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      Airborne route and bad use of ventilation systems as non-negligible factors in SARS-CoV-2 transmission

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          Summary

          The world is facing a pandemic of unseen proportions caused by a corona virus named SARS-CoV-2 with unprecedent worldwide measures being taken to tackle its contagion. Person-to-person transmission is accepted but WHO only considers aerosol transmission when procedures or support treatments that produce aerosol are performed. However, transmission mechanisms are not fully understood and there is evidence for an airborne route to be considered as the virus remains viable in aerosols for at least 3h and that mask usage was the best intervention to prevent infection.

          Heating, Ventilating and Air Conditioning Systems (HVAC) are used as a primary infection disease control measure. However, they may contribute to the transmission/spreading of airborne diseases as proposed in the past for SARS.

          The authors believe that airborne transmission is possible and that HVAC systems when not adequately used may contribute to the transmission of the virus, as suggested by descriptions of from Japan, Germany, and the Diamond Princess Cruise Ship. Previous SARS outbreaks reported at Amoy Gardens, Emergency Rooms and Hotels, for example, also suggested airborne transmission.

          Further studies are warranted to confirm our hypotheses but the assumption of such way of transmission would cause a major shift in measures recommended to prevent infection such as the disseminated use of masks and structural changes to hospital and other facilities HVAC systems.

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          Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany

          To the Editor: The novel coronavirus (2019-nCoV) from Wuhan is currently causing concern in the medical community as the virus is spreading around the world. 1 Since identification of the virus in late December 2019, the number of cases from China that have been imported into other countries is on the rise, and the epidemiologic picture is changing on a daily basis. We are reporting a case of 2019-nCoV infection acquired outside Asia in which transmission appears to have occurred during the incubation period in the index patient. A 33-year-old otherwise healthy German businessman (Patient 1) became ill with a sore throat, chills, and myalgias on January 24, 2020. The following day, a fever of 39.1°C (102.4°F) developed, along with a productive cough. By the evening of the next day, he started feeling better and went back to work on January 27. Before the onset of symptoms, he had attended meetings with a Chinese business partner at his company near Munich on January 20 and 21. The business partner, a Shanghai resident, had visited Germany between January 19 and 22. During her stay, she had been well with no signs or symptoms of infection but had become ill on her flight back to China, where she tested positive for 2019-nCoV on January 26 (index patient in Figure 1) (see Supplementary Appendix, available at NEJM.org, for details on the timeline of symptom development leading to hospitalization). On January 27, she informed the company about her illness. Contact tracing was started, and the above-mentioned colleague was sent to the Division of Infectious Diseases and Tropical Medicine in Munich for further assessment. At presentation, he was afebrile and well. He reported no previous or chronic illnesses and had no history of foreign travel within 14 days before the onset of symptoms. Two nasopharyngeal swabs and one sputum sample were obtained and were found to be positive for 2019-nCoV on quantitative reverse-transcriptase–polymerase-chain-reaction (qRT-PCR) assay. 2 Follow-up qRT-PCR assay revealed a high viral load of 108 copies per milliliter in his sputum during the following days, with the last available result on January 29. On January 28, three additional employees at the company tested positive for 2019-nCoV (Patients 2 through 4 in Figure 1). Of these patients, only Patient 2 had contact with the index patient; the other two patients had contact only with Patient 1. In accordance with the health authorities, all the patients with confirmed 2019-nCoV infection were admitted to a Munich infectious diseases unit for clinical monitoring and isolation. So far, none of the four confirmed patients show signs of severe clinical illness. This case of 2019-nCoV infection was diagnosed in Germany and transmitted outside Asia. However, it is notable that the infection appears to have been transmitted during the incubation period of the index patient, in whom the illness was brief and nonspecific. 3 The fact that asymptomatic persons are potential sources of 2019-nCoV infection may warrant a reassessment of transmission dynamics of the current outbreak. In this context, the detection of 2019-nCoV and a high sputum viral load in a convalescent patient (Patient 1) arouse concern about prolonged shedding of 2019-nCoV after recovery. Yet, the viability of 2019-nCoV detected on qRT-PCR in this patient remains to be proved by means of viral culture. Despite these concerns, all four patients who were seen in Munich have had mild cases and were hospitalized primarily for public health purposes. Since hospital capacities are limited — in particular, given the concurrent peak of the influenza season in the northern hemisphere — research is needed to determine whether such patients can be treated with appropriate guidance and oversight outside the hospital.
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            The reproductive number of COVID-19 is higher compared to SARS coronavirus

            Introduction In Wuhan, China, a novel and alarmingly contagious primary atypical (viral) pneumonia broke out in December 2019. It has since been identified as a zoonotic coronavirus, similar to SARS coronavirus and MERS coronavirus and named COVID-19. As of 8 February 2020, 33 738 confirmed cases and 811 deaths have been reported in China. Here we review the basic reproduction number (R 0) of the COVID-19 virus. R 0 is an indication of the transmissibility of a virus, representing the average number of new infections generated by an infectious person in a totally naïve population. For R 0 > 1, the number infected is likely to increase, and for R 0 < 1, transmission is likely to die out. The basic reproduction number is a central concept in infectious disease epidemiology, indicating the risk of an infectious agent with respect to epidemic spread. Methods and Results PubMed, bioRxiv and Google Scholar were accessed to search for eligible studies. The term ‘coronavirus & basic reproduction number’ was used. The time period covered was from 1 January 2020 to 7 February 2020. For this time period, we identified 12 studies which estimated the basic reproductive number for COVID-19 from China and overseas. Table 1 shows that the estimates ranged from 1.4 to 6.49, with a mean of 3.28, a median of 2.79 and interquartile range (IQR) of 1.16. Table 1 Published estimates of R 0 for 2019-nCoV Study (study year) Location Study date Methods Approaches R 0 estimates (average) 95% CI Joseph et al. 1 Wuhan 31 December 2019–28 January 2020 Stochastic Markov Chain Monte Carlo methods (MCMC) MCMC methods with Gibbs sampling and non-informative flat prior, using posterior distribution 2.68 2.47–2.86 Shen et al. 2 Hubei province 12–22 January 2020 Mathematical model, dynamic compartmental model with population divided into five compartments: susceptible individuals, asymptomatic individuals during the incubation period, infectious individuals with symptoms, isolated individuals with treatment and recovered individuals R 0 = \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$\beta$\end{document} / \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$\alpha$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$\beta$\end{document} = mean person-to-person transmission rate/day in the absence of control interventions, using nonlinear least squares method to get its point estimate \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$\alpha$\end{document} = isolation rate = 6 6.49 6.31–6.66 Liu et al. 3 China and overseas 23 January 2020 Statistical exponential Growth, using SARS generation time = 8.4 days, SD = 3.8 days Applies Poisson regression to fit the exponential growth rateR 0 = 1/M(−𝑟)M = moment generating function of the generation time distributionr = fitted exponential growth rate 2.90 2.32–3.63 Liu et al. 3 China and overseas 23 January 2020 Statistical maximum likelihood estimation, using SARS generation time = 8.4 days, SD = 3.8 days Maximize log-likelihood to estimate R 0 by using surveillance data during a disease epidemic, and assuming the secondary case is Poisson distribution with expected value R 0 2.92 2.28–3.67 Read et al. 4 China 1–22 January 2020 Mathematical transmission model assuming latent period = 4 days and near to the incubation period Assumes daily time increments with Poisson-distribution and apply a deterministic SEIR metapopulation transmission model, transmission rate = 1.94, infectious period =1.61 days 3.11 2.39–4.13 Majumder et al. 5 Wuhan 8 December 2019 and 26 January 2020 Mathematical Incidence Decay and Exponential Adjustment (IDEA) model Adopted mean serial interval lengths from SARS and MERS ranging from 6 to 10 days to fit the IDEA model, 2.0–3.1 (2.55) / WHO China 18 January 2020 / / 1.4–2.5 (1.95) / Cao et al. 6 China 23 January 2020 Mathematical model including compartments Susceptible-Exposed-Infectious-Recovered-Death-Cumulative (SEIRDC) R = K 2 (L × D) + K(L + D) + 1L = average latent period = 7,D = average latent infectious period = 9,K = logarithmic growth rate of the case counts 4.08 / Zhao et al. 7 China 10–24 January 2020 Statistical exponential growth model method adopting serial interval from SARS (mean = 8.4 days, SD = 3.8 days) and MERS (mean = 7.6 days, SD = 3.4 days) Corresponding to 8-fold increase in the reporting rateR 0 = 1/M(−𝑟)𝑟 =intrinsic growth rateM = moment generating function 2.24 1.96–2.55 Zhao et al. 7 China 10–24 January 2020 Statistical exponential growth model method adopting serial interval from SARS (mean = 8.4 days, SD = 3.8 days) and MERS (mean = 7.6 days, SD = 3.4 days) Corresponding to 2-fold increase in the reporting rateR 0 = 1/M(−𝑟)𝑟 =intrinsic growth rateM = moment generating function 3.58 2.89–4.39 Imai (2020) 8 Wuhan January 18, 2020 Mathematical model, computational modelling of potential epidemic trajectories Assume SARS-like levels of case-to-case variability in the numbers of secondary cases and a SARS-like generation time with 8.4 days, and set number of cases caused by zoonotic exposure and assumed total number of cases to estimate R 0 values for best-case, median and worst-case 1.5–3.5 (2.5) / Julien and Althaus 9 China and overseas 18 January 2020 Stochastic simulations of early outbreak trajectories Stochastic simulations of early outbreak trajectories were performed that are consistent with the epidemiological findings to date 2.2 Tang et al. 10 China 22 January 2020 Mathematical SEIR-type epidemiological model incorporates appropriate compartments corresponding to interventions Method-based method and Likelihood-based method 6.47 5.71–7.23 Qun Li et al. 11 China 22 January 2020 Statistical exponential growth model Mean incubation period = 5.2 days, mean serial interval = 7.5 days 2.2 1.4–3.9 Averaged 3.28 CI, Confidence interval. Figure 1 Timeline of the R 0 estimates for the 2019-nCoV virus in China The first studies initially reported estimates of R 0 with lower values. Estimations subsequently increased and then again returned in the most recent estimates to the levels initially reported (Figure 1). A closer look reveals that the estimation method used played a role. The two studies using stochastic methods to estimate R 0, reported a range of 2.2–2.68 with an average of 2.44. 1 , 9 The six studies using mathematical methods to estimate R 0 produced a range from 1.5 to 6.49, with an average of 4.2. 2 , 4–6 , 8 , 10 The three studies using statistical methods such as exponential growth estimated an R 0 ranging from 2.2 to 3.58, with an average of 2.67. 3 , 7 , 11 Discussion Our review found the average R 0 to be 3.28 and median to be 2.79, which exceed WHO estimates from 1.4 to 2.5. The studies using stochastic and statistical methods for deriving R 0 provide estimates that are reasonably comparable. However, the studies using mathematical methods produce estimates that are, on average, higher. Some of the mathematically derived estimates fall within the range produced the statistical and stochastic estimates. It is important to further assess the reason for the higher R 0 values estimated by some the mathematical studies. For example, modelling assumptions may have played a role. In more recent studies, R 0 seems to have stabilized at around 2–3. R 0 estimations produced at later stages can be expected to be more reliable, as they build upon more case data and include the effect of awareness and intervention. It is worthy to note that the WHO point estimates are consistently below all published estimates, although the higher end of the WHO range includes the lower end of the estimates reviewed here. R 0 estimates for SARS have been reported to range between 2 and 5, which is within the range of the mean R 0 for COVID-19 found in this review. Due to similarities of both pathogen and region of exposure, this is expected. On the other hand, despite the heightened public awareness and impressively strong interventional response, the COVID-19 is already more widespread than SARS, indicating it may be more transmissible. Conclusions This review found that the estimated mean R 0 for COVID-19 is around 3.28, with a median of 2.79 and IQR of 1.16, which is considerably higher than the WHO estimate at 1.95. These estimates of R 0 depend on the estimation method used as well as the validity of the underlying assumptions. Due to insufficient data and short onset time, current estimates of R 0 for COVID-19 are possibly biased. However, as more data are accumulated, estimation error can be expected to decrease and a clearer picture should form. Based on these considerations, R 0 for COVID-19 is expected to be around 2–3, which is broadly consistent with the WHO estimate. Author contributions J.R. and A.W.S. had the idea, and Y.L. did the literature search and created the table and figure. Y.L. and A.W.S. wrote the first draft; A.A.G. drafted the final manuscript. All authors contributed to the final manuscript. Conflict of interest None declared.
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              Fecal specimen diagnosis 2019 novel coronavirus–infected pneumonia

              Abstract The emergence and spread of 2019 novel coronavirus–infected pneumonia (COVID‐19) from Wuhan, China, it has spread globally. We extracted the data on 14 patients with laboratory‐confirmed COVID‐19 from Jinhua Municipal Central hospital through 27 January 2020. We found that compared to pharyngeal swab specimens, nucleic acid detection of COVID‐19 in fecal specimens was equally accurate. And we found that patients with a positive stool test did not experience gastrointestinal symptoms and had nothing to do with the severity of the lung infection. These results may help to understand the clinical diagnosis and the changes in clinical parameters of COVID‐19.
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                Author and article information

                Journal
                Med Hypotheses
                Med. Hypotheses
                Medical Hypotheses
                Published by Elsevier Ltd.
                0306-9877
                1532-2777
                25 April 2020
                25 April 2020
                : 109781
                Affiliations
                [a ]Medical Microbiology Research Group, CNC-Center for Neurosciences and Cell Biology, FMUC - Faculty of Medicine, University of Coimbra, Coimbra, Portugal
                [b ]Department of Nephrology, FMUC - Faculty of Medicine, University of Coimbra, Portugal
                [c ]ADAI, LAETA Department of Mechanical Engineering, University of Coimbra, Portugal
                Article
                S0306-9877(20)30801-X 109781
                10.1016/j.mehy.2020.109781
                7182754
                32361528
                c4754ba9-0a2c-44da-ae5f-b5d539717e53
                © 2020 Published by Elsevier Ltd.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 14 April 2020
                : 21 April 2020
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                Medicine
                Medicine

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