Covid-19: a puzzle with many missing piecesBMJ 2020; 368 doi: https://doi.org/10.1136/bmj.m627 (Published 19 February 2020) Cite this as: BMJ 2020;368:m627
All rapid responses
May I please be permitted a few thoughts? I do acknowledge my lack of personal experience of this disease.
1. It is an infectious disease (as was smallpox).
2. The organism is present in exhaled droplets.
3. The droplets might alight on furniture, cutlery, crockery.
4. The droplets might dry, leaving the “dry” nuclei floating in the air.
5. In some cultures you greet someone you have not seen for a while, with an embrace, a hug.
6. In some cultures you greet that someone with a kiss - regardless of the sex. Indeed sometimes you kiss three times.
7. No work has yet been published showing whether the semen of a recovered patient contains the virus and if so, how long the semen might remain infective.
8. To me it seems axiomatic that public health preventive measures should bear in mind, the foregoing 7 points.
9. It is also axiomatic that we the public should cut down travel in over-crowded public transport - be it bus, train, underground, cruises, aeroplanes.
10. Her Majesty’s Govt should make it mandatory for its own departments as well as private enterprises to ask office bound staff to use Smart Phones, Skype, Face Time and such like contrivances, instead of travelling to offices, meetings.
If any of the foregoing are products of an overheated imagination, kindly let me know.
Competing interests: No competing interests
As you pointed out rightly we do not know how long the viral shedding will continue after a patient gets better. We know more than 8 patients were discharged from the UK's hospitals. We do not know whether these patients were tested for clearing the virus from their throat or their respiratory tracts (or faeces).
From our experience the chance of transmitting respiratory viruses after immunocompetent patients become asymptomatic is low. However with a new virus such as with potential to cause a pandemic, discharging patients without evidence of clearance will put the patient's family members and their community at risk.
We also know that the molecular techniques currently in use will detect nonviable viruses as well and it is difficult to establish non-clearance. It is a very difficult challenge for doctors.
Do we know how China or Iran with a high number of infected people so far managed their patients on issues of discharging or discontinuing isolation or use of personal protective equipment? Could transmission from convalescent patients have played significant roles in spreading the virus?
I believe the public health will put emphasis on measures to reduce transmission of infection from convalescent patients and will continue to assess whether the discharged patients transmit the virus or not.
Competing interests: No competing interests
The coronavirus disease 2019 (COVID-19) outbreak initially occurred in Wuhan, China, and has now spread to many countries. It causes pneumonia, failure of multiple organs and systems, and death. [1,2] The World Health Organization has indicated that COVID-19 viruses can be killed by ether solvent. One can ask whether ether can be used to treat patients with COVID-19, especially in the case that no specific therapeutic intervention is available for this virus.
Diethyl ether is a volatile anesthetic that was used to induce general anesthesia. Its minimum alveolar concentration (MAC) is 2.0% in humans and its blood:gas partition coefficient is 12.  Thus, the concentrations reached in the blood may be 24% or higher if ether is used for general anesthesia. These concentrations could be higher enough to kill COVID-19 viruses. Volatile anesthetics that are currently used in clinical practice in the United States are isoflurane, sevoflurane and desflurane. Their MACs are 1.15%, 2.0% and 6.0%, respectively. The corresponding blood:gas partition coefficients are 1.4, 0.68 and 0.4.  Thus, these newer volatile anesthetics reach a much lower blood concentrations during general anesthesia. Since volatile anesthetics can induce vascular dilation and may improve ventilation:perfusion mismatch in patients with pneumonia (those lung segments that have ventilation will contain inhaled volatile anesthetics to dilate their vasculature),  these agents may improve oxygenation of patients with pneumonia. Thus, these agents could have role in treating patients with COVID-19, especially for those patients with pneumonia requiring endotracheal intubation and mechanical ventilation. In this regard, diethyl ether or its like could be very useful for its potential of viral killing effects. However, diethyl ether is highly explosive and inflammable, can inhibit liver enzymes and has other side-effects. It also increases oxidative stress and may modulate immune functions. [6,7] Thus, caution needs to be applied when using diethyl ether in patients with COVID-19.
I would suggest the following steps to test the potential of using volatile anesthetics in fighting COVID-19.
First, we will need to test the effective concentrations of volatile anesthetics to kill or inhibit COVID-19 viruses in vitro. If these concentrations are reachable in the blood during general anesthesia, ethical approval is needed before any clinical testing. The potential of diethyl ether or other volatile anesthetics can be tested in those patients with respiratory failure who require mechanical ventilation or mechanical support for their cardiac and pulmonary functions. Patients should be carefully monitored for their haptic functions, blood gas changes, acidosis and hemodynamics. The use of diethyl ether shall be in a well-ventilated room and applied via a close circuit system. It may be ideal to combine its use and immunoglobulin or other immune function modulators to maintain or enhance the immune functions of the patients. If diethyl ether is proved to be effective in helping patients with COVID 19, one can speculate that diethyl ether or its like could be used to fight other coronaviruses.
1. Li Q, Guan X, Wu P, et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med 2020. 10.1056/NEJMoa2001316
2. Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA 2020. 10.1001/jama.2020.1585
3. Das BB. Minimum blood concentration--a universal concept of anaesthetic potency. Br J Anaesth 1975;47:881-4.
4. Khan SK, Hayes I, Buggy DJ. Pharmacology of anesthetic agents II Continuing Education in Anesthesia Critical Care & Pain. 2014;14:106-11.
5. Sykes MK, Davies DM, Chakrabarti MK, Loh L. The effects of halothane, trichloroethylene and ether on the hypoxic pressor response and pulmonary vascular resistance in the isolated, perfused cat lung. Br J Anaesth 1973;45:655-63.
6. Normann PT, Ripel A, Morland J. Diethyl ether inhibits ethanol metabolism in vivo by interaction with alcohol dehydrogenase. Alcohol Clin Exp Res 1987;11:163-6.
7. Keefer LK, Garland WA, Oldfield NF, Swagzdis JE, Mico BA. Inhibition of N-nitrosodimethylamine metabolism in rats by ether anesthesia. Cancer Res 1985;45:5457-60.
Competing interests: No competing interests
Human coronaviruses (HCoVs) have long been considered the cause of the “common cold” in otherwise healthy individuals. This belief, however, was challenged by the spread of two highly pathogenic HCoVs that were transmitted for animals to humans in the 21st century: severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). These two global epidemics caused alarming morbidity and mortality.  The 2019 novel coronavirus (2019-nCoV) is another instance of cross-species infection from animals to humans. It was first recognized and reported in December 2019 in Wuhan, Hubei Province, China. 2019-nCoV explosively spread from Wuhan to throughout China and then worldwide. This novel illness was named Corona Virus Disease 2019 (COVID-2019) by the World Health Organization. Immediately following the first case report of COVID-2019 in China, confirmed cases were subsequently reported worldwide. After person-to-person transmission was confirmed by clustered familial cases, the World Health Organization declared that the outbreak was a Public Health Emergency of International Concern. As of February 24, 2020, a total of 79,727 confirmed cases have been reported globally, with 77,658 cases and 2663 deaths in China  and 2069 cases and 23 deaths in 29 countries outside China.
The rapid growth of the number of confirmed cases of infection and deaths have posed major challenges to both public health and national governments. The Chinese government has implemented rapid and comprehensive public health emergency interventions and put unprecedented and draconian efforts in place to detect and treat individuals who are suspected to have the disease. Confirmed cases are quarantined in an effort to control further spread. Internationally, nations’ governments and relevant institutions have responded rapidly by developing and implementing strategies to contain the outbreak.
China informed the World Health Organization quickly about the outbreak and shared genomic sequence information after discovering the causative agent. Scientists from China shared unbiased DNA sequencing data with the world to improve their understanding of disease occurrence and transmission. This helped 168 laboratories develop testing kits for the early detection of confirmed cases, which triggered public health emergency systems in many countries. COVID-2019 was suggested to occur through person-to-person transmission based on clinically clustered patients. The World Health Organization recommended limiting human-to-human transmission events and preventing further international spread. Multiple countries have commenced temperature screening, symptom screening, and health questionnaires for traveling passengers who arrive from China. Other countries issued their highest-level travel advisories for Hubei Province. These strategies have inevitably caused public panic and discrimination against Chinese individuals worldwide. China quickly collected epidemiological data from patients and developed an epidemiology prediction model through collaborations with foreign universities. The development and production of pharmacological treatments and a vaccine are underway.
The Director General of the World Health Organization expressed his respect for China with regard to their rapid response and international collaborations and emphasized the urgent need for solidarity and support worldwide. However, certain factors have complicated discernment of the pattern of the epidemic, including asymptomatic infected cases, possible rapid person-to-person transmission, and instances of transmission in France and the United Kingdom among people with no history of traveling to China. Scientists are preparing for the possible sustained transmission of 2019-nCoV beyond China, with careful consideration of lessons learned from prior epidemics and pandemics, such as SARS-CoV and MERS-CoV.  We support the recommendations of the World Health Organization with regard to worldwide efforts to curb the outbreak and develop effective treatments through comprehensive international collaborations.
Researchers and clinicians are still actively seeking to uncover the origins of the virus, identify respiratory pathogens, discover targeted and effective treatments, and design and produce vaccines to save lives. Teams of international multidisciplinary health professionals are being built, consisting of medical doctors, biological scientists, public health professionals, politicians, economists, and sociologists. China gained ample experience in engaging in international collaborations for surveillance, laboratory testing, and contact tracing during the SARS-CoV epidemic in China and MERS-CoV epidemic in other countries. To control the 2019-nCoV epidemic, transmission models with accurate parameters and transmissibility and severity characteristics are being fitted and predicted. More effective treatments and vaccines are urgently needed, which can only be achieved through comprehensive international cooperation.
International collaborations between China and other countries can protect the whole global population. Such collaborations should be built based on equality, respect, and trust, and any type of discrimination against Chinese people needs to stop. Long-term worldwide collaborations of capacity-building and infrastructure are encouraged to meet the challenges of potential future epidemics. We encourage further collaborations between China and other countries to establish long-term global health goals, share existing data on the epidemic, analyze response speed and strategies across countries, develop effective treatments and vaccines, and promote preparedness for future infectious disease outbreaks.
After the SARS-CoV outbreak in 2002 and MERS-CoV outbreak in 2012, the new 2019-nCoV has put global public health institutions on high alert once again. We call for international collaborations to help contain the outbreak and save more lives.
Yimiao Gong,1,# Yanping Bao,2,# Lin Lu1,3,*
1 Institute of Mental Health, National Clinical Research Center for Mental Disorders, Key Laboratory of Mental Health and Peking University Sixth Hospital, Peking University, Beijing 100191, China
2 Peking University Health Science Center, Peking University, Beijing 100191, China
3 Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100191, China
# Equal contribution to this work
Prof. Lin Lu
Institute of Mental Health/National Clinical Research Center for Mental Disorders/Peking University Sixth Hospital, Peking University, 51 HuayuanBei Road, Beijing 100191, China
We declare no competing interests.
LL was responsible for the study design. YG was responsible for the literature search and manuscript drafting. YB, and LL were responsible for critical revision of the manuscript.
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Competing interests: No competing interests