at 4, 22, 30, 35, 37, 38, 39 and 40°C for up to 5 days. The infectivity of residual virus was titrated using the Vero E6 cell line. The results showed that the virus remained viable for 5 days at 4°C, and for 1 day only at 22 and 30°C. We found that the infectivity of the virus was completely lost after less than 12 hours at 37, 38 and 39°C, while at 40°C, the inactivation time of the virus was rapidly reduced to 6 hours. We show that SARS‐CoV‐2 is sensitive to heat, is more stable at lower temperatures than higher temperature, remains viable for longer at lower temperatures, and loses viability rapidly at higher temperatures.

This study primarily explored the role of paeonol in doxorubicin (DOX)-induced chronic heart failure (CHF), considering the cardioprotective effect of paeonol on an epirubicin-induced cardiac injury.DOX-induced CHF-modeled rats were treated with paeonol. Cardiac function and myocardial damage in rats were evaluated by using the multifunction instrument, and the histopathology, apoptosis, and the expression of miR-21-5p and S-phase kinase-associated protein 2 (SKP2) in myocardium were detected. The target gene of miR-21-5p was confirmed by a dual-luciferase reporter assay. After the required transfection or paeonol treatment, the viability, apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) of the DOX-induced cardiomyocytes were determined. Reverse-transcription quantitative-PCR (RT-qPCR) and Western blot were performed to quantify the expressions of miR-21-5p, SKP2, and apoptosis-related factors.Paeonol improved cardiac function and also ameliorated the cardiac damage of CHF-modeled rats, where the downregulation of abnormally elevated myocardial damage markers, including brain natriuretic peptide, lactate dehydrogenase, renin, angiotensin II, aldosterone, and endothelin 1, was observed. Paeonol alleviated the histopathological injury and suppressed the apoptosis in CHF-modeled rats, inhibited miR-21-5p expression, and upregulated SKP2 expressionPaeonol shows a cardioprotective effect on DOX-induced CHF

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has spread across the world and impacted global healthcare systems. For clinical patients, COVID-19 not only induces pulmonary lesions but also affects extrapulmonary organs. An ideal animal model that mimics COVID-19 in humans in terms of the induced systematic lesions is urgently needed. Here, we report that Syrian hamster is highly permissive to SARS-CoV-2 and exhibit diffuse alveolar damage and induced extrapulmonary multi-organs damage, including spleen, lymph nodes, different segments of alimentary tract, kidney, adrenal gland, ovary, vesicular gland and prostate damage, at 3–7 days post inoculation (dpi), based on qRT-PCR,in situhybridization and immunohistochemistry detection. Notably, the adrenal gland is a novel target organ, with abundant viral RNA and antigen expression detected, accompanied by focal to diffuse inflammation. Additionally, viral RNA was also detected in the corpus luteum of the ovary, vesicular gland and prostate. Focal lesions in liver, gallbladder, myocardium, and lymph nodes were still present at 18 dpi, suggesting potential damage after disease. Our findings illustrate systemic histological observations and the viral RNA and antigen distribution in infected hamsters during disease and convalescence to recapitulate those observed in humans with COVID-19, providing helpful data to the pathophysiologic characterization of SARS-CoV-2-induced systemic disease and the development of effective treatment strategies.

The interpretation of conditionals is a long but ongoing debate in linguistics (cf. von Fintel 2007, 2011, 2012). In this paper, we focus on the meaning contribution of conditional connectives (CCs). According to Kratzer (1986, 1991), the English CC if has no semantics on its own and if-clauses are used to restrict modal or generic frequency operators. The restrictor analysis of conditionals and CCs has inspired many insightful follow-up studies through which it becomes clear that the interpretation of conditional sentences is subject to a process of semantic and pragmatic modulation. However, the role of CCs in the modulation process remains far from clear in the current literature, although CCs can influence the interpretation of conditional sentences in various ways. In this paper, we will argue with distributional observations and experimental evidence that Mandarin CCs can express different degrees of speaker commitment (Giannakidou and Mari 2015) towards the antecedent proposition, as non-at-issue meaning.

Numerical concepts are an integral part of everyday conversation and communication. Expressions relating to numbers in natural language can have precise or imprecise interpretations. While the precise interpretation most prominently appears in mathematical contexts, the imprecise interpretation seems to arise when numbers (as quantities) are applied to real world contexts (e.g., the rope is 50 m long). Earlier literature shows that the (im)precise interpretation can depend on different factors, e.g., the kind of approximator a numeral appears with (precise vs. imprecise, e.g., exactly vs. roughly) or the kind of numeral itself (round vs. non-round, e.g., 50 vs. 47). We report on a corpus-linguistic study and a rating experiment of English numerical expressions. The results confirm the effects of both factors and additionally an effect of the kind of unit (discrete vs. continuous, e.g., people vs. meters). This shows the contextual variability in the interpretation of numerical concepts in natural language.

It is impossible to talk about human cognition without talking about concepts—there simply is no human cognition without concepts. Concepts form an abstraction of reality that is central to the functioning of the human mind. Conceptual knowledge (of e.g., APPLE, LOVE and BEFORE) is crucial for us to categorize, understand, and reason about the world. Only equipped with concepts and words for them can we successfully communicate and carry out actions. But what exactly are concepts? How are concepts acquired? How does the human mind use concepts? In this introduction chapter, we elaborate on these questions (i.e., representation, learning, application), and provide summaries of the seven individual chapters in the volume, which from different scientific disciplines relate to one or the other of the questions.

Influenza A virus may circulate simultaneously with the SARS-CoV-2 virus, leading to more serious respiratory diseases during this winter. However, the influence of these viruses on disease outcome when both influenza A and SARS-CoV-2 are present in the host remains unclear. Using a mammalian model, sequential infection was performed in ferrets and in K18-hACE2 mice, with SARS-CoV-2 infection following H1N1. We found that co-infection with H1N1 and SARS-CoV-2 extended the duration of clinical manifestation of COVID-19, and enhanced pulmonary damage, but reduced viral shedding of throat swabs and viral loads in the lungs of ferrets. Moreover, mortality was increased in sequentially infected mice compared with single-infection mice. Compared with single-vaccine inoculation, co-inoculation of PiCoVacc (a SARS-CoV-2 vaccine) and the flu vaccine showed no significant differences in neutralizing antibody titers or virus-specific immune responses. Combined immunization effectively protected K18-hACE2 mice against both H1N1 and SARS-CoV-2 infection. Our findings indicated the development of systematic models of co-infection of H1N1 and SARS-CoV-2, which together notably enhanced pneumonia in ferrets and mice, as well as demonstrated that simultaneous vaccination against H1N1 and SARS-CoV-2 may be an effective prevention strategy for the coming winter.

Objectives Right ventricular (RV) failure occurring after left ventricular assist device (LVAD) implantation is associated with increased mortality. Purpose We sought to determine whether RV strain by echocardiography predicts outcomes following LVAD. Methods Consecutive patients who underwent continuous flow LVAD placement at our clinic between February 2007 and October 2018 were included. Patients with complex congenital heart disease and arrhythmogenic right ventricular cardiomyopathy were excluded. Baseline characteristics, pre-operative hemodynamic catheterization (1 week) transthoracic echocardiography (1 month) measurements were obtained from the medical record. Speckle tracking RV free wall longitudinal 2D strain was measured using TomTec Imaging System. Univariate and multivariable analysis performed to identify predictors of mortality following LVAD. Results The study group was comprised of 323 patients (mean age 60.8±11.5, 79.9% male) of which 256 had adequate image quality for RV strain. RV strain was impaired in most patients (mean −11.7±3.47). RV strain of −8.1% was identified as predictive of poor outcomes. RV strain did not correlate with other measures of RV dysfunction including pulmonary artery pulsatility index (PAPi) and RVFAC. After adjusting for PAPi, RA pressure, and clinical cumulative risk scores (Matthews, Kormos and Lietz-Miller) impaired RV free wall longitudinal strain (OR: 1.14; 95% CI: 1.01–1.29, p=0.025), tricuspid regurgitation (by vena contracta width (TRvc) (OR: 1.19; 95% CI: 1.05–1.36, p=:0.0021) and smaller LVEDD (OR: 0.95; 95% CI: 0.92–0.99, p:0.023) predicted 30-day all-cause mortality and RV failure. Decreased RV free wall strain also predicted peri-operative mortality (22.58% vs. 4.89%, p=0.0003) and prolonged inotropic support (247.0.±277.4 vs. 122.8±139.3, p=0.024). Conclusions RV free wall strain is a non-invasive independent predictor of 30-day adverse outcomes (RV failure or all-cause mortality) Routine measurement of RV free strain may identify those patients at highest risk for early and long term mortality following LVAD. Funding Acknowledgement Type of funding source: None

Aims Little is known about the relative importance of body volume and haemodynamic parameters in the development of worsening of renal function in acutely decompensated heart failure (ADHF). To study the relationship between haemodynamic parameters, body water content and worsening of renal function in patients with heart failure with reduced ejection fraction (HFrEF) hospitalised for ADHF. Methods and results This prospective observational study involved 51 consecutive patients with HFrEF (age: 73±14 years, male: 60%, left ventricular ejection fraction: 33.3%±9.9%) hospitalised for ADHF. Echocardiographic-determined haemodynamic parameters and body volume determined using a bioelectric impedance analyser were serially obtained. All patients received intravenous furosemide 160 mg/day for 3 days. There was a mean weight loss of 3.95±2.82 kg (p Conclusions Normal body volume and lower serum BNP on admission were associated with worsening of renal function in patients with HFrEF hospitalised for ADHF.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly transmitted through the respiratory route, but potential extra-respiratory routes of SARS-CoV-2 transmission remain uncertain. Here we inoculated five rhesus macaques with 1 × 106 TCID50 of SARS-CoV-2 conjunctivally (CJ), intratracheally (IT), and intragastrically (IG). Nasal and throat swabs collected from CJ and IT had detectable viral RNA at 1–7 days post-inoculation (dpi). Viral RNA was detected in anal swabs from only the IT group at 1–7 dpi. Viral RNA was undetectable in tested swabs and tissues after intragastric inoculation. The CJ infected animal had a higher viral load in the nasolacrimal system than the IT infected animal but also showed mild interstitial pneumonia, suggesting distinct virus distributions. This study shows that infection via the conjunctival route is possible in non-human primates; further studies are necessary to compare the relative risk and pathogenesis of infection through these different routes in more detail., SARS-CoV-2 mainly transmits via respiratory droplets. Here Deng et al. show that SARS-CoV-2 can infect rhesus macaques via ocular conjunctival inoculation.

We simulated 3 transmission modes, including close-contact, respiratory droplets and aerosol routes, in the laboratory. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be highly transmitted among naive human angiotensin-converting enzyme 2 (hACE2) mice via close contact because 7 of 13 naive hACE2 mice were SARS-CoV-2 antibody seropositive 14 days after being introduced into the same cage with 3 infected-hACE2 mice. For respiratory droplets, SARS-CoV-2 antibodies from 3 of 10 naive hACE2 mice showed seropositivity 14 days after introduction into the same cage with 3 infected-hACE2 mice, separated by grids. In addition, hACE2 mice cannot be experimentally infected via aerosol inoculation until continued up to 25 minutes with high viral concentrations., Severe acute respiratory syndrome coronavirus 2 can be highly transmitted among naive angiotensin-converting enzyme 2 mice via close-contact spreading by respiratory droplets. However, these mice cannot be experimentally infected through aerosol inoculation unless it is continued for 25 minutes with a high viral concentration.

Background: Since December 2019, an outbreak of the Corona Virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) in Wuhan, China, has become a public health emergency of international concern. The high fatality of aged cases caused by SARS-CoV-2 was a need to explore the possible age-related phenomena with non-human primate models. Methods: Three 3-5 years old and two 15 years old rhesus macaques were intratracheally infected with SARS-CoV-2, and then analyzed by clinical signs, viral replication, chest X-ray, histopathological changes and immune response. Results: Viral replication of nasopharyngeal swabs, anal swabs and lung in old monkeys was more active than that in young monkeys for 14 days after SARS-CoV-2 challenge. Monkeys developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema, notably, old monkeys exhibited diffuse severe interstitial pneumonia. Viral antigens were detected mainly in alveolar epithelial cells and macrophages. Conclusion: SARS-CoV-2 caused more severe interstitial pneumonia in old monkeys than that in young monkeys. Rhesus macaque models infected with SARS-CoV-2 provided insight into the pathogenic mechanism and facilitated the development of vaccines and therapeutics against SARS-CoV-2 infection. Key words: pathogenicity; pneumonia; rhesus macaque model; SARS-CoV-2

The outbreak of Corona Virus Disease 2019 caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) is highly transmitted. The potential extra-respiratory transmission routes remain uncertain. Five rhesus macaques were inoculated with 1×106 TCID50 of SARS-CoV-2 via conjunctival (CJ), intratracheal (IT), and intragastric (IG) routes, respectively. Remarkably, the CJ inoculated-macaques developed mild interstitial pneumonia and viral load was detectable in the conjunctival swabs at 1 days post-inoculation (dpi). Only via IT inoculation, viral load was detected in the anal swab at 1-7 dpi and macaque showed weight loss. However, viral load was undetectable after IG inoculation. Comparatively, viral load was higher in the nasolacrimal system but lesions of lung were relatively mild and local via CJ inoculation compared with that via IT inoculation, demonstrating distinct characteristics of virus dispersion. Both the two routes affected the alimentary tract. Therefore the clinicians need to protect eye while working with patients.