Dataset: 11.1K articles from the COVID-19 Open Research Dataset (PMC Open Access subset)
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2019-nCoV pneumonia are emerging attack at China and worldwide in the winter of 2019-2020. The identified 2019-nCoV genome has been sequenced the closest to some beta-coronaviruses detected in bats. Person-to-person transmission in family homes or hospital, and intercity spread of 2019-nCoV are occurring. At present, the mortality of 2019-nCoV in China is 2.3%, compared with 9.6% of SARS and 34.4% of MERS reported by WHO. It seems the new virus is not as fatally as many people thought. The most common symptoms were onset of fever, generalized weakness and dry cough. Notably, some patients were afebrile or confirmed biologically to have an asymptomatic infection. And the ground glass changes on chest CT scan were earlier than the positive for RT-PCR test in some cases. Repeat testing of nasopharyngeal swab or sputum samples are recommended in clinical suspected cases with an initially negative result. According to the current status, blocking transmission, isolation, respiratory and eye protection, and hand hygiene are the urgent management strategies against 2019-nCoV.
It is currently unclear how 2019-nCoV is spread, but it is suspected to be transmitted through contact with infected respiratory secretions, like other known coronaviruses. There are instances of sustained human-to-human transmission across generations of cases, especially near the epicenter in Wuhan City.21 Current evidence suggests that close contact with an infected person is a major factor in disease transmission. CDC defines “close contact”33 as being in or within two meters of an area with a confirmed patient or being directly exposed to infectious secretions without appropriate PPE. Healthcare facilities in China have reported spread from person to person. In addition, some mildly ill or potentially even asymptomatic patients may have a higher chance of spreading the disease to others as they may be less likely to seek medical care.34 The possibility that patients may be infectious prior to symptom onset further compounds the difficulty of containing the virus and effectively preventing transmission.
The current majority of 2019-nCoV cases have been within China and its bordering countries.2 Persons with recent travel (within 14 days) to Wuhan City or another region with widespread disease, or exposure to a patient under investigation, are considered to have an epidemiologic risk factor and should be assessed for signs and symptoms of a viral illness such as fever and respiratory symptoms. Coronavirus is a zoonotic virus that is transmitted to humans via contact with infected animals. Preliminary reports suggest the disease may have originated in a seafood and live animal market in Wuhan City, but it is still unknown how or whether such transmission occurred.
There were three boys, six girls and their 14 families admitted to Jinan Infectious Disease Hospital of Shandong University were investigated in this study. The youngest of the nine children was a pair of eleven-month-old twins and the oldest is nine years and 9 months old (mean age was 4.5 years, median age 3.5 years, Table 1). There were 16 families were infected by SARS-CoV-2, and 14 adults were enrolled in this study (two patients hospitalized in another hospital). The 14 patients consisted of 8 males and 6 females with a mean age of 42.9 years (median age, 37 years [range, 30–72 years]).
On 29 December 2019, the first four cases of an acute respiratory syndrome of unknown etiology were reported in Wuhan City, Hubei Province, China among people linked to a local seafood market (“wet market”). Research is underway to understand more about transmissibility, severity, and other features associated with COVID-19. It appears that most of the early cases had some sort of contact history with the original seafood market [2, 12–14]. Soon, a secondary source of infection was found to be human-to-human transmission via close contact. There was an increase of infected people with no history of exposure to wildlife or visiting Wuhan, and multiple cases of infection were detected among medical professionals [2, 14–17]. It became clear that the COVID-19 infection occurs through exposure to the virus, and both the immunosuppressed and normal population appear susceptible. Some studies have reported an age distribution of adult patients between 25 and 89 years old. Most adult patients were between 35 and 55 years old, and there were fewer identified cases among children and infants [14, 18]. A study on early transmission dynamics of the virus reported the median age of patients to be 59 years, ranging from 15 to 89 years, with the majority (59%) being male. It was suggested that the population most at risk may be people with poor immune function such as older people and those with renal and hepatic dysfunction.
The COVID-19 has been found to have higher levels of transmissibility and pandemic risk than the SARS-CoV, as the effective reproductive number (R) of COVID-19 (2.9) is estimated to be higher than the reported effective reproduction number (R) of SARS (1.77) at this early stage. Different studies of COVID-19 have estimated the basic reproduction (R0) range to be from 2.6 to 4.71 (Table 4). The average incubation duration of COVID-19 was estimated to be 4.8 ± 2.6, ranging from 2 to 11 days and 5.2 days (95% confidence interval, 4.1 to 7). The latest guidelines from Chinese health authorities stated an average incubation duration of 7 days, ranging from 2 to 14 days. Table 4 summarizes the findings on important indicators from these epidemiological studies.
In China, 11 791 cases were confirmed and 17 988 cases were suspected in 34 provinces as of 24:00, 31 January 2020 (Fig. 4). Studies indicated that the spread of COVID-19 was relatively quick and reported that it had spread to several other countries after its outbreak in China. On 31 January 2020, there were 213 deaths reported globally. Confirmed cases were reported in the following 19 countries outside of China: Australia (9), Canada (3), Cambodia (1), France (6), Finland (1), Germany (5), India (1), Italy (2), Japan (14), Nepal (1), Malaysia (8), the Philippines (1), the Republic of Korea (11), Singapore (13), Sri Lanka (1), Thailand (14), the United States of America (6), United Arab Emirates (4) and Vietnam (5) (Fig. 5).
On 31 December 2019, Wuhan Municipal Health Commission reported a number of unknown pneumonia cases related to Huanan Seafood Wholesale Market, 27 cases were hospitalized, seven of which were in serious condition. On 5 February 2020, Wuhan Municipal Health Committee reported that 59 cases of viral pneumonia with unknown etiology were detected in Wuhan, including seven severe cases, but no clear evidence was found for “human-to-human” transmission. On Jan 11, Wuhan Municipal Health Committee issued a new report confirming that the pathogen of the viral pneumonia of unknown cause was initially determined as a new coronavirus. On 20 February 2020, it was officially confirmed that “human-to-human” transmission and nosocomial infection had occurred.
Since 16 February 2020, the cumulative COVID-19 case number increased quickly; meanwhile, the daily emerging case number increased steadily to 3886 on 4 February 2020, and then fluctuated to 2015 on 11 February 2020. The fatality cases number increased steadily to 2004 cases on 18 February 2020. The cumulative and daily emerged cases number jumped to 59,804 and 15,152, respectively, on 12 February 2020 (Figure 1). This fierce growth of cumulative and daily emerged cases number in one day is due to the improvement of diagnosis standard for confirmed cases in Hubei province, in which the suspected cases with pneumonia imaging characteristics are categorized as clinical diagnosis cases. As a result, the patients can receive standard treatment as soon as possible. All data are from the National Health Commission of the People’s Republic of China.
The COVID-19 resulted in much lower mortality (about 2.67% up-to-date) among the confirmed cases, compared with Severe Acute Respiratory Syndrome (SARS) at 9.60% (November 2002–July 2003) and Middle East Respiratory Syndrome (MERS) at 34.4% (April 2012–November 2019) (Table 1). The median ages for the patients of COVID-19, SARS, and MERS are 55.5, 41.3, and 52.8 years old, respectively. COVID-19 and MERS patients share similargender composition of females (32%) and males (67%), but SARS patients show almost the same proportion of males (46.9%) and females (53.1%).
According to the “Diagnosis &Treatment Scheme for Novel Corona Virus Pneumonia (Trial) 6th Edition”, the source of infection is majorly the COVID-19 patients, even the asymptomatic patients can also be the source of infection. The transmission way is majorly through respiratory droplets and contacting. People are generally susceptible to this virus.
Learning from the SARS outbreak, which started as animal-to-human transmission during the first phase of the epidemic, all game meat trades should be terminate to prevent this portal of transmission. At the same time, we could not ignore the environmental assessments at the seafood market and investigations to identify the pathogen causing the outbreak.
Person-to-person transmission was efficient and super-spreading events had led to major outbreaks in public gathering places. The severity of disease is an important indirect factor helps to identify those who had been infected. If infection does not cause serious disease or asymptomatic infection, infected people probably end up in health care centers. Instead, they would go to work and travel, thereby potentially spreading the virus to their contacts. Recent epidemiological survey and studies showed the patients who did not travel to Wuhan became infected with the virus after several days of contact with the family members. None of the family members had contacts with Wuhan markets or animals, neither had visited a Wuhan hospital. Person-to-person transmission in family homes or hospital, and intercity spread of 2019-nCoV are occurring, and therefore vigilant control measures are warranted at the whole stage of the epidemic.
All nine pediatric patients came from eight families. As shown in Table 1, six children had no information on symptoms available, but have positive results in nucleic acid detection after the positive diagnosis of their families. By contrast, only one child has wild cough and two children have a mild fever (37.4–38.5°C). None of the nine children required intensive care or mechanical ventilation or had any severe complications.
For the 14 adult patients, the main clinical symptoms were fever (8/14, 57.1%), cough (5/14, 35.7%), chest tightness/pain (3/14, 21.4%), fatigue (3/14, 21.4%) and sore throat (1/14, 7.1%). Meanwhile, there were four patients had no clinical symptoms. From the epidemiological data, 7/14(50%) of the adults were infected through household contact, 5 (35.8%) was found to be infected after returning from Wuhan or Hubei in late January 2019 and 2 (14.2%) patients couldn’t find the exact source of infection.
Prevention of 2019-nCoV transmission, like any other infectious agent, involves minimizing risk of exposure. Vaccines are under accelerated development and may be useful in the future for post-exposure prophylaxis. Healthcare personnel are at increased risk and should practice standard, droplet, and airborne precautions when encountering an infected person, a PUI, or any symptomatic close contacts. Healthcare workers handling specimens should also adhere to CDC guidelines and should not attempt to perform any virus isolation or characterization.
Fever screening has been implemented at numerous airports, including major international hubs within Asia and the US. The efficacy of this intervention is not well documented, however, as some infected persons may be afebrile and disease transmission might occur prior to symptom onset.27 In addition, people can artificially lower their temperature readings, e.g., by applying ice to their foreheads.
We searched MEDLINE, ScienceDirect, Embase, the Cochrane Library, WanFang Database, VIP Database, SinoMed, China National Knowledge Infrastructure (CNKI), the CDC for COVID-19 website (https://www.cdc.gov/coronavirus/2019-ncov/publications.htm), Chinese Scientific Research Academic Exchange Platform for COVID-19 (http://medjournals.cn/2019NCP/index.do), and relevant references for papers related to "ophthalmology and SARS-CoV-2/COVID-19"; published till 12th March 2020. The search strategy was as follows: (SARS-CoV-2 or 2019-nCov or COVID-19 or NCP or coronavirus or "severe acute respiratory syndrome coronavirus 2" [Supplementary Concept] or "COVID-19" [Supplementary Concept]) and (ocular or eye or ophthalm* or ophthalmologist or tear or conjunctiv* or "Conjunctivitis"[Mesh] or "Conjunctivitis, Viral"[Mesh]).
We identified 33 articles in total published by Chinese scholars directly relevant to ophthalmology and SARS-CoV-2/COVID-19. Twenty-seven articles are published in Chinese journals, most articles are reviews, almost all regarding ophthalmic precautions and ocular surface transmission of SARS-CoV-2 infection (Table 1).
Starting from the December 2019 identification of the 2019 novel coronavirus (2019-nCoV), an overwhelming sense of panic has enveloped public discourse. This is likely to be amplified by WHO recently declaring the novel coronavirus outbreak a public health emergency of international concern. It is the third significant occurrence of a zoonotic coronavirus crossing the species barrier to infect humans, and it likely will not be the last. Hope is not lost; and a measured approach, one that is cognizant of the seriousness of this public health crisis without giving into hysteria, is imperative.
The coronavirus was identified in a wet food market in Wuhan, China, and has been the subject of a robust public health response by both Chinese authorities and the international community ever since. While debates about the primary reservoir of the virus are still ongoing, the virus is closely related to several bat corona-viruses. Coronaviruses (CoV) are positive-sense, single-stranded RNA viruses, possessing the largest viral RNA genome known to-date. They are known for their rapid spread, unpredictable emergence, and their threat to human health, magnified by the wide range of animal reservoirs and the lack of preventive or curative treatments [1, 2, 3, 4].
The 2019-nCoV is a beta-CoV similar in sequence (80%) with the severe acute respiratory syndrome coronavirus (SARS-CoV), the coronavirus strain implicated in the 2002 SARS outbreak, but even more closely related to several bat coronaviruses. Bats were also identified as the primary reservoir for SARS-CoV, although coronaviruses are found in many species. The Middle East respiratory syndrome coronavirus (MERS-CoV), another highly pathogenic CoV responsible for the 2012 MERS outbreak, has been transmitted through contact with camels, although with a different human tropism. The novel coronavirus is believed to infect human cells through its interaction with the human angiotensin-converting enzyme 2 (ACE2) receptor, similarly to SARS-CoV. Despite the differences between the SARS, MERS and novel coronavirus, the similarities within the beta-CoV genus allow us to extrapolate from our previous experience with corona-virus outbreaks and increase our understanding of the current one.
The infection affects patients with and without underlying diseases, although the majority of the fatalities are older patients or patients with significant comorbidities. The vast majority of reported cases have been in adults, decreasing our ability to draw inferences and make recommendations for pediatric patients. Despite its apparent increased infectivity (R0=2.2) the 2019-nCoV strain appears to be less virulent than SARS-CoV (case-fatality rate=9.5%) and MERS-CoV (case-fatality rate=34.4%); currently reported case-fatality rate of 2019-nCoV is 2.2% [3, 4]. Superspreaders (R0>10) have been identified in both MERS-CoV and SARS-CoV outbreaks and there are similar reports of 2019-nCoV superspreaders. One should be mindful of the possibility of systematic underreporting in our current dataset, but the numbers represent our best estimates as of January 31, 2020, 02:30 GMT. (For updated information see: https://tinyurl.com/Hopkin-sCSSE)
Recent case reports of human to human transmission, including in patients who have not visited Wuhan, are concerning but not surprising. Transmission is believed to occur only after symptoms of lower respiratory tract infections present, due to its tropism for intrapulmonary epithelial cells. A crucial lesson learned from our experience with SARS-CoV and MERS-CoV is that community transmission occurs primarily through large droplets, not aerosols. Transmission is also to a large degree nosocomial, which is why a measured approach, one that prevents overutilization of medical resources and panic in the general population.
From an infection-control perspective, medical professionals should exercise droplet and contact precautions, as well as airborne precautions when performing procedures that generate aerosols (i.e. endotracheal suctioning, intubation) in patients suspected of having 2019-nCoV. From a public-health perspective, patients presenting with acute respiratory illness require screening according to the WHO criteria. Patients suspected of being infected with 2019-nCoV should be managed according to governmental protocols. Patients who do not meet the criteria are unlikely to be infected with 2019-nCoV. Patients with acute respiratory illness, without positive WHO criteria, should not have their management changed solely based on unspecific symptoms. For patients without exposure to the virus, the immediate health risk is low; this should be communicated to both providers and patients.
Patients infected with 2019-nCoV typically present with symptoms indicative of viral pneumonia such as fever, cough, fatigue, and dyspnea. This is similar to the Middle East respiratory syndrome corona-virus (MERS-CoV) and the severe acute respiratory syndrome coronavirus (SARS-CoV) outbreaks. Patients typically exhibit radiographic findings of bilateral multiple lobular and subsegmental consolidations, progressing to ground-glass opacities on chest CT images. Secondary complications of 2019-nCoV include acute respiratory distress syndrome (ARDS), RNAemia (viremia), acute cardiac injury as well as secondary infections, with 23% requiring admission to the intensive care unit.
The competent critical care provider should not fear 2019-nCoV. While this is a new, incompletely understood strain, its management remains similar to previous CoV outbreaks. Patients may present with clinical pictures including uncomplicated respiratory infections, pneumonia, ARDS, sepsis or septic shock. Despite 2019-nCoV being a viral infection, patients meeting sepsis criteria should receive the customary treatment, including early initiation of broad-spectrum antibiotic therapy, due to the potential of secondary infections. The usage of corticosteroids for viral pneumonia or ARDS is discouraged in patients suspected of having 2019-nCoV unless otherwise indicated. With that being said, our current guidance is interim and good clinical judgment is still necessary when managing patients with 2019-nCoV. While 2019-nCV is novel, coronaviruses are not and the general principles of managing viral pneumonia still apply. Both local reporting guidelines, as well as WHO guidance on the management of 2019-nCoV, will continue to evolve as we better understand the outbreak.
Is the novel coronavirus the crown-jewel of pandemics? No. It is a serious infectious disease, but not one that is incredibly unusual. In the recent past, we have managed SARS, MERS, Ebola, and Zika. Our scientific community is prepared and vigilant, which is evidenced in the incredibly fast response to the current outbreak. This is also not the last time we will hear about coronaviruses. They have a significant infectivity potential, and more scientific resources should be devoted to understanding and reducing the severity of future outbreaks. However, due to our experience with managing coronaviruses outbreaks in the past, we are well prepared to tackle the current one. Despite the high infectivity, the case-fatality rate remains low; state governments and the WHO are implementing the necessary measures to reduce the spread of the infection.
Four of the seven human coronaviruses are endemic around the world but cause little more than the common cold. Currently, SARS-CoV-2 is a global epidemic, with the potential to be considered a pandemic. In one scenario, this outbreak may be contained, and the virus never seen again, like SARS-CoV. Alternatively, the virus may become an endemic virus with seasonality like influenza and the other human coronaviruses. However, it is too early to know whether SARS-CoV-2 spread will be affected by changing weather conditions. Nearly all cases of COVID-19 have been in China, where it is winter; whether cases will decrease as temperatures increase in the Northern Hemisphere, as is seen for influenza, remains to be seen.
Treatment principle: based on symptomatic treatment, actively prevent and treat complications, treat basic diseases, prevent secondary infection, and timely apply organ function support.Respiratory support: apply noninvasive mechanical ventilation for two hours, if the condition is not improved, or the patient is intolerable to noninvasive ventilation, accompanied with increased airway secretions, severe coughing, or unstable hemodynamics, the patient should be transferred to invasive mechanical ventilation in time. The “lung-protective ventilation strategy” with low tidal volume should be adopted in invasive mechanical ventilation to reduce ventilator-associated lung injury. If necessary, ventilation in the prone position, recruitment maneuver, or extracorporeal membrane oxygenation (ECMO) can be used.Circulation support: improve microcirculation based on full fluid resuscitation, use vasoactive drugs, and apply hemodynamic monitoring if necessary.Others: according to the degree of dyspnea and the progress of chest imaging, use glucocorticoids appropriately for a short time (3–5 days) with the recommended dose no more than what is equivalent to methylprednisolone 1–2 mg/kg·day.
One study focused on the cases of 41 patients hospitalized in Wuhan before January 2, all of whom had laboratory‐confirmed 2019‐nCoV infection (Huanget al., 2020). At this earliest phase of the outbreak, patients were mostly males (73%), half of whom had underlying diseases and 66% of whom were exposed to the Huanan seafood market. Common presenting symptoms were fever (98%), cough (76%) and myalgia or fatigue (44%). Dyspnoea (laboured or difficult breathing) developed in 55%; acute respiratory distress syndrome (ARDS) was seen in 29%; 32% of patients needed to be transferred to an intensive care unit (ICU); and 15% died. The patients showed lymphopenia (a reduction of lymphocytes in the circulating blood) and signs of a ‘cytokine storm’. A follow‐up study investigated 99 patients at Jinyintan Hospital in Wuhan between January 1 and January 20. All 99 patients had PCR‐confirmed 2019‐nCoV infection (Chen et al., 2020). During this next phase of the epidemic, fewer patients had had an exposure to the Huanan seafood market (49%), but they were still predominantly male (67%). The average age was 55 years, and again, half of them suffered from chronic diseases. The predominant clinical manifestations in these patients were fever (83%), cough (82%) and shortness of breath (31%). Imaging techniques showed bilateral pneumonia in 75% of the cases. Seventeen per cent developed ARDS, which worsened in 11%, leading to death from multiple organ failure. In a third report, 138 patients with confirmed novel coronavirus infection were admitted between January 1 and 28 at Zhongnan Hospital of Wuhan (Wang et al., 2020c). This report differed from the previous two in important respects. In this cohort, only 9% of the patients reported having had an exposure to the Huanan seafood market, and the gender ratio was not significantly biased. The presenting symptoms were fever (99%), fatigue (70%) and dry cough (59%), followed by anorexia, myalgia and dyspnoea. Bilateral shadows, or ground glass opacities, were revealed by imaging techniques in the lungs of all patients. Overall, 26% of the patients needed a transfer to ICU and 4% died. Half of the patients showed comorbidities (hypertension, cardiovascular disease and diabetes). Most notably, 41% were possibly infected in the hospital, including 40 healthcare workers. Until February 9, only nine cases of 2019‐nCoV infections were reported in infants under 1 year in China, all of whom had had infected family members. All infants had a mild form of disease (Wei et al., 2020).
Standard nosocomial preventive control measures are in urgent need to block further spreading of the disease. The in-hospital preventive control measures should vary among patients, close contacts, and health care workers in precision medicine approach.
The triage of patients by disease severity is the priority; patients should be triaged as soon as possible when they come to the clinic or hospital, depending on disease severity.
The infection is defined as severe when a patient meets any of the criteria established by the Diagnosis and Treatment Scheme issued by the National Health Commission4:
(i) A respiration rate greater than 30 breaths per minute, dyspnea;(ii) A blood oxygen saturation of <93% in resting state;(iii) A PaO2:FiO2 ratio (the ratio of arterial oxygen partial pressure to fractional inspired oxygen) of <300 mm Hg;(iv) Radiologic evidence of foci in multiple lobes or more than a 50% progression of lung inflammation.
The infection is defined as critical when any one of following is met:
(i) Respiratory failure and the need for mechanical ventilation;(ii) Shock;(iii) Multiple organ failure and admission to the intensive care unit.
According to the Diagnosis and Treatment Scheme, timely isolation of suspected cases is essential.4 Patients suspected of infection with 2019-nCoV should be examined only in an isolated area where health workers are protected by protective clothing with adequate protection level.
Once the virus is detected, patients should be admitted to a negative-pressure isolation ward or to private rooms. Several researchers have found that confinement to an isolation ward can prevent the airborne spread of pathogens.15 Patients with mild symptoms can be observed in separate isolation wards or during home quarantine if hospital beds are unavailable. However, all critically ill patients should be immediately admitted to isolation wards with environmental negative pressure equipment and medical protection.
Health care workers should be given appropriate equipment, including respirators (NIOSH-certified N95, EU FFP2, or higher-level protection), eye protection (goggles or a face shield), and clean, long-sleeved gown and gloves.12 Equipment should be thoroughly disinfected between patients, and health workers should wash their hands for at least 20 seconds after patient contact. Occupational exposures in workplace should be immediately reported to the infection control unit at the hospital, and the exposed doctor or nurse should be quarantined in the hospital.
People in close contact with patients or with those suspected of 2019-nCoV infection should be examined immediately if they experience respiratory symptoms, such as fever, or related symptoms. Even if their test result is negative, they should be temporarily isolated at home for 14 days after the last contact with confirmed patients—since 14 days is the disease maximum incubation period.16 The National Health Commission also recommends that members of the public should wash their hands with soap and water for at least 20 seconds and, when going outside, wear a medical face mask and cover their nose and mouth with a tissue, arm, or hand when coughing or sneezing.
Many domestic and wild animals, including camels, cattle, cats, and bats, may serve as hosts for coronaviruses. It is considered that, generally, animal coronaviruses do not spread among humans. However, there are exceptions, such as SARS and MERS, which are mainly spread though close contact with infected people via respiratory droplets from cough or sneezing. With regard to COVID-19, early patients were reported to have some link to the Huanan Seafood Market in Wuhan, China, suggesting that these early infections were due to animal-to-person transmission. However, later cases were reported among medical staff and others with no history of exposure to that market or visiting Wuhan, which was taken as an indication of human-to-human transmission [2, 4, 15–17].
The latest guidelines from Chinese health authorities [23, 43] described three main transmission routes for the COVID-19: 1) droplets transmission, 2) contact transmission, and 3) aerosol transmission. Droplets transmission was reported to occur when respiratory droplets (as produced when an infected person coughs or sneezes) are ingested or inhaled by individuals nearby in close proximity; contact transmission may occur when a subject touches a surface or object contaminated with the virus and subsequently touch their mouth, nose, or eyes; and aerosol transmission may occur when respiratory droplets mix into the air, forming aerosols and may cause infection when inhaled high dose of aerosols into the lungs in a relatively closed environment [23, 43]. In addition to these three routes, one study also indicated the digestive system as a potential transmission route for COVID-19 infection. Since patients had abdominal discomfort and diarrhea symptoms, researchers analyzed four datasets with single-cell transcriptomes of digestive systems and found that ACE2 was highly expressed in absorptive enterocytes from ileum and colon.
As more cases of COVID-19 occur, it is becoming established that the most severe cases and mortality are associated with underlying health conditions. The most common associated comorbidities are pulmonary disease, diabetes, and old age (10). Interesting questions as to how these comorbidities impact viral pathogenesis are open for investigation. More severe SARS cases were also associated with age, and work in mice has demonstrated this (12–14). Severe MERS is associated with diabetes and other underlying health conditions (15, 16), and again, work in mice has shown that diabetes can impact the immune response to infection, leading to increased pathogenesis (17). It will be interesting to see whether SARS-CoV-2 infection is similarly impacted.
According to the findings of the present study, hypertension, cardiovascular diseases, diabetes mellitus, smoking, COPD, malignancy, and chronic kidney disease were among the most prevalent underlying diseases among hospitalized patients with COVID-19, respectively.
In West China Hospital of Sichuan University at Chengdu, one of the top hospitals in China, we found that infections caused by human coronaviruses (HCoVs) have a seasonal pattern that varies among age groups (Fig. 2). Winter and spring are associated with the highest incidence of coronavirus epidemics, which is consistent with the current epidemic of 2019-nCoV. In this sense, the particularities of 2019-nCoV incidence should not be overemphasized.
To date, seven strains of coronaviruses have been confirmed to infect humans: HCoV-229E, HCoV-OC43, SARS-CoV, HCoV-NL63, Human coronavirus HKU1, MERS-CoV, and 2019-nCoV.1,3 Since HCoV-229 and HCoV-OC43 were identified in 1966 and 1967, respectively,8,9 the coronaviruses have been known to cause mild-to-severe respiratory disease. In the SARS-CoV epidemic in 2002 and 2003, more than 8000 people were infected and 916 died.10 Subsequently, by 28 February 2018, 2066 confirmed cases were attributed to MERS-CoV while more than 720 deaths were reported.10
Patients with SARS or MERS infections present with a spectrum of symptoms ranging from upper respiratory tract infection to ARDS, whereas other HCoVs cause severe lower respiratory tract infection, primarily in the elderly and neonates.10
Currently, the most common diagnostic method of coronaviruses is molecular detection.10 A precision medicine approach is crucial to quickly confirm the diagnosis with laboratory methods, control the spread of the virus, and better allocate hospital resources.
No data are associated with this article.
For planning public health measures, basic transmission data for the novel coronavirus are essential. The first 425 confirmed cases from Wuhan provided data for a first epidemiological analysis (Li et al., 2020a), but it should be kept in mind that the virus might evolve during the epidemic and change its properties. Over the three early phases of the infection (< Jan1, Jan1‐11, Jan 12‐22), no change in average age was seen (56–61 years); no cases < 15 years of age were observed. Male dominance among the patients disappeared, and the degree of ‘wet’ market exposure in the patients dropped over time. In addition, patient contact with persons showing respiratory symptoms was reported in fewer than 30% of the cases. These scientists calculated a mean incubation period of 5.2 days displaying a long tail (95th percentile: 12.5 days). Comparisons of index cases and secondary cases in five clusters yielded a ‘serial interval’ of 7 days. From onset of illness to a medical visit, and then to hospital admission, 5 and 12 days elapsed respectively. The Wuhan epidemic showed a doubling time of 7 days. From the cluster analysis, a basic reproduction number of 2.2 was estimated, i.e. each case led on average to 2.2 new infections. Another report investigated a case of a family from Shenzhen visiting relatives in Wuhan (Chan et al., 2020). One Wuhan relative had developed fever, cough and dyspnoea four days before the arrival of family members from Shenzhen. Four further relatives developed respiratory symptoms which led to hospitalization in two. From the six Shenzhen family visitors, the four adults developed symptoms (fever, cough, weakness and diarrhoea) during the 5 days of their Wuhan visit, while two children remained unaffected. Notably, a family member who remained in Shenzhen contracted the disease four days after the return of the visitors from Wuhan to Shenzhen. The data are evidence for efficient human‐to‐human virus transmission. The virus was detected in most nasopharyngeal and half of the throat swabs, a single serum sample, but no urine or stool sample of this family cluster. Of importance for easy sampling and virus diagnostics, 90% of hospitalized patients from Hongkong were positive for PCR virus detection in self‐collected saliva (Te et al., 2020). The viral load ranged from 103 to 108 viral copies per ml saliva and decreased over the duration of hospitalization, but in one patient, it was still detectable 11 days after hospitalization. Another study extended the epidemiological analysis to 88 infected patients living outside of Wuhan, but who had a recent travel history to Wuhan (Backer et al., 2020). This cohort allowed an estimation of the mean incubation period to 6.4 days. Upper estimates range up to 11 days, which is important to determine the appropriate duration of quarantine.
A novel epidemic is challenging the global health care system. Starting from probably November to December 2019, another Coronavirus entered the arena of human pathogens, to be then defined 2019- nCoV.1 The outbreak of respiratory illness caused by 2019-nCoV was initially detected in Wuhan City, Hubei Province, China. China Republic arranged strong restrictions to limit domestic people circulation. Within days, most European countries and the United States established an unrestricted scientific cooperation to exchange data and information, useful to design a defensive wall against the worldwide spreading of this new epidemic. Spreading is favored by universal access to intercontinental mobility by airplane, and propensity of Chinese people to massively migrate within, but also outside, their subcontinent especially during national holidays.
As of February 5, 2020, the number of confirmed cases was 24,554, with 492 deaths resulting in a crude fatality rate of 2% (https://www.ecdc.europa.eu/en/novelcoronavirus-china).
Spreading in Europe has been likely slowed down so far by the international coordinated effort, with only 28 cases reported. Yet, people are scared by this novel, unknown disease. Their daily lifestyle has been affected, with a marked decrease of unnecessary trips abroad, and reduction of events causing massive people accumulation. Basic sanitary checks have been enforced on people entering European countries directly from China. Questions have been raised even on the opportunity to keep the schools open.
The fear of unknown diseases is obviously even higher for children. As an immediate result, parents are taking their kids to the emergency room of their local hospital more often and in the presence of minimal signs and symptoms of respiratory disease. The public health system has arranged a sanitary chain to isolate and quickly screen all possible, but even suspected cases. However, this emergency belt might result expensive and hard to be sustained for a very long time.
In their report of the characteristics of the first 425 cases observed in Wuhan as of January 22, 2020, Li et al. show that none of the patients had less than 15 years of age.2 Is this children-sparing pattern common to other Coronavirus diseases?
Severe acute respiratory syndrome (SARS) spread in Hong-Kong and then worldwide from March to June 2003, caused by the SARS-associated coronavirus (SARS-CoV). Among over 1700 infected individuals, 6.9% were <18 years of age with a case fatality rate of 0%. (Source: e-SARS database, Hospital Authority, Hong Kong Special Administrative Region, data on file). In their analysis of 6 case series reporting 135 pediatric SARS patients (80 laboratory-confirmed, 27 probable and 28 suspect) from Canada, Hong Kong, Taiwan and Singapore, Stockman et al. reported that patients 12 years of age or younger had milder disease and were less likely than older children to be admitted to an intensive care unit, receive supplemental oxygen or be treated with methylprednisolone. No deaths were reported among children or adolescents with SARS.3 Only one published report of transmission of SARS virus from a pediatric patient was available at the time of writing in 2007.
In their retrospective analysis of the Middle East Respiratory Syndrome (MERS) spread in 2012, also caused by Corona Virus, Azhar et al. report that only 2% of cases occurred in children.4
This clearly shows that three different acute respiratory syndromes developed as epidemic in the last decades showed a reduced propensity to involve children. Coming to the hottest topic, data from Wuhan show that at an early evaluation, the pediatric population, even in this very-high risk area, appears to be at an unexpectedly low risk to develop the disease.2
Why may this happen remains unclear. Are children absolutely protected from infection or only from the risk to develop the disease following infection? Formal demonstration of the ability of 2019-nCov to infect a child has been provided by Chan et al. In their report, when screening for 2019-nCov the asymptomatic members of the family of a patient with pneumonia, they documented infection in a child who yet remained asymptomatic.5 Thus, this first and so far unique case shows that infection of children is possible although apparently extremely rare; furthermore, it was not followed by the development of the respiratory disease at the time of writing.
Persistence of maternal protective immunity extending to the entire pediatric age appears very unlikely. No other positively protective effect may be easily hypothesized. Are children cross-protected by having met other Coronaviruses? Coronaviruses (CoVs) is one of the common viruses that invade the lungs as rhinoviruses, respiratory syncytial virus (RSV), and influenza, which all have an RNA genome and are very frequent in children. Innate immune evasion links to the innate immune responses elicited by respiratory and other (RNA) viruses.6
One explanation could be that pneumonia results from virus-induced immune response causing destruction of pulmonary tissue.7 Such mechanisms could be less effective in children.
As a bottom-line message, although we do not know how massively 2019-CoV will spread and affect the population worldwide, we may try to reassure the population about the real risk represented by this novel ordeal: their children are apparently at a minimal risk to develop this new disease, and at virtually no risk of a fatal course.
2019-nCoV is placed within the beta-coronavirus family, where SARS-CoV and MERS-CoV were also found. The 2019-nCoV genome has been reported to show a 70% similarity with the SARS CoV. The genomes of these viruses and beta coronaviruses have shown to be closely related to the bat SARS-like coronavirus isolate Bat-SL-CoVZC45. The origin of 2019-nCoVs is still under investigation [4, 5].
Cases of pneumonia of unknown etiology were first reported on December 31, 2019, in Wuhan City, Hubei Province, China. It is stated that there is a cluster in the employees of Wuhan South China Seafood City Market (a wholesale fish and livestock market selling different animal species) in the south of Wuhan. Findings compatible with fever, dyspnea and bilateral lung pneumonic infiltration were detected in most cases. Fatal cases were reported so far have generally been older individuals or individuals with concomitant systemic disease [6–8]. The first imported case is a 61-year-old Chinese woman reported from Thailand on January 13, 2020. On January 14, 2020, a male patient in his 30s was reported by the Ministry of Health of Japan as the second imported case. The two imported cases were reported from Thailand and Japan, who have a travel history to Wuhan province, with no history of visiting the seafood market where the first cluster was identified. The virus was defined by authorities as coronaviruses on January 7, 2020, and refined down the total number of the cases. As the number of cases has increased, Chinese authorities have quarantined the city of Wuhan and many other cities, suspended travel in and out in Hubei province [6–8].
An early report of 41 patients published in The Lancet, provided even more detailed information and many epidemiological and clinical studies have been reported consequently. Common symptoms of infection were respiratory symptoms, fever, cough, and dyspnea. More severe cases were presented with pneumonia, severe acute respiratory infection, kidney failure. Asymptomatic people reported carrying the virus in the respiratory tract. A 33 years old German businessman infected from a Chinese colleague who has no symptoms or signs.
At the end of January 2020, 2019-nCoV declared as global health emergency by the World Health Organization. The researchers tried to estimate the size of the epidemic in Wuhan and predict the risk for local and global dimensions. The mean incubation period was found to be 5.2 days (4.1 to 7), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9). The researchers calculated the number of infected patients as 75.800 for January 2020 (about 10 times that reported) using travel data. They found doubling time as 6.4 days and R0 as 2.68. The researchers were assumed that the outbreak would peak in April and if necessary measures are taken and the growth rate of the epidemics slows down, the transmission of the virus can be reduced by 25%. Thus, the total number of cases can be decreased by 50%. The fatality rate of disease was reported as 2% by early February. Non-survivors that have been reported so far are generally older or have concomitant systemic disease. Systemic symptoms, lymphopenia and thrombocytopenia were found more common and radiological involvement was more severe among people over 60. High CRP and LDH levels were also reported more frequently among older patients. A study found that the median age of patients died as 75 (48–89). On the other hand, children were less susceptible to viruses or had a mild infection as compared with adults [7, 11]. Studies calculated a basic reproduction number (R0) of the disease to foresee how far the virus spread. A study of 425 patients found a basic reproduction number as 2.2% (95% CI, 1,4 to 3.9). The WHO (World Health Organization) estimated that each individual infected with 2019-nCoV transmitted the virus to an average of 1.4 to 2.5 others for the earlier phase of the outbreak. That means 2019-nCoV less contagious than SARS, which had an R0 of 3, but more contagious than seasonal flu.
An important group affected by these outbreaks is healthcare workers. During the SARS-CoV outbreak, Dr. Carlos Urbani has gone during his scientific investigations. In recent outbreak also Dr. Li, who tried to warn people about the virus, shared the same fate with his colleague and has also died from novel coronavirus.
Polymerase Chain Reaction-based tests are used for the diagnosis of the disease, preferably from the obtained low respiratory tract samples (such as sputum and/or endotracheal aspirate). Researches also detected the virus from the blood and feces specimens [7, 13]. To our knowledge, there is no specific antiviral treatment for 2019-nCoV. Since the pathogenesis is not fully known, the treatment is supportive and aimed to prevent secondary infections and complications. Randomized controlled studies are underway in China for some drugs, such as Remdesivir (a nucleotide analogue), which was first developed for the treatment of Ebola. Compassionate use of this drug also successfully experienced in a US patient during the outbreak. Also, chloroquine, interferon and protease inhibitors, such as ritonavir, lopinavir/ritonavir, reported being effective in inhibiting the virus invitro [13, 14]. To our knowledge, there is currently no vaccine to prevent 2019-nCoV infection.
On the 11th of February, WHO announced an official name for the disease caused by new coronavirus disease: COVID-19, which refers to Co (Corona), VI (virus), D (disease), and 19 (the year 2019 that it is first discovered). To date (15th February 2020), the virus was detected in 67.191 people worldwide, about 66 thousand of which are within the borders of mainland China. The other countries reporting the highest number of cases are Japan (338), Singapore (72), Hong Kong (56), Thailand (34) and South Korea (28). While nearly 200 thousand people were kept under observation, the number of people who lost their lives increased to 1,527. Only four deaths out of China were reported from Hong Kong (1), Philippines (1), Japan (1) and France (1).
Based on the current information, most patients had a good prognosis, while a few patients were in critical condition, especially the elderly and those with chronic underlying diseases. As of 1 March 2020, a total of 79,968 confirmed cases, including 14,475 (18.1%) with severe illness, and 2873 deaths (3.5%) in mainland China had been reported by WHO. Complications included acute respiratory distress syndrome (ARDS), arrhythmia, shock, acute kidney injury, acute cardiac injury, liver dysfunction and secondary infection. The poor clinical outcome was related to disease severity. The disease tends to progress faster in elderly people, with the median number of days from the occurrence of the first symptoms to death shorter among people aged 65 years or more [56, 57]. Similar to H7N9 patients, the elderly male with comorbidities and ARDS showed a higher death risk. Additionally, more than 100 children were infected, with the youngest being 30 h after birth. Neonates and the elderly need more attention and care due to their immature or weak immune system.
Additional information about 2019-nCoV is needed to better understand transmission, disease severity, and risk to the general population. Although CDC and partners are actively learning about 2019-nCoV, initial CDC guidance is based on guidance for management and prevention of respiratory illnesses including influenza, MERS, and SARS. No vaccine or specific treatment for 2019-nCoV infection is currently available. At present, medical care for patients with 2019-nCoV is supportive.
On January 31, CDC published its third Health Advisory with interim guidance for clinicians and public health practitioners.††† In addition, CDC issued a Clinical Action Alert through its Clinician Outreach and Communication Activity network on January 31.§§§ Interim guidance for health care professionals is available at https://www.cdc.gov/coronavirus/2019-nCoV/hcp/clinical-criteria.html. Health care providers should identify patients who might have been exposed and who have signs or symptoms related to 2019-nCoV infection, isolate these patients, and inform public health departments. This includes obtaining a detailed travel history for patients being evaluated with fever and lower respiratory tract illness. Criteria to guide evaluation and testing of PUIs for 2019-nCoV include 1) fever or signs or symptoms of lower respiratory tract illness (e.g., cough or shortness of breath) in any person, including health care workers, who has had close contact¶¶¶ with a patient with laboratory-confirmed 2019-nCoV infection within 14 days of symptom onset; 2) fever and signs or symptoms of lower respiratory tract illness (e.g., cough or shortness of breath) in any person with a history of travel from Hubei Province, China, within 14 days of symptom onset; or 3) fever and signs or symptoms of lower respiratory tract illness (e.g., cough or shortness of breath) requiring hospitalization in any person with a history of travel from mainland China within 14 days of symptom onset. Additional nonhospitalized PUIs may be tested based on consultation with state and local public health officials. Clinicians should evaluate PUIs for other possible causes of illness (e.g., influenza and respiratory syncytial virus) as clinically indicated.
CDC currently recommends a cautious approach to the examination of PUIs. These patients should be asked to wear a surgical mask as soon as they are identified, and directed to a separate area, if possible, separated by at least 6 ft (2 m) from other persons. Patients should be evaluated in a private room with the door closed, ideally an airborne infection isolation room, if available. Health care personnel entering the room should use standard precautions, contact precautions, airborne precautions, and eye protection (e.g., goggles or a face shield).
Clinicians should immediately notify the health care facility’s infection control personnel and local health department. The health department will determine whether the patient needs to be considered a PUI for 2019-nCoV and be tested for infection. If directed by the health department, to increase the likelihood of detecting 2019-nCoV infection, CDC recommends collecting and testing both upper and lower respiratory tract specimens.**** Additional specimen types (e.g., stool or urine) may be collected and stored. Specimens should be collected as soon as possible once a PUI is identified regardless of time since symptom onset.
For persons who might have 2019-nCoV infection and their close contacts, information and guidance on how to reduce the risk for transmitting and acquiring infection is available at https://www.cdc.gov/coronavirus/2019-ncov/hcp/guidance-prevent-spread.html. Close contacts should immediately call their health care providers if they develop symptoms. In addition, CDC is working closely with state and local health partners to develop and disseminate information to the public on general prevention of respiratory illness, including the 2019-nCoV. This includes everyday preventive actions such as washing your hands, covering your cough, and staying home when you are ill. Additional information and resources for this outbreak are available on the CDC website (https://www.cdc.gov/coronavirus/2019-ncov/index.html).
Control number of visiting patients
Reducing outpatient visitors will be critical to decrease cross-infection. Patients are asked to make an appointment before going to the hospital.
b)Make good use of online platforms
Online platforms such as the hospital’s official website or WeChat should be well utilized. Online platforms can provide notice for decreasing outpatient visits and updates on COVID-19, help patients distinguish between urgent and non-urgent ocular diseases, recommend safe and self-executing treatments for common nonurgent ocular diseases, remind patients to prepare correct personal protection before coming to the hospital, advise patients with suspicious symptoms such as fever to first visit the screening center before coming to the ophthalmic clinic, and give targeted guidance for common chronic eye diseases during this period.
c)Online ordering and delivery of prescribed medication
Both hospital and patients can benefit from submitting prescriptions online and having patient medication sent to their doorsteps via non-contact delivery.