Aim: Many concerns still existed about the safety of hydroxychloroquine (HCQ) in the treatment of Corona Virus Disease 2019 (COVID-19). The purpose of this study was to evaluate the safety of HCQ by performing a systematic review and meta-analysis. Methods: Randomized controlled trials reporting the safety of HCQ in PubMed, Embase, and Cochrane Library were retrieved from the establishment of the database to February 27, 2020. Literature screening, data extraction, and assessment of risk bias were performed independently by two reviewers. Results: We identified 34 eligible studies that involved 3,639 patients. The difference in the cumulative number of AEs between the HCQ and control group was statistically significant (P<0.0001). The pooled incidence of gastrointestinal AEs, which occurred most frequently in the HCQ group was higher than that in the control group (P<0.0001) according to the system organ class. In addition, the risks of skin and subcutaneous tissue AEs (P = 0.011), renal and urinary disorders (P=0.011), ear and labyrinth AEs (P = 0.045) and surgical and medical procedures AEs (P = 0.020) in HCQ group are also significantly increased compared with the control group. Meanwhile, the cumulative number of SAEs was similar between the two groups (P=0.222). Meta-analysis results indicated that the pooled incidences of all the AEs reported by two or more studies were similar except for the treatment discontinuation caused by AEs (RD 0.02, 95% CI: 0.00 to 0.06). Conclusion: HCQ was well tolerated and might be safe for clinical application under the outbreak of COVID-19.

More than one million patients worldwide have been diagnosed with coronavirus disease 19 (COVID-19) to date (WHO situation report, 8th April 2020). There is neither a vaccine to prevent infection with the causative organism, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), nor a cure. In the struggle to devise potentially useful therapeutics in record time, the repurposing of existing drugs is a key route of action. In this review we argue that the bisbenzylisoquinoline and calcium channel blocker tetrandrine, originally extracted from the plant Stephania tetrandra and utilised in traditional Chinese medicine, could be repurposed to treat COVID-19. We collate and review evidence for tetrandrine’s putative mechanism of action in viral infection, specifically its recently discovered antagonism of the two-pore channel 2 (TPC2). Consideration of its pharmacodynamics and pharmacokinetics suggests that oral tetrandrine at doses currently used in clinical practice could be an effective agent for the treatment of SARS-CoV-2 infection in humans.

IntroductionThe coronavirus disease 2019 (COVID-19) first outbreak at the end of 2019 in Wuhan, China, and quickly spread into more than 200 countries worldwide, turning into a global pandemic. As a new emerging and severe contagious disease, all people are vulnerable to it. Therefore, it’s not surprising that more and more pregnant patients are being reported.1, 2 The maternal and fetus outcomes of COVID-19 pregnant women are the focus of our attention. Fortunately, based on the results of current studies, the clinical characteristic and outcomes of COVID-19 maternal patients are similar to that of non-pregnant women. No maternal death has been reported.1, 2 But the consequences of infection with SARS-CoV-2 for fetus or newborn are uncertain; especially, there is still huge controversy regarding whether SARS-CoV-2 can be transplacentally transmitted from infected pregnant women to their fetuses. A previous review, through analyzing a total of 38 pregnant women with COVID-19 in China, didn’t found intrauterine transmission of SARS-CoV-2.2 However, a recent study by L Dong et al3 described a newborn born to a COVID-19 mother with elevated IgM antibody level to SARS-CoV-2, indicating a possible transplacental transmission.Here, we reported a newborn born to a convalescent COVID-19 mother has a viral pneumonia on the day of birth and elevated IgM/IgG antibody levels to SARS-CoV-2 at 3 days age.

The ongoing wide spread of Covid-19, also referred to as 2019-nCoV or SARS-CoV-2, is undoubtedly one of the deadliest zoonotic diseases the whole world has grappled with. As of April 10, 2020, this disease has infected above 1.6 million people in over 200 countries worldwide, and claimed the lives of more than 96,000.1 Figure 1 shows the distribution of confirmed cases in the first 20 nations with the highest number of Covid-19 patients as of April 10, 2020, the least of which has over 9,000 cases.**Figure 1**With the increasing trend of daily new cases and daily death from the beginning of March to April 9, 2020, as displayed on Figure 2, it could be predicted that this fatal pandemic could last well beyond a year. According to the modeling completed by pandemic intelligence experts at the Imperial College, London, the 2019 novel coronavirus is likely to remain for another 12-18 months.2 Typically, past pandemics have lasted between one to three years.3Examples of such recent pandemics are the H1N1 influenza,4 SARS-CoV,5Ebola,6 and MERS-CoV,7 which all lasted for more than 12 months. As the emergence of these novel viruses keep increasing, how could biosafety and biosecurity measures guard against the introduction of the harmful causative organisms to humans in the future?**Figure 2**The terms biosafety and biosecurity are broadly used in diverse frameworks and refer not only to protection of humans and their surrounding environment against lethal biological agents, but also to global deactivation of arms of mass destruction.8 In the concept of biorisk management, these two terms refer to best practices that prevent the spillover of toxic organisms to human beings and into the environment.9,10 Although these two terms have been used interchangeably and often denoted with similar meanings, scientists have distinguished between the two concepts. According to Zaki,11 biosafety involves all the preventive measures undertaken to eradicate strains of pathogenic microorganisms and their potential toxins. On the other hand, biosecurity includes a set of preventive strategies intended to reduce the risk of transmission of infectious diseases in humans, crops, livestock, isolated pests and genetically modified organisms.12The World Health Organization (WHO) has classified disease-causing microorganisms into four different groups based on their principal characteristics, hazardous threat to individuals and the community, and their route of transmission.13,14 Table 1 presents the four different groups with their associated risk levels.**Table 1**Concluding from the descriptions for the various pathogenic organisms and their risk levels to individuals and the community in Table 1, the novel coronaviruses that cause Covid-19, SARS-CoV, MERS-CoV, and many other pandemic-causing pathogens, could be classified as risk level 4 pathogens. As spillover events keep occurring in recent years, and more of these high-risk emerging infectious diseases (EIDs) are likely to be introduced into the environment, it is necessary for the general public and stakeholders around the globe to institute biosafety and biosecurity measures in preventing the transmission of these biological toxins to mankind, livestock and their inhabitations. Among the core elements of the principles of biosafety measures and biosecurity strategies, the following are principal in guiding against EIDs:Effective regulations have to be put in place to avoid and manage intentional exposures to the sources and hosts of pathogenic organisms of medium to high risk levels. Strict observation of such policies around the world will minimize human activities that have caused several spillover events in the past.As the sources of novel pathogens have been identified in the past, it is necessary for scientists to inform the general public about the sources and hosts of such toxic organisms. Further research should also be targeted towards identifying these pathogens in animals and plants which are usually exposed to the environment. Such knowledge will help stakeholders and policymakers to notify the general public about the potential spillover events that are likely from contacts with identified sources and hosts of these pathogens.The risk assessment of pathogenic diseases of the past and a predicted assessment of likely EIDs in the future should be made available to the general public. Such awareness will inform the mass about the economic, social, and health impacts of these diseases. This will reinforce public adherence to policies and regulations which are instituted to limit contacts with pathogenic sources as people are aware of the potential losses to national and global economy, and the adverse effects on social life and health facilities.As health personnel, scientists, and leaders in various capacities often find themselves in the frontline during the emergence of epidemic and pandemic diseases, they need to be trained adequately to guarantee proper apprehension and execution of biosafety procedures to ensure the maintenance of a safe working environment for individuals and the wider community. This will ensure appropriate measures are taken to limit the spread of infections.Finally, routine upgrades are required to render instituted biosafety and biosecurity measures more effective and efficient in this ever-changing world. As the etiology and epidemiology of EIDs keep evolving, constant updates to safe practices in health centers around the world are required to adapt these practices to effectively manage the emerging diseases.As various country-based mitigation measures are being implemented around the world to contain and control the course of Covid-19,15 it is essential that the above biosafety and biosecurity measures are adopted and implemented to effectively manage the ongoing outbreak, and prevent future emerging infections.

Angiotensin converting enzyme 2 activation: a novel potential Covid-19 therapeutic strategyIn late December 2019, the Covid-19 epidemic, caused by a novel coronavirus SARS-CoV-2, emerged in Wuhan, Hubei province, China. This epidemic has a doubling period of 1.8 days, and there are concerns about its progression to pandemic scales due to its exponential rate of spread. No specific drugs or vaccines are currently available for the treatment and/or prevention of SARS-CoV-2 infection. Hence, there is an imperative need to search for a safe and effective therapeutic strategy for Covid-19 infected patients, especially the critically ill individuals.Angiotensin-converting enzyme 2 (ACE2) is a crucial component of the renin-angiotensin-system (RAS) axis because it converts Angiotensin II into angiotensin (1–7), which exerts an antifibrotic, antihypertrophic and vasodilatory effect. ACE2 is a membrane-bound aminopeptidase which has been reported to be a functional receptor for coronaviruses, including SARS-CoV and SARS-CoV-2. The first step of SARS-CoV-2 infection is binding of the spike protein of the virus to ACE2 which is widely distributed on the alveolar type II cells and capillary endothelium (Lu et al., 2020). It has been demonstrated that SARS-CoV downregulates ACE2 protein in mice, contributing to severe lung injury (Kuba et al., 2005). This suggests that augmented ACE2 activation may result in enhanced binding with SARS-CoV-2. Thus, increasing ACE2 activation may have a dual function to both neutralize the virus and rescue cellular ACE2 activity protecting the lung from damage.Diminazene (DIZE) is an antitripanosomal drug which has been shown to serve as an ACE2 activator and reduce bleomycin-induced pulmonary fibrosis (Shenoy, Qi, Gupta, Katovich & Raizada, 2012). In addition, it has been reported that activation of ACE2 by DIZE prevented asthma progression in rats by altering AKT, p38, NF-κB and other inflammatory markers. DIZE also halted the development and progression of experimentally induced pulmonary hypertension in rats, improved right ventricular function, and diminished proinflammatory cytokines effects that were accompanied with increased lung ACE2 activity. Given the reported safety of DIZE administration in humans (Hutchinson & Watson, 1962; Pepin & Milord, 1994) and the pressing need for Covid-19 therapeutic, in addition to the well-documented pharmacological effects of DIZE, clinical studies are warranted to elucidate the potential safety and efficacy of DIZE in Covid-19 infected patients.In conclusion, SARS-CoV-2 represents a global health challenge. Unfortunately, no specific therapeutic options are currently available. Thus, there is an imperative need for a safe and effective drug in order to put this pandemic to an end. DIZE has a reported acceptable safety profile. Moreover, DIZE increased lung ACE2 activity in different experimental models, an effect which conferred lung protection against various insults. Taking into consideration the reported effect of SARS-CoV-2 on pulmonary ACE2 activity, it could be suggested that DIZE administration could offer some therapeutic merit for SARS-CoV-2 infected patients. However, clinical studies are required to unravel the potential safety and efficacy of DIZE administration in Covid-19 infected patients.Competing interests The author declares no competing interests.

Streamline maternal health care provision to mitigate the risk for pregnant women under COVID-19 pandemicHong Jiang1, Mu Li2, Huijing Shi1*, Xu Qian11School of Public Health; Global Health Institute; National Health Commission Key Laboratory of Health Technology Assessment, Fudan University, Mailbox 175, No. 138 Yixueyuan Road, Shanghai 200032, China;2School of Public Health; China Studies Centre, Room 313, Edward Ford Building, University of Sydney, Sydney 2006, Australia*Corresponding author: Huijing Shi, hjshi@fudan.edu.cn, School of Public Health; Global Health Institute; NHC Key Laboratory of Health Technology Assessment, Fudan University, Mailbox 175, No. 138 Yixueyuan Road, Shanghai 200032, China;The novel Coronavirus Disease 2019 (COVID-19) outbreak started in Wuhan City China in early December 20191,2, and has rapidly spread across the world. The pandemic has strained health system3, which presents a huge challenge to maintain other essential health services, including maternal health care. As the first country to experience the COVID-19 outbreak, there are lessons could be learnt for establishing a better preparedness mechanism from a service delivery perspective to provide essential maternal health care and mitigate health risk for pregnancy women.First, all health facilities providing antenatal care should apply high standard of precaution to ensure pregnant women are not exposed to the COVID-19 transmission. This includes setting up a triage area to screen for COVID-19 symptoms and contact history with confirmed cases before pregnant women entering antenatal clinics. People with COVID-19 exposure history, suspected cases or COVID-19 patients should be separated from other pregnant women and placed in designated areas. This will also protect antenatal care providers. Appointment is required in advance for antenatal service to ensure adequate social distancing and manage the patient flow in health facilities.Second, as routine service provision might be disrupted, perinatal care availability and any changes to service provision should be disseminated widely, preferably through online platforms4. Women with low risk pregnancy may reduce the risk of contracting COVID-19 by reducing the number of antenatal visits. Women with pregnancy complications and other health conditions should contact their antenatal care provider to seek specific advice. Communication and counselling can be provided to pregnant and postnatal women online, including recognizing warning signs of going to hospital urgently. During movement restriction or self-isolation guidance of keeping healthy diet and physical activity, and mental health support are important for the well-being of pregnant women.Third, balancing the demands of emergency responding to COVID-19 and maintaining essential perinatal health service at national, provincial and local levels. Guidelines on conditions that require continuing antenatal care and those can be delayed should be developed5. Designated hospitals for treating pregnant women with COVID-19 should be enlisted to ensure they will receive appropriate care from a multi-disciplinary team6. At the provincial/regional level, health authorities should adapt to local context and develop uniformed perinatal operational guidelines across all local health facilities and monitor the equitable access to service and service quality. Local health facilities are responsible for disseminating service information via official channels, e.g. account on social media platforms such as WhatsApp, Facebook, and providing services following the provincial/regional operational guidelines.As the pandemic intensifies globally7,8, the experience and lessons of China on the response and streamline health system may help other counties to mitigate adverse impact of the pandemic on maternal and newborns.Disclosure of interestsWe declare no competing interests.

Lopinavir combined with ritonavir were reported to benefit the patients with SARS by reducing the viral loads. However, in the latest clinical trials, no benefit was observed with lopinavir-ritonavir treatment beyond standard care in patients with COVID-19. We comment here that this disappointed result of clinical trial might result from the low volume of the lung distribution of lopinavir. The major reasons were listed below: 1) The binding affinity of ACE2 with SARS-CoV-2 spike protein is ~10- to 20-fold higher than the binding affinity of ACE2 with SARS-CoV spike protein, indicating that SARS-CoV-2 can enter AT2 cells in lung much easier than SARS-CoV. Therefore, the viral loads of SARS-CoV-2 might be much higher than viral loads of SARS-CoV in the lung tissue. 2) The concentration of lopinavir in the lung tissue was 1.18 μg equiv/ml in rats. The low volume of the lung distribution of lopinavir might not be enough to inhibit the coronavirus replication due to the high viral loads in the lung tissue. 3) In contrast, the concentration of chloroquine in the lung tissue was much higher (30.76 ± 0.85 μg equiv/ml) in rats, which might lead to its clinical and virologic benefits in the treatment of COVID-19 patients. Together, we proposed here that anti-SARS-CoV-2 drug repurposing studies should pay more attentions to the lung tissue distribution of antiviral drugs. The efficacy of antiviral drugs might depend on their lung tissue distributions

Dear Editor,Although a worldwide phenomenon, severe acute respiratory syndrome (SARS)-coronavirus (Cov)-2 infection is apparently less severe in some parts of the world. However, some countries present a surprisingly low death toll (https://coronavirus.jhu.edu/map.html downloaded in March 22, 11:00 AM). Epidemiology is crucial to tackle this pandemic as well as the search for compounds to treat. Turmeric (Indian saphron), a much-appreciated spice has India is by far the greater producer, and consumer, together with Pakistan, Malaysia, Bangladesh, Sri Lanka, Taiwan, China, Burma (Myanmar), and Indonesia (http://www.fao.org/fileadmin/user_upload/inpho/docs/Post_Harvest_Compendium_-_Turmeric.pdf downloaded in March 21, 2020). Curcuma or curcuminoids isolated from Turmeric have long been reported to have anti-inflammatory and immunomodulatory activity. Due to its very low bioavailability, alternatives to improve turmeric absorption have been developed. That is not to say that edible consumption would be of no effect (Aggarwal, Gupta & Sung, 2003). A world coronavirus map reveals that countries in southeast Asia present very low numbers of SARS-Cov-2 infections. Although numbers of infected people may not be reliable, the death rate is hard to be hidden. We focused our list on the major turmeric consumers but Taiwan given the strict rules for isolation implemented there. As of March 26, the death covid-19 toll reported in Indonesia, Malaysia, India, Pakistan, Bangladesh, Sri Lanka, and Burma, that represent over one-quarter of the world population was 128, being 78, 23, 14, 8, 5, 0, 0, respectively. On the other hand, Iran, which was a greater consumer of Turmeric, has experienced a shortage of this product due to economic sanctions, and had 2,234 deaths in March 22 (https://economictimes.indiatimes.com/news/economy/foreign-trade/turmeric-exports-hit-by-us-sanctions-against-iran/articleshow/70446034.cms?from=mdr). Community isolation has been hard to be implemented in Iran, which probably has shortage of health facilities and supplies to face this epidemic. Faced with data from developing countries, the death coronavirus disease (covid)-19 toll from high curcumin consumers is apparently very low as compared to those from developed countries, some of them with severe rules restricting social activities and better health infrastructure to treat patients. Would this just be coincidental? There are claims that drugs acting in the angiotensin converting enzyme (ACE) pathway may worsen the clinical picture of patients affected by SARS-Cov-2 (https://www.acc.org/latest-in-cardiology/articles/2020/03/17/08/59/hfsa-acc-aha-statement-addresses-concerns-re-using-raas-antagonists-in-covid-19 downloaded in March 21, 2020). ACE blocking compounds may lead to upregulation of the ACE2 gene receptor expression. It follows that ACE2 receptors are used by SARS-Cov-2 as a cell entry. It has been previously shown that rats subjected to thioacetamide induced hepatotoxicity are protected by Curcumin administration, an effect that was associated with down-regulation of the ACE gene (Akinyemi et al., 2015). Further, rats subjected to induced systemic arterial hypertension were protected by pre-treatment with ginger and turmeric rhizome supplementation, that led to reduction in ACE activity (Fazal, Fatima, Shahid & Mahboob, 2015). Hence, it might well be that Curcumin, by down-regulating ACE gene expression, can be of help against covid-19 disease. Notwithstanding, previous reports have shown that curcumin presents both direct and indirect antiviral activity against the human immunodeficiency virus (HIV) by inhibiting virus replication or via blocking inflammatory pathways operating in the acquired immunodeficiency syndrome (Prasad & Tyagi, 2015). Hard times pose hard problems that demand urgent policies. Health authorities worldwide are struggling to decide which is best to prevent people from getting covid-19 infection and, when the disease unleashes, which attitudes to preserve lives. There are various compounds being tested against covid-19. Hydroxychloroquine, given the safety profile of this well-known immunomodulating compound used in rheumatology for prolonged periods, is being indicated pending robust data to document its efficacy, if any, on the basis that it may be a non-expensive life-saving strategy posing no additional harm to an already affected SARS-Cov-2 patient (Touret & de Lamballerie, 2020). Using the best rationale to look for evidence about the therapeutic effects of turmeric in COVID19, we can do an exercise on Hill’s causality criteria. The strength of the association is high, based on the incidence map, and has been a repeated pattern in many countries with similar consumption of turmeric. There is some consistency between epidemiological and laboratory findings given that Curcumin apparently down-regulates ACE2 gene receptor expression, a major pathway in covid-19 cell entry (see above). We cannot yet claim specificity or biological gradient (dose-response relationship). Temporality is guaranteed because the consumption of saffron has long been incorporated into the culture of those countries. Similarly, chloroquine appears to interfere with the terminal glycosylation of the ACE2 cell receptor (Touret & de Lamballerie, 2020). At this time, we do not believe a ginger tea or adding turmeric to our meal would be of any harm. If in vitro data prove curcumin to be effective, clinical studies could be then proposed.

Since December 2019, the Severe Acute Respiratory Syndrome Coronavirus 2（SARS-CoV-2）has swept 200 countries and regions worldwide1 and has become a ”Public Health Emergency of International Concern” (PHEIC). Pregnant women are susceptible to COVID-19 due to the changes in their physiology and the adaptability of their immune system2. During the outbreak of COVID-19, prenatal examinations may be postponed, however, delivery cannot be delayed, and the delivery room should work as usual. During this period, it is particularly important to quickly identify high-risk groups and to provide appropriate protection for childbirth and the puerperium. In accord with experience in China (Guidelines for the Prevention and Control of New Coronavirus Infections in Medical Institutions issued by the National Health Commission ), we strongly recommend that during the outbreak of COVID-19, all medical institutions should conduct graded, staged, comprehensive and continuous training of all staff, based on the particular epidemic prevention and control needs of for of different positions, to constantly improve staff’s awareness of the prevention and control of COVID-19. To strengthen staff comprehension of the necessary precautions during a COVID-19 epidemic, an assessment method that combines theory with scenario testing should also be applied 3,4. At the same time, based on our experience of delivery room management, we recommend a delivery room processing flow (Fig.1) and graded protection 5 (Table 1) for pregnant women with different infection risks，as detailed below:(1) Primary screening of all women (First level protective equipment should be applied): Check the axillary temperature and the fetal heart rate, and enquire whether there is fever, respiratory symptoms (cough, chest tightness, etc.), gastrointestinal symptoms (vomiting, diarrhea, etc.) and other symptoms before allowing women to sit in the maternity waiting area. Ask whether there is increased risk of contact with a COVID-19 positive patient (fever of any family member within two weeks, a history of traveling to the epidemic area or contact with a suspected or confirmed patient). Any positive history of the above indicates ‘potential risk’ status.(2) Pregnant women with potential-risk and/or suspected infection merit further screening (Second level protective equipment should be applied): attending staff should immediately apply second or third level of protective equipment, screening tests (which include respiratory pathogens tests like adenovirus, respiratory syncytial virus, influenza A virus, influenza B virus and parainfluenza virus, Mycoplasma pneumoniae and Chlamydia pneumoniae, blood routine tests, and C-reactive protein) should be undertaken and the new coronavirus nucleic acid test for pregnant women with potential-risk/suspected infection should be performed. A chest CT scan with informed consent to observe the lungs should be performed if signs or symptoms provide any indication (inform the patients about the necessity of chest CT and ask them to cover their abdomen properly). Obstetric management should not be delayed by testing for COVID-19.(3) Delivery room management (for vaginal delivery): ① Pregnant women suspected to be COVID-19 positive should be immediately transferred to an isolated delivery room (avoiding contact with other patients) or negative pressure delivery room and be required to wear surgical mask6. Accompanying family must not be permitted. Patients should be managed by specific experienced senior medical specialists, and third level protective equipment must be applied to avoid cross-infection; ② pregnant women at potential risk of infection: Accompanying family should not be allowed. Patients are recommended to wear surgical masks6 and should be transferred to isolated delivery rooms, with management/supervision by specific experienced senior medical specialists. Second level protective equipment should be applied to prevent cross-infection, if availability of protective materials is adequate. ③ low-risk pregnant women (those without any history of epidemiological exposure or clinical symptoms) should be transferred to an ordinary delivery room for delivery (avoiding contact with other patients). Second level protective equipment should be applied. It is recommended that these women wear disposable medical masks 6. Only family members who have no history of epidemiological contact and clinical symptoms within the past 2 weeks are allowed to attend the childbirth, and accompanying family members are also required to wear disposable medical masks.As fetal compromise is relatively common in pregnancies complicated by COVID-19 infection, continuous electronic fetal monitoring in labor is recommended for all women suspected with COVID-19, following transfer to the appropriate delivery room.7We advocate attempts to deliver vaginally without undue obstetric intervention and recommend caution regarding procedures such as episiotomy and ventouse/forceps delivery. Currently, we do not recommend water deliveries for pregnant women with suspected infection. There is no evidence that epidural analgesia or spinal anesthesia is contraindicated, therefore, epidural analgesia should be recommended to pregnant women suspected of COVID-19 infection before or in early labor to minimize the need for general anesthesia in emergency situations7.(4) Emergency caesarean section treatment：Suspected COVID-19 infection is not an indication for cesarean section, unless the woman’s respiratory condition demands urgent delivery, or pregnant women have other indications. Multi-disciplinary consultation involving anaesthetists, neonatologists, obstetricians, and infectious disease physicians is required before deciding to deliver prematurely in cases of suspected infection, and if Caesarean section is indicated, the procedure should be performed in a negative pressure isolation operating room (third level protective equipment should be applied). The choice of anesthetic mode is determined by the anaesthetist, based on the patient’s respiratory function. For pregnant women with potential infection (potential-risk), their pregnancy can be terminated in the isolated operating room (second level protective equipment should be applied) if properly protected. First level protective equipment is recommended when performing cesarean section for pregnant women with low-risk infection.(5) Postpartum management: postpartum vital signs, uterine contractions, maternal mental health and other conditions of the mother should be monitored, and attention paid to the prevention of postpartum hemorrhage, thrombosis, etc. For pregnant women with suspected infection, the neonatologist should be notified at least half an hour before delivery to take appropriate measures to isolate the newborn. Delayed cord clamping is still recommended given a lack of evidence to the contrary, unless there are other contraindications7. 14 days of isolation for newborns is recommended8; there is currently no evidence to support the suspension of breastfeeding in pregnant women with suspected infection, indeed, we advocate breastfeeding, as the wider benefits outweigh the potential risks of transmission through breastmilk 7. Isolation and preventive measures should be undertaken if referral is needed 5. If there are no abnormal signs/symptoms within two hours after delivery, mothers with suspected infection can be transferred to an isolation ward for further observation; ‘potential-risk’ pregnant women can be transferred to the isolation ward (avoiding contact with other patients) and low-risk mothers managed according to conventional procedures. Pregnant woman with suspected or potential infection should undergo diagnostic testing immediately. If infection is confirmed, the corresponding management should follow the previous guidelines for dealing with confirmed cases of COVID-192.(6) After-delivery protection procedures: After the mother was transferred to the ward, routine cleaning should be undertaken. The surfaces of the equipment (including the obstetric table, ultrasound machine, and neonatal warm bed) in the isolation delivery room and the negative-pressure delivery room need to be wiped and disinfected immediately, preferably with 1000 mg/L chlorine-containing disinfectant; 75% ethanol can be used for the non-corrosion resistance instruments7,9. Spraying is not a recommended method of disinfecting the equipment as this can affect the components. Dedicated cleaning tools are required to avoid cross contamination. The inspection room should be disinfected with ultraviolet light, ≥60 min each time, once or twice a day, with at least 30 min ventilation after irradiation. The ultrasound probe should be protected with a dark cloth during the irradiation. The room should be vacated when ultraviolet lamps are used.(7) Medical waste disposal: Protective supplies used by medical personnel and all patient waste should be regarded as infectious medical waste, which requires double-layer sealing, clear labeling, and airtight transport 10. If testing of the placenta and/or amniotic fluid is required, strict sampling and sealing should be carried out to avoid contamination of the surface of the container and the spread of infection. The surface of the container should be disinfected before sample inspection to further avoid infection of any personnel.

COVID-19 is a disease which is sweeping the globe, often with devastating consequences. The more we understand, the more it appears that infection has a very wide clinical spectrum from totally asymptomatic to life threatening. Without widespread community testing it is impossible to ascertain true infection rates and develop strategies which reduce or prevent transmission without the need for on-going draconian measures such as complete national lockdown. These measures are mandatory at the time of writing, however widespread adoption of face masks has been shown to help prevent transmission of other respiratory pathogens, and also infections acquired by healthcare staff. Combining mass testing with a combination of social distancing and face mask use might offer a way forward until a mass COVID-19 vaccination programme can be established.

The COVID19 outbreak has affected many aspects of people’s lives, including those of pregnant women. Apart from social-distancing, prohibition of assemblies, isolation, quarantine and many other imposed measures, there are restrictions on access to planned medical consultations, diagnostic procedures and interventions. These restrictions may both, directly and indirectly, disturb the stability of healthcare systems.The previous commentaries presented in this journal have discussed the novel virus and the readiness of obstetricians for dealing with COVID 19 positive mothers. [1][2] But what about the rest? What about those without symptoms, that in some countries are home on lockdown? Are we ready to take our pregnant women completely “online”? Do they all qualify? Is it safe? Is it efficient? Is it ethical? What if something goes wrong? Are there laws protecting both sides: the patient and the medical professional?Pregnant women are a specific group of patients. The majority of them are young women without co-morbidities. But pregnancy is a time of increased medical supervision aimed at achieving the best perinatal outcome, reduction of both maternal and neonatal morbidity and mortality.  Pregnancy is a risk factor of COVID-19 infection,  especially in the 3rd trimester [3]. Adequate antenatal care according to both national and international standards may be affected by several factors: healthcare providers limiting consultations to those classified as urgent both in outpatient and inpatient facilities, limited access to medical facilities due to restrictions of travel and transport. All these restrictions have been imposed in good faith as a measure of social distancing. But it has to be noted that as a result, women may be reluctant to visit medical facilities because of fear of contracting the virus, therefore voluntarily waiving their right to access antenatal visits.Statements have been published regarding the use of personal protective equipment (PPE) aimed at minimizing the risk of exposition of medical personnel. As reality shows, access to PPE is limited even in the most efficient health systems [4]. This may also be a burden in the provision of optimal antenatal care in some settings.COVID-19 pandemic has reached more than 200 countries [5]. The mortality rate varies and depends mainly on age and comorbidities. The highest is recorded in countries such as Italy and Spain [5]. The average reported by WHO is 3.4%. Recent reports indicate a significantly lower mortality of 0.66% [6] because previous registries have not included asymptomatic patients.Adequate antenatal care is a standardized medical process aimed at achieving perinatal results characterized by a low percentage of prematurity, low maternal and fetal mortality and morbidity. The preventive measures implemented over the years helped prevent in many cases, serious complications. In recent years, our country Poland has achieved the lowest maternal mortality in the entire European region and one of the lowest perinatal mortality rates.These results can be attributed to doctor or midwife assisted antenatal visits every 3-4 weeks and recommended 3-4 ultrasound examinations in each pregnancy. This system was built on experience, research and organization of a national perinatal care system. We fear that the failure of the system to perform adequately in the light of the imposed restrictions may, in a short time, lead to a deterioration of perinatal results. This the least will be caused by COVID-19 infections in pregnancy. According to previous reports, the course of coronavirus infection is not worse than in the non-pregnant population of the same age [7]. Particular attention should be paid to pregnant women with co-morbidities because those are at most significant risk of complication both with and without coronavirus infection.When managing a pregnancy, unassisted 4-5 weeks may have a substantial impact on the outcome. Non-adherence to the right timing of acetylsalicylic acid prophylaxis, vaginal progesterone treatment, glucose tolerance test or anti D immunoglobulin injection, can lead to significant complications. Women that suffer from pre-pregnancy morbidities such as hypertension, diabetes, renal problems, obesity are in these times at risk of an even higher risk of adverse outcome due to reduction in surveillance. In their case, there is a need for more than less scrutiny. In this group of women, on the one hand, we fear that restricted access to health care facilities may lead to deterioration of control of blood pressure values, glucose levels or excessive weight gain. On the other hand, they may become exposed to the coronavirus, which again in this group may lead to an adverse outcome, because these women are at higher risk of severe complications associated with the viral infection. As mentioned before, without fully adhering to the recommended protocols for both low and high risk, but especially high-risk pregnancies, the goals of optimal perinatal care cannot be achieved. In the time of the pandemic adherence to protocols is put to the test, and although interim protocols are published by national and international societies to adjust means to the measure, it may not be enough. [8] Two reports [9,10] show the impact of co-morbidities on the percentage of severe cases among infected with COVID-19 pregnant women. In a study from China, 38 women infected with SARS-CoV-2 were analyzed; none of them had pre-pregnancy comorbidities. Of those women, 3 developed gestational diabetes and one hypertension and one preeclampsia during the course of pregnancy. In the New York group, more than 41% demonstrated associated diseases such as asthma, chronic hypertension and type II diabetes. More than 60% of women in the New York group was diagnosed with obesity – a factor neglected in the China group (Table 1). These factors could have a decisive impact on the reported differences regarding the course of the COVID-19 disease, notably since the age of the patients did not differ based on the published data. Analysis of these two studies shows that the course of the viral infection was quite different. In the study group from China, no severe and critical events were observed, and for women in New York, they totalled 14%. From the WHO report from all provinces of China in which 147 pregnant women were analyzed, 8% of severe cases and 1% of critical cases were reported [11]. Despite a relatively small group, these results show that co-morbidities, including obesity, like in the non-pregnant population, decide about the course of the disease in a given age group.Restrictions of access to routine care, fear of exposition, deliberate avoiding of contact with medical personnel, isolation and quarantine orders, and many other factors can lead to hindered pregnancy surveillance. If affecting weight gain, blood pressure and diabetes control in high-risk groups, it may, as a consequence, affect perinatal outcome regardless of COVID-19 infection.The current situation related to the pandemic requires an intensified effort from medical personnel caring for pregnant women. In many cases, new forms of medical care are implemented, such as telephone and video consultations. This cannot always replace traditional perinatal visits but often is a necessity. RCOG warns their pregnant patients to always discuss with their medical professional the decision about not attending their prenatal visit. [12] Regular monitoring of pregnancy is crucial to achieve an optimal outcome. It is the medical community’s responsibility on all levels (local, national, international) not to allow the burdens resulting from epidemiological restrictions to impact negatively the perinatal results achieved thus far.At the beginning of this commentary, we have asked a series of questions. We do not have answers to them. COVID-19 may be the first pandemic in the modern world, but most probably it is not the last. We do not know and cannot tell for how long this situation is going to continue. We propose to begin a discussion of how this can be managed best. Perhaps this should prompt new ideas of how to incorporate telemedicine and artificial intelligence into obstetric practice. The proposed solutions, of course, should be followed by new protocols and laws protecting both the patient and the medical professional.

Coronavirus predictions in NZ and othersNew Zealand is one of the few countries that seem to have got a control over the recent covid19 outbreak.\cite{james_suppression_nodate} Here we present the incidence of Coronavirus in New Zealand and some predictions as to how and when we can expect to get to a point of zero incident cases in NZ. We used the  incidence  package within R statistical software to create incidence objects\cite{Kamvar_2019}  from data obtained from the JHU CSSE covid19 archives, and use  the graphs to obtain these estimates. We used a realistic estimate of R0 2.4 for the first four weeks of the projected numbers and a series of effect reproductive numbers of 0.70 and 0.90 for the downward trend \cite{dietz_estimation_1993}.

The current Covid-19 pandemic is a significant global health threat. The outbreak has profoundly affected all healthcare professionals, including heart surgeons. To adapt to these exceptional circumstances, cardiac surgeons had to change their practice significantly. We herein discuss the challenges and broad implications of the Covid-19 pandemic from the perspective of the heart surgeons.

Outbreak AlertsNovel coronavirus, also known as SARS-CoV-2 linked pandemic, started from Wuhan China during December 2019 (Guo et al., 2020 ). Transmission from the original place took place long before the World Health Organization (WHO) declared it a public emergency on 30th January 2020. As of 12th April, WHO has confirmed 1,614,951 live infected cases and 99,887 deaths in around 200 countries. In India, the first coronavirus positive case was reported from Kerala on 30th January 2020 (Ministry of Health and Family Welfare, 2020d ). Later, the positive cases in India came from Delhi dweller who returned from Italy and a man from Telangana who returned from Dubai. After that, some positive cases were detected within Italian tourists and their tour guide in Rajasthan. Overall, the virus spread in the country has primarily occurred due to foreign travelers or Indian travelers coming from abroad.Currently, India is standing up in the initial stage of community transmission. As per 30th March 2020 Ministry of Health and Family Welfare, Government of India has announced 1224 COVID-19 cases from all over the 27 states and union territories with maximum from Maharashtra (192 cases) and Kerala (202 cases) (Ministry of Health and Family Welfare, 2020a ). The trend of COVID-19 in India has marked slow increase with the primary reproduction number R0 value 1.5 as compared to China (R0 value 2.3), Italy (R0 value 2.34) and Iran (R0 value 2.73) during their 3rd week from the onset of initial SARS CoV-2 positive cases (Cereda et al., 2020; Mandal et al., 2020; Zhao et al., 2020 ). On average, each patient transmits the infection to an additional 2.2 individuals. Based on data from the first cases in Wuhan and investigations by the China CDC, the incubation time can be from 3 to 7 days and up to 2 weeks as the longest time (95% CI, 9.2 to 18) (Singhal, 2020 ). As per the WHO 70th situation report, most of the European regions like Italy, Spain, France are dealing with up to 11%, 7.8%, 6.2%, of case-fatality rate, even more than China (4%)(Onder, Rezza, & Brusaferro, 2020; World Health Organization, 2020 ). Globally, the case-fatality rate is around 2-3% however, severely affected patients may die due to excessive alveolar damage, which leads to progressive respiratory failure as evident from many countries, including Italy and China. SARS-CoV-2 is the seventh coronavirus known to infect humans. Along with SARS-CoV, MERS-CoV, and SARS-CoV-2 severe symptoms causing epidemics whereas HKU1, NL63, OC43 and 229E are associated with mild symptoms (Li et al., 2020; Yang et al., 2020 ).For now, more than 500 whole-genome sequences of different strains of SARS-CoV are reported. Out of these, around 160 isolates have been reported in recent outbreaks mostly from China, Italy, Iran, the USA, Japan, Australia, France, and two from India as well. Two known Indian isolates SARS-CoV-2/166/human/2020/IND (GeneBank: MT050493.1) of 29,851 bp and SARS-CoV-2/29/human/2020/IND (GenBank: MT012098.1) of 29,854 bp are deposited by National Institute of Virology, Pune, Maharashtra. Although both strains are isolated from swabs of infected patients from Kerala, the sequencing of more isolates should be carried out regional wise across major infected areas. Further, systematic gene-level mutational analysis of local strains will enable researchers to identify several unique features of the SARS-CoV-2 genome and the development of more efficient therapeutics and vaccines.Several properties of SARS-CoV-2 make its prevention difficult, namely, non-specific features of the disease, the infectivity even before the onset of symptoms, transmission from asymptomatic people, and long incubation period. Hence, the Indian Government has projected proactive measures to inhibit the spread of SARS-CoV-2 from initial careers coming from abroad to the local community. Implementation of 21 days lockdown all over the country has greatly helped to flatten the logarithm spread within the community (Government of India, 2020) . Meanwhile, to meet the requirement of personal protection equipment, masks and ventilators, and other essential items, the government is allowing domestic companies and manufacturers clearing quality tests to come-up with more supplies. The supply of N95 masks has been ramped up to 1,00,000/day by local manufactures mostly and DRDO (Ministry of Health and Family Welfare, 2020b ).Moreover, total government laboratories approved and supported by Indian Council of Medical Research (ICMR) to provide diagnostic kit for SARS-CoV-2 testing has been increased to 123 all over the country(Indian Council of Medical Research, 2020b) . The government-led awareness programs based on WHO, CDC, and FAO recommendation on COVID-19 has been enforced to all the states (Ministry of Health and Family Welfare, 2020c ). Besides, the state government issued instructions on the closing of all schools and colleges, malls, and any form of the public gathering. As per reports, a widely-used drug Chloroquine, has recently been reported as a potential broad-spectrum antiviral drug. It blocks the virus infection by increasing endosomal pH required for virus/cell fusion, as well as to interfere with the glycosylation of cellular receptors of SARS-CoV (Savarino, Di Trani, Donatelli, Cauda, & Cassone, 2006; Wang et al., 2020; Yan et al., 2013) . Indian government has allowed restricted use of Chloroquine among doctors and other staff members coming in direct contact with severe patients to avoid transmission (Indian Council of Medical Research, 2020a ). Besides, the Central Drugs Standard Control Organization approved constricted public health use of lopinavir/ritonavir combination amongst symptomatic COVID-19 patients(Bhatnagar et al., 2020 ).

Angiotensin converting enzyme-2 (ACE2) is the receptor for the coronavirus SARS-CoV-2, which causes COVID-19. We propose the following hypothesis: Imbalance in the action of ACE1- and ACE2-derived peptides, thereby enhancing Angiotensin-II (ANG II) signaling, a primary driver of COVID-19 pathobiology. ACE1/ACE2 imbalance occurs due to the binding of SARS-CoV-2 to ACE2, reducing ACE2-mediated conversion of ANG II to ANG peptides that counteract pathophysiological effects of ACE1-generated ANGII. This hypothesis suggests several approaches to treat COVID-19 by restoring ACE1/ACE2 balance: 1) ANG II receptor blockers (ARBs); 2) ACE1 inhibitors (ACEIs); 3) Agonists of receptors activated by ACE2-derived peptides [e.g., ANG (1-7), which activates MAS1]; 4) Recombinant human ACE2 or ACE2 peptides as decoys for the virus. Reducing ACE1/ACE2 imbalance is predicted to blunt COVID-19-associated morbidity and mortality, especially in vulnerable patients. Importantly, approved ARBs and ACEIs can be rapidly repurposed to test their efficacy in treating COVID-19.

The emergence of coronavirus disease 2019 (COVID-19) is caused by the 2019 novel coronavirus (2019-nCoV). The 2019-nCoV first broke out in Wuhan and subsequently spread worldwide owing to its extreme transmission efficiency. The fact that the COVID-19 cases and mortalities are reported in globally and the WHO has declared this outbreak as the pandemic. The international health authorities have focused on rapid diagnosis and isolation of patients as well as the search for therapies able to counter the disease severity. Due to the lack of a known efficient therapy and public health emergency, repurposing drugs chloroquine (CQ) analogues appear to be the best tool against 2019-nCoV infection. These analogues have shown potential efficacy to inhibit 2019-nCoV in vitro that leads to focus in several new trials. This review discusses the possible effective roles and mechanisms of CQ analogues for interfering with the 2019-nCoV replication cycle and infection.

In this review, we identify opportunities for drug discovery in the treatment of COVID-19 and in so doing, provide a rational roadmap whereby pharmacology and pharmacologists can mitigate against the global pandemic. We assess the scope for targetting key host and viral targets in the mid-term, by first screening these targets against drugs already licensed; an agenda for drug re-purposing, which should allow rapid translation to clinical trials. A simultaneous, multi-pronged approach using conventional drug discovery methodologies aimed at discovering novel chemical and biological means targetting a short-list of host and viral entities should extend the arsenal of anti-SARS-CoV-2 agents. This longer-term strategy would provide a deeper pool of drug choices for future-proofing against acquired drug resistance. Second, there will be further viral threats, which will inevitably evade existing vaccines. This will require a coherent therapeutic strategy which pharmacology and pharmacologists are best placed to provide.

The emergence in December 2019 of SARS-CoV-2, and its infectious disease COVID-19, has resulted in a worldwide pandemic. Despite the realization that humanity is under a constant threat from respiratory viruses with pandemic potential, such as coronaviruses and influenza viruses, the discovery of a safe and effective prophylactic drug against such infections has remained elusive. The benefits of such a drug for the prevention, containment, or mitigation of emerging and endemic viral threats would be significant. As research on the mechanisms of viral infection has advanced, the repositioning and repurposing of existing drugs and therapeutics has played a significant role in our attempts to find efficacious treatments. This is especially true for COVID-19, though numerous existing drugs were previously studied for their usefulness in treating both SARS-CoV and MERS-CoV infections. Ambroxol, a semi-synthetic derivative of the alkaloid vasicine, has been researched and marketed for more than half a century. Ambroxol was originally marketed as a respiratory mucolytic, mucokinetic, expectorant, and secretolytic. Decades of research have shown it to possess multiple effects, with minimal side effects and a favorable safety profile. Among the mechanisms of action and molecular targets that have been shown for Ambroxol, some of these are potentially of benefit for the prevention and treatment of viral infections caused by influenza viruses, rhinoviruses, and coronaviruses. If proven to be safe and effective, the repurposing of Ambroxol as a phylactic and treatment for these viral infections would be a major advancement in public health, by lowering the morbidity and mortality caused by these viruses.

Background: Fangcang hospital (cabin hospitals) played a key role in isolation and control of the infection sources during COVID-19 epidemic. The patients at Fangcang hospitals were complicated, and many had different symptoms of COVID-19, some had comorbidities or mental stress, and many were confused with the drug usages etc. Objective: Due to the limitation and high work pressure of first line medical workers, patients’ various problems couldn’t be explained well. Under this circumstance, online pharmaceutical care was provided by clinical pharmacists. This study was a retrospective study to evaluate the role and usefulness of clinical pharmacists at Jianghan Fangcang Hospital. Besides, this new mode of service was also introduced in detail to provide options for pharmacists in other hospitals. Methods: The pharmaceutical care included medication education via broadcast station, and medication reconciliation, optimization of drug use, monitor of adverse drug events, and psychological comfort via WeChat® one-to-one service. In this study, we analyzed patients’ characteristics and drug usages, concluded almost 200 patients’ problems classified into 6 aspects solved by clinical pharmacists, and also assessed the patients’ satisfaction with our service. Results: The clinical pharmacist help patients solved almost 200 questions, which mainly focused on the drug related problems including drug usage (65.38%), medication reconciliation (55.13%), drug precautions (23.1%), adverse drug reactions (35.9%), and psychological counseling (32.05%). Through 35 days’ services, Most patients were satisfied with clinical pharmacist service(66.7%great, 18.0%good). Besides, most patients thought the service had positive effect on their mental stress(16.7%great, 43.6%good, 26.9%fair). Conclusion: The results of the retrospective study indicated that clinical pharmacist can effectively reduce and prevent drug-related, life-related and COVID-19-related problems for COVID-19 patients. This work may provide possible work patterns for clinical pharmacist in other hospital and give more professional service for Fangcang hospital patients.

The recent pandemic caused by the 2019 outbreak of novel coronavirus (2019-nCoV) has affected more than 1.3 million people resulting ~75000 deaths across 212 countries/territories as on 7th April 2020. The importation of the cases owing to enormous international travels from the affected countries is the foremost reason for local cycle of transmission. For a country like India, the second most populous country in the world with ~1.35 billion population, the management and control of 2019-nCoV domestic spread heavily relied on effective screening and strict quarantine of passengers arriving at various international airports in India from affected countries. Here, by extracting the data from FLIRT, an online airline database for more than 800 airlines, and scanning more than 180000 flights and 39.9 million corresponding passenger seats during 4th – 25th March, we show that India experienced the highest risk index of importing the passengers from middle eastern airports. Contrary to perception, travelers from China imposed lowest risk of importing the infected cases in India. This is clearly evident form the fact that while the number of infected cases were on the peak in China India was one of the least affected countries. The number of cases in India started exhibiting a sharp increase in the infected cases only after the European countries and USA recorded large number of infected cases. We further argue that while the number of cases in middle eastern countries may still be very low, the airports in middle eastern countries, particularly Dubai, being one of the largest transit hubs for international passengers, including arriving in India, might have posed a higher risk of getting infected with 2019-nCoV. We suggest that any future travel related disease infection screening at the airports should critically assess the passengers from major transit hubs in addition to affected country of origin.

The ongoing outbreak of Coronavirus disease 2019 (COVID-19) has already caused a worldwide pandemic, World Health Organization has raised COVID-19 global risk to very high. We aimed to share the Joint Prevention and Control Mechanism taken in Mainland China and evaluate the effectiveness. Data were collected from the daily epidemic reports released by the national and provincial health commissions of China from January 21 to March 26, 2020. Global data were collected from daily situation reports by World Health Organization. Under the first-level public health emergency response, great achievements have been made in controlling the spread of COVID-19 in Mainland China. As of March 26, the daily new deaths were less than 50 in nationwide recently. However, it is still a major challenge worldwide. The comprehensive and powerful control measures taken by Mainland China have proved to be effective and might be applicable to other regions.

Tyrosine kinase inhibitors (TKIs) have revolutionized the management of chronic myeloid leukemia (CML), and currently in patients with CML in chronic phase (CML-CP) the first-line treatment is based on BCR-ABL targeted therapy with TKIs [1]. Although generally well tolerated, all BCR-ABL TKIs can be associated with hematologic and non-hematologic toxicities [2]. Most of the patients with CML-CP continue receiving TKIs, unless there is lack of optimal response and/or serious toxicities.

A document by M Veera Krishna, written on Authorea.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), along with Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) are three emerging coronaviruses with huge public health in the 21st century. Especially, SARS-CoV-2 causes an unprecedented global pandemic and has spread in over than 200 countries. Clinically, SARS-CoV-2 could co-infected with respiratory pathogens including influenza virus and adenovirus in some present cases. This suggests that the differential diagnosis cannot be ignored. To investigate whether SARS-CoV-2 exists earlier and identify possible co-infection in human with respiratory disease, we performed the detections of SARS-CoV-2 and influenza virus using real-time RT-PCR method and colloidal gold test strip in 534 throat swab samples collected in influenza epidemic season (from January to May of 2019). 336 samples (62.9%) were tested positive for influenza virus, which involved into 230 single influenza A virus (IAV)-positive samples, 4 single influenza B virus (IBV)-positive samples, and 102 IAV and IBV co-infection samples. Unfortunately, we found no positive signal of SARS-CoV-2 in 534 samples. Our finding reveals absence of SARS-CoV-2 infection in human archived samples in before the outbreak of SARS-CoV-2 in China. In addition, this study suggests that IAV was still major respiratory pathogen responsible for respiratory disease in the influenza season.